Lipoprotein (a) and development of intermittent claudication and major cardiovascular events in men and women: the Edinburgh Artery Study. Long term prognosis in patients with peripheral arterial disease treated with antiplatelet agents. Oral Buflomedil in the Prevention of Cardiovascular Events in Patients With Peripheral Arterial Obstructive Disease: A Randomized, Placebo-Controlled, 4-Year Study Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic Peripheral Artery Disease Incidence, natural history and cardiovascular events in symptomatic and asymptomatic peripheral arterial disease in the general population. The fate of patients with intermittent claudication in the 21st century revisited – results from the CAVASIC Study Ten Year Mortality in Different Peripheral Arterial Disease Stages: A Population Based Observational Study on Outcome. Serum concentrations of L-arginine and L-homoarginine in male patients with intermittent claudication: a cross-sectional and prospective investigation in the CAVASIC Study. Treatment of intermittent claudication with beraprost sodium, an orally active prostaglandin I2 analogue: a double-blinded, randomized, controlled trial. Secondary prevention of atherosclerosis through chlamydia pneumoniae eradication (SPACE Trial): a randomised clinical trial in patients with peripheral arterial disease. Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. Low-Density Lipoprotein Cholesterol Lowering With Evolocumab and Outcomes in Patients With Peripheral Artery Disease: Insights From the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease. Design and rationale for the Effects of Ticagrelor and Clopidogrel in Patients with Peripheral Artery Disease (EUCLID) trial. A prospective investigation of elevated lipoprotein (a) detected by electrophoresis and cardiovascular disease in women. The Framingham Heart Study. Impact of exercise training on inflammation and platelet activation in patients with intermittent claudication. Extended Duration Dual Antiplatelet Therapy After Coronary Stenting Among Patients With Peripheral Arterial Disease: A Subanalysis of the Dual Antiplatelet Therapy Study. Reduction of iron stores and cardiovascular outcomes in patients with peripheral arterial disease: a randomized controlled trial. Cholesterol Reduction With Atorvastatin Improves Walking Distance in Patients With Peripheral Arterial Disease Prevention of myocardial infarction and stroke in patients with intermittent claudication; effects of ticlopidine. Results from STIMS, the Swedish Ticlopidine Multicentre Study. Microalbuminuria and peripheral arterial disease are independent predictors of cardiovascular and all-cause mortality, especially among hypertensive subjects: five-year follow-up of the Hoorn Study. Cellular Aging Reflected by Leukocyte Telomere Length Predicts Advanced Atherosclerosis and Cardiovascular Disease Risk Peripheral Arterial Occlusive Disease: Prognostic Value of Signs, Symptoms, and the Ankle-Brachial Pressure Index Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. Exercise for intermittent claudication Cardiovascular morbidity and mortality in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) in chronic renal failure: a multicenter, randomized, controlled trial. Mortality over a period of 10 years in patients with peripheral arterial disease. Peripheral Arterial Disease as an Independent Predictor for Excess Stroke Morbidity and Mortality in Primary-Care Patients: 5-Year Results of the getABI Study Pioglitazone and the risk of cardiovascular events in patients with Type 2 diabetes receiving concomitant treatment with nitrates, renin-angiotensin system blockers, or insulin: results from the PROactive study (PROactive 20). Italian multicenter study on reversible cerebral ischemic attacks: VI--Prognostic factors and follow-up results. The harms of smoking and benefits of smoking cessation in women compared with men with type 2 diabetes: an observational analysis of the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial Does weight loss reduce plasma fibrinogen? Renal Dysfunction as a Risk Factor for Mortality and Cardiovascular Disease in Renal Transplantation: Experience from the Assessment of Lescol in Renal Transplantation Trial Impact of achieved blood pressure on cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial. One-year cardiovascular event rates in outpatients with atherothrombosis. Physical demands at work, physical fitness, and 30-year ischaemic heart disease and all-cause mortality in the Copenhagen Male Study. Assessment of absolute risk of death after myocardial infarction by use of multiple-risk-factor assessment equations: GISSI-Prevenzione mortality risk chart. A population survey of cardiovascular disease in elderly people: design, methods and prevalence results. Mortality over four years in SHEP participants with a low ankle-arm index. Uric Acid Levels Are Associated With All-Cause and Cardiovascular Disease Mortality Independent of Systemic Inflammation in Men From the General Population: The MONICA/KORA Cohort Study Long-term association of brachial artery flow-mediated vasodilation and cardiovascular events in middle-aged subjects with no apparent heart disease. Endothelial Dysfunction, Oxidative Stress, and Risk of Cardiovascular Events in Patients With Coronary Artery Disease Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. Hypertension and borderline isolated systolic hypertension increase risks of cardiovascular disease and mortality in male physicians. J-curve revisited: An analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial. Kidney function and risk of cardiovascular disease and mortality in women: a prospective cohort study Panic attacks and risk of incident cardiovascular events among postmenopausal women in the Women's Health Initiative Observational Study. Change in depression as a precursor of cardiovascular events. SHEP Cooperative Research Group (Systoloc Hypertension in the elderly). Risk of Myocardial Infarction or Vascular Death After First Ischemic Stroke: The Northern Manhattan Study Asymmetric dimethylarginine correlates with measures of disease severity, major adverse cardiovascular events and all-cause mortality in patients with peripheral arterial disease Effects of individual risk factors on the incidence of cardiovascular events in the treated hypertensive patients of the Hypertension Optimal Treatment Study. HOT Study Group. Is it possible to reduce the risk of cardiovascular events in subjects suffering from intermittent claudication of the lower limbs? Diabetes and the HOPE study: implications for macrovascular and microvascular disease. Cardiovascular disease and risk factors in PCOS women of postmenopausal age: a 21-year controlled follow-up study. Is hyperuricemia a risk factor of stroke and coronary heart disease among Africans? Aspirin prescription and outcomes in hemodialysis patients: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Long-term effects of intensive glucose lowering on cardiovascular outcomes. Non-invasively detected carotid stenosis and ischaemic heart disease in men with leg arteriosclerosis Ticagrelor Compared With Clopidogrel in Patients With Prior Lower Extremity Revascularization for Peripheral Artery Disease Effect of cloricromene on intermittent claudication. A randomized, double-blind, placebo-controlled trial in patients treated with aspirin: effect on claudication distance and quality of life Erectile Dysfunction Predicts Cardiovascular Events in High-Risk Patients Receiving Telmisartan, Ramipril, or Both: The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (ONT Depression treatment after myocardial infarction and long-term risk of subsequent cardiovascular events and mortality: a randomized controlled trial. Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals. Increased arterial wave reflections predict severe cardiovascular events in patients undergoing percutaneous coronary interventions. Activation products of the haemostatic system in coronary, cerebrovascular and peripheral arterial disease. The combined use of aspirin, a statin, and blood pressure-lowering agents (polypill components) and the risk of vascular morbidity and mortality in patients with coronary artery disease. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. Compliance and adverse event withdrawal: their impact on the West of Scotland Coronary Prevention Study. Urinary albumin concentration and long-term cardiovascular risk in acute coronary syndrome patients: a PROVE IT-TIMI 22 substudy Cardiovascular Disease and Mortality in Older Adults with Small Abdominal Aortic Aneurysms Detected by Ultrasonography: The Cardiovascular Health Study Left ventricular hypertrophy on electrocardiogram: prognostic implications from a 10-year cohort study of older subjects: a report from the Bronx Longitudinal Aging Study. Association of Diet, Exercise, and Smoking Modification With Risk of Early Cardiovascular Events After Acute Coronary Syndromes Is C-Reactive Protein Specific for Vascular Disease in Women? SUPERvised exercise therapy or immediate PTA for intermittent claudication in patients with an iliac artery obstruction--a multicentre randomised controlled trial; SUPER study design and rationale. Managing PAD with multiple platelet inhibitors: the effect of combination therapy on bleeding time. Alcohol intake and mortality in middle aged men with diagnosed coronary heart disease Ethnic variation in adverse cardiovascular outcomes and bleeding complications in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study. Systolic blood pressure variability as a risk factor for stroke and cardiovascular mortality in the elderly hypertensive population Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg) Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE): rationale and design overview. Effect of rosuvastatin on outcomes in chronic haemodialysis patients – design and rationale of the AURORA study Design of the blockade of the glycoprotein IIb/IIIa receptor to avoid vascular occlusion (BRAVO) trial. Impact of Diabetes on Long-Term Prognosis in Patients With Unstable Angina and Non–Q-Wave Myocardial Infarction: Results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry Beneficial impact of Xuezhikang on cardiovascular events and mortality in elderly hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS). Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality: the cardiovascular health study. Psychosocial nursing therapy following sudden cardiac arrest: impact on two-year survival. Effect of aspirin on mortality in women with symptomatic or silent myocardial ischemia. Israeli BIP Study Group. Multivitamins in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial.
Lipoprotein ( a ) may be an important risk factor for atherosclerosis . It is widely accepted that  lipoprotein ( a ) levels are raised in patients with coronary heart disease , but there is some doubt about the causality of the relationship . In addition , little is known about the relationship between lipoprotein ( a ) and either stroke or peripheral arterial disease , nor about the role of lipoprotein ( a ) in women . Subjects aged 55 - 74 years ( n=1592 ) were selected at r and om from 11 general practice s in Edinburgh , Scotl and and followed up for 5 years . The incidences of myocardial infa rct ion , intermittent claudication and stroke were 13.4 , 9.4 and 3.7 % , respectively . Raised lipoprotein ( a ) levels at baseline were associated with an increased risk ( 95 % confidence interval ) of myocardial infa rct ion RR 1.15 ( 1.00 , 1.32 ) , intermittent claudication RR 1.32 ( 1.10 , 1.57 ) but not significantly for stroke RR 1.24 ( 0.93 , 1.64 ) . This increased risk persisted for intermittent claudication after adjustment for baseline cardiovascular disease and other risk factors RR 1.20 ( 1.00 , 1.43 ) , but for myocardial infa rct ion became non-significant RR 1.06 ( 0.91 , 1.23 ) . The risk of disease associated with raised lipoprotein ( a ) was slightly higher in women than in men , especially for intermittent claudication ( men RR 1.09 ( 0.87 , 1.36 ) compared to women RR 1.37 ( 1.01 , 1.87 ) ) . In conclusion , we found that lipoprotein ( a ) was an independent predictor of cardiovascular events in both sexes . The association between lipoprotein ( a ) and cardiovascular events may have been stronger in women than in men , and for peripheral arterial disease than myocardial infa rct ion and stroke OBJECTIVE To determine the fatal and non-fatal cardiovascular event rate in patients with intermittent claudication treated with antiplatelet agents .  METHODS AND DESIGN Patients with PAD-II stage Fontaine ( n=223 ) and sex and age matched controls ( n=446 ) were followed up from 1974 to 1998 . All patients were treated with antiplatelet agents ( aspirin , 325 mg once daily or ticlopidine , 250 mg twice daily ) and for risk factors , if present . The end points were death for any cause ( vascular event , cancer , and others ) and non-fatal vascular events ( myocardial infa rct ion , ischemic/hemorrhagic stroke , and leg amputation ) . RESULTS PAD patients had a significantly higher mortality rate than controls ( 3.99 vs. 2.53 deaths for 100 patients per year , respectively ) , cancer ( mostly lung , stomach and colon ) and vascular mortality accounted for such difference . The incidence of non-fatal vascular events was three times higher in patients than in controls ( 1.7 vs. 0.56 , 100 patients per year , respectively , p<0.05 ) even considering amputation separately ( 0.28 vs. 0.00 , 100 patients per year , p<0.05 ) . No difference between patients treated with aspirin or ticlopidine could be found in both end points . CONCLUSIONS Vascular mortality and morbidity , despite the use of antiplatelet agents , are still higher than sex and age matched controls ; however , the commonest cause of death is cancer Background — Cardiovascular-related morbidity and mortality in patients with peripheral arterial obstructive disease remain high . We performed an international , multicenter , r and omized , double-blind , placebo-controlled trial to investigate whether long-term administration of oral buflomedil could reduce the rate of cardiovascular events in patients with intermittent claudication . Methods and Results — Patients > 40 years of age with documented peripheral arterial obstructive disease , intermittent claudication , and an ankle-brachial index between 0.30 and 0.80 were eligible for inclusion and were r and omized to receive orally either buflomedil or placebo for 2 to 4 years . Aspirin was recommended for all patients ( unless they were receiving other antithrombotic treatments at inclusion ) . The primary efficacy outcome was critical cardiovascular events , defined as the composite of cardiovascular death , nonfatal myocardial infa rct ion , nonfatal stroke , symptomatic deterioration of peripheral arterial obstructive disease , or leg amputation .  A total of 2078 patients were recruited . Mean treatment duration was 33 months . The rate of critical cardiovascular events was significantly lower in buflomedil-r and omized patients than in placebo-r and omized patients ( 9.1 % versus 12.4 % ; hazard ratio , 0.742 ; 95 % confidence interval , 0.603 to 0.915 ; P=0.0163 ) . Ankle-brachial index increased by 9.2 % in buflomedil-r and omized patients and decreased by 3.6 % in placebo-r and omized patients ( P<0.001 ) . Tolerance of buflomedil and placebo was comparable . Conclusions — Compared with placebo , buflomedil administered for 3 years reduced the occurrence of symptomatic cardiovascular events by 26 % . The main contributor to the difference in the composite outcome was the reduction in symptomatic deterioration of peripheral arterial disease . The use of buflomedil should be considered in addition to an antiplatelet agent in patients with peripheral arterial obstructive disease and intermittent claudication Background — Our aim was to assess the mortality and vascular morbidity risk of elderly individuals with asymptomatic versus symptomatic peripheral artery disease ( PAD ) in the primary care setting . Methods and Results — This prospect i ve cohort study included 6880 representative unselected patients ≥65 years of age with monitored follow-up over 5 years . According to physician diagnosis , 5392 patients had no PAD , 836 had asymptomatic PAD ( ankle brachial index < 0.9 without symptoms ) , and 593 had symptomatic PAD ( lower-extremity peripheral revascularization , amputation as  a  result  of PAD , or intermittent claudication symptoms regardless of ankle brachial index ) . The risk of symptomatic compared with asymptomatic PAD patients was significantly increased for the composite of all-cause death or severe vascular event ( myocardial infa rct ion , coronary revascularization , stroke , carotid revascularization , or lower-extremity peripheral vascular events ; hazard ratio , 1.48 ; 95 % confidence interval , 1.21 to 1.80 ) but not for all-cause death alone ( hazard ratio , 1.13 ; 95 % confidence interval , 0.89 to 1.43 ) , all-cause death/myocardial infa rct ion/stroke ( excluding lower-extremity peripheral vascular events and any revascularizations ; hazard ratio , 1.18 ; 95 % confidence interval , 0.92 to 1.52 ) , cardiovascular events alone ( hazard ratio , 1.20 ; 95 % confidence interval , 0.89 to 1.60 ) , or cerebrovascular events alone ( hazard ratio , 1.33 ; 95 % confidence interval , 0.80 to 2.20 ) . Lower ankle brachial index categories were associated with increased risk . PAD was a strong factor for the prediction of the composite end point in an adjusted model . Conclusions — Asymptomatic PAD diagnosed through routine screening in the offices of primary care physicians carries a high mortality and /or vascular event risk . Notably , the risk of mortality was similar in symptomatic and asymptomatic patients with PAD and was significantly higher than in those without PAD . In the primary care setting , the diagnosis of PAD has important prognostic value BACKGROUND Intermittent claudication is associated with a poor prognosis , but less is known of the risks associated with asymptomatic peripheral arterial disease . The aims of this study were to determine the incidence and natural history of claudication , and the incidence of cardiovascular events in symptomatic and asymptomatic peripheral arterial disease . METHODS In 1988 , 1592 subjects aged 55 - 74 years were selected r and omly from the age-sex register of 10 general practice s in Edinburgh , Scotl and . The presence of peripheral arterial disease was determined by the World Health Organization question naire on intermittent claudication , the ankle brachial pressure index and a reactive hyperaemia test . This cohort was followed prospect ively over 5 years for subsequent cardiovascular events and death . RESULTS One hundred and sixteen new cases of claudication were identified ( incidence density 15.5 per 1000 person-years ) . Of those with claudication at baseline , 28.8 % and still had pain after 5 years , 8.2 % underwent  vascular surgery or amputation , and 1.4 % developed leg ulceration .  Claudicants had a significantly increased risk of developing angina compared with normals ( RR : 2.31 , 95 % CI : 1.04 - 5.10 ) , and asymptomatic subjects had a slightly increased risk of myocardial infa rct ion and stroke . Deaths from cardiovascular disease were more likely in both claudicants ( RR : 2.67 , 95 % CI : 1.34 - 5.29 ) and subjects with major ( RR : 2.08 , 95 % CI : 1.13 - 3.83 ) or minor asymptomatic disease ( RR : 1.74 , 95 % CI : 1.09 - 2.76 ) . Subjects with major asymptomatic disease also had an increased risk of non-cardiovascular death ( RR : 2.19 , 95 % CI : 1.33 - 3.59 ) , and therefore had the highest overall risk of death ( RR : 2.44 , 95 % CI : 1.59 - 3.74 ) . CONCLUSIONS Subjects with asymptomatic peripheral arterial disease appear to have the same increased risk of cardiovascular events and death found in claudicants Patients with intermittent claudication carry a high risk for cardiovascular complications . The TransAtlantic Inter-Society Consensus ( TASC ) Group estimated a five-year overall mortality of 30 % for these patients , the majority dying from cardiovascular causes . We investigated whether this evaluation is still applicable in nowadays patients . We therefore prospect ively followed 255 male patients with intermittent claudication from the CAVASIC Study during 7 years for overall mortality , vascular morbidity and mortality and local PAD outcomes . Overall mortality reached 16.1 % ( n = 41 ) . Most patients died from cancer ( n = 20 ) . Half of patients ( n = 22 ; 8.6 % ) died within the first five years . Incident cardiovascular events were observed among 70 patients ( 27.5 % ) , 54 ( 21.2 % ) during the first five years . Vascular mortality was low with 5.1 % ( n = 13 ) for the entire and 3.1 % for the first five years of follow-up . Prevalent coronary artery disease did not increase the risk to die from all or vascular causes . PAD symptoms remained stable or improved in the majority of patients ( 67 % ) . In summary , compared to TASC , the proportion of cardiovascular events did not markedly decrease over the last two decades . Vascular mortality , however , was low among our population . This indicates that nowadays patients more often survive cardiovascular events and a major number dies from cancer OBJECTIVE The aim was to determine long-term mortality rates and the underlying cause of death for subjects with different peripheral arterial disease ( PAD ) stages in a population based setting . METHODS A r and omly selected population sample of 5080 subjects was enrolled in the study in 2004 - 2005 . Participants completed health state question naires and underwent ankle brachial index ( ABI ) measurements for classification into PAD severity stages and reference subjects . A follow-up was conducted by the end of 2015 using data from Swedish governmental national registers for cause of death , which was then compared with PAD stage determined at baseline in 2005 . RESULTS The 10 year all cause mortality was 27 % for reference cases , 56 % for asymptomatic PAD ( APAD ) , 63 % for intermittent claudication ( IC ) , and 75 % for severe limb ischaemia ( SLI ) . Among all PAD subjects , cardiovascular ( CV ) causes were the most common main cause of death ( 45 % ) and a CV event was present as either the main or one of the three most common contributing causes of death in 64 % of the cases . The age adjusted hazard ratios for a main cause of death by a CV event were 1.9 ( 95 % CI 1.5 - 2.3 ) for APAD , 2.6 ( 95 % CI 2.1 - 3.4 ) for IC , and 3.5 ( 95 % CI 2.3 - 5.2 ) for SLI . CONCLUSION PAD subjects , including the APAD subjects , are still at high risk of CV death . The mortality risks are more than doubled in symptomatic PAD patients compared with reference subjects and increase by severity of PAD stage . Awareness and improved risk reduction management of PAD are still warranted BACKGROUND High serum concentrations of l-arginine and l-homoarginine increase nitric oxide ( NO ) availability and thereby improve endothelial function . Information about the association of these markers with peripheral arterial disease ( PAD ) and related outcomes is sparse . METHODS l-arginine , its metabolites and l-homoarginine were analyzed in the CAVASIC Study including 232 male patients diagnosed with intermittent claudication and 246 age- and diabetes-matched controls . After the baseline investigation PAD patients were prospect ively followed ( median 7 years ) . The association of these markers with symptomatic PAD at baseline , incident cardiovascular events and all-cause mortality was assessed . RESULTS At baseline each increase of ln-l-homoarginine and l-arginine by one st and ard deviation was associated with symptomatic PAD : OR=0.75 , 95%CI 0.59 - 0.96 , P=0.02 and OR=1.36 , 95%CI 1.07 - 1.73 , P=0.01 , respectively ( both models adjusted for ln-CRP , GFR , HDL cholesterol , and current smoking ) . Only l-arginine remained significant after additional adjustment for ln-NT-proBNP and hs-cTnT : OR=1.49 , P=0.002 . In the Cox regression analysis elevated ln-l-homoarginine significantly reduced the risk to die ( n=38 ) even independent from ln-NT-proBNP and hs-cTnT : HR=0.59 , 95%CI 0.41 - 0.84 , P=0.004 . l-arginine was significantly predicting incident cardiovascular events ( n=65 ) : HR=1.68 , 95%CI 1.35 - 2.10 , P < 0.001 . CONCLUSIONS This study in male patients with intermittent claudication and age- and diabetes-matched controls showed an association of l-homoarginine and l-arginine with PAD . During follow-up , l-arginine was associated with incident cardiovascular events probably due to its primary role in NO metabolism and impact on endothelial integrity . l-homoarginine was related to all-cause mortality implying a broader role in metabolic processes besides endothelial function OBJECTIVES In the current study , we hypothesized that beraprost would : 1 ) improve treadmill exercise performance and quality of life ; and 2 ) decrease rates of ischemic events in patients with intermittent claudication . BACKGROUND Previous trials with beraprost sodium , an orally active prostagl and in I(2 ) analogue , in the treatment of claudication in patients with peripheral arterial disease ( PAD ) have been inconsistent . METHODS Patients with intermittent claudication ( n = 897 ) were r and omized to receive either 40 microg three times a day of beraprost with meals ( n = 385 ) or placebo ( n = 377 ) in a double-blinded manner for one year . The primary efficacy parameter was treadmill-measured maximum walking distance , as assessed at three and six months after r and omization . Secondary efficacy parameters included treadmill-measured pain-free walking distance and change in quality of life . RESULTS There was no significant improvement in maximum walking distance in the beraprost group ( 16.7 % ) as compared with the placebo group ( 14.6 % , p = NS ) . Administration of beraprost did not improve the pain-free walking distance ( p = NS between treatment groups ) , and there was no improvement in the quality -of-life measures between the treatment groups . The incidence of critical cardiovascular events was 7.3 % in the beraprost group and 11.4 % in the placebo group ( p = NS ) . There was a significant reduction in the combination of cardiovascular death and myocardial infa rct ion in the beraprost group ( p = 0.01 ) . CONCLUSIONS Despite previous investigations suggesting efficacy , these results indicate that beraprost is not an effective treatment to improve symptoms of intermittent claudication in patients with PAD . The potential benefit of beraprost on critical cardiovascular events would require confirmation in a larger prospect i ve investigation BACKGROUND Sero-epidemiological and experimental studies suggest that Chlamydia pneumoniae infections play an important role in the development of atherosclerosis . Clinical trials have shown contradictory results regarding the efficacy of antibiotics to prevent atherosclerosis-related complications in patients with coronary artery disease . Our aim was to study the effect of a short course of azithromycin on the incidence of cardiovascular events and peripheral vascular function in patients with stable peripheral arterial disease ( PAD ) . PATIENTS AND METHODS Five hundred and nine PAD- patients were r and omised to receive either a 3-day course of azithromycin ( 500 mg daily ) or placebo , with 2 years of follow-up . C. pneumoniae serology was determined at baseline . Clinical endpoints were death , coronary events ( myocardial infa rct ion , unstable angina , and /or coronary revascularization procedures ) , cerebral events ( stroke , TIA , and /or carotid endarterectomy ) and peripheral arterial complications ( increased PAD-symptoms with decreased ankle-brachial index ( ABPI , 0.1-point decrease after 12 months ) , and /or peripheral revascularization procedures ) . RESULTS Five hundred and nine patients ( 160 women ) with an atherosclerotic risk factor profile were r and omised , 257 patients to azithromycin and 252 to placebo .  Four hundred and forty nine patients ( 88 % ) had intermittent claudication and 60 ( 12 % ) had critical limb ischemia . By 24-month follow up , 182 patients ( 36 % ) developed 252 complications ( 45 deaths , 34 coronary events , 34 cerebral events and 139 peripheral arterial complications ) . C. pneumoniae IgA-titres were associated with the development of cardiovascular events . Nevertheless , the number of complications ( 131 in the azithromycin group vs. 121 in the placebo group ) and the number of patients that developed complications ( 98 ( 38 % ) in the azithromycin vs. 84 ( 33 % ) in the placebo group ) was comparable in both treatment groups . Life table analysis showed no effect of azithromycin on survival or ABPI . CONCLUSION A short-term course of azithromycin offers no benefits for survival or ankle pressure in PAD- patients BACKGROUND Atherosclerotic peripheral arterial disease is associated with an increased risk of myocardial infa rct ion , stroke , and death from cardiovascular causes . Antiplatelet drugs reduce this risk , but the role of oral anticoagulant agents in the prevention of cardiovascular complications in patients with peripheral arterial disease is unclear . METHODS We assigned patients with peripheral arterial disease to combination therapy with an antiplatelet agent and an oral anticoagulant agent ( target international normalized ratio [ INR ] , 2.0 to 3.0 ) or to antiplatelet therapy alone . The first co primary outcome was myocardial infa rct ion , stroke , or death from cardiovascular causes ; the second co primary outcome was myocardial infa rct ion , stroke , severe ischemia of the peripheral or coronary arteries leading to urgent intervention , or death from cardiovascular causes . RESULTS A total of 2161 patients were r and omly assigned to therapy . The mean follow-up time was 35 months . Myocardial infa rct ion , stroke , or death from cardiovascular causes occurred in 132 of 1080 patients receiving combination therapy ( 12.2 % ) and in 144 of 1081 patients receiving antiplatelet therapy alone ( 13.3 % ) ( relative risk , 0.92 ; 95 % confidence interval [ CI ] , 0.73 to 1.16 ; P=0.48 ) . Myocardial infa rct ion , stroke , severe ischemia , or death from cardiovascular causes occurred in 172 patients receiving combination therapy ( 15.9 % ) as compared with 188 patients receiving antiplatelet therapy alone ( 17.4 % ) ( relative risk , 0.91 ; 95 % CI , 0.74 to 1.12 ; P=0.37 ) . Life-threatening bleeding occurred in 43 patients receiving combination therapy ( 4.0 % ) as compared with 13 patients receiving antiplatelet therapy alone ( 1.2 % ) ( relative risk , 3.41 ; 95 % CI , 1.84 to 6.35 ; P<0.001 ) . CONCLUSIONS In patients with peripheral arterial disease , the combination of an oral anticoagulant and antiplatelet therapy was not more effective than antiplatelet therapy alone in preventing major cardiovascular complications and was associated with an increase in life-threatening bleeding . ( Clinical Trials.gov number , NCT00125671 [ Clinical Trials.gov ] . ) Background : The PCSK9 ( proprotein convertase subtilisin/kexin type 9 ) inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER trial ( Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk ) . We investigated the efficacy and safety of evolocumab in patients with peripheral artery disease ( PAD ) as well as the effect on major adverse limb events . Methods : FOURIER was a r and omized trial of evolocumab versus placebo  in 27 564 patients with atherosclerotic disease on statin therapy followed for a median of 2.2 years . Patients were identified as having PAD at baseline if they had intermittent claudication and an ankle brachial index of < 0.85 , or if they had a prior peripheral vascular procedure . The primary end point was a composite of cardiovascular death , myocardial infa rct ion , stroke , hospital admission for unstable angina , or coronary revascularization . The key secondary end point was a composite of cardiovascular death , myocardial infa rct ion , or stroke . An additional outcome of interest was major adverse limb events defined as acute limb ischemia , major amputation , or urgent peripheral revascularization for ischemia . Results : Three thous and six hundred forty-two patients ( 13.2 % ) had PAD ( 1505 with no prior myocardial infa rct ion or stroke ) . Evolocumab significantly reduced the primary end point consistently in patients with PAD ( hazard ratio [ HR ] 0.79 ; 95 % confidence interval [ CI ] , 0.66–0.94 ; P=0.0098 ) and without PAD ( HR 0.86 ; 95 % CI , 0.80–0.93 ; P=0.0003 ; Pinteraction=0.40 ) . For the key secondary end point , the HRs were 0.73 ( 0.59–0.91 ; P=0.0040 ) for those with PAD and 0.81 ( 0.73–0.90 ; P<0.0001 ) for those without PAD ( Pinteraction=0.41 ) . Because of their higher risk , patients with PAD had larger absolute risk reductions for the primary end point ( 3.5 % with PAD , 1.6 % without PAD ) and the key secondary end point ( 3.5 % with PAD , 1.4 % without PAD ) . Evolocumab reduced the risk of major adverse limb events in all patients ( HR , 0.58 ; 95 % CI , 0.38–0.88 ; P=0.0093 ) with consistent effects in those with and without known PAD . There was a consistent relationship between lower achieved low-density lipoprotein cholesterol and lower risk of limb events ( P=0.026 for the beta coefficient ) that extended down to < 10 mg/dL. Conclusions : Patients with PAD are at high risk of cardiovascular events , and PCSK9 inhibition with evolocumab significantly reduced that risk with large absolute risk reductions . Moreover , lowering of low-density lipoprotein cholesterol with evolocumab reduced the risk of major adverse limb events . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifier : NCT01764633 BACKGROUND Peripheral artery disease ( PAD ) is associated with heightened ischemic and bleeding risk in patients with prior myocardial infa rct ion ( MI ) . OBJECTIVES This study evaluated the efficacy and safety of ticagrelor on major cardiovascular ( CV ) events and major adverse limb events in patients with PAD and a prior MI . METHODS PEGASUS-TIMI 54 ( Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infa rct ion 54 ) r and omized 21,162 patients with prior MI ( 1 to 3 years ) to ticagrelor 90 mg twice daily , ticagrelor 60 mg twice daily , or placebo  , all on a background of low-dose aspirin . History of PAD was obtained at baseline . Occurrences of major adverse cardiovascular events ( MACE ) ( defined as CV death , MI , or stroke ) and major adverse limb events ( MALE ) ( defined as acute limb ischemia or peripheral revascularization for ischemia ) were recorded in follow-up . RESULTS A total of 1,143 patients ( 5 % ) had known PAD . In the placebo arm , those with PAD ( n = 404 ) had higher rates of MACE at 3 years than those without ( n = 6,663 ; 19.3 % vs. 8.4 % ; p < 0.001 ) , which persisted after adjusting for baseline differences ( adjusted hazard ratio : 1.60 ; 95 % confidence interval : 1.20 to 2.13 ; p = 0.0013 ) , and higher rates of acute limb ischemia ( 1.0 % vs. 0.1 % ) and peripheral revascularization procedures ( 9.15 % vs. 0.46 % ) . Whereas the relative risk reduction in MACE with ticagrelor was consistent , regardless of PAD , patients with PAD had a greater absolute risk reduction of 4.1 % ( number needed to treat : 25 ) due to their higher absolute risk . The absolute excess of TIMI major bleeding was 0.12 % ( number needed to harm : 834 ) . The 60-mg dose had particularly favorable outcomes for CV and all-cause mortality . Ticagrelor ( pooled doses ) reduced the risk of MALE ( hazard ratio : 0.65 ; 95 % confidence interval : 0.44 to 0.95 ; p = 0.026 ) . CONCLUSIONS Among stable patients with prior MI , those with concomitant PAD have heightened ischemic risk . In these patients , ticagrelor reduced MACE , with a large absolute risk reduction , and MALE . ( Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [ PEGASUS-TIMI 54 ] ; NCT01225562 ) BACKGROUND Despite overwhelming data demonstrating the efficacy of antiplatelet therapy in heart disease and stroke , data in peripheral artery disease ( PAD ) are less compelling . Aspirin has modest evidence supporting a reduction in cardiovascular events in patients with PAD , whereas clopidogrel monotherapy may be more effective in PAD . Ticagrelor , a potent , reversibly binding P2Y12 receptor antagonist , is beneficial in patients with acute coronary syndrome and prior myocardial infa rct ion . The EUCLID trial is design ed to address the need for effective antiplatelet therapy in PAD to decrease the risk of cardiovascular events . STUDY DESIGN EUCLID is a r and omized , double-blind , parallel-group , multinational clinical trial design ed to evaluate the efficacy and safety of ticagrelor compared with clopidogrel for the prevention of major adverse cardiovascular events in subjects with symptomatic PAD . Subjects with established PAD will be r and omized in a 1:1 fashion to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily . The primary end point is a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . Other end points address limb events including acute leg ischemia , need for revascularization , disease progression by ankle-brachial index , and quality of life . The primary safety objective is Thrombolysis in Myocardial Infa rct ion-defined major bleeding .  Recruitment began in December 2012 and was completed in March 2014 ; 13,887 patients were r and omized . The trial will continue until at least 1,364 adjudicated primary end points occur . CONCLUSIONS The EUCLID study is investigating whether treatment with ticagrelor versus clopidogrel , given as antiplatelet monotherapy , will reduce the incidence of cardiovascular and limb-specific events in patients with symptomatic PAD BACKGROUND Sinking prebeta lipoprotein is a putative marker for elevated levels of lipoprotein ( a ) . Although prospect i ve data suggest that increased plasma lipoprotein ( a ) is an independent risk factor for coronary heart disease in men , no prospect i ve studies are available in women . METHODS AND RESULTS From 1968 through 1975 , sinking prebeta lipoprotein  was determined by paper electrophoresis in 3103 women Framingham Heart Study participants who were free of prevalent cardiovascular disease . A  sinking prebeta lipoprotein b and was detectable in 434 of the women ( 14 % ) studied . The median follow-up interval was approximately 12 years . Incident cardiovascular disease was associated with b and presence using a proportional hazards model that included age , smoking , body mass index , systolic blood pressure , glucose intolerance , low- and high-density lipoprotein cholesterol , and ECG left ventricular hypertrophy . Multivariable adjusted relative risk estimates ( with 95 % confidence intervals ) for outcomes in the b and present versus absent groups were as follows : myocardial infa rct ion ( 82 events ) , 2.37 ( 1.48 to 3.81 ) ; intermittent claudication ( 62 events ) , 1.94 ( 1.07 to 3.50 ) ; cerebrovascular disease ( 83 events ) , 1.88 ( 1.12 to 3.15 ) ; total coronary heart disease ( 174 events ) , 1.61 ( 1.13 to 2.29 ) ; and total cardiovascular disease ( 305 events ) , 1.44 ( 1.09 to 1.91 ) . A subset analysis indicated that b and presence was 50.9 % sensitive and 95.4 % specific for detecting plasma lipoprotein ( a ) levels of > 30 mg/dL , the threshold value linked to increased cardiovascular disease risk in men . CONCLUSIONS Sinking prebeta lipoprotein was a valid surrogate for elevated lipoprotein ( a ) levels in Framingham Heart Study women . B and presence and , equivalently , elevated plasma lipoprotein ( a ) , was a strong , independent predictor of myocardial infa rct ion , intermittent claudication , and cerebrovascular disease . Confirmation of these findings in other longitudinal studies of women is needed BACKGROUND Serum markers of inflammation and platelet activation are related to cardiovascular risk . Cardiovascular risk reduction is a major treatment goal in patients with peripheral arterial disease ( PAD ) . Although current guidelines recommend supervised exercise training ( SET ) for PAD patients with intermittent claudication , its contribution to risk reduction remains unclear . Aim of the present study was to assess the impact of SET on inflammation and platelet activation as surrogates for cardiovascular risk . METHODS Fifty-three patients with intermittent claudication were r and omly assigned to SET on top of best medical treatment ( BMT ) for 6 months ( SET-group ) or to BMT only ( BMT-group ) . High sensitivity C-reactive protein ( hs-CRP ) , interleukin-6 ( IL-6 ) and fibrinogen as well as soluble P-selectin ( sP-sel ) , prothrombin fragment 1 + 2 ( F1.2 ) and monocyte-platelet aggregates ( MPA ) were determined at study entry , after 3 , 6 and 12 months . RESULTS While clinical improvement , reflected by an increase of walking capacity , was observed upon SET , no lasting changes of markers of inflammation and platelet activation were found within the SET-group during the training period . Compared to the BMT-group no improvements of these markers were observed in response to training at any time point ( all p > 0.05 ) . CONCLUSION Regular SET added no further anti-inflammatory effect and had no effect on platelet activation when provided on top of BMT in PAD patients with intermittent claudication OBJECTIVES This study sought to determine whether patients with peripheral arterial disease ( PAD ) experience different reductions in ischemic event and increases in bleeding events with extended duration dual antiplatelet therapy versus those without PAD . BACKGROUND Patients with PAD have increased ischemic and bleeding risks after coronary stenting . METHODS The DAPT ( Dual Antiplatelet Therapy ) study r and omized 11,648 patients free from ischemic and bleeding events 12 months after coronary stenting to continued thienopyridine plus aspirin therapy for an additional 18 months versus aspirin therapy alone . The effects of continued thienopyridine on myocardial infa rct ion ( MI ) or stent thrombosis , major adverse cardiovascular and cerebrovascular events ( death , MI , or stroke ) and bleeding ( GUSTO [ Global Utilization of t-PA and Streptokinase for Occluded Coronary Arteries ] moderate or severe ) were assessed among those with versus without PAD . RESULTS Among 11,648 r and omized patients , 649 ( 5.57 % ) had PAD . Between 12 and 30 months , r and omized patients with PAD had higher rates of MI/stent thrombosis ( 6.03 % vs. 2.92 % ; p < 0.001 ) , major adverse cardiovascular and cerebrovascular events ( 11.65 % vs. 4.62 % ; p < 0.001 ) , and bleeding ( 4.86 % vs. 1.74 % ; p < 0.001 ) . Continued thienopyridine versus placebo was associated with consistent treatment effects for MI/stent thrombosis ( with PAD , HR : 0.63 ; 95 % CI : 0.32 to 1.22 ; without PAD , HR : 0.53 ; 95 % CI : 0.42 , 0.66 ; interaction p = 0.631 ) , major adverse cardiovascular and cerebrovascular events ( with PAD , HR : 1.06 ; 95 % CI : 0.67 to 1.67 ; without PAD , HR : 0.70 ; 95 % CI : 0.59 to 0.84 ; interaction p = 0.103 ) , and bleeding ( with PAD , HR , 1.82 ; 95 % CI : 0.87 to 3.83 ; without PAD , HR : 1.66 ; 95 % CI : 1.23 to 2.24 ; interaction p = 0.811 ) . CONCLUSIONS Among patients undergoing coronary stenting , those with PAD have more ischemic and bleeding events versus those without PAD . Extended duration dual antiplatelet therapy is associated with consistent ischemic benefit and bleeding harm among patients with and without PAD CONTEXT Accumulation of iron in excess of physiologic requirements has been implicated in risk of cardiovascular disease because of increased iron-catalyzed free radical-mediated oxidative stress . OBJECTIVE To test the hypothesis that reducing body iron stores through phlebotomy will influence clinical outcomes in a cohort of patients with symptomatic peripheral arterial disease ( PAD ) . DESIGN , SETTING , AND PATIENTS Multicenter , r and omized , controlled , single-blinded clinical trial based on the Iron ( Fe ) and Atherosclerosis Study ( FeAST ) ( VA Cooperative Study # 410 ) and conducted between May 1 , 1999 , and April 30 , 2005 , within the Department of Veterans Affairs Cooperative Studies Program and enrolling 1277 patients with symptomatic but stable PAD . Those with conditions likely to cause acute-phase increase of the ferritin level or with a diagnosis of visceral malignancy within the preceding 5 years were excluded . Analysis was by intent-to-treat . INTERVENTION Patients were assigned to a control group  ( n = 641 ) or to a group undergoing reduction of iron stores by phlebotomy with removal of defined volumes of blood at 6-month intervals ( avoiding iron deficiency ) ( n = 636 ) , stratified by hospital , age , and baseline smoking status , diagnosis of diabetes mellitus , ratio of high-density to low-density lipoprotein cholesterol level , and ferritin level . MAIN OUTCOME MEASURES The primary end point was all-cause mortality ; the secondary end point was death plus nonfatal myocardial infa rct ion and stroke . RESULTS There were no significant differences between treatment groups for the primary or secondary study end points . All-cause deaths occurred in 148 patients ( 23 % ) in the control group and in 125 ( 20 % ) in the iron-reduction group ( hazard ratio ( HR ) , 0.85 ; 95 % confidence interval ( CI ) , 0.67 - 1.08 ; P = .17 ) . Death plus nonfatal myocardial infa rct ion and stroke occurred in 205 patients ( 32 % ) in the control group and in 180 ( 28 % ) in the iron-reduction group ( HR , 0.88 ; 95 % CI , 0.72 - 1.07 ; P = .20 ) . CONCLUSION Reduction of body iron stores in patients with symptomatic PAD did not significantly decrease all-cause mortality or death plus nonfatal myocardial infa rct ion and stroke . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT00032357 Background —Cholesterol modification reduces cardiovascular events in patients with atherosclerosis , including those with peripheral arterial disease . The purpose of this study was to determine whether cholesterol lowering with atorvastatin improves walking performance in patients with intermittent claudication . Methods and Results —This r and omized , double-blind , parallel- design study included 354 persons with claudication attributable to peripheral arterial disease . Patients were treated with placebo , atorvastatin ( 10 mg per day ) , or atorvastatin ( 80 mg per day ) for 12 months . The outcome measures included change in treadmill exercise time and patient-reported measures of physical activity and quality of life based on question naires . Maximal walking time after 12 months of treatment with atorvastatin did not change significantly . However , there was improvement in pain-free walking time after 12 months of treatment for the 80-mg ( P = 0.025 ) group compared with placebo . A physical activity question naire demonstrated improvement in ambulatory ability for the 10- and 80-mg groups ( P = 0.011 ) , whereas 2 quality of life instruments , the Walking Impairment Question naire and Short Form 36 Question naire , did not show significant change . Conclusions —Atorvastatin improves pain-free walking distance and community-based physical activity in patients with intermittent claudication . When treated with atorvastatin , patients with peripheral arterial disease may experience improvement in symptoms to complement the anticipated reduction in cardiovascular events reported in other studies of statins The Swedish Ticlopidine Multicentre Study ( STIMS ) was a double-blind placebo-controlled trial design ed to determine whether ticlopidine , a platelet antiaggregatory agent , reduces the incidence of myocardial infa rct ion , stroke and transitory ischaemic attacks in patients with intermittent claudication . A total of 687 patients was monitored for a minimum of 5 years or until an end-point was reached . The number of end points ( 99 vs. 89 ) , analysed according to the intention-to-treat principle , was 11.4 % lower in the ticlopidine group ( P = 0.24 ) . The mortality rate was 29.1 % lower in the ticlopidine group ( 64 vs. 89 , P = 0.015 ) ; this observation could be accounted for by a reduced mortality from ischaemic heart disease . On-treatment analysis showed there to be significantly fewer end points in the ticlopidine group ( 47 vs. 76 , P = 0.017 ) . Diarrhoea was the most common side-effect . Reversible leucopenia or thrombocytopenia was reported in seven patients on ticlopidine . It is concluded that the high morbidity and mortality from cardio- and cerebrovascular disease in patients with intermittent claudication can be reduced by long-term treatment with ticlopidine Microalbuminuria ( MA ) is associated with increased  cardiovascular and all-cause mortality .  It has been proposed that MA reflects generalized atherosclerosis and may thus predict mortality . To investigate this hypothesis , we studied the associations between , on the one h and , MA and peripheral arterial disease ( PAD ) , a generally accepted marker of generalized atherosclerosis , and , on the other h and , cardiovascular and all-cause mortality in an age- , sex- , and glucose tolerance-stratified sample ( n=631 ) of a population -based cohort aged 50 to 75 years followed prospect ively for 5 years . At baseline , the  albumin-to-creatinine ratio ( ACR ) was measured in an overnight spot urine sample ; MA was defined as ACR > 2.0 mg/mmol . PAD was defined as an ankle-brachial pressure index below 0.90 and /or a history of a peripheral arterial bypass or amputation . After 5 years of follow-up , 58 subjects had died ( 24 of cardiovascular causes ) . Both MA and PAD were associated with a 4-fold increase in cardiovascular mortality . After adjusting for age , sex , diabetes mellitus , hypertension , levels of total and HDL-cholesterol and triglyceride , body mass index , smoking habits , and preexistent ischemic heart disease , the relative risks ( RR ) ( 95 % confidence intervals ) were 3.2 ( 1.3 to 8.1 ) for MA and 2.4 ( 0.9 to 6.1 ) for PAD . When both MA and PAD were included in the multivariate analysis , the RRs were 2.9 ( 1.1 to 7.3 ) for MA and 2.0 ( 0.7 to 5.7 ) for PAD . MA and PAD were both associated with an about 2-fold increase in all-cause mortality . The RRs of all-cause mortality associated with MA and PAD were about 4 times higher among hypertensive than among normotensive subjects . We conclude that both MA and PAD are associated with an increased risk of cardiovascular mortality . MA and PAD are mutually independent risk indicators . The associations of MA and PAD with all-cause mortality are somewhat weaker . They are more pronounced in the presence of hypertension than in its absence . These data suggest that MA affects mortality risk through a mechanism different from generalized atherosclerosis Objective —To determine the association between  leukocyte telomere length ( TL ) and atherosclerosis and its clinical sequelae stroke and myocardial infa rct ion . Methods and Results —Within the scope of the prospect i ve population -based Bruneck Study ,  leukocyte TL  was measured by quantitative polymerase chain reaction in 800 women and men aged 45 to 84 years ( in 1995 ) . The manifestation of cardiovascular disease ( CVD ) ( 1995–2005 ) and the progression of atherosclerosis ( 1995–2000 ) were carefully assessed . The TL was shorter in men than in women ( age-adjusted mean [ 95 % CI ] , 1.41 [ 1.33 to 1.49 ] versus 1.55 [ 1.47 to 1.62 ] ; P=0.02 ) and inversely correlated to age ( r=−0.22 , P<0.001 ) and family history of CVD ( P=0.03 ) . Participants with CVD events during follow-up ( n=88 ) had significantly shorter telomeres ( age- and sex-adjusted mean [ 95 % CI ] , 1.25 [ 1.08 to 1.42 ] versus 1.51 [ 1.45 to 1.57 ] ; P<0.001 ) . In multivariable Cox models , baseline TL emerged as a significant and independent risk predictor for the composite CVD end point and its individual components ( myocardial infa rct ion and stroke ) ; however , this was not the case for de novo stable angina and intermittent claudication . Subjects in the top and bottom TL tertile group differed in their CVD risk by a factor of 2.72 ( 95 % CI , 1.41 to 5.28 ) , which is the risk ratio attributable to a 13.9-year difference in chronological age . Remarkably , in our atherosclerosis progression model , TL was strongly associated with advanced , but not early , atherogenesis . All findings were consistent in women and men . Conclusion —Our findings indicate a differential role of telomere shortening in the various stages of atherosclerosis , with preferential involvement in advanced vessel pathology and acute vascular syndromes Objectives . To determine whether different levels of the ankle-brachial pressure index ( ABPI ) are associated with an increased risk for progressive limbischemia , nonfatal and fatal cardiovascular events . To investigate the prognostic value of signs and symptoms associated with peripheral arterial occlusive disease ( PAOD ) . Design . Prospect i ve follow-up study . Setting . Eighteen general practice centers in the Netherl and s. Participants . Three thous and six hundred forty-nine participants ( 53 % female ) with a mean age of 59 years ( range : 40 - 78 years ) . Main outcome measures . Progressive limbischemia , cardiovascular morbidity and mortality . Results . At baseline , 458 participants had PAOD , defined as an ABPI < 0.95 . Among these , 148 ( 32.2 % ) had an ABPI < 0.70 . Cox proportional hazards models showed that after a mean follow-up period of 7.2 years , PAOD patients with an ABPI < 0.70 were at higher risk for cardiovascular death , compared with participants with a moderately reduced ABPI ( < 0.95 - 0.70 ) : HR 2.3 versus 1.2 . Older age , complaints of intermittent claudication , abnormal pedal pulses , elevated blood pressure , and coexisting cardiovascular disease at baseline were also significant independent prognostic factors for one or more of the adverse outcome events in these patients . Conclusion . The ABPI is inversely associated with cardiovascular mortality  in PAOD patients . A low ABPI is an independent predictor for cardiovascular mortality in PAOD patients IMPORTANCE Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown . A recent r and omized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety . OBJECTIVES To assess the association between testosterone therapy and all-cause mortality , myocardial infa rct ion ( MI ) , or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease . DESIGN , SETTING , AND PATIENTS A retrospective national cohort study of men with low testosterone levels ( < 300 ng/dL ) who underwent coronary angiography in the Veterans Affairs ( VA ) system between 2005 and 2011 . MAIN OUTCOMES AND MEASURES Primary outcome was a composite of all-cause mortality , MI , and ischemic stroke . RESULTS Of the 8709 men with a total testosterone level lower than 300 ng/dL , 1223 patients started testosterone therapy after a median of 531 days following coronary angiography . Of the 1710 outcome events , 748 men died , 443 had MIs , and 519 had strokes . Of 7486 patients not receiving testosterone therapy  , 681 died , 420 had MIs , and 486 had strokes . Among 1223 patients receiving testosterone therapy , 67 died , 23 had MIs , and 33 had strokes . At 3 years after coronary angiography , the Kaplan-Meier estimated cumulative percentages with events were 19.9%in the no testosterone therapy group vs 25.7%in the testosterone therapy group , with an absolute risk difference of 5.8%(95%CI , -1.4%to 13.1 % ) [corrected].The Kaplan-Meier estimated cumulative percentages with events among the no testosterone therapy group vs testosterone therapy group at 1 year after coronary angiography were 10.1 % vs 11.3 % ; at 2 years , 15.4 % vs 18.5 % ; and at 3 years , 19.9 % vs 25.7 [corrected].There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease ( test for interaction , P = .41 ) . CONCLUSIONS AND RELEVANCE Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level , the use of testosterone therapy was associated with increased risk of adverse outcomes . These findings may inform the discussion about the potential risks of testosterone therapy Intermittent claudication is a common condition leading to significant functional impairment and enhanced risk of cardiovascular morbidity and mortality . However , despite the functional impairment caused by intermittent claudication , the natural history in the affected limb is fairly benign . Only about 25 % of patients show symptomatic deterioration and only 2 % eventually lose the affected limb.1 This epidemiological evidence has led most clinicians in both primary and hospital care to manage intermittent claudication conservatively , addressing cardiovascular risk factors2 and giving advice on exercise . This may well be appropriate but merely giving advice about exercise is unlikley to be the most effective treatment . Exercise as a treatment for intermittent claudication is not new , with improvements in walking described from as early as 1898 . A recent Cochrane review of 10 r and omised trials of exercise therapy estimated an overall improvement in walking distance of about 150%.3 The exercise component in all but one of these OBJECTIVES The Atherosclerosis and Folic Acid Supplementation Trial ( ASFAST ) aim ed to establish whether high-dose folic acid would slow the progression of atherosclerosis and reduce cardiovascular events in patients with chronic renal failure ( CRF ) . BACKGROUND Hyperhomocysteinemia is a potential contributor to the high rates of cardiovascular morbidity and mortality in patients with CRF . METHODS A total of 315 subjects with CRF , mean age 57 years ( range 24 to 79 years ) were r and omized to 15 mg folic acid daily or placebo and followed for a median of 3.6 years . The primary intima-media thickness ( IMT ) and clinical end points were : rate of progression of mean maximum carotid IMT and a composite of myocardial infa rct ion ( MI ) , stroke , and cardiovascular death . Secondary end points included all cardiovascular events and change in pulse wave velocity , systemic arterial compliance and augmentation index . Data were analyzed by intention-to-treat . RESULTS Plasma total homocysteine was reduced by 19 % in the folic acid group . There was no significant difference between the treatment groups in rate of change of IMT or any measure of artery function . Seventy-seven events occurred in the folic acid group ( 14.9 per 100 patient-years ) as compared with 86 in the placebo group ( 16.3 per 100 patient-years ) . The rates of the primary and secondary clinical end points at five years were not significantly different after adjustment for baseline differences between the groups ( adjusted hazard ratio for MI , stroke , and cardiovascular death : 0.98 [ 95 % confidence interval : 0.66 to 1.47 ] ; p = 0.94 ; for all cardiovascular events : 0.95 [ 95 % confidence interval : 0.69 to 1.30 ] ; p = 0.75 ) . CONCLUSIONS High-dose folic acid does not slow atheroma progression or improve cardiovascular morbidity or mortality in patients with CRF BACKGROUND Previous investigators have observed a doubling of the mortality rate among patients with intermittent claudication , and we have reported a fourfold increase in the overall mortality rate among subjects with large-vessel peripheral arterial disease , as diagnosed by noninvasive testing . In this study , we investigated the association of large-vessel peripheral arterial disease with rates of mortality from all cardiovascular diseases and from coronary heart disease . METHODS We examined 565 men and women ( average age , 66 years ) for the presence of large-vessel peripheral arterial disease by means of two noninvasive techniques -- measurement of segmental blood pressure and determination of flow velocity by Doppler ultrasound . We identified 67 subjects with the disease ( 11.9 percent ) , whom we followed prospect ively for 10 years . RESULTS Twenty-one of the 34 men ( 61.8 percent ) and 11 of the 33 women ( 33.3 percent ) with large-vessel peripheral arterial disease died during follow-up , as compared with 31 of the 183 men ( 16.9 percent ) and 26 of the 225 women ( 11.6 percent ) without evidence of peripheral arterial disease . After multivariate adjustment for age , sex , and other risk factors for cardiovascular disease , the relative risk of dying among subjects with large-vessel peripheral arterial disease as compared with those with no evidence of such disease was 3.1 ( 95 percent confidence interval , 1.9 to 4.9 ) for deaths from all causes , 5.9 ( 95 percent confidence interval , 3.0 to 11.4 ) for all deaths from cardiovascular disease , and 6.6 ( 95 percent confidence interval , 2.9 to 14.9 ) for deaths from coronary heart disease . The relative risk of death from causes other than cardiovascular disease was not significantly increased among the subjects with large-vessel peripheral arterial disease . After the exclusion of subjects who had a history of cardiovascular disease at base line , the relative risks among those with large-vessel peripheral arterial disease remained significantly elevated . Additional analyses revealed a 15-fold increase in rates of mortality due to cardiovascular disease and coronary heart disease among subjects with large-vessel peripheral arterial disease that was both severe and symptomatic . CONCLUSIONS Patients with large-vessel peripheral arterial disease have a high risk of death from cardiovascular causes Background : There is controversial evidence with regard to the significance of peripheral arterial disease ( PAD ) as an indicator for future stroke risk . We aim ed to quantify the risk increase for mortality and morbidity associated with PAD . Methods : In an open , prospect i ve , noninterventional cohort study in the primary care setting , a total of 6,880 unselected patients ≧65 years were categorized according to the presence or absence of PAD and followed up for vascular events or deaths over 5 years . PAD was defined as ankle-brachial index ( ABI ) < 0.9 or history of previous peripheral revascularization and /or limb amputation and /or intermittent claudication . Associations between known cardiovascular risk factors including PAD and cerebrovascular mortality/events were analyzed in a multivariate Cox regression model . Results : During the 5-year follow-up [ 29,915 patient-years ( PY ) ] , 183 patients had  a stroke ( incidence per 1,000 PY : 6.1 cases ) . In  patients with PAD  ( n = 1,429 ) compared to those without PAD ( n = 5,392 ) , the incidence of all stroke types st and ardized per 1,000 PY , with the exception of hemorrhagic stroke , was about doubled ( for fatal stroke tripled ) . The corresponding adjusted hazard ratios were 1.6 ( 95 % confidence interval , CI , 1.1–2.2 ) for total stroke , 1.7 ( 95 % CI 1.2–2.5 ) for ischemic stroke , 0.7 ( 95 % CI 0.2–2.2 ) for hemorrhagic stroke , 2.5 ( 95 % CI 1.2–5.2 ) for fatal stroke and 1.4 ( 95 % CI 0.9–2.1 ) for nonfatal stroke . Lower ABI categories were associated with higher stroke rates . Besides high age , previous stroke and diabetes mellitus , PAD was a significant independent predictor for ischemic stroke . Conclusions : The risk of stroke is substantially increased in PAD patients , and PAD is a strong independent predictor for stroke BACKGROUND Patients with Type 2 diabetes mellitus ( T2DM ) are often treated with multiple glucose-lowering and cardiovascular agents . The concomitant use of nitrates , renin-angiotensin system ( RAS ) blockers , or insulin has been linked to a potential increase in myocardial ischemic risk with rosiglitazone . The PROactive data base provides an opportunity to investigate the effects of these medications on the potential macrovascular benefits reported with pioglitazone . METHODS The PROactive study was a r and omized double-blind prospect i ve trial that evaluated mortality and cardiovascular morbidity in 5238 patients with T2DM and macrovascular disease . Patients received pioglitazone or placebo in addition to their baseline glucose-lowering and cardiovascular medications . The effect of pioglitazone on composite endpoints was evaluated , including all-cause death , myocardial infa rct ion ( MI ) , and stroke , as well as safety events of edema and serious heart failure , in subgroups using nitrates , RAS blockers , or insulin at baseline . RESULTS The risk of all-cause death , MI , and stroke for pioglitazone versus placebo was similar regardless of the baseline use of nitrates , RAS blockers , or insulin , with hazard ratios ranging from 0.81 to 0.87 . Similar results were obtained for the other composite endpoints analyzed . There were no significant interactions between baseline medication subgroups and treatment . The increased risk of edema and serious heart failure was consistent across the baseline medication subgroups . CONCLUSIONS This post hoc analysis did not reveal an increased risk of macrovascular events with pioglitazone in patients receiving nitrates , RAS blockers , or insulin . Rather , all patients realized the same trend towards benefit with pioglitazone , and adverse events of edema and heart failure were predictable A total of 462 patients ( mean age 52 years ) affected by reversible focal ischemic attacks ( RIAs ) were followed prospect ively in 8 neurologic institutions in Italy for 4 years . All cases were evaluated with a cerebral angiography and 21 % of angiograms were normal . At the end of the follow-up period the cumulated probability for death , stroke , cardiac event and new RIA was respectively 7 % , 8 % , 3 % and 36 % . The predictive value of the baseline characteristics of this series was evaluated by a multifactorial analysis which showed that RIA and stroke ( specific cerebrovascular risk ) were more likely to develop in patients with a history of more than one RIA and in those in whom multiple vascular territories were involved . Moreover , previous myocardial infa rct ion , intermittent claudication , angina pectoris , time elapsed since the first attack , and duration and severity of the attack itself were independently associated with general cardiovascular risk ( death , stroke and myocardial infa rct ion ) . We conclude that predictive factors , and thus also pathogenetic mechanisms , may be different for general cardiovascular risk and specific cerebrovascular risk in RIA patients Objectives In general population s , the adverse effects of smoking on coronary risk have been demonstrated to be greater in women than in men ; whether this is true for individuals with diabetes is unclear . Design Cohort study . Setting 20 countries worldwide participating in the ADVANCE ( Action in Diabetes and Vascular Disease : Preterax and Diamicron modified release Controlled Evaluation ) trial . Participants 11 140 patients with type 2 diabetes aged ≥55 years and in cardiovascular risk at the time of r and omisation . Primary and secondary outcome measures Major cardiovascular events ( death from cardiovascular disease , non-fatal stroke or non-fatal myocardial infa rct ion ( MI ) ) , all cardiovascular events ( major cardiovascular event or peripheral arterial disease or transient ischaemic attack ) , and all-cause mortality . Secondary outcome measures were major coronary events ( fatal and non-fatal MI ) , major cerebrovascular events ( fatal and non-fatal stroke ) , nephropathy ( new or worsening renal disease ) , and all cancer . Results At baseline , 6466 ( 56 % women ) participants were never-smokers , 1550 ( 28 % women ) were daily smokers and 3124 ( 21 % women ) were former smokers . Median follow-up time was 5 years . In Cox regression models after multiple adjustments , compared with never smoking , daily smoking was associated with increased risk of all primary and secondary outcomes with the exception of major cerebrovascular disease . Only for major coronary events was there any evidence of a stronger effect in women than in men ( ratio of the adjusted HRs women : men ; 1.64 ( 0.83 to 3.26 ) p=0.08 ) . For all other outcomes considered , the hazards of smoking were similar in men and women . Quitting smoking was associated with a 30 % reduction in all-cause mortality ( p=0.001 ) in both sexes . Conclusions In individuals with diabetes , the effects of smoking on all major forms of cardiovascular disease are equally as hazardous in women and men with the possible exception of major coronary events where there was some evidence of a greater hazard in women . Trial registration number NCT00145925 Much interest is being shown in fibrinogen as a possible cardiovascular risk factor . ' The concept that fibrinogen is causally related to cardiovascular events is supported by several lines of evidence . Perhaps the strongest indication stems from seven prospect i ve epidemiological trials2all of which showed that fibrinogen predicts major cardiovascular events such as stroke and myocardial infa rct ion . Clinical trials on survivors of a first myocardial infa rct ion9 or stroke'0 also showed that fibrinogen was a risk factor for further cardiovascular disasters . Several plausible pathological mechanisms could explain this association ' : fibrinogen is an important clotting factor and it determines the flow properties of blood , represents a co-factor for platelet aggregation , and may cause atherosclerosis by direct effects on the arterial wall . Acceptance that fibrinogen is a major cardiovascular risk factor will lead to attempts to lower its plasma concentration . Methods to achieve this are still in their infancy . Though dietary influences seem to be small , ' there is a striking association between body weight and fibrinogen . I will review the data suggesting that weight loss might be one practical way of influencing fibrinogen concentrations Background . Renal-transplant recipients have shortened life expectancy primarily because of premature cardiovascular disease . Traditional and nontraditional risk factors for cardiovascular disease are prevalent in renal patients . In renal-transplant recipients , immunosuppressive therapy can be nephrotoxic and aggravate cardiovascular disease risk factors . Renal dysfunction has been established as a risk factor for cardiovascular disease and mortality in different population s. We evaluated the effects of baseline renal-transplant function on mortality and cardiovascular and renal endpoints in 1,052 placebo-treated patients of the Assessment of Lescol in Renal Transplantation trial . Methods . All renal-transplant recipients were on cyclosporine-based immunosuppressive therapy .  Follow-up was 5 to 6 years , and endpoints included cardiac death , noncardiovascular death , all-cause mortality , major adverse cardiac event ( MACE ) , stroke , nonfatal myocardial infa rct ion , and graft loss . Results . Baseline serum creatinine was strongly and independently associated with increased cardiac , noncardiovascular , and all-cause mortality , as well as MACE and graft loss . Serum creatinine was not a risk factor for stroke or nonfatal myocardial infa rct ion . Conclusions . Elevated baseline serum creatinine in renal-transplant recipients is a strong and independent risk factor for all-cause , noncardiovascular and cardiac mortality , MACE , and graft loss Elevated arterial pressure enhances the risk for cardiovascular ( CV ) events in patients with diabetic nephropathy . The optimal BP and the component of the elevated BP that affect the risk have not been defined . A post hoc analysis was performed to assess the impact of achieved systolic , diastolic , and pulse pressures on CV outcomes in 1590 adults who had overt diabetic nephropathy and were enrolled in the Irbesartan Diabetic Nephropathy Trial ( IDNT ) and had a baseline serum creatinine above the normal range , up to 266 micromol/L ( 3.0 mg/dL ) , 24-h urine protein > 900 mg/d , and at least 6 mo of follow-up . Patients were r and omized to irbesartan , amlodipine , or placebo , with other antihypertensive agents to a BP goal of < or = 135/85 mmHg . Progressively lower achieved systolic BP ( SBP ) to 120 mmHg predicted a decrease in CV mortality and congestive heart failure ( CHF ) but not myocardial infa rct ions ( MI ) . A SBP below this threshold was associated with increased risk for CV deaths and CHF events . Achieved diastolic BP < 85 mmHg was associated with a trend to increase in all-cause mortality , significant increase in MI , but decreased risk for strokes . Increased pulse pressure predicted increased all-cause mortality , CV mortality , MI , and CHF . It is concluded that achieved SBP approaching 120 mmHg and diastolic BP of 85 mmHg are associated with the best protection against CV events in these patients . BP < or = 120/85 may be associated with an increase in CV events CONTEXT Few data document current cardiovascular ( CV ) event rates in stable patients with atherothrombosis in a community setting . Differential event rates for patients with documented coronary artery disease ( CAD ) , cerebrovascular disease ( CVD ) , or peripheral arterial disease ( PAD ) or those at risk of these diseases have not been previously evaluated in a single international cohort . OBJECTIVE To establish contemporary , international , 1-year CV event rates in out patients with established arterial disease or with multiple risk factors for atherothrombosis . DESIGN , SETTING , AND PARTICIPANTS The Reduction of Atherothrombosis for Continued Health ( REACH ) Registry is an international , prospect i ve cohort of 68 236 patients with either established atherosclerotic arterial disease ( CAD , PAD , CVD ; n = 55 814 ) or at least 3 risk factors for atherothrombosis ( n = 12 422 ) , who were enrolled from 5587 physician practice s in 44 countries in 2003 - 2004 . MAIN OUTCOME MEASURES Rates of CV death , myocardial infa rct ion ( MI ) , and stroke . RESULTS As of July 2006 , 1-year outcomes were available for 95.22 % ( n = 64 977 ) of participants . Cardiovascular death , MI , or stroke rates were 4.24 % overall : 4.69 % for those with established atherosclerotic arterial disease vs 2.15 % for patients with multiple risk factors only . Among patients with established disease , CV death , MI , or stroke rates were 4.52 % for patients with CAD , 6.47 % for patients with CVD , and 5.35 % for patients with PAD . The incidences of the end point of CV death , MI , or stroke or of hospitalization for atherothrombotic event(s ) were 15.20 % for CAD , 14.53 % for CVD , and 21.14 % for PAD patients with established disease . These event rates increased with the number of symptomatic arterial disease locations , ranging from 5.31 % for patients with risk factors only to 12.58 % for patients with 1 , 21.14 % for patients with 2 , and 26.27 % for patients with 3 symptomatic arterial disease locations ( P<.001 for trend ) . CONCLUSIONS In this large , contemporary , international study , out patients with established atherosclerotic arterial disease , or at risk of atherothrombosis , experienced relatively high annual CV event rates . Multiple disease locations increased the 1-year risk of CV events OBJECTIVE No previous long-term prospect i ve studies have examined if workers with low cardiorespiratory fitness have an increased risk of cardiovascular mortality due to high physical work dem and s. We tested this hypothesis . METHOD We carried out a 30-year follow-up of the Copenhagen Male Study of 5249 employed men aged 40 - 59 years . We excluded from follow-up 274 men with a history of myocardial infa rct ion , prevalent symptoms of angina pectoris , or intermittent claudication . We estimated physical fitness [ maximal oxygen consumption ( VO (2)Max ) ] using the Astr and cycling test and determined physical work dem and s with two self-reported questions . RESULTS In the Copenhagen Male Study , 587 men ( 11.9 % ) died due to ischaemic heart disease ( IHD ) . Using men with low physical work dem and s as the reference group , Cox analyses -- adjusted for age , blood pressure , smoking , alcohol consumption , body mass index , diabetes , and hypertension -- showed that high physical work dem and s were associated with an increased risk of IHD mortality in the least fit [ VO (2)Max range 15 - 26 , N=892 , hazard ratio ( HR ) 2.04 , 95 % confidence interval ( 95 % CI ) 1.20 - 3.49 ] and moderately fit ( VO (2)Max range 27 - 38 , N=3037 , HR 1.75 , 95 % CI 1.24 - 2.46 ) , but not among the most fit men ( VO (2)Max range 39 - 78 , N=1014 , HR 1.08 , 95 % CI 0.52 - 2.17 ) . We found a similar , although slightly weaker , relationship with respect to all-cause mortality . CONCLUSIONS The hypothesis was supported . Men with low and medium physical fitness have an increased risk of cardiovascular and all-cause mortality if exposed to high physical work dem and s. Ours observations suggest that , among men with high physical work dem and s , being physically fit protects against adverse cardiovascular effects AIMS To present and discuss a comprehensive and ready to use prediction model of risk of death after myocardial infa rct ion based on the very recently concluded follow-up of the large GISSI-Prevenzione cohort and on the integrated evaluation of different categories of risk factors : those that are non-modifiable , and those related to lifestyles , co-morbidity , background , and other conventional clinical complications produced by the index myocardial infa rct ion . METHODS The 11 - 324 men and women recruited in the study within 3 months from their index myocardial infa rct ion have been followed-up to 4 years . The following risk factors have been used in a Cox proportional hazards model : non-modifiable risk factors : age and sex ; complications after myocardial infa rct ion : indicators of left ventricular dysfunction ( signs or symptoms of acute left ventricular failure during hospitalization , ejection fraction , NYHA class and extent of ventricular asynergy at echocardiography ) , indicators of electrical instability ( number of premature ventricular beats per hour , sustained or repetitive arrhythmias during 24-h Holter monitoring ) , indicators of residual ischaemia ( spontaneous angina pectoris after myocardial infa rct ion , Canadian Angina Classification class , and exercise testing results ) ; cardiovascular risk factors : smoking habits , history of diabetes mellitus and arterial hypertension , systolic and diastolic blood pressure , blood total and HDL cholesterol , triglycerides , fibrinogen , leukocytes count , intermittent claudication , and heart rate . Multiple regression modelling was assessed by receiver operating characteristic ( ROC ) analysis . Generalizability of the models was assessed through cross validation and bootstrapping techniques . POPULATION AND RESULTS During the 4 years of follow-up , a total of 1071 patients died . Age and left ventricular dysfunction were the most relevant predictors of death . Because of pharmacological treatments , total blood cholesterol , triglycerides , and blood pressure values were not significantly associated with prognosis . Sex-specific prediction equations were formulated to predict risk of death according to age , simple indicators of left ventricular dysfunction , electrical instability , and residual ischaemia along with the following cardiovascular risk factors : smoking habits , history of diabetes mellitus and arterial hypertension , blood HDL cholesterol , fibrinogen , leukocyte count , intermittent claudication , and heart rate . The predictive models produced on the basis of information available in the routine conditions of clinical care after myocardial infa rct ion provide ready to use and highly discriminant criteria to guide secondary prevention strategies . CONCLUSIONS AND IMPLICATION S Besides documenting what should be the preferred and practicable focus of clinical attention for today 's patients , the experience of GISSI-Prevenzione suggests that periodically and prospect ively collected data bases on naturalistic ' cohorts could be an important option for updating and verifying the impact of guidelines , which should incorporate the different components of the complex profile of cardiovascular risk . The GISSI Prevenzione risk function is a simple tool to predict risk of death and to improve clinical management of subjects with recent myocardial infa rct ion . The use of predictive risk algorithms can favour the shift from medical logic , based on the treatment of single risk factors , to one centred on the patient as a whole as well as the tailoring of medical interventions according to patients ' overall risk A cross-sectional survey of an age- and sex-stratified r and om sample of the elderly population living in Southampton was undertaken with the object of measuring the frequency of cardiovascular disease by question naire and examination , and assessing cardiac anatomy and physiological function by noninvasive methods . The response rate was 64 % and 259 men and women aged between 65 and 95 years were interviewed and examined and had a twelve-lead ECG and chest radiograph . Forty per cent of men and 47 % of women reported a diagnosis of one or more cardiovascular diseases , of which high blood pressure 33 % , coronary heart disease 14 % ( angina pectoris 11 % and myocardial infa rct ion 8 % ) , peripheral arterial disease of the lower limbs 7 % , and cerebrovascular disease 6 % occurred most frequently . With the exception of high blood pressure , which women reported more frequently than men ( 40 % vs 27 % ) , the prevalence of these diagnoses by sex was similar . The self-administered WHO question naires gave point prevalence estimates for angina pectoris of 13 % , possible myocardial infa rct ion 7 % and intermittent claudication 5 % , which were similar to reported prevalences of these diseases , although disagreement in the classification of individuals for each disease was common . When comparing the WHO chest pain question naire with the doctors ' independent diagnosis of angina pectoris in this population , the sensitivity of the WHO question naire was 79 % , with a specificity of 98 % and a predictive value of 88 % . For each sex the sensitivity of the WHO chest pain question naire was similar but specificity and predictive value were both lower for women . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES To assess the risk of total and cardiovascular mortality in older adults with systolic hypertension and with a low ankle-arm index ( AAI ) as a marker of sub clinical peripheral arterial disease ( PAD ) . DESIGN Prospect i ve observational study PARTICIPANTS A subgroup of 1537 participants in the Systolic Hypertension in the Elderly Program ( SHEP ) were screened for lower extremity arterial disease using the AAI . Participants were evaluated at 4 years to determine vital status and cause of death . Total and cardiovascular disease ( CVD ) mortality rates were assessed in relationship to clinical CVD at baseline , cardiovascular risk factors and the presence of a low AAI ( sub clinical PAD ) . RESULTS Total mortality rates increased as the AAI decreased in those with and without clinical CVD at baseline . In those without clinical CVD at baseline , the presence of an AAI < or = .9 was associated with an age-adjusted relative risk ( RR ) of 3.00 for total mortality in men and 2.67 in women . Results were similar for CVD mortality and persisted after adjustment for cardiovascular risk factors including the presence of an abnormal electrocardiogram . CONCLUSIONS A low ankle arm-index predicted a two to three-fold increase in total and cardiovascular mortality in older adults with systolic hypertension of risk for incident cardiovascular disease . In this study of older adults with systolic hypertension , 19.7 % of the participants had sub clinical PAD . Risk factor modification could be targeted to older adults based on markers of asymptomatic atherosclerosis Objective —The purpose of this study was to assess whether increasing serum uric acid ( UA ) levels are related to cardiovascular disease ( CVD ) mortality , all-cause mortality , and incident ( fatal and nonfatal ) myocardial infa rct ion ( MI )  in men from the general population taking into account C-reactive protein ( CRP ) , a sensitive marker of systemic inflammation . Methods and Results —The study was based on 3604 men ( 45 to 74 years of age ) who participated in 1 of the 3 MONICA Augsburg surveys between 1984 and 1995 . All participants were prospect ively followed within the framework of the Cooperative Health Research in the Region of Augsburg ( KORA ) . Up to December 31 , 2002 , there occurred 809 total deaths , 359 CVD deaths , and 297 incident MIs . In a Cox model , comparing extreme quartiles of the UA distribution , the hazard ratio for CVD mortality was 1.44 ( 95 % confidence interval [ CI ] 1.04 to 2.0 ) , and for all-cause mortality it was 1.40 ( 95 % CI 1.13 to 1.74 ) after adjustment for conventional cardiovascular risk factors , CRP , and diuretic intake . However , UA was not associated with incident MI after multivariable adjustment . Conclusions —High UA levels were independently associated with CVD mortality as well as all-cause mortality but not with incident MI in middle-aged men from the general population BACKGROUND Endothelial dysfunction is considered an important prognostic factor in atherosclerosis . The aim of this study was to detect the long-term association of peripheral vascular endothelial function and clinical outcome in healthy subjects without apparent coronary artery disease ( CAD ) . METHODS We prospect ively assessed brachial flow-mediated  dilation ( FMD ) in 435 consecutive healthy subjects : 281 ( 65 % ) men , mean age 54+/-12 years and body mass index 28+/-4 kg/m(2 ) . After overnight fasting and discontinuation of all medications for > or = 12 h ,  FMD and endothelium-independent nitroglycerin-mediated vasodilation were assessed using high resolution linear array ultrasound . RESULTS Subjects were divided into 2 groups : below ( n=221 ) and above ( n=214 ) the median FMD of 10.7 % , and were comparable regarding CAD risk factors , lipoproteins , fasting glucose , C-reactive protein , and concomitant medications , with a mean clinical follow-up of 32+/-2 months . Composite cardiovascular endpoints ( all-cause mortality , non-fatal myocardial infa rct ion , heart failure or angina pectoris hospitalization , stroke , coronary artery bypass grafting and percutaneous coronary interventions ) were significantly more common in subjects with below median FMD of 10.7 % , than above ( 11.8 % vs 4.7 % , p=0.007 , respectively ) . Univariate analysis demonstrated that median FMD significantly predicted cardiovascular events [ odds ratio ( OR ) of 2.78 and 95 % CI 1.35 to 5.71 ( p=0.003 ) ] . After multivariate analysis including conventional CAD risk factors , median FMD was the best independent predictor of long-term cardiovascular adverse events [ OR of 2.70 and 95 % CI 1.16 to 6.32 ( p=0.011 ) ] . CONCLUSIONS Brachial artery median FMD independently predicts long-term adverse cardiovascular events in healthy subjects in addition to traditional risk factor assessment Background —Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations . Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events . This study was design ed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease . Methods and Results —Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography . The effect of the coadministration of vitamin C ( 24 mg/min ) was assessed in a subgroup of 179 patients .  Cardiovascular events , including death from cardiovascular causes , myocardial infa rct ion , ischemic stroke , coronary angioplasty , and coronary or peripheral bypass operation , were studied during a mean follow-up period of 4.5 years . Patients experiencing cardiovascular events ( n=91 ) had lower vasodilator responses to acetylcholine ( P < 0.001 ) and sodium nitroprusside ( P < 0.05 ) , but greater benefit from vitamin C ( P < 0.01 ) . The Cox proportional regression analysis for conventional risk factors demonstrated that blunted acetylcholine-induced vasodilation ( P = 0.001 ) , the effect of vitamin C ( P = 0.001 ) , and age ( P = 0.016 ) remained independent predictors of cardiovascular events . Conclusions —Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease . These data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity BACKGROUND Among apparently healthy men , elevated levels of C-reactive protein ( CRP ) , a marker for systemic inflammation , predict risk of myocardial infa rct ion and thromboembolic stroke . Whether increased levels of CRP are also associated with the development of symptomatic peripheral arterial disease ( PAD ) is unknown . METHODS AND RESULTS Using a prospect i ve , nested , case-control design , we measured baseline levels of CRP in 144 apparently healthy men participating in the Physicians ' Health Study who subsequently developed symptomatic PAD ( intermittent claudication or need for revascularization ) and in an equal number of control subjects matched on the basis of age and smoking habit who remained free of vascular disease during a follow-up period of 60 months .  Median CRP levels at baseline were significantly higher among those who subsequently developed PAD ( 1.34 versus 0.99 mg/L ; P=.04 ) . Furthermore , the risks of developing PAD increased significantly with each increasing quartile of baseline CRP concentration such that relative risks of PAD from lowest ( referent ) to highest quartile of CRP were 1.0 , 1.3 , 2.0 , and 2.1 ( Ptrend=.02 ) . Compared with those with no clinical evidence of disease , the subgroup of case patients who required revascularization had the highest baseline CRP levels ( median= 1.75 mg/L ; P= .04 ) ; relative risks from lowest to highest quartile of CRP for this end point were 1.0 , 1.8 , 3.8 , and 4.1 ( Ptrend=.02 ) . Risk estimates were similar after additional control for body mass index , hypercholesterolemia , hypertension , diabetes , and a family history of premature atherosclerosis . CONCLUSIONS These prospect i ve data indicate that among apparently healthy men , baseline levels of CRP predict future risk of developing symptomatic PAD and thus provide further support for the hypothesis that chronic inflammation is important in the pathogenesis of atherothrombosis BACKGROUND The objective of this study was to examine whether definite hypertension and borderline isolated systolic hypertension predict subsequent cardiovascular disease and mortality . METHODS AND RESULTS This was a prospect i ve cohort study with a mean follow-up of 11.7 years . The subjects were a group of 18,682 apparently healthy US men , aged 40 to 84 years , participating in the Physicians ' Health Study , a r and omized trial of low-dose aspirin and beta-carotene .  The main outcome measures were total cardiovascular disease , myocardial infa rct ion , stroke , cardiovascular death , and all-cause mortality . Hypertension was associated with substantially increased risks of total cardiovascular disease ( relative risk [ RR ] 1.92 ; 95 % confidence interval [ CI ] , 1.70 to 2.18 ) , myocardial infa rct ion ( RR,1.78 ; 95 % CI , 1.49 to 2.13 ) , stroke ( RR , 2.19 ; 95 % CI , 1.78 to 2.69 ) , and cardiovascular death ( RR , 2.10 ; 95 % CI , 1.68 to 2.63 ) . Borderline isolated systolic hypertension was associated with significantly increased risks of cardiovascular disease ( RR , 1.32 ; 95 % CI , 1.09 to 1.59 ) , stroke ( RR , 1.42 ; 95 % CI , 1.04 to 1.93 ) , and cardiovascular death ( RR , 1.56 ; 95 % CI , 1.13 to 2.15 ) , as well as a possible but non-significant increased risk of myocardial infa rct ion ( RR , 1.26 ; 95 % CI , 0.95 to 1.67 ) . Hypertension and borderline isolated systolic hypertension were associated with significantly increased risks of 41 % and 22 % , respectively , for all-cause mortality . CONCLUSIONS Hypertension as well as borderline isolated systolic hypertension are associated with elevated risks of cardiovascular diseases , especially stroke and cardiovascular death . Hypertension is associated with an increased risk of myocardial infa rct ion , and borderline isolated systolic hypertension predicts a possible but more modest increase in risk . These data add to the existing evidence that hypertension is a major cardiovascular risk factor and extend the findings to borderline isolated systolic hypertension AIM In patients with coronary artery disease ( CAD ) , a J-curve relationship has been reported between blood pressure ( BP ) and future cardiovascular events . However , this is controversial . The purpose of the study was to determine the relationship between on-treatment BP and cardiovascular outcomes in patients with CAD . METHODS AND RESULTS We evaluated 10 001 patients with CAD and a low-density lipoprotein ( LDL ) cholesterol level < 130 mg/dL , r and omized to atorvastatin 80 vs. 10 mg , enrolled in the TNT trial . The post-baseline , time-dependent BPs [ systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) ] were categorized into 10 mmHg increments . The primary outcome was a composite of death from coronary disease , non-fatal myocardial infa rct ion ( MI ) , resuscitated cardiac arrest , and fatal or non-fatal stroke . Among the 10 001 patients , 982 ( 9.82 % ) experienced a primary outcome at 4.9 years ( median ) of follow-up . The relationship between SBP or DBP and primary outcome followed a J-curve with increased event rates above and below the reference BP range , both unadjusted and adjusted ( for baseline covariates , treatment effect , and LDL levels ) . A time-dependent , non-linear , multivariate Cox proportional hazard model identified a nadir of 146.3/81.4 mmHg where the event rate was lowest . A similar non-linear relationship with a higher risk of events at lower pressures was found for most of the secondary outcomes of all-cause mortality , cardiovascular mortality , non-fatal MI , or angina . However , for the outcome of stroke , lower was better for SBP . CONCLUSION In patients with CAD , a low BP ( < 110 - 120/<60 - 70 mmHg ) portends an increased risk of future cardiovascular events ( except stroke ) Objective To evaluate the association of kidney function with  cardiovascular disease and mortality among apparently healthy women . Design Prospect i ve cohort study . Setting Women ’s Health Study , United States . Participants 27 939 female health professionals aged ≥45 who were free of cardiovascular disease and other major disease and who provided a blood sample at study entry . Main outcome measures Time to cardiovascular disease ( non-fatal stroke , non-fatal myocardial infa rct ion , coronary revascularisation procedures , or death from cardiovascular cause ) , specific cardiovascular disease events , and all-cause mortality . End points were confirmed after review of medical records and death certificates . Results Glomerular filtration rate ( GFR ) was estimated with the abbreviated Modification of Diet in Renal Disease Study equation . At baseline , 1315 ( 4.7 % ) women had GFR < 60 ml/min/1.73 m2 . During 12 years of follow-up , 1199 incident cardiovascular disease events and 856 deaths ( 179 from cardiovascular disease ) occurred . Compared with women with GFR ≥90 ml/min/1.73 m2 , the multivariable adjusted hazard ratios for any first cardiovascular disease were 0.95 ( 95 % CI 0.83 to 1.08 ) , 0.84 ( 0.70 to 1.00 ) , and 1.00 ( 0.79 to 1.27 ) among women with GFR of 75 - 89.9 , 60 - 74.9 , and < 60 ml/min/1.73 m2 , respectively ; the equivalent hazard ratios for all cause mortality were 0.93 ( 0.79 to 1.09 ) , 1.03 ( 0.85 to 1.26 ) , and 1.09 ( 0.83 to 1.45 ) . Similar null findings were observed for myocardial infa rct ion , stroke , coronary revascularisation , and non-cardiovascular death . However , an increased risk of death from cardiovascular disease was found among women with GFR < 60 ml/min/1.73 m2 ( hazard ratio 1.68 ( 1.02 to 2.79 ) ) . Conclusions In this large cohort of women , a glomerular filtration rate < 60 ml/min/1.73 m2 was associated with increased risk of cardiovascular disease death but not other cardiovascular disease events or non-cardiovascular disease mortality . We observed no increase in risk of any of the outcomes among women with less severe impairment of kidney function CONTEXT Previous studies have documented an association of depression and phobic anxiety with cardiovascular morbidity and mortality , but little is known about the cardiovascular sequelae of panic anxiety . OBJECTIVE To determine whether panic attacks are associated with risk of cardiovascular morbidity and mortality in postmenopausal women . DESIGN Prospect i ve cohort survey . SETTING Ten clinical centers of the 40-center Women 's Health Initiative . PARTICIPANTS A total of 3369 community-dwelling , generally healthy postmenopausal women ( aged 51 - 83 years ) enrolled between 1997 and 2000 in the Myocardial Ischemia and Migraine Study who completed a question naire about occurrence of panic attacks in the previous 6 months .  MAIN OUTCOME MEASURES Cardiovascular/cerebrovascular outcomes ( fatal and nonfatal myocardial infa rct ion and stroke ) and all-cause mortality were ascertained after a mean of 5.3 years of follow-up . RESULTS A 6-month history of full-blown panic attacks , endorsed by 10 % of postmenopausal women in this cohort , was associated with both coronary heart disease ( hazard ratio , 4.20 ; 95 % confidence interval , 1.76 - 9.99 ) and the combined end point of coronary heart disease or stroke ( hazard ratio , 3.08 ; 95 % confidence interval , 1.60 - 5.94 ) after controlling for multiple potential confounders . The hazard ratio for all-cause mortality , excluding those with a history of cardiovascular/cerebrovascular events , was 1.75 ( 95 % confidence interval , 1.04 - 2.94 ) . CONCLUSION Panic attacks are relatively common among postmenopausal women and appear to be an independent risk factor for cardiovascular morbidity and mortality in older women OBJECTIVE To determine the relationship between increasing depressive symptoms and  cardiovascular events or mortality . DESIGN Cohort analytic study of data from r and omized  placebo-controlled  double-blind clinical trial of antihypertensive therapy . Depressive symptoms were assessed semi-annually with the Center for Epidemiological Studies -Depression ( CES-D ) scale during an average follow-up of 4.5 years . SETTING Ambulatory patients in 16 clinical centers of the Systolic Hypertension in the Elderly Program . PATIENTS Generally healthy men and women aged 60 years or older r and omized to active antihypertensive drug therapy or placebo who were 70 % white and 53 % women and had follow-up CES-D scores and no outcome events during the first 6 months ( N=4367 ) . MAIN OUTCOME MEASURES All-cause mortality , fatal or nonfatal stroke , or myocardial infa rct ion . RESULTS Baseline depressive symptoms were not related to subsequent events ; however , an increase in depression was prognostic . Cox proportional hazards regression analyses with the CES-D scale as a time-dependent variable , controlling for multiple covariates , indicated a 25 % increased risk of death per 5-unit increase in the CES-D score ( relative risk [ RR ] , 1.25;95 % confidence interval [ CI ] , 1.15 to 1.36 ) . The RR for stroke or myocardial infa rct ion was 1.18(95%CI,1.08 to 1.30 ) . Increase in CES-D score was an independent predictor in both placebo and active drug groups , and it was strongest as a risk factor for stroke among women ( RR,1.29;95%CI,1.07 to 1.34 ) . CONCLUSIONS Among elderly persons , a significant and substantial excess risk of death and stroke or myocardial infa rct ion was associated with an increase in depressive symptoms over time , which may be a marker for subsequent major disease events and warrants the attention of physicians to such mood changes . However , further studies of casual pathways are needed before wide-spread screening for depression in clinical practice is to be recommended Background and Purpose — In national guidelines , absolute long-term risk of myocardial infa rct ion ( MI ) or coronary death determines target low-density lipoprotein levels , but stroke patients are not explicitly addressed . We determined the absolute 5-year risk of cardiovascular outcomes and their predictors after first ischemic stroke in a multiethnic cohort . Methods — A population -based cohort of first ischemic stroke patients ≥40 years old was prospect ively followed annually for recurrent stroke , MI and cause-specific mortality . Kaplan-Meier 5-year risks for MI or vascular death ( primary outcome ) , and other cardiovascular events , were calculated . Univariate and multivariate Cox proportional hazards models were used to calculate hazard ratios and 95 % CI for predictors of cardiovascular outcomes . Results — Mean age ( n=655 ) was 69.7±12.7 years ; 55.4 % of participants were women , and 51.3 % Hispanic .  The 5-year risk of MI or vascular death was 17.4 % ( 95 % CI , 14.2 % to 20.6 % ) . Independent historical predictors of MI or vascular death were age > 70 years ( hazard ratio 1.62 , 1.07 to 2.44 ) , history of coronary artery disease ( hazard ratio 1.76 , 1.13 to 2.74 ) , and atrial fibrillation ( hazard ratio 1.76 , 1.05 to 2.94 ) . In the lowest risk group , those ≤70 years old without coronary artery disease , 5-year risk of MI or vascular death was 9.7 % . Conclusions — The absolute risk of MI or vascular death after ischemic stroke , even in those without high-risk features , approximates levels used by national organizations to design ate groups of patients at high risk of vascular events . The comparability of levels of absolute risk among stroke and cardiac patients may have treatment implication Peripheral arterial disease ( PAD ) is associated with major cardiovascular morbidity and mortality . Abnormalities in nitric oxide metabolism due to excess of the NO synthase inhibitor asymmetric dimethylarginine ( ADMA ) may be pathogenic in PAD . We explored the association between ADMA levels and markers of atherosclerosis , function , and prognosis .  A total of 133 patients with symptomatic PAD were enrolled .  Ankle — brachial index ( ABI ) , walking time , vascular function measures ( arterial compliance and flow-mediated vasodilatation ) and plasma ADMA level  were assessed for each patient at baseline . ADMA correlated inversely with ABI ( r = —0.238 , p = 0.003 ) and walking time ( r = —0.255 , p = 0.001 ) , independent of other vascular risk factors . We followed up 125 ( 94 % ) of our 133 initial subjects with baseline measurements ( mean 35 months ) . Subjects with ADMA levels in the highest quartile ( > 0.84 μmol/l ) showed a significantly greater occurrence of a major adverse cardiovascular event ( MACE ) compared to those with ADMA levels in the lower three quartiles ( p = 0.001 ) . Cox proportional-hazards regression analysis revealed that ADMA was a significant predictor of MACE , independent of other risk factors including age , sex , blood pressure , smoking history , diabetes and ABI ( hazard ratio = 5.1 , p < 0.001 ) . Measures of vascular function , such as compliance , flow-mediated vasodilatation ( FMVD ) and blood pressure , as well as markers of PAD severity , including ABI and walking time , were not predictive . In conclusion , circulating levels of ADMA correlate independently with measures of disease severity and major adverse cardiovascular events . Agents that target this pathway may be useful for this patient population . Clinical Trial Registration — URL : http:// www . clinical trials.gov . Unique identifier : BACKGROUND The Hypertension Optimal Treatment ( HOT ) Study has provided information about cardiovascular events in 18790 hypertensives , subjected to pronounced blood pressure ( BP ) lowering for a mean of 3.8 years . The HOT study data have subsequently been analysed after stratification of the patients according to global cardiovascular risk , and it has been found that , despite intensive blood pressure lowering in all risk strata , morbid event rates increased with increasing risk stratum . OBJECTIVES Previously analysed global risk strata were based on combinations of risk factors . The analyses presented here were intended to provide information on the relative role that the presence of each individual factor may have in increasing cardiovascular risk , despite good BP control . METHODS Risk ratios ( RR ) for patients with and those without a risk factor were calculated with 95 % confidence intervals ( CI ) using a Cox proportional hazard model , and adjusted for all variables except the one under examination . RESULTS For all risk factors considered and for all types of event , RR were always greater than 1 , indicating a greater risk in the presence , compared with that in the absence of each factor . The male gender was a statistically significant risk for cardiovascular ( CV ) events , CV and total mortality and particularly for myocardial infa rct ion ( MI ) ; age > or = 65 years for CV events , stroke , CV and particularly total mortality ; smoking for all events analysed , but particularly for total mortality ( twice higher in smokers than in non-smokers ) ; high serum cholesterol ( > 6.8 mmol/l ) for CV events , MI and CV mortality ; high serum creatinine ( > 155 micromol/l ) for CV events , stroke , CV and total mortality ; diabetes for CV events , stroke , total mortality and particularly CV mortality ; and ischaemic heart disease for all events analysed . Adjusted RR were often close to or greater than 2 . CONCLUSIONS Each of the risk factors considered was found to be an important cause of residual risk , despite good BP control . These findings emphasize the importance of addressing other correctable risk factors , e.g. smoking , hypercholesterolaemia and diabetes , as well as rigorous control of blood pressure , and of initiating antihypertensive therapy before cardiovascular and renal damage becomes manifest This study meta-analysed r and omized , double-blind , placebo controlled trials in patients with intermittent claudication of the lower limbs comparing  ticlopidine to placebo  in order to test the hypothesis that the drug , a pure antiplatelet agent , is able to reduce the incidence of thrombotic cardio-vascular events on atherosclerotic arteries in these patients . A highly significant reduction , from 9 % to 3 % ( p ranging from 0.006 to 0.002 ) , was observed for fatal or non-fatal cardio-vascular events in a total of 611 patients ( 301 with ticlopidine , 310 with placebo ) . The duration of follow-up ranged from 6 to 12 months . Side-effects , defined as withdrawal from study medication for any reason but death , cardio-vascular events or cancer , were 2.4 times more frequent in the ticlopidine treated patients as compared to placebo . We concluded that in this high risk population , prevention of cardio-vascular events is likely to be effective Diabetes is a major risk factor for cardiovascular events . Indeed , people with diabetes are 2 - 4 times more likely to die from cardiovascular causes than individuals without diabetes . Despite evidence to suggest that the burden of cardiovascular disease may be decreasing in Western population s , this trend has not been repeated in diabetic population s. Diabetes is also the most common cause of new-onset end-stage renal disease , blindness and amputations . The growing incidence of diabetes throughout the world , particularly in developing nations , suggests that diabetes-related cardiovascular disease and other chronic cardiovascular diseases will constitute a serious global threat to health and well-being . The HOPE ( Heart Outcomes Prevention Evaluation ) study was design ed to determine if the angiotensin converting enzyme ( ACE ) inhibitor , ramipril , prevents cardiovascular events in high risk patients . As people with diabetes have a high risk of such events , this group was specified for inclusion and analysis in the HOPE study . The HOPE study was design ed to include up to 4,000 people with diabetes and was design ed with high power to detect an 18 % risk reduction in the diabetic sub group alone . A total of 3,577 individuals with diabetes were r and omised to receive either 10 mg of ramipril or placebo . After a period of 4.5 years of follow-up , the group of patients receiving ramipril had a statistically and clinical ly significant risk reduction of 25 % in the primary outcome of myocardial infa rct ion ( MI ) , stroke or cardiovascular ( CV ) death . This comprises a 37 % risk reduction in CV death , a 22 % risk reduction in MI , a 33 % reduction in stroke and a 24 % reduction in all-cause mortality . The MICRO-HOPE ( Microalbuminuria , Cardiovascular , and Renal Outcomes ) sub study assessed the effect of ramipril on diabetic nephropathy . This was detected by a central ly measured urine albumin : creatinine ratio and confirmed by timed urine collection . Ramipril significantly reduced the risk of overt nephropathy by 22 % ( P = 0.045 ) , and overt nephropathy , laser therapy or dialysis by 15 % ( P = 0.05 ) . ACE inhibition with ramipril represents a new macrovascular and microvascular preventive therapy for people with diabetes CONTEXT Polycystic ovary syndrome ( PCOS ) is associated with the metabolic syndrome and , consequently , with a potentially increased risk of cardiovascular disease ( CVD ) and related mortality later in life . Studies regarding CVD and mortality in PCOS women well into the postmenopausal age are lacking . OBJECTIVE Our objective was to examine whether postmenopausal PCOS women differ from controls regarding cardiovascular risk factors , myocardial infa rct ion ( MI ) , stroke and mortality . DESIGN AND SETTING We conducted , at a university hospital , a prospect i ve study of 35 PCOS women ( 61 - 79 yr ) and 120 age-matched controls . The study was performed 21 yr after the initial study . PARTICIPANTS Twenty-five PCOS women ( Rotterdam criteria ) and 68 controls participated in all examinations . Data on morbidity were based on 32 of 34 PCOS women and on 95 of 119 controls . INTERVENTIONS INTERVENTIONS included reexamination , interviews , and data from the National Board of Health and Welfare and from the Hospital Discharge Registry . MAIN OUTCOME MEASURES Blood pressure , glucose , insulin , triglycerides , total cholesterol , high- and low-density lipoprotein , apolipoprotein A1 and B , fibrinogen , and plasminogen activator inhibitor antigen were studied . Incidences of MI , stroke , hypertension , diabetes , cancer , cause of death , and age at death were recorded . RESULTS PCOS women had a higher prevalence of hypertension ( P = 0.008 ) and higher triglyceride levels ( P = 0.012 ) than controls . MI , stroke , diabetes , cancer , and mortality prevalence was similar in the two cohorts with similar body mass index . CONCLUSIONS The well-described cardiovascular/metabolic risk profile in pre- and perimenopausal PCOS women does not entail an evident increase in cardiovascular events during the postmenopausal period BACKGROUND Uric acid stabilizes platelet aggregation and enhances thrombotic tendency . OBJECTIVE To examine the relationship between raised serum uric acid and subsequent  cardiovascular events ( mortality , myocardial infa rct ion , stroke ) . METHODS This is a longitudinal study in a small r and om number ( 418 ) of patients in Kinshasa , Congo . In this hospital-based study , uricemia was determined with respect to gender , obesity and hypertension as well correlated with traditional cardiovascular risk factors . A univariate regression model was used to investigate the association of serum uric acid with the incidence of mortality , stroke and myocardial infa rct ion . RESULTS Serum uric acid was higher ( P<0.05 ) in obese women and men as well in hypertensives , than in their controls . The significant ( P<0.05 and 0.001 ) highest frequency of hyperuricemia was observed in both diabetic and hypertensive patients . Blood pressure ( BP ) was higher ( P<0.001 ) in patients with hyperuricemia than in those with normal serum uric acid . Serum uric acid was significantly correlated with body weight , BP , glucose , fibrinogen , urea , creatinin and total cholesterol . In men , hyperuricemia was significantly ( P<0.01 ) associated with a twofold increased risk of both myocardial infa rct ion and stroke incidence . However , hyperuricemia was significantly related to a double risk of all mortality and stroke onset . CONCLUSION Our results indicate that hyperuricemia among african patients is a strong predictor of myocardial infa rct ion  in men , stroke in both sexes and all causes of mortality in women BACKGROUND We investigated aspirin-prescribing patterns and potential benefits on cardiovascular morbidity and mortality  in hemodialysis patients . STUDY DESIGN Cohort study . SETTING & PARTICIPANTS Data included 28,320 r and omly selected hemodialysis patients from the Dialysis Outcomes and Practice Patterns Study I and II . PREDICTOR Aspirin prescription at study baseline . OUTCOMES & MEASUREMENTS Prescription was investigated by means of logistic regression . All-cause mortality , all-cause hospitalization , cardiac event , myocardial infa rct ion , cerebrovascular ( CVA ) , gastrointestinal bleed , transient ischemic attack , and subdural hematoma were examined . Cox regression examined the risk of mortality and hospitalization . All models accounted for facility clustering and demographics and comorbid conditions . RESULTS Wide variation was found in aspirin prescription , from 8 % in Japan to 41 % in Australia and New Zeal and . Characteristics significantly associated with increased odds of prescription included coronary artery disease , cerebrovascular disease , diabetes , male sex , nonblack race , peripheral vascular disease , age , hypertension , and absence of gastrointestinal bleeding .  Aspirin was associated with decreased risk of stroke in all patients ( relative risk [ RR ] , 0.82 ; P < 0.01 ) and increased risk of myocardial infa rct ion ( RR , 1.21 ; P = 0.01 ) and cardiac event ( RR , 1.08 ; P < 0.01 ) in all patients , with similar results for patients with coronary artery disease . There was no increase in gastrointestinal bleeding . LIMITATIONS Observational studies are not protected from biases , despite adjustments . There is potential for aspirin use to be underreported because of its availability without prescription . CONCLUSIONS The hypothesis that prescribing aspirin to hemodialysis patients decreases cardiovascular disease risk is not supported . Aspirin might decrease CVA and appears not to increase hemorrhagic risk . This should be an incentive for r and omized controlled trials BACKGROUND Intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease . This report describes the 5-year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events . METHODS We r and omly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy ( targeting a glycated hemoglobin level below 6.0 % ) or st and ard therapy ( targeting a level of 7 to 7.9 % ) . After termination of the intensive therapy , due to higher mortality in the intensive-therapy group , the target glycated hemoglobin level was 7 to 7.9 % for all participants , who were followed until the planned end of the trial . RESULTS Before the intensive therapy was terminated , the intensive-therapy group did not differ significantly from the st and ard-therapy group in the rate of the primary outcome ( a composite of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes ) ( P=0.13 ) but had more deaths from any cause ( primarily cardiovascular ) ( hazard ratio , 1.21 ; 95 % confidence interval [ CI ] , 1.02 to 1.44 ) and fewer nonfatal myocardial infa rct ions ( hazard ratio , 0.79 ; 95 % CI , 0.66 to 0.95 ) . These trends persisted during the entire follow-up period ( hazard ratio for death , 1.19 ; 95 % CI , 1.03 to 1.38 ; and hazard ratio for nonfatal myocardial infa rct ion , 0.82 ; 95 % CI , 0.70 to 0.96 ) . After the intensive intervention was terminated , the median glycated hemoglobin level in the intensive-therapy group rose from 6.4 % to 7.2 % , and the use of glucose-lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups . CONCLUSIONS As compared with st and ard therapy , the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6 % reduced 5-year nonfatal myocardial infa rct ions but increased 5-year mortality . Such a strategy can not be recommended for high-risk patients with advanced type 2 diabetes . ( Funded by the National Heart , Lung and Blood Institute ; Clinical Trials.gov number , NCT00000620 . ) Since the excess mortality rate associated with an ankle-brachial blood-pressure index ( ABPI ) less than 0.9 was only partly explained by an excess cardiovascular mortality , we believe that leg artery disease should not only be regarded as a marker of generalised arteriosclerosis but also as a sign associated with an increased risk of premature death .  439 men who were part of a prospect i ve population study in Malmö , Sweden , were , at 68 years of age , invited to a health examination including , ABPI , carotid-artery ultrasonography , and 24 h ambulatory electrocardiographic monitoring .  Cause-specific mortality and incidence of myocardial infa rct ion ( MI ) during 8 years of follow-up was compared in men with and without signs of arteriosclerotic disease . Of 60 men with an ABPI < 0.9 , 20 ( 33 % ) had angina pectoris or previous MI . Another 11 ( 18 % ) had silent ST-segment depression ( > or = 1 mm ) ; 3 ( 5 % ) had a history of stroke ; and 17 ( 28 % ) had symptom-free carotid stenosis ( > 30 % reduction of the cross-sectional diameter ) . Total mortality rate in men with no signs of arteriosclerotic disease was 19.6 per 1000 person-years and cardiac event rate ( fatal and non-fatal MI and death from chronic ischaemic heart disease was 8.6 per 1000 person-years ) . Leg artery disease , carotid stenosis , and ischaemic heart disease were in a univariate analysis all associated with an increased cardiac event rate and an increased total mortality rate . In a multivariate analysis an ABPI less than 0.9 was associated with a 2.4 times higher total mortality ( 95 % CI 1.5 - 3.9 ) and a 2.0 times higher cardiac event rate ( 1.1 - 3.9 ) . Carotid stenosis and ischaemic heart disease contributed to the risk for MI ( RR 2.1 ; 95 % CI 1.2 - 3.8 ; and 2.1 ; 1.2 - 3.9 , respectively ) , whereas no independent association with total mortality was found Background : In patients with symptomatic peripheral artery disease with a history of limb revascularization , the optimal antithrombotic regimen for long-term management is unknown . Methods : The EUCLID trial ( Examining Use of Ticagrelor In PAD ) r and omized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily . Patients were enrolled based on an abnormal ankle-brachial index ⩽0.80 or a previous lower extremity revascularization . This analysis focuses on the 7875 ( 57 % ) patients enrolled based on the previous lower extremity revascularization criterion . Patients could not be enrolled within 30 days of most recent revascularization , and patients with an indication for dual antiplatelet therapy were excluded . The primary efficacy end point was a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . The primary safety end point was major bleeding . Results : Patients with a previous revascularization had a mean age of 66 years , 73 % were male , and the median baseline ankle-brachial index was 0.78 . After adjustment for baseline characteristics , patients enrolled based on previous revascularization had similar rates of the primary composite end point ( hazard ratio [ HR ] 1.10 , 95 % confidence interval [ CI ] 0.98–1.23 , P=0.12 ) and statistically significantly higher rates of myocardial infa rct ion ( HR 1.29 , 95 % CI 1.08–1.55 , P=0.005 ) and acute limb ischemia ( HR 4.23 , 95 % CI 2.86–6.25 , P<0.001 ) when compared with patients enrolled based on ankle-brachial index criteria . No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point ( 11.4 % vs 11.3 % ; HR 1.01 , 95 % CI 0.88–1.15 ; P=0.90 ) , all-cause mortality ( 9.2 % vs 9.2 % ; HR 0.99 , 95 % CI 0.86–1.15 ; P=0.93 ) , acute limb ischemia ( 2.5 % vs 2.5 % ; HR 1.03 , 95 % CI 0.78–1.36 ; P=0.84 ) , or major bleeding ( 1.9 % vs 1.8 % ; HR 1.15 , 95 % CI 0.83–1.59 ; P=0.41 ) . The median duration of follow-up was ≈30 months . Conclusions : After adjustment for baseline characteristics , patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infa rct ion and acute limb ischemia , with similar composite rates of cardiovascular death , myocardial infa rct ion , and stroke when compared with patients enrolled based on the ankle-brachial index criterion . No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events . Clinical Trial Registration : URL : http://www . clinical trials.gov . Unique identifier : NCT01732822 The main aim of medical treatment for intermittent claudication ( IC ) is the reduction of mortality and morbidity from ischemic cardiovascular disease . However , symptomatic treatment with the aim of improving exercise performance and the overall quality of life may also be an important target of the clinical management of patients with intermittent claudication .  Cloricromene , a drug with antithrombotic and anti-ischemic activities , has previously shown some promising results in patients with claudication . We have carried out a clinical trial to assess the effect of cloricromene on the claudication distance and on the quality of life of patients with IC chronically treated with aspirin . A total of 159 patients with IC , Stage II ( Fontaine ) , were enrolled in a double-blind , r and omized , prospect i ve , multicenter study comparing cloricromene ( 100 mg orally b.i.d . ) or an identical placebo for 6 months . All patients received 160 mg/day aspirin . The primary end-point was the improvement of initial claudication distance ( ICD ) at 6 months as measured by a st and ardized treadmill test . The secondary end-points were the absolute claudication distance ( ACD ) at 6 months , the percentage of patients defined as responders to treatment ( improvement of ICD of at least 40 % ) , changes in the ischemic window ( IW ) , quality of life as assessed by the SF-36 question naire , and the occurrence of major cardiovascular events . The ICD increased in both treatment groups , with a non-significant difference at 6 months in favor of cloricromene of + 12.3 m. The ACD , percentage of responders to treatment and ischemic window also improved in both groups with a slight , non-significant trend in favor of cloricromene . Pretreatment quality of life scores showed only a slight worsening compared with an age-matched , healthy population and did not change upon treatment . A post hoc subgroup analysis showed a significant benefit from cloricromene in patients with an ICD at enrollment higher than the median of the patient population . In conclusion , treatment with cloricromene for 6 months does not significantly improve  claudication in patients with Stage II Fontaine peripheral arteriopathy chronically treated with aspirin . An improvement of 40 - 60 m in the ICD on a st and ardized treadmill test does not translate into a self-perceived improvement in the quality of life as assessed by the SF-36 question naire Background — Although erectile dysfunction ( ED ) is associated with cardiovascular risk factors and atherosclerosis , it is not known whether the presence of ED is predictive of future events in individuals with cardiovascular disease . We evaluated whether ED is predictive of mortality and cardiovascular outcomes , and because inhibition of the renin-angiotensin system in high-risk patients reduces cardiovascular events , we also tested the effects on ED of r and omized treatments with telmisartan , ramipril , and the combination of the 2 drugs ( ONTARGET ) , as well as with telmisartan or placebo in patients who were intolerant of angiotensin-converting enzyme inhibitors ( TRANSCEND ) . Methods and Results — In a prespecified sub study , 1549 patients underwent double-blind r and omization , with 400 participants assigned to receive ramipril , 395 telmisartan , and 381 the combination thereof ( ONTARGET ) , as well as 171 participants assigned to receive telmisartan and 202 placebo ( TRANSCEND ) . ED was evaluated at baseline , at 2-year follow-up , and at the penultimate visit before closeout . ED was predictive of all-cause death ( hazard ratio [ HR ] 1.84 , 95 % confidence interval [ CI ] 1.21 to 2.81 , P=0.005 ) and the composite primary outcome ( HR 1.42 , 95 % CI 1.04 to 1.94 , P=0.029 ) , which consisted of cardiovascular death ( HR 1.93 , 95 % CI 1.13 to 3.29 , P=0.016 ) , myocardial infa rct ion ( HR 2.02 , 95 % CI 1.13 to 3.58 , P=0.017 ) , hospitalization for heart failure ( HR 1.2 , 95 % CI 0.64 to 2.26 , P=0.563 ) , and stroke ( HR 1.1 , 95 % CI 0.64 to 1.9 , P=0.742 ) . The study medications did not influence the course or development of ED . Conclusions — ED is a potent predictor of all-cause death and the composite of cardiovascular death , myocardial infa rct ion , stroke , and heart failure in men with cardiovascular disease . Trial treatment did not significantly improve or worsen ED . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT 00153101 OBJECTIVE Evaluating the effects of implementing an antidepressant treatment strategy in depressed myocardial infa rct ion (MI)- patients on long-term cardiovascular outcomes and all-cause mortality . METHODS MI- patients were evaluated for the presence of a diagnosis of post-MI depression at 3 , 6 , 9 and 12months after hospitalization for MI . A total of 331 depressed MI- patients were r and omized to intervention or care-as-usual ( CAU ) . Patients r and omized to the intervention were offered several antidepressant treatment options including pharmacological and non-pharmacological therapy . Patients r and omized to CAU were not given feedback about their depression status . All patients were free to seek depression treatment outside the study , which was monitored . The primary outcome was a combined endpoint of cardiovascular events and cardiac mortality between r and omization and 8years later . All-cause mortality was evaluated as secondary endpoint . RESULTS The intervention did not reduce the risk of the primary outcome ( HR : 0.97 ( 95 % CI : 0.67 - 1.40 ) n=330 ) or all-cause mortality ( HR : 0.74 ( 95 % CI : 0.41 - 1.33 ) n=330 ) . Regardless of r and omization status , patients who received  depression treatment ( n=168 ) had reduced all-cause mortality rates compared to those who did not receive treatment ( n=143 , HR : 0.52 ( 95 % CI : 0.28 - 0.97 ) ) . CONCLUSION Implementing an antidepressant treatment strategy did not reduce the risk of cardiovascular morbidity and mortality compared to usual care . Receiving depression treatment increased survival . It remains unclear whether this represents a direct treatment effect or is due to unmeasured factors that relate to both receiving depression treatment and mortality , such as patients ' intrinsic motivation to care for their health OBJECTIVES This study was design ed to evaluate the relationship between elevated creatinine levels and cardiovascular events . BACKGROUND End-stage renal disease is associated with high cardiovascular morbidity and mortality . The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear . METHODS We analyzed data from the Cardiovascular Health Study , a prospect i ve population -based study of subjects , aged > 65 years , who had a serum creatinine measured at baseline ( n = 5,808 ) and were followed for a median of 7.3 years . Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity . Renal insufficiency was defined as a creatinine level > or = 1.5 mg/dl in men or > or = 1.3 mg/dl in women . RESULTS An elevated creatinine level  was present in 648 ( 11.2 % ) participants . Subjects with elevated creatinine had higher overall ( 76.7 vs. 29.5/1,000 years , p < 0.001 ) and cardiovascular ( 35.8 vs. 13.0/1,000 years , p < 0.001 ) mortality than those with normal creatinine levels . They were more likely to develop cardiovascular disease ( 54.0 vs. 31.8/1,000 years , p < 0.001 ) , stroke ( 21.1 vs. 11.9/1,000 years , p < 0.001 ) , congestive heart failure ( 38.7 vs. 17/1,000 years , p < 0.001 ) , and symptomatic peripheral vascular disease ( 10.6 vs. 3.5/1,000 years , p < 0.001 ) . After adjusting for cardiovascular risk factors and sub clinical disease measures , elevated creatinine remained a significant predictor of all-cause and cardiovascular mortality , total cardiovascular disease ( CVD ) , claudication , and congestive heart failure ( CHF ) . A linear increase in risk was observed with increasing creatinine . CONCLUSIONS Elevated creatinine levels are common in older adults and are associated with increased risk of mortality , CVD , and CHF . The increased risk is apparent early in renal disease AIMS Increased arterial wave reflections are associated with the presence and extent of coronary atherosclerosis and with cardiovascular mortality in selected population s. We prospect ively evaluated their prognostic value in the short- and long-term following percutaneous coronary interventions ( PCIs ) . METHODS AND RESULTS We non-invasively quantified wave reflections [ expressed as augmentation index corrected for heart rate of 75 b.p.m . ( AIx@75 ) ] using applanation tonometry of the radial artery and a vali date d transfer function to obtain the corresponding aortic values in 262 patients undergoing PCI .  During 2-year follow-up , 61 patients reached the primary endpoint [ death , myocardial infa rct ion ( MI ) , and restenosis ] . Increasing tertiles of Alx@75 were related to the rate of patients reaching the primary endpoint [ 15.2 , 20 and 35.3 % , respectively ( P = 0.001 ) ] , as well as the secondary endpoints total mortality , myocardial infa rct ion and death plus myocardial infa rct ion ( RR for the third vs. the first tertile 4.33 , 3.25 and 3.46 , respectively , P < 0.05 ) . In a multivariable Cox-regression model , AIx@75 added prognostic value above and beyond clinical risk factors , angiographic variables , and medications ( RR 1.8 , 95%CI 1.18 - 2.76 per increasing AIx@75-tertile , P < 0.01 ) . CONCLUSION Increased arterial wave reflections are independently associated with an increased risk for severe short- and long-term cardiovascular events in patients undergoing PCI To determine the presence of a ' hypercoagulable state ' as assessed by indices of thrombin and plasmin generation and of the amount of fibrin that is lysed , in patients with stable coronary , cerebral and peripheral arterial disease a population -based cross-sectional study was performed . From a population -based cohort comprising 7983 men and women aged 55 years and over , we r and omly selected 127 subjects with a history of myocardial infa rct ion , 124 with a history of stroke and /or transient ischemic attack , 131 patients with peripheral arterial disease and 263 control subjects in the same age group without arterial disease . Subjects using anticoagulant drugs were not selected . F1 + 2 , TAT , and PAP were not associated with a history of cardiovascular events , nor with peripheral arterial disease . In contrast , positive associations were found for D-Dimer . Mean D-Dimer level was 40 microg/l ( 95 % CI 35 , 44 ) in control subjects ; 53 microg/l ( 47 , 61 ) in those with a history of myocardial infa rct ion and 51 microg/l ( 45 , 58 ) in those with a history of stroke and or transient ischemic attack . D-Dimer increased gradually with increasing severity of peripheral atherosclerosis ; a decrease in ankle/arm systolic blood pressure ratio of 0.1 was associated with an increase in D-Dimer of 3.9 microg/l ( p<0.01 ) . This was more pronounced in subjects with higher F1 + 2 , TAT and PAP concentration . In conclusion , the markers of onset of coagulation F1 + 2 , TAT and PAP are not associated with the presence of arterial disease , but increased levels of these markers are necessary for the positive association between D-Dimer and arterial disease BACKGROUND AND AIMS Patients with established coronary artery disease ( CAD ) are likely to receive a combination of aspirin , a statin , and blood pressure (BP)-lowering agents . Combining these pharmacologic agents into a cardiovascular combination pill , such as a polypill , could be considered to reduce prescription gaps and nonadherence in high-risk patients . We aim ed to evaluate the effect of the concomitant use of aspirin , a statin , and BP-lowering agent(s ) in patients with CAD on vascular morbidity and mortality  in current clinical practice in an observational study to provide insights in the combination pill concept related to feasibility and applicability . METHODS In total , 2,706 patients with CAD enrolled in the Second Manifestations of ARTerial disease study were followed for the occurrence of a subsequent vascular event ( ie , myocardial infa rct ion , ischemic cerebrovascular accident , vascular death ) and all-cause mortality . The relationship between combination therapy and cardiovascular events and all-cause mortality was assessed using Cox proportional hazards regression models to calculate hazards ratios ( HRs ) with a 95 % CI . Both covariate and propensity score adjusting methods were used to reduce confounding by indication . RESULTS A combination of aspirin , a statin , and ≥1 BP-lowering agent(s ) was used by 67 % of the patients . During a median of 5.0 years ( interquartile range 2.4 - 10.2 years ) , 347 vascular events occurred and 162 patients died . Combination therapy with aspirin , statin , and ≥1 BP-lowering agent was associated with a lower risk of myocardial infa rct ion ( HR 0.68 , 95 % CI 0.49 - 0.96 ) , ischemic cerebrovascular accident ( HR 0.37 , 95 % CI 0.16 - 0.84 ) , composite vascular end point ( HR 0.66 , 95 % CI 0.49 - 0.88 ) , vascular mortality ( HR 0.53 , 95 % CI 0.33 - 0.85 ) , and all-cause mortality ( HR 0.69 , 95 % CI 0.49 - 0.96 ) compared with the absence of combination therapy , after adjusting for confounding covariates in a propensity score . The use of 1 or only 2 components of combination therapy was associated with a higher risk for cardiovascular events compared with the combined use of aspirin , a statin , and ≥1 BP-lowering agent(s ) . CONCLUSION Two-thirds of the patients with CAD use a combination of aspirin , a statin , and ≥1 BP-lowering agent(s ) , components of a cardiovascular fixed-dose combination pill . Combination therapy with these agents is associated with a lower risk of vascular events and total mortality . Although treatment effect in observational studies should be interpreted with caution , the results of this study support supposed benefits from combination therapy . However , the effect of fixed-dose combination pill on clinical outcome needs to be demonstrated in r and omized clinical trials CONTEXT A low ankle brachial index ( ABI ) indicates atherosclerosis and an increased risk of cardiovascular and cerebrovascular events . Screening for a low ABI can identify an asymptomatic higher risk group potentially amenable to preventive treatments . OBJECTIVE To determine the effectiveness of aspirin in preventing events in people with a low ABI identified on screening the general population . DESIGN , SETTING , AND PARTICIPANTS The Aspirin for Asymptomatic Atherosclerosis trial was an intention-to-treat double-blind r and omized controlled trial conducted from April 1998 to October 2008 , involving 28,980 men and women aged 50 to 75 years living in central Scotl and , free of clinical cardiovascular disease , recruited from a community health registry , and had an ABI screening test . Of those , 3350 with a low ABI ( < or = 0.95 ) were entered into the trial , which was powered to detect a 25 % proportional risk reduction in events . INTERVENTIONS Once daily 100 mg aspirin ( enteric coated ) or placebo . MAIN OUTCOME MEASURES The primary end point was a composite of initial fatal or nonfatal coronary event or stroke or revascularization . Two secondary end points were ( 1 ) all initial vascular events defined as a composite of a primary end point event or angina , intermittent claudication , or transient ischemic attack ; and ( 2 ) all-cause mortality . RESULTS After a mean ( SD ) follow-up of 8.2 ( 1.6 ) years , 357 participants had a primary end point event ( 13.5 per 1000 person-years , 95 % confidence interval [ CI ] , 12.2 - 15.0 ) . No statistically significant difference was found between groups ( 13.7 events per 1000 person-years in the aspirin group vs 13.3 in the placebo group ; hazard ratio [ HR ] , 1.03 ; 95 % CI , 0.84 - 1.27 ) . A vascular event comprising the secondary end point occurred in 578 participants ( 22.8 per 1000 person-years ; 95 % CI , 21.0 - 24.8 ) and no statistically significant difference between groups ( 22.8 events per 1000 person-years in the aspirin group vs 22.9 in the placebo group ; HR , 1.00 ; 95 % CI , 0.85 - 1.17 ) . There was no significant difference in all-cause mortality between groups ( 176 vs 186 deaths , respectively ; HR , 0.95 ; 95 % CI , 0.77 - 1.16 ) . An initial event of major hemorrhage requiring admission to hospital occurred in 34 participants ( 2.5 per 1000 person-years ) in the aspirin group and 20 ( 1.5 per 1000 person-years ) in the placebo group ( HR , 1.71 ; 95 % CI , 0.99 - 2.97 ) . CONCLUSION Among participants without clinical cardiovascular disease , identified with a low ABI based on screening a general population , the administration of aspirin compared with placebo did not result in a significant reduction in vascular events . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N66587262 AIMS To assess the additional benefit gained from high  compliance in the West of Scotl and Coronary Prevention Study and to examine cases where withdrawal from trial medication was due to an adverse event . METHODS The incidence of definite coronary heart disease or non-fatal myocardial infa rct ion , cardiovascular mortality , definite or suspect coronary heart disease death or non-fatal myocardial infa rct ion , the need for coronary revascularization procedures , all-cause mortality and incident cancers were measured in the entire cohort and compared with the high compliance group . The adverse events associated with withdrawal were coded by body system . RESULTS In subjects with compliance > or = 75 % , treatment with pravastatin result ed in a 38 % risk reduction for definite coronary heart disease death or non-fatal myocardial infa rct ion and for cardiovascular mortality , a 46 % reduction in risk or coronary revascularization and a 32 % risk reduction ( P = 0.015 ) for all-cause mortality . CONCLUSIONS The analysis of the effect of pravastatin in the subgroup of high compliers to r and omized medication demonstrated a substantial increase in the estimated risk reductions in comparison with that achieved in the intention-to-treat analysis . This result has significant implication s for the motivation of high compliance among patients and for the assessment of the cost-effectiveness of treatment Albuminuria has been shown to be associated with mortality and cardiovascular events , independent of traditional cardiovascular risk factors . This suggests that albuminuria may not just represent glomerular damage , but may be a marker of more diffuse endothelial dysfunction . We investigated the relationship between urinary albumin levels after an acute coronary syndrome and cardiovascular outcomes in  statin treated subjects after acute coronary syndromes ( ACS ) . Furthermore we assessed the effect of intensive statin treatment on albuminuria among patients in the PROVE IT-TIMI 22 trial , in which patients who had been hospitalized with ACS were r and omized to pravastatin 40 mg ( st and ard therapy ) or atorvastatin 80 mg daily ( intensive therapy ) . In univariate analyses , increasing urine albumin concentration was associated with increased risk of myocardial infa rct ion , stroke , heart failure , and composite of death , myocardial infa rct ion and stroke at 2 years . However , in a multivariable model containing traditional cardiovascular risk factors , albuminuria was not an independent predictor of the primary PROVE IT endpoint of death , myocardial infa rct ion , unstable angina , revascularization and stroke , and was only an independent predictor of all-cause mortality at urinary albumin concentration > 300 mcg/ml . There was no significant change in urinary albumin concentration from enrolment to end of study in either the st and ard or intensive statin therapy groups , and no significant difference between treatment groups . Our results suggest that after an acute coronary syndrome in statin treated patients , microalbuminuria may reflect traditional cardiovascular risk factor burden and offer little prognostic information independent of those factors Rupture of abdominal aortic aneurysm remains an important cause of death in older adults , although screening and monitoring are easily done by using abdominal ultrasonography ( 1 , 2 ) . Determining the timing of surgery is complex because these persons are already at increased risk for cardiovascular complications of surgery ( 3 ) and have a higher prevalence of cardiovascular risk factors ( 4 - 8 ) . However , few data are available on the natural history and relative risk for other interim cardiovascular events and mortality . Given the characteristics associated with abdominal aortic aneurysm , it is not surprising that persons with aneurysm followed in screening programs have high mortality rates . For example , participants in the UK Small Aneurysm Trial had mortality rates of at least 7 % in both the surveillance and early surgery groups , and no long-term benefit was seen with early surgery ( 3 ) . Even after successful repair of abdominal aortic aneurysm , average life expectancy is lower in these persons than in the general population ( 9 ) . In many screening studies , investigators have not had the opportunity to fully examine and follow the source population and thus can not evaluate whether the high risk for death in persons with abdominal aortic aneurysm is due to associated characteristics . Knowledge of the relative risks for all cardiovascular outcomes , including rupture and repair , in persons with aneurysm compared with those without aneurysm would show who may be more likely to die of other cardiovascular disease before repair would be indicated . The Cardiovascular Health Study was a longitudinal cohort study design ed to identify risk factors for development and progression of cardiovascular disease , including abdominal aortic aneurysm , in older adults .  Ultrasonographic screening for abdominal aortic aneurysm was performed in 19921993 , and data on subsequent mortality and morbidity were available through June 1997 . We hypothesized that persons with aneurysm would have an increased risk for total mortality and incident cardiovascular disease . Our primary goal was to evaluate whether the risks for mortality and cardiovascular disease associated with aneurysm were related to higher levels of risk factors and greater extent of atherosclerosis on other noninvasive testing that was previously found to be associated with the presence of abdominal aortic aneurysm ( 4 ) . We also compared rates of other cardiovascular morbidity and mortality , including risks for repair or rupture , by aneurysm size and classification . Methods Study Cohort In the Cardiovascular Health Study , men and women 65 years of age or older were r and omly selected from the Medicare eligibility lists of four communities in the United States : Forsyth County , North Carolina ; Sacramento County , California ; Washington County , Maryl and ; and Pittsburgh ( Allegheny County ) , Pennsylvania . Participants were recruited if they were not disabled or institutionalized and had no active cancer ( 10 , 11 ) . Initially ( in 19891990 ) , the study included 5201 participants ; an additional 687 African-Americans participants were recruited in 19921993 , bringing the total number of participants originally enrolled to 5888 .  Ultrasonographic screening for abdominal aortic aneurysm was performed in 4734 participants at all centers in 1992 to 1993 . Participants were excluded because they were deceased ( n = 259 ) , were unable to attend a clinic examination ( n = 755 ) , had a visit but no scan ( n = 93 ) , or had an unreadable scan ( n = 47 ) . The risk for mortality and incident cardiovascular events in participants with aneurysms was assessed over the subsequent 4.5 years as a predictor of mortality . All participants gave informed consent for examination and follow-up . The protocol was approved by the institutional review board of each participating institution . Study Design Ultrasonographers who were trained at a central location obtained ultrasonographic B-mode gray-scale images of the abdominal aorta in transverse and longitudinal projections . The suprarenal measure of aortic diameter was taken 1 cm distal to the origin of the superior mesenteric artery , just above the level of the left renal artery . Either the superior mesenteric artery or the renal artery had to be visualized to accept the image for measurement . The infrarenal measure of aortic diameter was determined by the site of the maximum diameter aortic artery ( lumen plus wall ) below the renal arteries . An aneurysm was defined as an infrarenal aortic diameter of 3.0 cm or greater or an infrarenal-to-suprarenal ratio of 1.2 or greater ( 4 ) . This definition does not necessarily represent disease that would cause clinical concern ; rather , it represents the measurements that would establish the lowest level of disease that can be reliably detected by B-mode ultrasonography . Our intent was to identify early disease so that the natural history of abdominal aortic aneurysm could be evaluated . All studies were recorded on super VHS videotape and sent weekly to a central ultrasonographic reading center for st and ardized readings . Interfaces were identified on selected digitized images by readers who were blinded to all clinical information , and measurements were calculated by using a specially design ed computer program . All scans with aneurysms and those obtained in age- and sex-matched controls were central ly reread by a single vascular physician . Question able scans were adjudicated by consultation with a second physician . The presence of aneurysm and its size was reported to the participant and the primary care physician . The central physician-readers were blinded to the participant 's cardiovascular history , and neither the ultrasonographers nor the physician-readers participated in subsequent assessment of outcomes . Risk factors for cardiovascular disease , cardiovascular history , and noninvasive measures of the extent of cardiovascular disease were included in analyses as potential confounders . Characteristics assessed at the 19921993 examination included age at scan , sex , African-American ethnicity , and measured height and weight . Risk factors for cardiovascular disease included current , past , or no cigarette smoking ; pack-years of smoking ( transformed to log pack-years ) ; self-reported hypertension and diabetes ; sibling history of myocardial infa rct ion or stroke ; and plasma lipid levels ( high-density and low-density cholesterol ) . The extent of vascular disease was assessed by using carotid ultrasonography , the anklearm index , and electrocardiography . Carotid disease was defined as right or left internal or common carotid intimamedia near-wall thickness greater than the 80th percentile ( 12 ) . An abnormal anklearm index was defined as a ratio less than 0.9 ( 13 ) . Major electrocardiographic abnormalities were ventricular conduction defects , major Q or QS abnormalities , minor Q or QS with ST-Twave abnormalities , left ventricular hypertrophy , isolated major ST-Twave changes , atrial fibrillation , and first-degree atrioventricular block ( 14 ) . At the time of the scan , all participants were classified as having prevalent cardiovascular disease if they had a history of myocardial infa rct ion , angina , coronary artery bypass grafting , angioplasty , congestive heart failure , stroke , or peripheral artery disease ( 15 ) . Outcomes were total mortality from cardiac and noncardiac causes , incident cardiovascular disease , recurrent cardiovascular disease among participants with cardiovascular disease at the time of the scan , and repair and rupture of abdominal aortic aneurysm . Follow-up consisted of annual clinic visits followed by a telephone call 6 months later .  Outpatient ultrasonographic surveillance  of the aneurysm was not monitored . Cardiovascular disease mortality was defined to include death from coronary heart disease , myocardial infa rct ion , sudden death , stroke , or peripheral artery disease . Cardiovascular disease morbidity and mortality included any death or incident event related to cardiovascular disease ( 16 ) . Cases of abdominal aortic aneurysm repair and rupture were identified by review of all International Classification of Disease codes for procedures or diagnosis compatible with these diagnoses ( 38.44 , 38.45 , 441.3 , 441.4 ) . All participants had adequate clinical information in hospital records to confirm rupture or repair . The codes captured four cases of thoracic aortic dissection , which were defined as cardiovascular disease deaths but were excluded from the group of participants with complications of abdominal aortic aneurysm . Statistical Analysis Incidence rates according to abdominal aortic aneurysm status were calculated by dividing the total number of events in each group by person-years at risk . Cox proportional-hazards models were run to compute hazard ratios adjusted for demographic and risk factors . The Cox model assumes that the hazard ratio of participants with and those without aneurysm remains constant over time ( 17 ) . We tested this assumption and found no interaction between the presence of aneurysm and time to the end point , suggesting that the proportional hazards assumption was appropriate ( P > 0.45 in all models ) . Even though incidence rates differed by sex , relative risks in men and women were similar , and no significant interaction was found between each classification of abdominal aortic aneurysm and sex . We therefore modeled men and women together in the overall assessment of abdominal aortic aneurysm and death or cardiovascular disease . Because we found a significant interaction between infrarenal size and sex , we ran separate models for men and women to compute the relative risk of size of the aneurysm on death and cardiovascular disease . The log-rank test was used to compare survival curves by size of the aneurysm . To determine the point at which the risk for mortality appeared to increase , the size ratio was classified into six groups : 1.2 or less , 1.21 to 1.3 , 1.31 to 1.4 , 1.41 to 1.5 , 1.51 to 1.8 , and greater than 1.8 . For OBJECTIVE The objective of this study was to report on the prevalence , incidence and prognosis of left ventricular hypertrophy ( LVH ) on the electrocardiogram ( ECG ) in a cohort of ambulatory older men and women . DESIGN A prospect i ve , longitudinal study of 10 years duration with ECGs obtained at baseline and on an annual basis . SETTING AND PATIENTS A community-based cohort study consisting of 459 subjects ( aged 75 - 85 , mean age 79 years ) . MEASUREMENTS Baseline and follow up ECGs  were interpreted using the Minnesota Code . Prevalence and incidence of  LVH  and  ECG  were determined as well as regression of ECG LVH . Clinical event rates measured were incidence of total mortality , myocardial infa rct ion ( MI , fatal and non-fatal ) , cardiovascular mortality , cardiovascular disease ( fatal and non-fatal ) , stroke ( fatal and non-fatal ) , all-cause dementia , and multi-infa rct dementia . Differences in event rates between groups ( those subjects with and without LVH ) were compared as tests between proportions . A Cox Proportional Hazards Regression Analysis was performed to compare the relative independent predictive values of different competing factors , including age , gender , serum cholesterol , digitalis use , body mass , index , Blessed Dementia Scale , cigarette smoking , LVH at baseline , LVH ar baseline ( persisting ) , new LVH , new LVH ( persisting ) , new LVH ( regressed ) , previous MI by history of ECG , hypertension by history , and cardiomegaly by X-ray ( cardiothoracic ratio > or = 50 % ) . RESULTS At baseline , 9.2 % of subjects ( n = 42 ) had LVH on ECG and a mortality rate of 11.7/100 persons years versus 4.9/100 persons years for subjects without baseline LVH ( P < .0001 ) , and MI rate of 7.5/100 persons years with LVH versus 2.6/100 persons years without LVH ( P < .0001 ) , and a cardiovascular mortality rate of 7.2/100 persons years without LVH versus 2.7/100 person years without LVH . Subjects who developed new LVH on ECG ( n = 39 ) had a mortality rate of 14.4/100 person-years compared with 4.4/100 person-years for those without LVH ( P < .0001 ) , a cardiovascular mortality rate of 11.1/100 person years versus 2.0/100 person years without LVH ( P < .0001 ) , and an MI rate of 6.1/100 person years versus 2.0/100 person years without LVH ( P < .01 ) . Subjects in whom the ECG LVH pattern disappeared over time had fewer cardiovascular mortal and morbid events than those with persistent LVH . According to the regression analyses , persistent LVH from baseline was an independent predictor of MI , overall cardiovascular disease , and total mortality . Newly developing LVH with subsequent regression was an independent predictor of overall cardiovascular disease and death . CONCLUSIONS An increased prevalence and incidence of LVH on ECG , irrespective cause , is associated with a poor prognosis in very old men and women . Regression of ECG LVH in older people , irrespective of cause , may confer improvement in risk for cardiovascular disease Background — Although preventive drug therapy is a priority after acute coronary syndrome , less is known about adherence to behavioral recommendations . The aim of this study was to examine the influence of adherence to behavioral recommendations in the short term on risk of cardiovascular events . Methods and Results — The study population included 18 809 patients from 41 countries enrolled in the Organization to Assess Strategies in Acute Ischemic Syndromes ( OASIS ) 5 r and omized clinical trial . At the 30-day follow-up , patients reported adherence to diet , physical activity , and smoking cessation . Cardiovascular events ( myocardial infa rct ion , stroke , cardiovascular death ) and all-cause mortality were documented to 6 months . About one third of smokers persisted in smoking . Adherence to neither diet nor exercise recommendations was reported by 28.5 % , adherence to either diet or exercise by 41.6 % , and adherence to both by 29.9 % . In contrast , 96.1 % of subjects reported antiplatelet use , 78.9 % reported statin use , and 72.4 % reported angiotensin-converting enzyme/angiotensin receptor blocker use . Quitting smoking was associated with a decreased risk of myocardial infa rct ion compared with persistent smoking ( odds ratio , 0.57 ; 95 % confidence interval , 0.36 to 0.89 ) . Diet and exercise adherence was associated with a decreased risk of myocardial infa rct ion compared with nonadherence ( odds ratio , 0.52 ; 95 % confidence interval , 0.4 to 0.69 ) . Patients who reported persistent smoking and nonadherence to diet and exercise had a 3.8-fold ( 95 % confidence interval , 2.5 to 5.9 ) increased risk of myocardial infa rct ion/stroke/death compared with never smokers who modified diet and exercise . Conclusions — Adherence to behavioral advice ( diet , exercise , and smoking cessation ) after acute coronary syndrome was associated with a substantially lower risk of recurrent cardiovascular events . These findings suggest that behavioral modification should be given priority similar to other preventive medications immediately after acute coronary syndrome . Clinical Trial Registration Information— URL : http:// clinical trials.gov/ct2/show/NCT00139815 . Unique identifier : NCT00139815 Context Inflammatory markers , such as C-reactive protein ( CRP ) , independently predict future coronary artery disease in patients without known disease at baseline . However , an elevated CRP level also predicts all-cause mortality ; therefore , it may not be specific for cardiovascular disease . Contribution This prospect i ve casecontrol study showed that CRP level predicted the development of acute cardiovascular events but not cancer among 28 345 women followed for a mean of 58 months . Clinical Implication s parental history of coronary heart disease . In women , CRP level appears specifically predictive of car-diovascular disease but not cancer . This study adds further evidence that CRP levels may be useful in the clinical prediction of cardiovascular risk , at least in population s. The Editors Recent evidence suggests that atherosclerosis is in part a chronic low- grade inflammatory condition ( 1 ) , and prospect i ve epidemiologic studies have demonstrated that plasma markers of inflammation , such as C-reactive protein ( CRP ) , are strong independent predictors of future coronary events in apparently healthy persons ( 2 - 6 ) . However , as an acute-phase reactant , CRP increases dramatically in various pathologic conditions . Moreover , CRP has been shown to predict all-cause mortality ( 7 , 8) , an observation that raises the possibility that CRP may not be specific for vascular disease . To evaluate this hypothesis , we directly compared the predictive value of CRP for incident cancer and cardiovascular disease , the two most important determinants of all-cause mortality in the western world . Methods We performed a prospect i ve , nested casecontrol analysis within the Women 's Health Study , an ongoing r and omized , double-blind , placebo-controlled trial of aspirin and vitamin E for primary prevention of heart disease and cancer , which involves 39 876 U.S. women 45 years of age and older . Of these study participants , 28 345 ( 71 % ) provided baseline blood sample s  , which were stored at 70 C until the time of laboratory analysis . In the Women 's Health Study , all participants are followed prospect ively for incident health events , including cancer and cardiovascular events . The methods used for cohort follow-up , end-point ascertainment , and adjudication for both cancer and cardiovascular events are described in detail elsewhere ( 5 , 9 ) . For this study , we defined case- patients as apparently healthy women who provided an adequate baseline plasma sample and who subsequently developed cancer ( n = 513 ) or an acute cardiovascular event ( myocardial infa rct ion , stroke , or cardiovascular death ) ( n = 130 ) over a mean follow-up period of 58 months . For each woman who had confirmed cancer or cardiovascular event during follow-up , one control of the same age ( 1 year ) and smoking habit ( former smoker , current smoker , or nonsmoker ) was selected from among participants who provided baseline plasma sample s and remained free of reported disease during the same follow-up period . Using these criteria , we evaluated 643 case- patients and an equal number of controls in two separate matched pairs , one for cancer ( n = 513 ) and another for cardiovascular events ( n = 130 ) . The Institutional Review Board of the Brigham and Women 's Hospital approved this study . For each case-patient and control , plasma stored since the baseline examination was thawed and assayed for CRP levels by using a high-sensitivity assay ( Dade Behring , Newark , Delaware ) ( 10 ) . Blood specimens were analyzed in blinded pairs with the position of the patient 's specimen varied at r and om to reduce the possibility of systematic bias and to decrease interassay variability . The day-to-day precision values , at CRP concentrations of 0.15 mg/L and 0.49 mg/L , were 4.9 % and 6.4 % , respectively . Because CRP values are skewed rightward , median plasma concentrations were computed , and the significance of any difference in the distributions between the case- patients and controls was assessed by performing the Wilcoxon rank-sum test . We then used conditional logistic regression models to determine the risk for developing cancer or cardiovascular end points after dividing the study sample into quartiles on the basis of the distribution of the control group . Adjusted estimates of risk were obtained by use of similar models that accounted for the matching variables and that controlled for r and omized treatment assignment ( for vitamin E , aspirin , or both ) , body mass index , diabetes mellitus , history of hyperlipidemia , history of hypertension , and parental history of coronary heart disease . All analyses were performed by using SAS software , release 8.2 ( SAS Institute , Inc. , Cary , North Carolina ) . All P values were two tailed , and CIs were computed at the 95 % level . The funding sources played no role in the design , conduct , or reporting of the study . Results Table 1 shows the baseline characteristics of the study participants . We noted no significant differences at baseline between women who subsequently developed cancer and those who did not . As expected , women who subsequently developed cardiovascular events had an increased baseline prevalence of hyperlipidemia , hypertension , diabetes , and obesity compared with controls who did not develop vascular events during follow-up . Table 1 . Baseline Clinical Characteristics of the Study Participants Overall , median levels of CRP  at baseline among women who subsequently developed cancer ( 2.6 mg/L [ interquartile range , 1.1 to 5.9 mg/L ] ) were not significantly different from those of the control group ( 2.5 mg/L [ interquartile range , 0.9 to 5.5 mg/L ] ) ( P > 0.2 ) . Furthermore , we observed no evidence of an association between baseline CRP level and the development of cancer in site-specific analyses evaluating carcinoma of the breast ( n = 223 ) , ovary or uterus ( n = 75 ) , colon ( n = 44 ) , lung ( n = 32 ) , hematopoietic system ( n = 31 ) , thyroid ( n = 14 ) , bladder ( n = 9 ) , brain ( n = 8) , or pancreas ( n = 8) ; melanoma ( n = 31 ) ; or other types of cancer ( n = 38 ) . In contrast , and consistent with previous work in this cohort for the end point of any vascular event ( 5 ) , median CRP levels at baseline among women who subsequently developed cardiovascular disease ( 5.1 mg/L [ interquartile range , 2.6 to 8.5 mg/L ] ) were significantly higher than those of the control group ( P < 0.001 ) . Table 2 presents relative risks for developing either cancer or cardiovascular disease according to increasing quartiles of CRP levels obtained at study entry . As Table 2 shows , there was little evidence that baseline levels of CRP predicted incident cancer in either crude or adjusted analyses . We found similar results after additional correction for alcohol use and age at menarche ( data not shown ) . In contrast , increasing quartiles of baseline CRP level were a strong marker of risk for incident cardiovascular disease in crude and adjusted analyses . For example , the adjusted relative risks from the lowest to the highest quartiles of baseline CRP levels were 1.0 , 2.9 , 3.4 , and 5.6 , respectively ( P for trend < 0.001 ) . Table 2 . Relative Risk for Future Cancer and Cardiovascular Events , according to Baseline Plasma C-Reactive Protein Level Discussion In this prospect i ve study of apparently healthy middle-aged and older women , baseline plasma CRP concentrations were not significantly related to the incidence of future cancer but were a strong independent predictor of future myocardial infa rct ion , stroke , and cardiovascular death . We believe these data have importance for general medical practice for several reasons . First , our data corroborate the findings in several previous reports ( 2 - 6 ) that baseline levels of CRP predict future vascular events among apparently healthy men and women ( 2 - 6 ) and that CRP level adds to the predictive value of total and high-density lipoprotein cholesterol levels ( 5 , 11 ) . As a result of these earlier findings , outpatient screening for CRP has recently become available . However , if CRP is clinical ly nonspecific , as two recent studies evaluating all-cause mortality suggest ( 7 , 8) , then screening for this inflammatory marker might have reduced diagnostic utility . Thus , our finding that CRP appears to be specific for incident vascular disease but not for incident cancer has substantial clinical importance and suggests that data linking CRP level to overall death rates may have been due to the large contribution that vascular disorders make to all-cause mortality , particularly in the western world . Second , the relative risks for future myocardial infa rct ion or stroke observed among women in the top versus bottom quartile of baseline CRP in this analysis are somewhat greater than those previously reported from this cohort for the end point of any vascular eventan end point that included not only myocardial infa rct ion , stroke , and cardiovascular disease mortality , but also coronary revascularization ( 5 ) . Thus , these data also suggest that CRP level may be a stronger marker for events involving atherosclerotic plaque rupture and acute thrombosis than for events primarily involving progression of lesional stenosis . These epidemiologic data are thus consistent with the hypothesis that inflammation is an important determinant of plaque vulnerability ( 12 ) . Finally , we believe that our observation that CRP levels do not strongly predict future cancers is itself of pathophysiologic interest ; this is of particular interest because levels of CRP and other inflammatory biomarkers are known to increase after development of certain malignancies ( 13 , 14 ) . As such , our data also suggest that the systemic inflammatory component of cancer previously reported in cross-sectional studies may be a late development in the genesis of that disease but is not likely to prove useful in determining risk among healthy persons . Several limitations of our study deserve attention . Plasma CRP levels increase acutely in a wide variety of pathologic conditions , including febrile illness , various inflammatory states , and trauma ( 15 ) . In INTRODUCTION Treatment of intermittent claudication ( IC ) due to peripheral arterial disease ( PAD ) is aim ed at improving walking distance and includes secondary prevention of cardiovascular disease . Both supervised exercise therapy ( SET ) and percutaneous transluminal angioplasty ( PTA ) have proven to be effective in increasing maximum and pain-free walking distance in IC . However , the optimal treatment strategy in patients with IC due to iliac artery stenosis or occlusion remains unclear . OBJECTIVE To compare the ( cost- ) effectiveness of initial PTA versus initial SET in patients with disabling IC due to an iliac artery obstruction . DESIGN In a multicentre r and omised controlled trial 400 consecutive patients with IC will be r and omly assigned to PTA ( with additional stent placement on indication ) or SET . Primary outcomes are maximum walking distance and health-related quality of life measured using the disease-specific VascuQol instrument after 1 year . Secondary outcomes are pain-free walking distance , functional status , generic quality of life , complications related to each of the interventions , additional interventions , treatment failures and costs ( cost-effectiveness and cost-utility ) after 1 year . CONCLUSION AND IMPLICATION S Based on the results of this proposed large study well-founded adjustments of existing guidelines on the treatment of iliac artery occlusive disease can be implemented ( Clinical Trials.gov NCT01385774 ; Nederl and s Trial Register NTR2776 ) PURPOSE Patients with lower-extremity peripheral arterial disease ( PAD ) face a high risk of cardiovascular morbidity and mortality . Platelet inhibition ( PI ) significantly reduces this risk . Combination PI is common and increasingly indicated in patients with PAD ; however , the effect on platelet function has not been objective ly evaluated . Aspirin ( ASA ) , clopidogrel ( Clop ) , and cilostazol ( Cilo ) are the three most commonly used PI drugs in patients with PAD . A prospect i ve , sequential evaluation of platelet function using the template bleeding time ( BT ) was performed for PAD patients taking these medications singly and in combination . METHODS Twenty-one patients with PAD , averaging 65.9 years of age , were studied . Patients were placed on sequential two-week regimens of the following therapies : washout ( no PI ) , ASA ( 325 mg daily ) , ASA + Cilo ( 100 mg twice daily ) , washout , Cilo , Cilo + Clop ( 75 mg each day ) , washout , Clop , Clop + ASA , and Clop + ASA + Cilo . At the end of each phase , trained personnel measured the BT . RESULTS Baseline bleeding time for the group was 4.29 + /- 1.69 minutes . ASA ( BT = 6.64 + /- 3.52 ) and Clop ( BT = 10.17 + /- 5.4 ) significantly prolonged bleeding time ( P < 0.01 ) ; however , no significant effect was observed with Cilo alone ( BT = 5.41 + /- 2.69 ) . Combined treatment with ASA + Clop ( BT = 17.39 + /- 4.59 ) had a more pronounced effect on BT compared with either agent alone ( P < 0.01 ) . The addition of Cilo to either ASA ( BT = 8.3 + /- 4.27 ) or Clop ( BT = 12.7 + /- 7.46 ) or the combination of ASA + Clop ( BT = 17.92 + /- 4.69 ) did not prolong BT . CONCLUSION All patients with PAD require platelet inhibition , and many require pharmacotherapy for intermittent claudication . The platelet inhibitors aspirin and clopidogrel are used for the reduction of ischemic events . They significantly prolong bleeding time individually and to a greater extent in combination . Cilo is used to improve walking distance in patients with intermittent claudication . When Cilo is added to ASA , Clop , or the combination of the two , there is no additional increase in bleeding time . Therefore , Cilo can be used in combination with other platelet inhibitors without an additional effect on platelet function as reflected by the bleeding time OBJECTIVE To examine the effects of alcohol on risk of mortality from coronary heart disease ( CHD ) , cardiovascular disease , and all causes in men with established CHD . METHODS AND RESULTS In a population based prospect i ve study of 7169 men aged 45–64 years followed for a mean of 12.8 years , 655 men ( 9.1 % ) had a physician diagnosis of CHD ( myocardial infa rct ion 455 , angina only 200 ) . In these 655 men , there were 294 deaths from all causes including 175 CHD deaths . Ex-drinkers had the highest risk of CHD , cardiovascular mortality , and all cause mortality even after adjustment for lifestyle characteristics and pre-existing disease . Using occasional drinkers as the reference group , lifelong teetotallers , occasional drinkers , and light drinkers all showed similar risks of mortality from CHD , cardiovascular disease , and all causes . Moderate/heavy drinkers showed increased risk of mortality from CHD , cardiovascular disease , and all causes compared to occasional drinkers . The adverse effect of moderate/heavy drinking was confined to the 455 men with previous myocardial infa rct ion ( adjusted relative risk for all cause mortality 1.50 , 95 % confidence interval 1.01 to 2.23 ) . In contrast to lighter drinking , giving up smoking within five years of the start of follow up was associated with a considerable reduction in risk of all cause and cardiovascular mortality compared to those who continued to smoke . CONCLUSION Compared to occasional drinking , regular light alcohol consumption ( 1–14 units per week ) in men with established coronary heart disease is not associated with any significant benefit or deleterious effect for CHD , cardiovascular disease or all cause mortality . Higher levels of intake ( ⩾ 3 drinks per day ) are associated with increased mortality in men with previous myocardial infa rct ion . In contrast , smoking cessation in men with established CHD substantially reduces the risk of mortality BACKGROUND Atherothrombosis is a common condition affecting individuals worldwide . Its impact on different ethnic groups receiving evidence -based therapy is unclear . We aim ed to determine if ethnicity is an independent predictor for cardiovascular events and bleeding complications in a contemporary clinical trial on antiplatelet therapy . METHODS This was a prospect i ve observational study of 15,603 patients enrolled in the CHARISMA trial followed up every 6 months for a median of 28 months . The primary efficacy end point was the first occurrence of cardiovascular death , myocardial infa rct ion , or stroke . The primary safety end point was bleeding . RESULTS The cohort comprised 12,502 ( 80.1 % ) white , 486 ( 3.1 % ) black , 775 ( 5.0 % ) Asian , and 1,613 ( 10.3 % ) Hispanic patients . There was no difference in the occurrence of the primary composite end point among the 4 ethnic groups . Compared with Asians , cardiovascular and all-cause mortality occurred more frequently among black ( adjusted hazard 2.19 and 2.04 ) and Hispanic ( adjusted hazard , 1.83 and 1.69 ) patients . Although the occurrence of severe bleeding was similarly low among the 4 ethnic groups , Asian ( adjusted hazard , 2.21 ) and black ( adjusted hazard , 3.06 ) patients were more likely to have moderate bleeding complications than Hispanic patients . CONCLUSION In this trial of individuals at risk of vascular events , ethnicity was not a significant , independent predictor of the primary composite cardiovascular event . However , ethnicity was a significant , independent predictor of the secondary outcomes , cardiovascular and all-cause mortality ( blacks and Hispanics ) , and moderate bleeding complications ( blacks and Asians ) Objective To investigate whether baseline systolic blood pressure variability was a risk factor for stroke , cardiovascular mortality or cardiac events during the Syst-Eur trial . Design The Syst-Eur study was a r and omized , double-blind , placebo-controlled trial , powered to detect differences in stroke rate between participants on active antihypertensive treatment and placebo .  Systolic blood pressure variability measurements were made on 744 participants at the start of the trial . Systolic blood pressure variability was calculated over three time frames : 24 h , daytime and night-time . The placebo and active treatment subgroups were analysed separately using an intention-to-treat principle , adjusting for confounding factors using a multiple Cox regression model . Participants An elderly hypertensive European population . Main outcome measures Stroke , cardiac events ( fatal and non-fatal heart failure , fatal and non-fatal myocardial infa rct ion and sudden death ) and cardiovascular mortality ( death attributed to stroke , heart failure , myocardial infa rct ion , sudden death , pulmonary embolus , peripheral vascular disease and aortic dissection ) . Results The risk of stroke increased by 80 % ( 95 % confidence interval : 17–176 % ) for every 5 mmHg increase in night-time systolic blood pressure variability in the placebo group . Risk of cardiovascular mortality and cardiac events was not significantly altered . Daytime variability readings did not predict outcome . Antihypertensive treatment did not affect systolic blood pressure variability over the median 4.4-year follow-up . Conclusion In the placebo group , but not the active treatment group , increased night-time systolic blood pressure variability on admission to the Syst-Eur trial was an independent risk factor for stroke during the trial Background It has been suggested that a higher calcium intake might favourably modify cardiovascular risk factors . However , findings of an ultimately decreased risk of cardiovascular disease ( CVD ) are limited . Instead , recent evidence warns that taking calcium supplements might increase myocardial infa rct ion ( MI ) risk . Objective To prospect ively evaluate the associations of dietary calcium intake and calcium supplementation with MI and stroke risk and overall CVD mortality . Methods Data from 23 980 Heidelberg cohort participants of the European Prospect i ve Investigation into Cancer and Nutrition study , aged 35–64 years and free of major CVD events at recruitment , were analysed . Multivariate Cox regression models were used to estimate HRs and 95 % CIs . Results After an average follow-up time of 11 years , 354 MI and 260 stroke cases and 267 CVD deaths were documented . Compared with the lowest quartile , the third quartile of total dietary and dairy calcium intake had a significantly reduced MI risk , with a HR of 0.69 ( 95 % CI 0.50 to 0.94 ) and 0.68 ( 95 % CI 0.50 to 0.93 ) , respectively . Associations for stroke risk and CVD mortality were overall null . In comparison with non-users of any supplements , users of calcium supplements had a statistically significantly increased MI risk ( HR=1.86 ; 95 % CI 1.17 to 2.96 ) , which was more pronounced for calcium supplement only users ( HR=2.39 ; 95 % CI 1.12 to 5.12 ) . Conclusions Increasing calcium intake from diet might not confer significant cardiovascular benefits , while calcium supplements , which might raise MI risk , should be taken with caution BACKGROUND AND OBJECTIVES The dramatically high rates of mortality and cardiovascular morbidity observed among dialysis patients highlights the importance of identifying and implementing strategies to lower cardiovascular risk in this population . Results from clinical trials undertaken thus far , including trials on lipid reduction , normalization of hematocrit , and increased dialysis dosage , have been unsuccessful . Available data indicate that abnormalities in calcium and phosphorus metabolism , as a result of either secondary hyperparathyroidism alone or the therapeutic measures used to manage secondary hyperparathyroidism , are associated with an increased risk for death and cardiovascular events . However , no prospect i ve trials have evaluated whether interventions that modify these laboratory parameters result in a reduction in adverse cardiovascular outcomes . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events is a global , phase 3 , double-blind , r and omized , placebo-controlled trial evaluating the effects of cinacalcet on mortality and cardiovascular events in hemodialysis patients with secondary hyperparathyroidism . Approximately 3800 patients from 22 countries will be r and omly assigned to cinacalcet or placebo . Flexible use of traditional therapies will be permitted . The primary end point is the composite of time to all-cause mortality or first nonfatal cardiovascular event ( myocardial infa rct ion , hospitalization for unstable angina , heart failure , or peripheral vascular disease , including lower extremity revascularization and nontraumatic amputation ) . RESULTS The study will be event driven ( terminated at 1882 events ) with an anticipated duration of approximately 4 yr . CONCLUSIONS Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events will determine whether management of secondary hyperparathyroidism with cinacalcet reduces the risk for mortality and cardiovascular events in hemodialysis patients Background Patients with end-stage renal disease ( ESRD ) are at high risk of cardiovascular events . Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population . In contrast to patients with normal renal function , the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospect i ve r and omised trials . A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis : an Assessment of survival and cardiovascular events ( AURORA ) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis . Methods More than 2,750 ESRD patients who have been receiving chronic haemodialysis treatment for at least 3 months have been r and omised ( 1:1 ) , irrespective of baseline lipid levels , to treatment with  rosuvastatin 10 mg or placebo . The primary study endpoint is the time to a major cardiovascular event ( first occurrence of cardiovascular death , non-fatal myocardial infa rct ion or non-fatal stroke ) . Secondary endpoints include all-cause mortality , major cardiovascular event-free survival time , time to cardiovascular death , time to non-cardiovascular death , cardiovascular interventions , tolerability of treatment and health economic costs per life-year saved . Study medication will be given until 620 subjects have experienced a major cardiovascular event . Conclusion Our hypothesis is that results from AURORA will establish the clinical efficacy and tolerability of rosuvastatin in patients with ESRD receiving chronic haemodialysis and guide the optimal management of this exp and ing population BACKGROUND Platelets play a key role in the pathogenesis of atherosclerosis , thrombosis , and acute coronary and cerebrovascular syndromes . Inhibition of platelet function by acetylsalicylic acid ( aspirin ) has been shown to reduce the incidence atherothrombotic events in patients with coronary , cerebrovascular , or peripheral vascular disease .  Thienopyridine agents , however , including ticlopidine and clopidogrel , inhibit the adenosine diphosphate receptor and have modestly superior effects compared with aspirin on reduction of death , myocardial infa rct ion , and stroke among a broad group of patients with vascular disease . More effective antithrombotic agents are still required to treat patients at high risk for recurrent vascular events . METHODS Lotrafiban , a selective , nonpeptide antagonist of the human platelet fibrinogen receptor ( glycoprotein [ GP ] IIb/IIIa [ alphaIIb/beta3 integrin ] ) , blocks the binding of fibrinogen to the GP IIb/IIIa receptor , which is the final common pathway of platelet aggregation . Lotrafiban at doses of up to 50 mg twice daily was well-tolerated in a 12-week , double-blind , placebo-controlled , dose-ranging study in patients with recent myocardial infa rct ion , unstable angina , transient ischemic attack , or stroke when added to aspirin therapy . On the basis of these results , a dosing regimen was selected for the phase III Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion ( BRAVO ) trial based on pharmacodynamics and drug tolerability . In the pivotal BRAVO study , lotrafiban therapy is being evaluated in patients who have had a recent myocardial infa rct ion , unstable angina , transient ischemic attack , or ischemic stroke , or who present at any time after a diagnosis of peripheral vascular disease combined with either cardiovascular or cerebrovascular disease . RESULTS The efficacy evaluation will be based on a composite end point of clinical events ( death by any cause , myocardial infa rct ion , stroke , recurrent ischemia requiring hospitalization , or urgent ischemia-driven revascularization ) .  The target enrollment is 9200 patients worldwide . Approximately 700 centers will participate and will be distributed within 30 countries across North America , Europe , Australia , and Asia Background Although unstable coronary artery disease is the most common reason for admission to a coronary care unit , the long-term prognosis of patients with this diagnosis is unknown . This is particularly true for patients with diabetes mellitus , who are known to have a high morbidity and mortality after an acute myocardial infa rct ion . Methods and Results Prospect ively collected data from 6 different countries in the Organization to Assess Strategies for Ischemic Syndromes ( OASIS ) registry were analyzed to determine the 2-year prognosis of diabetic and nondiabetic patients who were hospitalized with unstable angina or non – Q-wave myocardial infa rct ion . Overall , 1718 of 8013 registry patients ( 21 % ) had diabetes . Diabetic patients had a higher rate of coronary bypass surgery  than nondiabetic patients ( 23 % versus 20 % , P < 0.001 ) but had similar rates of catheterization and angioplasty . Diabetes independently predicted mortality ( relative risk [ RR ] , 1.57 ; 95 % CI , 1.38 to 1.81;P < 0.001 ) , as well as cardiovascular death , new myocardial infa rct ion , stroke , and new congestive heart failure . Moreover , compared with their nondiabetic counterparts , women had a significantly higher risk than men ( RR , 1.98 ; 95 % CI , 1.60 to 2.44 ; and RR , 1.28 ; 95 % CI , 1.06 to 1.56 , respectively ) . Interestingly , diabetic patients without prior cardiovascular disease had the same event rates for all outcomes as nondiabetic patients with previous vascular disease . Conclusions Hospitalization for unstable angina or non – Q-wave myocardial infa rct ion predicts a high 2-year morbidity and mortality ; this is especially evident for patients with diabetes . Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease Coronary heart disease , hypertension , and dyslipidemia are highly prevalent and commonly coexist in people who are middle-aged and older . Previous data suggested that lowering cholesterol concentrations in individuals at high risk of cardiovascular disease improved clinical outcomes . Xuezhikang , a partial extract of red yeast rice containing statin , has a marked impact on lipids . The purpose of this study , therefore , was to evaluate the impact of Xuezhikang on reducing cardiovascular events and mortality in elderly Chinese hypertensive patients with a history of myocardial infa rct ion ( MI ) enrolled in the Chinese Coronary Secondary Prevention Study . In this r and omized trial , 1530 elderly hypertensive patients ( > or = 65-years-old ) with previous MI were assigned either to placebo ( n = 758 ) or to Xuezhikang ( n = 772 ) daily for an average of 4.5 years . The primary endpoint was recurrent coronary events ; the secondary endpoint was all-cause mortality and other clinical events , including adverse effects . There were 68 cases of coronary events ( 8.8 % ) detected in the Xuezhikang group and 108 cases ( 14.3 % ) in the placebo group ( 38.2 % risk reduction by Xuezhikang therapy ) . Death from coronary heart disease ( CHD ) totaled 49 cases in the Xuezhikang group ( 6.4 % ) and 68 cases in the placebo group ( 9.0 % ) , indicating that Xuezhikang significantly decreased the risk of CHD death by 29.2 % . Our study demonstrated that Xuezhikang therapy could effectively and safely reduce cardiovascular events and all-cause death in Chinese elderly hypertensive patients with previous MI . This finding may have an important implication for the treatment of elderly hypertensive patients with CHD BACKGROUND Recent reports have drawn attention to the importance of pulse pressure as a predictor of cardiovascular events .  Pulse pressure is used neither by clinicians nor by guidelines to define treatable levels of blood pressure . METHODS In the Cardiovascular Health Study , 5888 adults 65 years and older were recruited from 4 US centers . At baseline in 1989 - 1990 , participants underwent an extensive examination , and all subsequent cardiovascular events were ascertained and classified . RESULTS At baseline , 1961 men and 2941 women were at risk for an incident myocardial infa rct ion or stroke . During follow-up that averaged 6.7 years , 572 subjects had a coronary event , 385 had a stroke , and 896 died . After adjustment for potential confounders , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , and pulse pressure were directly associated with the risk of incident myocardial infa rct ion and stroke . Only SBP was associated with total mortality . Importantly , SBP was a better predictor of cardiovascular events than DBP or pulse pressure . In the adjusted model for myocardial infa rct ion , a 1-SD change in SBP , DBP , and pulse pressure was associated with hazard ratios ( 95 % confidence intervals ) of 1.24 ( 1.15 - 1.35 ) , 1.13 ( 1.04 - 1.22 ) , and 1.21 ( 1.12 - 1.31 ) , respectively ; and adding pulse pressure or DBP to the model did not improve the fit . For stroke , the hazard ratios ( 95 % confidence intervals ) were 1.34 ( 1.21 - 1.47 ) with SBP , 1.29 ( 1.17 - 1.42 ) with DBP , and 1.21 ( 1.10 - 1.34 ) with pulse pressure . The association between blood pressure level and cardiovascular disease risk was generally linear ; specifically , there was no evidence of a J-shaped relationship . In those with treated hypertension , the hazard ratios for the association of SBP with the risks for myocardial infa rct ion and stroke were less pronounced than in those without treated hypertension . CONCLUSION In this population -based study of older adults , although all measures of blood pressure were strongly and directly related to the risk of coronary and cerebrovascular events , SBP was the best single predictor of cardiovascular events BACKGROUND Although psychosocial therapy has been shown to reduce mortality after myocardial infa rct ion , it is unknown whether the benefits of psychosocial therapy on mortality reduction extend to out-of-hospital sudden cardiac arrest , a main cause of cardiovascular mortality . OBJECTIVE Describe efficacy of psychosocial therapy on two-year cardiovascular mortality in sudden cardiac arrest survivors . METHOD Survivors of out-of-hospital ventricular fibrillation or asystole ( N = 129 ) , documented by electrocardiograms from registries of a citywide Medic One unit and two countywide emergency units , were r and omized into a two group , experimental , longitudinal design . The intervention consisted of 11 individual sessions , implementing three components : physiologic relaxation with biofeedback training focused on altering autonomic tone ; cognitive behavioral therapy aim ed at self-management and coping strategies for depression , anxiety , and anger ; and cardiovascular health education . The primary outcome measure was cardiovascular mortality . RESULTS Risk of cardiovascular death was significantly reduced 86 % by psychosocial therapy , p = .03 . Six of the seven cardiovascular deaths in the control group were caused by ventricular arrhythmias . The cardiovascular death in the therapy group was due to stroke . Controlling for depression , previous myocardial infa rct ion , low ejection fraction , decreased heart rate variability , and ventricular ectopic beats had little impact on estimated treatment effect . The risk of all-cause mortality was reduced by 62 % in the therapy group , p = .13 . There were a total of three deaths in the therapy group and eight deaths in the control group . CONCLUSIONS Psychosocial therapy significantly reduced the risk of cardiovascular death in sudden cardiac arrest survivors The benefit of aspirin therapy among women with coronary artery disease ( CAD ) is not well established . Previous studies have shown conflicting results among women . Data from 2,418 women with CAD screened for participation in the ongoing Bezafibrate Infa rct ion Prevention ( BIP ) study were analyzed : 45 % reported aspirin therapy . Baseline characteristics were similar in both groups . Cardiovascular mortality at 3.1 + /- 0.9 years of follow-up was 2.7 % in the aspirin treated group versus 5.1 % in the non-aspirin-treated women ( p = 0.002 ) . All cause mortality was 5.1 % and 9.1 % , respectively ( p = 0.0001 ) . Treatment with aspirin emerged as an independent predictor of reduced cardiovascular ( RR = 0.61 , 95 % confidence interval [ CI ] 0.38 to 0.97 ) and all cause ( RR = 0.66 , 95 % CI 0.47 to 0.93 ) mortality after multiple adjustment for possible confounders such as age , history of myocardial infa rct ion , systemic hypertension , diabetes mellitus , peripheral vascular disease , current smoking , New York Heart Association classification , and concomitant treatment with digitalis . Women who benefited the most from aspirin therapy were older , diabetic , symptomatic , or had a previous myocardial infa rct ion . Thus , treatment with aspirin was associated with reduced mortality among women with CAD . This study suggests that women with CAD should be treated with aspirin , unless specific contraindications exist CONTEXT Although multivitamins are used to prevent vitamin and mineral deficiency , there is a perception that multivitamins may prevent cardiovascular disease ( CVD ) . Observational studies have shown inconsistent associations between regular multivitamin use and CVD , with no long-term clinical trials of multivitamin use . OBJECTIVE To determine whether long-term multivitamin supplementation decreases the risk of  major cardiovascular events among men . DESIGN , SETTING , AND PARTICIPANTS The Physicians ' Health Study II , a r and omized , double-blind , placebo-controlled trial of a common daily multivitamin , began in 1997 with continued treatment and follow-up through June 1 , 2011 . A total of 14,641 male US physicians initially aged 50 years or older ( mean , 64.3 [ SD , 9.2 ] years ) , including 754 men with a history of CVD at r and omization , were enrolled . INTERVENTION Daily multivitamin or placebo . MAIN OUTCOME MEASURES Composite end point of major cardiovascular events , including nonfatal myocardial infa rct ion ( MI ) , nonfatal stroke , and CVD mortality . Secondary outcomes included MI and stroke individually . RESULTS During a median follow-up of 11.2 ( interquartile range , 10.7 - 13.3 ) years , there were 1732 confirmed major cardiovascular events . Compared with placebo , there was no significant effect of a daily multivitamin on major cardiovascular events ( 11.0 and 10.8 events per 1000 person-years for multivitamin vs placebo , respectively ; hazard ratio [ HR ] , 1.01 ; 95 % CI , 0.91 - 1.10 ; P = .91 ) . Further , a daily multivitamin had no effect on total MI ( 3.9 and 4.2 events per 1000 person-years ; HR , 0.93 ; 95 % CI , 0.80 - 1.09 ; P = .39 ) , total stroke ( 4.1 and 3.9 events per 1000 person-years ; HR , 1.06 ; 95 % CI , 0.91 - 1.23 ; P = .48 ) , or CVD mortality ( 5.0 and 5.1 events per 1000 person-years ; HR , 0.95 ; 95 % CI , 0.83 - 1.09 ; P = .47 ) . A daily multivitamin was also not significantly associated with total mortality ( HR , 0.94 ; 95 % CI , 0.88 - 1.02 ; P = .13 ) . The effect of a daily multivitamin on major cardiovascular events did not differ between men with or without a baseline history of CVD ( P = .62 for interaction ) . CONCLUSION Among this population of US male physicians , taking a daily multivitamin did not reduce major cardiovascular events , MI , stroke , and CVD mortality after more than a decade of treatment and follow-up . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00270647
Antiplatelet agents have a beneficial effect in reducing all cause mortality and fatal cardiovascular events in patients with IC .
BACKGROUND Peripheral arterial disease ( PAD ) is common and is a marker of systemic atherosclerosis .
Patients with symptoms of intermittent claudication ( IC ) are at increased risk of cardiovascular events ( myocardial infa rct ion ( MI ) and stroke ) and of both cardiovascular and all cause mortality .
OBJECTIVES To determine the effectiveness of antiplatelet agents in reducing mortality ( all cause and cardiovascular ) and cardiovascular events in patients with intermittent claudication .