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Presentations of major peripheral arterial disease and risk of major outcomes in patients with type 2 diabetes: results from the ADVANCE-ON study Inflammatory, haemostatic, and rheological markers for incident peripheral arterial disease: Edinburgh Artery Study. Tissue (muscle) oxygen saturation (StO2): a new measure of symptomatic lower-extremity arterial disease. [Prevalence of peripheral arterial disease and correlative risk factors among natural population in China]. Intensive Blood Pressure Control Reduces the Risk of Cardiovascular Events in Patients With Peripheral Arterial Disease and Type 2 Diabetes Beneficial effects of autologous bone marrow cell infusion and antioxidants/L-arginine in patients with chronic critical limb ischemia Design and rationale for the Effects of Ticagrelor and Clopidogrel in Patients with Peripheral Artery Disease (EUCLID) trial. Near-Infrared Spectroscopy Assessment Following Exercise Training in Patients With Intermittent Claudication and in Untrained Healthy Participants Brief Communication: Ramipril Markedly Improves Walking Ability in Patients with Peripheral Arterial Disease Effects of a long-term exercise program on lower limb mobility, physiological responses, walking performance, and physical activity levels in patients with peripheral arterial disease. Unsupervised walking therapy and atherosclerotic risk-factor management for patients with peripheral arterial disease: A pilot trial Adhesion molecules and cardiovascular risk in peripheral arterial disease. Soluble vascular cell adhesion molecule-1 improves risk stratification. Granulocyte colony-stimulating factor: a noninvasive regeneration therapy for treating atherosclerotic peripheral artery disease. Association of increased levels of homocysteine and peripheral arterial disease in a Japanese-Brazilian population. 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One-year cardiovascular event rates in outpatients with atherothrombosis. The Vascular and Biochemical Effects of Cilostazol in Diabetic Patients With Peripheral Arterial Disease Major Adverse Limb Events and Mortality in Patients With Peripheral Artery Disease: The COMPASS Trial. The RATIO study: oral contraceptives and the risk of peripheral arterial disease in young women. Endothelial Dysfunction and Cardiovascular Risk Prediction in Peripheral Arterial Disease: Additive Value of Flow-Mediated Dilation to Ankle-Brachial Pressure Index High-intensity progressive resistance training improves flat-ground walking in older adults with symptomatic peripheral arterial disease. Role of systolic blood pressure and plasma triglycerides in diabetic peripheral arterial disease. The Edinburgh Artery Study. 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Effect of niacin, warfarin, and antioxidant therapy on coagulation parameters in patients with peripheral arterial disease in the Arterial Disease Multiple Intervention Trial (ADMIT). The effects of tertatolol on lipid profile. Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease. Determinants of male reproductive health disorders: the Men in Australia Telephone Survey (MATeS) Serum concentrations of L-arginine and L-homoarginine in male patients with intermittent claudication: a cross-sectional and prospective investigation in the CAVASIC Study. Beta blockade and intermittent claudication.
Aims : Peripheral arterial disease ( PAD ) can be diagnosed in asymptomatic stage , measuring ankle-brachial index ( ABI ) . Low ABI is an indicator of increased cardiovascular risk and its inclusion to traditional risk factors can improve risk prediction . The objective of the present cross-sectional part of our large-scale , multicenter , observational study was to evaluate the prevalence of PAD in a large cohort of hypertensive patients . Methods and results : A total of 21 892 hypertensive men and women ( 9162 men ; mean age 61.45 years ) were included in our prospect i ve study in hypertension clinics . Clinical history , physical examination , and blood analysis were taken , and the ABI was measured with the Doppler method in all patients . The prevalence of PAD ( ABI ⩽0.9 ) was 14.4 % . In 15.6 % of the patients an ABI of 0.91–0.99 , and in 9.4 % of the patients high ABI ( > 1.3 ) was measured . In the low , moderate , high , and very high Systematic Coronary Risk Evaluation risk groups , the prevalence of low ABI was 8.1 , 11.1 , 16.3 , and 26 % , respectively . The prevalence of PAD was lower in hypertensive patients achieving their blood pressure target ( 9.6 vs. 16.8 % ; P < 0.001 ) . Conclusions : Asymptomatic PAD was highly prevalent in the studied hypertensive population . The use of ABI screening may improve cardiovascular risk prediction . Optimal blood pressure goal values in PAD patients and cardiovascular morbidity/mortality data will be evaluated after the 5-year long prospect i ve phase of the Evaluation of Ankle-Brachial Index in Hungarian Hypertensives program BACKGROUND AND AIM The ankle-brachial index ( ABI ) is being used increasingly to diagnose peripheral arterial disease ( PAD ) that predicts cardiovascular morbidity and mortality . The aim of this study is to determine the prevalence of PAD  and associated risk factors in a Spanish r and om population sample of age > or = 40 . METHODS AND RESULTS PAD is defined as an ABI<0.9 in either leg . 784 participants of age > or = 40 were r and omly selected in a Spanish province . 55.4 % of them were female . The prevalence of PAD in this sample was 10.5 % ( 95 % confidence interval ( CI ) 8.4 - 12.8 ) ; 9.7 % in females and 11.4 % in males . In logistic regression analyses , adjusted for age and gender , smoking per 10 pack-years ( odds ratio ( OR ) 1.40 , 95 % CI 1.23 - 1.58 ) , hypertension ( OR 1.85 , 95 % CI 1.05 - 3.28 ) , hypercholesterolemia ( OR 1.76 , 95 % CI 1.04 - 2.98 ) , and diabetes ( OR 1.80 , 95 % CI 1.04 - 3.11 ) were positively associated with prevalent PAD . More than 91 % of persons with PAD had one or more cardiovascular disease risk factors . CONCLUSIONS We conclude that in our study hypertension , hypercholesterolemia , diabetes mellitus and smoking are associated with PAD . The majority of individuals with PAD had at least one important cardiovascular risk factor advanced enough to be considered eligible for an aggressive treatment Peripheral artery disease ( PAD ) is a manifestation of systemic atherosclerosis and is associated with increased cardiovascular morbidity and mortality . We describe the prevalence and risk factors of PAD in a multi-ethnic Asian population ( Chinese , Malays and Indians ) in Singapore . The Singapore Prospect i ve Study Program recruited 4132 individuals between 2004 and 2006 in which the ankle — brachial index ( ABI ) was measured using the  Smartdop ™ 20EX bi-directional blood flow detector . PAD was defined as ≤ 0.9 and a high ABI > 1.4 , with ABI 1.11—1.20 as reference . The mean age ( SD ) of individuals in the study was 49.9 ( 11.8 ) years , with 51.8 % females . PAD was present in 4.3 % of the population and a high ABI ( > 1.4 ) was rare . Malays and Indians had a higher risk ( especially in females ) . Compared to those with an ABI between 1.11 and 1.20 , those with PAD were more likely to be of Malay and Indian ethnicity , female sex , with higher systolic blood pressure and pulse pressure , with increased prevalence of diabetes mellitus , hypertension , albuminuria and renal impairment , and with a past history of stroke . In conclusion , in this large multi-ethnic Asian population , we document the distribution and risk factor associations for PAD . PAD shows an ethnic distribution similar to that of coronary artery disease in Singapore , with differences in sex distribution . Apart from traditional vascular risk factors , pulse pressure , renal impairment and a past history of stroke are important determinants of PAD 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 Aims Whereas product labels of beta blockers list peripheral arterial disease ( PAD ) as a contraindication , current PAD guidelines state otherwise . We aim ed to evaluate the clinical efficacy and safety of the ß1 selective blocker nebivolol in hypertensive patients with PAD . Methods and results This multicentre , prospect i ve , double-blind , active controlled , parallel-group study compared once-daily treatment with nebivolol ( Neb ) 5 mg vs. hydrochlorothiazide ( HCTZ ) 25 mg , in hypertensive patients with Fontaine stage II ( intermittent claudication ) . The primary endpoint was the initial claudication distance ( ICD ) during treadmill exercise after 24-week treatment in the per protocol population , using a noninferiority statistical approach . A total of 177 patients ( mean age was 66.3 ± 9.2 years , 76.7 % men ) were r and omized to study treatment and 127 completed the study ; the intent-to-treat ( ITT ) analysis was performed on 163 patients , the per protocol analysis on 127 patients . Both drugs lowered blood pressure significantly . After 24-week treatment , ICD increased in the Neb group in the ITT population by 28.3 % ( 95 % CI 15.6–41.0 ) vs. in the HCTZ group by 26.5 % ( 14.4–38.5 ) , and in the per protocol population in the Neb group by 26.4 % ( 13.4–39.4 ) vs. in the HCTZ group by 32.1 % ( 18.4–45.7 ) . Thus , noninferiority of Neb could neither be confirmed nor rejected . An increase of absolute claudication distance ( ACD , mean percentage increase after 24 weeks on Neb 15.8 ± 33.2 vs. on HCTZ 20.2 ± 46.6 ) was observed without statistical differences between groups . Ankle-brachial index ( ABI ) increased slightly in both groups . Generally , both treatments were well tolerated . Conclusion The increases in ICD , ACD and ABI with nebivolol suggest that this medication does not have negative effects on hypertensive patients with symptomatic PAD , and can be used for treatment of hypertension in these patients at high cardiovascular risk without reducing the walking ability 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 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 OBJECTIVE To determine the utility of  ankle-brachial index ( ABI )  in screening for unrecognized peripheral arterial disease ( PAD ) . Although PAD is a consistent predictor of cardiovascular morbidity and mortality , it is often under-diagnosed and under-treated . METHODS In this prospect i ve , observational , real-life , epidemiologic study ( ELLIPSE ) the prevalence of  PAD ( ABI < 0.9 )  was calculated in 2146 asymptomatic patients > or = 55 years of age who were at high cardiovascular risk and who were hospitalized in departments of cardiology , diabetology , geriatrics , internal medicine , or neurology in metropolitan France .  Univariate and multivariate analyses were performed to identify PAD risk factors . The discriminatory power of the model was evaluated by calculating the area under the curve ( AUC ) of the receiver operating characteristic curve . RESULTS The ABI was < 0.9 in 41.1 % of patients . In the multivariate analysis , absence of > or = 1 pulse ( odds ratio [ OR ] , 2.18 ; 95 % confidence interval [ CI ] , 1.81 to 2.63 ; P < .0001 ) , arterial bruit ( OR , 1.92 ; 95%CI , 1.34 to 2.75 ; P < .0004 ) , previous non-Q-wave myocardial infa rct ion ( OR , 1.50 ; 95%CI , 1.08 to 2.08 ; P = .02 ) , regular smoking ( OR , 1.49 ; 95%CI , 1.22 to 1.80 ; P < .0001 ) , age > or = 81 years ( OR , 1.45 ; 95%CI , 1.15 to 1.82 ; P = .001 ) , creatinine clearance < 60 mL/min ( OR , 1.33 ; 95%CI , 1.08 to 1.63 ; P = .008 ) , and treated hypertension ( OR , 1.28 ; 95%CI , 1.03 to 1.59 ; P = .03 ) were significantly associated with PAD . Although risk increased with the number of variables , the model , based on clinical symptoms and on medical history parameters , was not discriminatory ( AUC = 0.66 ) . On average , physicians took 15 minutes to perform the ABI test . CONCLUSIONS The high prevalence of asymptomatic PAD in this patient population suggests that ABI should systematic ally be performed in high-risk hospitalized patients to ensure that appropriate secondary prevention programs are initiated 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 OBJECTIVES We sought to investigate the effect of cardiac medication on long-term mortality in patients with peripheral arterial disease ( PAD ) . BACKGROUND Peripheral arterial disease is associated with increased cardiovascular morbidity and mortality . Treatment guidelines recommend aggressive management of risk factors and lifestyle modifications . However , the potential benefit of cardiac medication in patients with PAD remains ill defined . METHODS In this prospect i ve observational cohort study , 2,420 consecutive patients ( age , 64 + /- 11 years , 72 % men ) with PAD ( ankle-brachial index < or = 0.90 ) were screened for clinical risk factors and cardiac medication . Follow-up end point was death from any cause . Propensity scores for statins , beta-blockers , aspirin , angiotensin-converting enzyme ( ACE ) inhibitors , calcium channel blockers , diuretics , nitrates , coumarins , and digoxin were calculated . Cox regression models were used to analyze the relation between cardiac medication and long-term mortality . RESULTS Medical history included diabetes mellitus in 436 patients ( 18 % ) , hypercholesterolemia in 581 ( 24 % ) , smoking in 837 ( 35 % ) , hypertension in 1,162 ( 48 % ) , coronary artery disease in 1,065 ( 44 % ) , and a history of heart failure in 214 ( 9 % ) . Mean ankle-brachial index was 0.58 ( + /-0.18 ) . During a median follow-up of eight years , 1,067 patients ( 44 % ) died . After adjustment for risk factors and propensity scores , statins ( hazard ratio [ HR ] 0.46 , 95 % confidence interval [ CI ] 0.36 to 0.58 ) , beta-blockers ( HR 0.68 , 95 % CI 0.58 to 0.80 ) , aspirins ( HR 0.72 , 95 % CI 0.61 to 0.84 ) , and ACE inhibitors ( HR 0.80 , 95 % CI 0.69 to 0.94 ) were significantly associated with a reduced risk of long-term mortality . CONCLUSIONS On the basis of this observational longitudinal study , statins , beta-blockers , aspirins , and ACE inhibitors are associated with a reduction in long-term mortality in patients with PAD 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 Peripheral arterial disease ( PAD ) is a growing and often underdiagnosed health problem that predicts cardiovascular events and mortality . Estimating its prevalence in the general popula tion is a major issue for assessing health needs and planning health services . The aim of this study was to determine the prevalence of PAD and its risk factors in an urban Mexican popu lation . A r and om sample of 400 adult subjects was selected from a Family Medical Unit of the Mexican Institute of the Social Security .  Clinical examination was performed and a question naire was applied to all subjects . After an overnight fast , serum glucose , triglyceride , and cholesterol concentrations were measured . Blood pressure was taken and the ankle-brachial index ( ABI ) was calculated by Doppler examination in both sides . PAD was diagnosed if one of the ABIs was less than 0.90 . Prevalence was estimated with 95 % confidence intervals ( CI95 % ) , and odds ratios ( OR ) with CI95 % were obtained to assess association with some atherogenic risk factors in a multiple logistic regression analysis . The prevalence of PAD was 10.0 % ( CI95 % , 7.24%-13.37 % ) , and it was higher in men . Most subjects with PAD had no signs or symptoms , although the presence of either signs or symptoms was more frequent in subjects with PAD . The main risk factors related to PAD were serum triglycerides ≥150 mg/dL ( OR 2.25 ; CI95 % 1.0 - 5.1 ) , heavy smoking ( OR 2.5 ; CI95 % 0.9 - 6.7 ) and a history of diabetes mellitus for longer than 7 years ( OR 1.9 ; CI95 % 0.6 - 5.8 ) . The prevalence of PAD is high in this Mexican urban population . Asymptomatic PAD may be highly frequent , and low-cost , noninvasive Doppler ultrasonography should be considered as an adequate screening procedure in primary care to detect individuals at high risk for major cardiovascular events OBJECTIVE To assess the prophylactic efficacy of aspirin and a high-dose antioxidant vitamin combination in patients with peripheral arterial disease ( PAD ) in terms of reduction of the risk of a first vascular event ( myocardial infa rct ion , stroke , vascular death ) and critical limb ischaemia . DESIGN R and omized , placebo-controlled , double-blind clinical trial with 2 x 2 factorial design . SETTING Thirty-seven European angiology/vascular medicine units . SUBJECTS A total of 366 out patients with stage I-II PAD documented by angiography or ultrasound , with ankle/brachial index < 0.85 or toe index < 0.6 ; 210 patients completed the follow-up . INTERVENTIONS Four treatment groups : ( i ) oral aspirin ( 100 mg daily ) , ( ii ) oral antioxidant vitamins ( 600 mg vitamin E , 250 mg vitamin C and 20 mg beta-carotene daily ) , ( iii ) both or ( iv ) neither , given for 2 years . MAIN OUTCOME MEASURE Major vascular events ( cardiovascular death , myocardial infa rct ion or stroke ) and critical leg ischaemia . RESULTS Seven of 185 patients allocated aspirin and 20 of 181 allocated placebo suffered a major vascular event ( risk reduction 64 % , P = 0.022 ) ; five and eight patients , respectively , suffered critical leg ischaemia ( total 12 vs. 28 , P = 0.014 ) . There was no evidence that antioxidant vitamins were beneficial ( 16/185 vs. 11/181 vascular events ) . Neither treatment was associated with any significant increase in adverse events . Inclusion of this trial in a meta- analysis of other r and omized trials of anti-platelet therapy in PAD makes the overall results highly significant ( P < 0.001 ) and suggests that low-dose aspirin reduces the incidence of vascular events by 26 % . CONCLUSIONS For the first time direct evidence shows that low-dose aspirin should routinely be considered for PAD patients , including those with concomitant type 2 diabetes Background Peripheral artery disease ( PAD ) is associated with high cardiovascular mortality and a poor quality of life . The AT1-receptor blocker telmisartan has been shown to have pleiotropic effects and it may also improve endothelial function . The aim of this study was to analyze the effects of telmisartan on absolute walking distance ( WD ) and endothelial function in patients with PAD . Methods In a single centre , single-blinded , prospect i ve study , 36 patients with PAD at stage Fontaine II or higher and mild to moderate arterial hypertension were treated with telmisartan 40/80 mg once daily or placebo for 12 months . Primary endpoint was the improvement of the absolute treadmill WD . Flow-mediated vasodilation ( FMD ) , carotid intima-media thickness ( IMT ) , ankle-brachial index ( ABI ) and disease-related quality of life ( DRQL ) were examined as well . Results After 12 months , maximum WD increased by 26 % in the telmisartan group ( P < 0.001 ) . However , in the placebo group it was comparable to baseline . FMD rose by 40 % in the telmisartan group while it deteriorated in the placebo group ( P < 0.001 ) . IMT and ABI were comparable in both groups at baseline and did not change considerably after 12 months . In non-diabetic patients ( 72.2 % ) , the ABI did not change in the placebo group , whereas it increased by 11 % in the telmisartan group ( P < 0.001 ) . While the DRQL remained stable in the telmisartan group , placebo treatment was associated with a marked deterioration ( P < 0.01 ) . Conclusion Telmisartan improves WD and endothelial function , the ABI in non-diabetic patients and it may prevent further loss of quality of life in patients with advanced PAD Body-image dissatisfaction is a problem that affects a substantial minority ofwomen and cuts across various diagnostic groups . College women with a significant level ofbody-image dissatisfaction were r and omly assigned to either a cognitive-behavioral treatment ( CBT ) program  ( n = 15 ) or to a waiting-list control group  ( n = 16 ) . The CBT program consisted of six structured , individual sessions that applied cognitive-behavioral procedures to the problem of negative body image . At pretest , posttest , and 7-week foUow-up , multiple aspects of body image and other areas of psychosocial functioning were assessed . Relative to the control condition , the CBT program successfully improved affective body image , weakened maladaptive body-image cognitions , and enhanced social self-esteem and feelings about physical fitness and sexuality . Treatment effects were largely maintained at followup . After posttest , the control group received a 3-week treatment with immediate effects that generally replicated those obtained in the 6-wer program Hypertension is a common risk factor for peripheral arterial disease ( PAD ) . Guidelines suggest treating PAD patients to a blood pressure < 130/80 mm Hg ; therefore , our objective was to explore whether attainment of this target blood pressure is associated with improved outcomes . We performed a post hoc analysis of the INternational VErapamil-SR/Tr and olapril STudy , a r and omized clinical trial , which included hypertensive patients with concomitant PAD and coronary artery disease . There were 2699 PAD patients followed for a mean of 2.7 years ( 60 970 patient-years ) . The primary outcome , all-cause death , nonfatal myocardial infa rct ion , or nonfatal stroke , occurred in 16.3 % of PAD patients versus 9.2 % without PAD ( adjusted hazard ratio : 1.26 [ 95 % CI : 1.13 to 1.40 ] ; P<0.0001 ) . The primary outcome occurred least frequently among PAD patients treated to an average systolic blood pressure of 135 to 145 mm Hg and an average diastolic blood pressure of 60 to 90 mm Hg . PAD patients displayed a J-shape relationship with systolic blood pressure and the primary outcome , although individuals without PAD did not . PAD patients may require a different target blood pressure than those without PAD Background Peripheral arterial disease ( PAD ) of the lower limbs is a cardiovascular disease highly prevalent particularly in the asymptomatic form . Its prevalence starts to be a concern in low coronary risk countries like Spain . Few studies have analyzed the relationship between ankle-brachial index ( ABI ) and cardiovascular morbi-mortality in low cardiovascular risk countries like Spain where we observe significant low incidence of ischemic heart diseases together with high prevalence of cardiovascular risk factors . The objective of this study is to determine the relationship between pathological ABI and incidence of cardiovascular events ( coronary disease , cerebrovascular disease , symptomatic aneurism of abdominal aorta , vascular surgery ) and death in the > 49 year population -based cohort in Spain ( ARTPER ) . Methods  Baseline ABI  was measured in 3,786 r and omly selected patients from 28 Primary Health Centers in Barcelona , distributed as : ABI<0.9 peripheral arterial disease ( PAD ) , ABI ≥1.4 arterial calcification ( AC ) , ABI 0.9 - 1.4 healthy ; and followed during 4 years . Results 3,307 subjects were included after excluding those with previous vascular events . Subjects with abnormal ABI were older with higher proportion of men , smokers and diabetics . 260 people presented cardiovascular events ( incidence 2,117/100,000 person-years ) and 124 died from any cause ( incidence 978/100,000 person-years ) . PAD had two-fold greater risk of coronary disease ( adjusted hazard ratio ( HR ) = 2.0 , 95 % confidence interval ( CI ) 1.3 - 3.2 ) and increased risk of vascular surgery ( HR = 5.6 , 95%CI 2.8 - 11.5 ) and mortality ( HR = 1.8 , 95%CI 1.4 - 2.5 ) . AC increased twice risk of cerebrovascular events ( HR = 1.9 , 95%CI 1.0 - 3.5 ) with no relationship with ischemic heart disease . Conclusions PAD increases coronary disease risk and AC cerebrovascular disease risk in low cardiovascular risk Mediterranean population . ABI could be a useful tool to detect patients at risk in Primary Health Care OBJECTIVE A population -based point-prevalence study was conducted to determine the prevalence of peripheral arterial disease ( PAD ) in Sweden , with special attention to critical limb ischemia and sex differences . METHODS An age-st and ardized r and omly selected population sample of 8000 women and men , aged 60 to 90 years , from four different regions in Sweden was invited to participate . The sample had the same age and gender distribution as the Swedish population in this age group . Participating subjects completed question naires on medical history , present medication , and symptoms , and their ankle-brachial index ( ABI ) was measured . Subjects were analyzed for presence of PAD according to reported symptoms and an ABI<0.9 . RESULTS A total of 5080 subjects were included , giving a participation rate of 64 % . The prevalence of any PAD , asymptomatic PAD , intermittent claudication , and severe limb ischemia was , respectively , 18 % ( 95 % confidence interval [ CI ] , 16 % to 20 % ) 11 % ( 9 % to 13 % ) , 7 % ( 6.5 to 7 % ) and 1.2 % ( 1 % to 1.5 % ) . Women had a higher prevalence than men when PAD was diagnosed with ABI only ; that is , asymptomatic PAD ( 12.6 % vs 9.4 % , P=.03 ) and severe limb ischemia ( 1.5 % vs 0.8 % , P<.008 ) . The prevalence of any PAD was 7.9 % in the age group 60 to 65 years and increased to 47.2 % among the age group 85 to 90 years . Severe limb ischemia occurred in 0.3 % in the youngest age group , was highest in the age group 80 to 84 years at 3.3 % , and declined to 2.5 % among the oldest . The prevalence of PAD differed between regions ( P<.0001 ) . CONCLUSIONS PAD is common in Sweden , and almost a fifth of all elderly individuals have some stage of this disease . Women are more often afflicted than men . The prevalence of severe ischemia , as a measure of critical limb ischemia , is about 1 % the population 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 : CONTEXT Among individuals with lower-extremity peripheral arterial disease ( PAD ) , specific leg symptoms and the ankle brachial index ( ABI ) are cross-sectionally related to the degree of functional impairment . However , relations between these clinical characteristics and objective ly measured functional decline are unknown . OBJECTIVE To define whether PAD , ABI , and specific leg symptoms predict functional decline at 2-year follow-up . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study among 676 consecutively identified individuals ( aged > or = 55 years ) with and without PAD ( n = 417 and n = 259 , respectively ) , with baseline functional assessment s occurring between October 1 , 1998 , and January 31 , 2000 , and follow-up assessment s scheduled 1 and 2 years thereafter . PAD was defined as ABI less than 0.90 , and participants with PAD were categorized at baseline into 1 of 5 mutually exclusive symptom groups . MAIN OUTCOME MEASURES Mean annual changes in 6-minute walk performance and in usual-paced and fast-paced 4-m walking velocity , adjusted for age , sex , race , prior-year functioning , comorbid diseases , body mass index , pack-years of cigarette smoking , and patterns of missing data . RESULTS Lower baseline ABI values were associated with greater mean ( 95 % confidence interval ) annual decline in 6-minute walk performance ( -73.0 [ -142 to -4.2 ] ft for ABI < 0.50 vs -58.8 [ -83.5 to -34.0 ] ft for ABI 0.50 to < 0.90 vs -12.6 [ -40.3 to 15.1 ] ft for ABI 0.90 - 1.50 , P = .02 ) . Compared with participants without PAD , PAD participants with leg pain on exertion and rest at baseline had greater mean annual decline in 6-minute walk performance ( -111 [ -173 to -50.0 ] ft vs -8.67 [ -36.9 to 19.5 ] ft , P = .004 ) , usual-pace 4-meter walking velocity ( -0.06 [ -0.09 to -0.02 ] m/sec vs -0.01 ( -0.03 to 0.003 ] m/sec , P = .02 ) , and fastest-pace 4-meter walking velocity ( -0.07 [ -0.11 to -0.03 ] m/sec vs -0.02 [ -0.04 to -0.006 ] m/sec , P = .046 ) . Compared with participants without PAD , asymptomatic PAD was associated with greater mean annual decline in 6-minute walk performance ( -76.8 ( -135 to -18.6 ] ft vs -8.67 ( -36.9 to 19.5 ] ft , P = .04 ) and an increased odds ratio for becoming unable to walk for 6 minutes continuously ( 3.63 ; 95 % confidence interval , 1.58 - 8.36 ; P = .002 ) . CONCLUSIONS Baseline ABI and the nature of leg symptoms predict the degree of functional decline at 2-year follow-up . Previously reported lack of worsening in claudication symptoms over time in patients with PAD may be more related to declining functional performance to than lack of disease progression Asymptomatic peripheral arterial disease ( PAD ) can be easily identified using the  ankle – brachial index ( ABI ) . This study was design ed to investigate the benefits of performing ABI in patients aged 50 - 70 years . A r and om sample of 107 patients was chosen and data on gender , age , risk factors and laboratory tests were collected and the ABI measured . Twenty ( 19 % ) patients were found to have PAD . Smoking , high total cholesterol , high triglycerides and diabetes mellitus were shown to be associated with a low ABI and the presence of PAD . Age , diabetes and smoking were identified as the strongest predictors of PAD . Having more risk factors for PAD also predicted a lower ABI . These results suggest that measuring ABI  is not necessary in patients aged 50 - 70 years if they only have one risk factor , with the exception of patients with diabetes and those who smoke . In contrast , measuring ABI seems to be useful for patients with multiple risk factors for PAD , although additional studies are required 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 —Bone-marrow mononuclear cell ( BM-MNC ) implantation improves ischemic symptoms in patients with critical limb ischemia ( CLI ) . The purpose of this study was to evaluate long-term clinical outcomes after autologous BM-MNC implantation in patients with CLI . Methods and Results —We assessed long-term clinical outcomes after BM-MNC implantation in 51 patients with CLI , including 25 patients with peripheral arterial disease ( PAD ) and 26 patients with Buerger disease . Forty-six CLI patients who had no BM-MNC implantation served as control subjects . Median follow-up period was 4.8 years . The 4-year amputation-free rates after BM-MNC implantation were 48 % in PAD patients and 95 % in Buerger disease , and they were 0 % in control PAD patients and 6 % in control Buerger disease . The 4-year overall survival rates after BM-MNC implantation  were 76 % in PAD patients and 100 % in Buerger disease , and they were 67 % in control PAD patients and 100 % in control Buerger disease . Multivariable Cox proportional hazards analysis revealed that BM-MNC implantation correlated with prevention of major amputation and that hemodialysis and diabetes mellitus correlated with major amputation . In Buerger disease , ankle brachial pressure index and transcutaneous oxygen pressure were significantly increased after 1 month and remained high during 3-year follow-up . However , in patients with PAD , ankle brachial pressure index and transcutaneous oxygen pressure significantly increased after 1 month and gradually decreased during 3-year follow-up and returned to baseline levels . Conclusions —These findings suggest that BM-MNC implantation is safe and effective in patients with CLI , especially in patients with Buerger disease . Clinical Trial Registration —URL : http://home.hiroshima-u.ac.jp/angio/. Unique identifier : 001769 The primary objectives of the pilot study were to : ( 1 ) evaluate the feasibility of recruiting patients with peripheral arterial disease ( PAD ) ; ( 2 ) measure the efficacy and safety of high-density lipoprotein (HDL)-raising treatment , low-density lipoprotein (LDL)-lowering therapy , antioxidant therapy , antithrombotic therapy , and their combinations ; and ( 3 ) assess adherence to a complex multiple drug regimen . Secondary objectives included measurement of the effect of the interventions on prespecified biochemical markers , maintenance of therapy masking ( in particular with niacin ) , and measurement of the intervention 's impact on functional status and on quality of life . To date , no secondary prevention trial has been conducted specifically among patients with PAD . Intermittent claudication affects about 0.5 % to 1.0 % of persons aged > 35 years . There is a striking increase in incidence of PAD with age , particularly among those aged > 50 years in both sexes , although men are twice as likely as women to develop PAD . The Arterial Disease Multiple Intervention Trial was a double-blind r and omized pilot trial of 468 participants with documented PAD . A 2 x 2 x 2 factorial design was used to evaluate the effect of 3 interventions . The pilot incorporated several major novel design features : first , the use of a simple noninvasive method ( measurement of ankle brachial index ) to identify a population with either symptomatic or asymptomatic PAD ; and second , a lipid modifying strategy to increase HDL with nicotinic acid in the intervention group while lowering LDL levels equally with an hydroxymethylglutaryl-coenzyme A reductase inhibitor as needed in the intervention and control group . Two other arms , the antioxidant arm ( consisting of beta-carotene and vitamins E and C ) and the antithrombotic arm ( using warfarin ) were also added . Adherence to therapy was measured by pill count , and success in treatment was measured by the proportion of values in target range for HDL , LDL , and the international normalized ratio Current guidelines recommend obtaining an ankle – brachial index ( ABI ) to screen for peripheral artery disease ( PAD ) in subjects at risk . Previous work demonstrated that a combination of β2-microglobulin , cystatin C , high-sensitivity C-reactive protein and glucose was associated with PAD . This study evaluated the ability of these biomarkers combined with clinical parameters to predict PAD in at-risk subjects . This study enrolled 1025 subjects from 99 primary care clinics who were smokers and /or diabetics ≥ 50 years or any individual ≥ 70 years . Consented subjects underwent a clinical assessment , fasting blood draw , and an ABI measurement with PAD defined as an ABI < 0.90 in either leg . The biomarkers and their interactions were evaluated using logistic regression and performance was evaluated at a cut point of the biomarker panel selected to maximize sensitivity while minimizing the false positive rate of the test . Of the 1025 subjects enrolled , 46 did not meet the ABI or other criteria for inclusion in the analysis . Among the evaluable subjects ( n = 979 )  , PAD was detected in 83 ( 8.5 % ) . The model had a C-statistic of 0.73 ( 95 % CI 0.67–0.79 ) . There were 20 patients with PAD who were judged to be at low to moderate risk for cardiovascular events by clinical assessment ; the model correctly identified 17 of these 20 patients . The model also performed well in subjects with no prior history of PAD . Thus , a biomarker panel may have a role for identifying PAD 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 INTRODUCTION Though being physically active has associated with a healthier ankle-brachial index ( ABI ) in observational studies , ABI usually does not change with exercise training in patients with peripheral artery disease ( PAD ) . Less is known about the effect of exercise training on ABI in patients without PAD but at high risk due to the presence of type 2 diabetes ( T2DM ) . METHODS Participants ( n = 140 ) with uncomplicated T2DM , and without known cardiovascular disease or PAD , aged 40 - 65 years , were r and omized to supervised aerobic and resistance training 3 times per week for 6 months or to a usual care control group . ABI was measured before and after the intervention . RESULTS Baseline ABI was 1.02 ± 0.02 in exercisers and 1.03 ± 0.01 in controls ( p = 0.57 ) . At 6 months , exercisers vs. controls improved ABI by 0.04 ± 0.02 vs. -0.03 ± 0.02 ( p = 0.001 ) . This change was driven by an increase in ankle pressures ( p < 0.01 ) with no change in brachial pressures ( p = 0.747 ) . In subgroup analysis , ABI increased in exercisers vs. controls among those with baseline ABI < 1.0 ( 0.14 ± 0.03 vs. 0.02 ± 0.02 , p = 0.004 ) , but not in those with a baseline ABI ≥1.0 ( p = 0.085 ) . The prevalence of ABI between 1.0 and 1.3 increased from 63 % to 78 % in exercisers and decreased from 62 % to 53 % in controls . Increased ABI correlated with decreased HbA1c , systolic and diastolic blood pressure , but the effect of  exercise on ABI change remained significant after adjustment for these changes ( β = 0.061 , p = 0.004 ) . CONCLUSION These data suggest a possible role for exercise training in the prevention or delay of PAD in T2DM , particularly among those starting with an ABI < 1.0 . Clinical trials.gov Registry Number : NCT00212303 Background Peripheral arterial disease ( PAD ) is known to be associated with high cardiovascular risk , but the individual impact of PAD presentations on risk of macrovascular and microvascular events has not been reliably compared in patients with type 2 diabetes . We aim ed to evaluate the impact of major PAD , and its different presentations , on the 10-year risk of death , major macrovascular events , and major clinical microvascular events in these patients . Methods Participants in the action in diabetes and vascular disease :  PreterAx and DiamicroN modified-release controlled evaluation ( ADVANCE ) trial and the ADVANCE-ON post-trial study were followed for a median of 5.0 ( in-trial ) , 5.4 ( post-trial ) , and 9.9 ( overall ) years . Major PAD at baseline was subdivided into lower-extremity chronic ulceration or amputation secondary to vascular disease and history of peripheral revascularization by angioplasty or surgery . Results Among 11,140 participants , 516 ( 4.6 % ) had major PAD at baseline : 300 ( 2.7 % ) had  lower-extremity  ulceration or amputation alone , 190 ( 1.7 % ) had peripheral revascularization alone , and 26 ( 0.2 % ) had both presentations . All-cause mortality , major macrovascular events , and major clinical microvascular events occurred in 2265 ( 20.3 % ) , 2166 ( 19.4 % ) , and 807 ( 7.2 % ) participants , respectively . Compared to those without PAD , patients with major PAD had increased rates of all-cause mortality ( HR 1.35 , 95 % CI 1.15–1.60 , p = 0.0004 ) , and major macrovascular events ( 1.47 [ 1.23–1.75 ] , p < 0.0001 ) , after multiple adjustments for region of origin , cardiovascular risk factors and treatments , peripheral neuropathy markers , and r and omized treatments . We have also observed a trend toward an association of baseline PAD with risk of major clinical microvascular events [ 1.31 ( 0.96–1.78 ) , p = 0.09 ] . These associations were comparable for patients with a lower-extremity ulceration or amputation and for those with a history of peripheral revascularization . Furthermore , the risk of retinal photocoagulation or blindness , but not renal events , increased in patients with lower-extremity ulceration or amputation [ 1.53 ( 1.01–2.30 ) , p = 0.04 ] . Conclusions Lower-extremity ulceration or amputation , and peripheral revascularization both increased the risks of death and cardiovascular events , but only lower-extremity ulceration or amputation increased the risk of severe retinopathy in patients with type 2 diabetes .  Screening for major PAD and its management remain crucial for cardiovascular prevention in patients with type 2 diabetes ( Clinical Trials.gov number , NCT00949286 ) AIMS Recently , markers of inflammation , haemostasis , and blood rheology have received much attention as risk factors for coronary heart disease and stroke . However , their role in peripheral arterial disease ( PAD ) is not well established and some of them , including the pro-inflammatory cytokine interleukin-6 ( IL-6 ) , have not been examined before in prospect i ve epidemiological studies . METHODS AND RESULTS In the Edinburgh Artery Study , we studied the development of PAD in the general population and evaluated 17 potential blood markers as predictors of incident PAD . At baseline ( 1987 ) , 1519 men and women free of PAD aged 55 - 74 were recruited . After 17 years , 208 subjects had developed symptomatic PAD . In analysis adjusted for cardiovascular risk factors and baseline cardiovascular disease ( CVD ) , only C-reactive protein , fibrinogen , lipoprotein ( a ) , and haematocrit [ hazard ratio ( 95 % CI ) corresponding to an increase equal to the inter-tertile range 1.30 ( 1.08 , 1.56 ) , 1.16 ( 1.05 , 1.17 ) , 1.22 ( 1.04 , 1.44 ) , 1.22 ( 1.08 , 1.38 ) ] were significantly ( P < 0.01 ) associated with PAD . However , these markers provided very little prognostic information for incident PAD to that obtained by cardiovascular risk factors and the ankle brachial index . Other markers including IL-6 , intracellular adhesion molecule 1 , d-dimer , tissue plasminogen activator antigen , and plasma and blood viscosities showed weak associations , which were considerably attenuated when CVD risk factors were accounted for . CONCLUSIONS Our prospect i ve data showed that several inflammatory , haemostatic , and rheological markers are associated with incident PAD ; however , their clinical utility is likely to be limited . Future research is necessary to vali date the importance of these biomarkers explicitly on PAD and to address the causality of the reported associations OBJECTIVES Near-infrared spectroscopy provides a noninvasive method of measuring tissue oxygen saturation and has been used to monitor extremity compartment syndrome . Tissue O(2 ) saturation ( StO(2 ) ) is potentially useful in assessing patients with peripheral arterial disease ( PAD ) . The purpose s of this feasibility study are to ( 1 ) explore the diagnostic sensitivity of StO(2 ) in subjects with PAD and symptoms of intermittent claudication ( IC ) compared with normal subjects , and ( 2 ) correlate the change in StO(2 ) during and after exercise with the ankle brachial index ( ABI ) in patients with IC . Material and methods Forty-nine subjects , 35 normal and 14 PAD , from two centers were evaluated in a prospect i ve cross-sectional analysis comparing StO(2 ) by using the InSpectra tissue spectrometer and ABI at rest ( baseline ) and after treadmill exercise . Measurements were obtained at baseline and peak exercise ( normal subjects ) and at baseline , initial claudication distance ( ICD ) and absolute claudication distance ( ACD ) in PAD subjects . Endpoint values were the mean of 15 data points . Times to 50 % of StO(2 ) recovery to baseline ( T(50 ) ) and complete recovery to baseline ( T(100 ) ) were measured . Receiver-operator characteristic curves were constructed to assess the sensitivity/specificity values associated with various StO(2 ) cut-points . RESULTS The PAD patients were older ( P = .0002 ) and 57 % were male , compared with 37 % males in the normal group . The ABI was 0.68 + /- 0.14 in PAD patients versus 1.14 + /- 0.08 in normal subjects ( P < .0001 ) . The baseline StO(2 ) was 65 % in both groups . The peak exercise StO(2 ) was significantly lower and the absolute change in StO(2 ) and the percent change in StO(2 ) were significantly greater in PAD patients ( P < 0.45 ) . The T(50 ) and T(100 ) were longer in the PAD patients compared to normal subjects ( P = .0001 and .002 , respectively ) . A T(50 ) of > 70 seconds yielded a sensitivity of 89 % and a specificity of 85 % for PAD . CONCLUSIONS StO(2 ) is a new and potentially useful technique to evaluate patients with PAD . Resting StO(2 ) was similar in PAD-IC subjects and normals . There was a significantly greater drop in StO(2 ) and longer recovery times in PAD-IC subjects . Interestingly , StO(2 ) at the ICD and ACD was similar . StO(2 ) offers a different and perhaps more appropriate end point for diagnosis and monitoring of the management of patients with PAD , and may offer additional insight into the pathophysiology of exercise-induced muscle ischemia and its recovery OBJECTIVE To investigate the prevalence of peripheral arterial disease ( PAD ) and correlative risk factors among natural population in China . METHODS  Ankle brachial index ( ABI ) was measured by trained doctors and related data were collected in residents from Beijing , Shanghai , Changsha , Guangdong , Neimenggu , and Xinjiang selected through cluster multistage and r and om sampling method . PAD was defined as an ABI < or = 0.9 in either leg . RESULTS The  prevalence of PAD among 21 152 eligible participants was 3.08 % , the st and ardized prevalence was 3.04 % . The prevalence in males and females was 2.52 % and 3.66 % and the st and ardized prevalence was 1.84 % and 4.31 % respectively , the prevalence rate was significantly lower in males than that in females ( P < 0.01 ) . The prevalence in both males and females increased significantly in proportion to aging ( P < 0.01 ) . The prevalence in Han Chinese was significantly higher than that in non-Han Chinese ( P < 0.01 ) . Logistic regression analysis showed that older age , female gender , Han Chinese , waist circumference , smoking , lipid disorder , diabetes mellitus , coronary artery disease and a history of ischemic stroke were associated with the increased prevalence of PAD . Incidence of known PAD was 1.38 % in this cohort . CONCLUSIONS Older age , female gender , Han Chinese , waist circumference , smoking , lipid disorder , diabetes mellitus , coronary artery disease and a history of ischemic stroke were associated with the increased prevalence of PAD in natural Chinese population Background —Peripheral arterial disease ( PAD ) and diabetes are both associated with a high risk of ischemic events , but the role of intensive blood pressure control in PAD has not been established . Methods and Results —The Appropriate Blood Pressure Control in Diabetes study followed 950 subjects with type 2 diabetes for 5 years ; 480 of the subjects were normotensive ( baseline diastolic blood pressure of 80 to 89 mm Hg ) . Patients r and omized to placebo ( moderate blood pressure control ) had a mean blood pressure of 137±0.7/81±0.3 mm Hg over the last 4 years of treatment . In contrast , patients r and omized to intensive treatment with enalapril or nisoldipine had a mean 4-year blood pressure of 128±0.8/75±0.3 mm Hg ( P < 0.0001 compared with moderate control ) . PAD , which is defined as an ankle-brachial index < 0.90 at the baseline visit , was diagnosed in 53 patients . In patients with PAD , there were 3 cardiovascular events ( 13.6 % ) on intensive treatment compared with 12 events ( 38.7 % ) on moderate treatment ( P = 0.046 ) . After adjustment for multiple cardiovascular risk factors , an inverse relationship between ankle-brachial index and cardiovascular events was observed with moderate treatment ( P = 0.009 ) , but not with intensive treatment ( P = 0.91 ) . Thus , with intensive blood pressure control , the risk of an event was not increased , even at the lowest ankle-brachial index values , and was the same as in a patient without PAD . Conclusions —In PAD patients with diabetes , intensive blood pressure lowering to a mean of 128/75 mm Hg result ed in a marked reduction in cardiovascular events Background Short-term ( within 6 weeks follow-up ) clinical studies indicate that implantation of bone marrow cells ( BMC s ) into ischemic limbs may improve peripheral ischemia . Here , the long-term safety and feasibility of intraarterial autologous BMC s with oral treatment with antioxidants and L-arginine were investigated in patients with critical ischemia on account of advanced atherosclerotic peripheral arterial disease ( PAD ) . Methods Eighteen patients with PAD ( advanced III/IV Fontaine stages ) were enrolled in this study ( NCT00306085 ) . An additional group of 18 patients taking maximal drug therapy that refused BMC therapy served as control . The BMC -treated group received two doses of BMC s in the leg arteries ( time 0 and 45 days ) . After 30 days from the first BMC dose , patients received daily antioxidants , and l-arginine .  Therapeutic neoangiogenesis was estimated by angiography and laser Doppler capillaroscopy . Results Ankle brachial index improvement ( ΔABI : > 0.1 ) was seen in 10 patients at 3 months and in 12 patients at 12–18 months . Ischemic ulcers improved in 13 patients ( after 6–12 months ) . Although two patients underwent amputation , the mean maximum walking distance significantly increased at 3 months and was sustained up to 18 months . Among conservative patients , 10 underwent amputation in comparison with two BMC -treated patients ( 55.6 vs. 13.3 % ; P = 0.014 ) . Conclusion This small study shows that intraarterial autologous BMC and antioxidants and l-arginine therapy is safe and effective in patients with advanced atherosclerotic PAD with positive effects until 18 months . Eur J Cardiovasc Prev Rehabil 15:709–718 © 2008 The European Society of 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 Selected near-infrared spectroscopy ( NIRS ) parameters were assessed in healthy untrained participants and in peripheral arterial disease ( PAD ) trained patients to evaluate their usefulness in rehabilitative outcome . Forty-five PAD and 15 healthy participants were studied at entry and at 34 ± 2 weeks . Healthy participants performed their usual activities . Patients with PAD performed 2 home-based programs : structured at prescribed pace ( S-pre , n = 31 ) and unstructured at free pace ( U-free , n = 14 ) . We measured ankle – brachial index ( ABI ) , NIRS calf oxygen consumption at rest , NIRS dynamic muscle perfusion during an incremental test , and walking capacity . In all patients with PAD the NIRS parameters significantly increased approaching the stable values of untrained healthy participants . Among PAD , only S-pre group showed significant improvements in hemodynamic , functional , and NIRS parameters with selective adaptations in the worse legs . The assessment of NIRS parameters , that were found stable without training in healthy and modified in PAD only following structured training , might outline the local exercise-induced adaptations Context Few therapies substantially reduce symptoms and improve exercise performance in patients with peripheral arterial disease ( PAD ) . Contribution In this double-blind trial , investigators r and omly assigned 40 older adults without diabetes and with symptomatic PAD to receive either ramipril or placebo , 10 mg once daily for 24 weeks . Compared with placebo , ramipril increased maximum and pain-free walking time and walking speed and distance . Caution s The trial was small and involved selected patients with limited mobility and exercise tolerance . Implication s Ramipril may improve symptoms in some patients with PAD . The Editors This article has been retracted . See Notice of Retraction . Peripheral arterial disease ( PAD ) is a common disorder , with 12 % of adults older than 50 years of age having an anklebrachial index ( ABI ) that is diagnostic of PAD ( < 0.9 ) ( 1 ) . Approximately one third of these patients experience intermittent claudication during walking , limiting normal activities . Medical treatments to improve walking distance are limited . The angiotensin-converting enzyme ( ACE ) inhibitor ramipril reduced cardiovascular morbidity and mortality compared with placebo in patients with established atherosclerotic disease , including PAD , in the Heart Outcomes Prevention Evaluation ( HOPE ) study ( 2 ) . This effect seemed to be independent of blood pressure reduction ( 3 ) and may relate to the known benefits of ACE inhibitors on both coronary and brachial endothelial function ( 4 ) . No previous controlled studies have investigated the effect of ACE inhibitors on symptoms of intermittent claudication . Given the positive effects of ramipril in the HOPE trial and its convenient once-daily dosing formulation , we hypothesized that therapy with ramipril would improve intermittent claudication symptoms . We aim ed to examine the effect of 6-month ramipril therapy on walking distance and claudication pain in a defined group of patients with claudication due to infrainguinal PAD by using a double-blind , r and omized , placebo-controlled design . Methods This article has been retracted . See Notice of Retraction . We screened 152 patients with PAD from general practice clinics in the Melbourne , Australia , metropolitan area ( Figure 1 ) . Of them , 40 patients ( mean age , 66 years [ SD , 4 ] ) were recruited and completed the trial . All patients gave written informed consent to participate in the study . The Ethics Committee of the Alfred Hospital , Melbourne , Australia , approved the study , and we performed the study in accordance with the Declaration of Helsinki 2000 . All participants had an ABI less than 0.9 at rest in at least 1 leg ; had a history of intermittent claudication ( unilateral or bilateral ) , which was stable for 6 months ; had evidence of superficial femoral artery stenosis or occlusion on duplex ultrasonography ; had blood pressure of 160/90 mm Hg or less ; had a stable medication regimen for at least 6 months ; and had not previously been treated with ACE inhibitors . We excluded patients with limiting coronary artery disease , renal failure , history of hypertension , or type 2 diabetes mellitus . Figure 1 . Flow of patients through the study . Computer-generated numbers specified the allocation sequence . A tamper-proof r and omization process generated by the hospital research center r and omly assigned participants into blocks of 10 to receive either ramipril ( Tritace , Aventis Pharma Pty . Ltd. , Macquarie Park , Australia , 10 mg once daily for 24 weeks ) or placebo ( 10 mg once daily for 24 weeks ) in a parallel-group , double-blind design . Both investigators and patients were blinded to drug assignment . Furthermore , investigators did not have access to baseline data when they performed follow-up measurements and patients were not asked which treatment they thought they were receiving . No patient assigned to placebo crossed over to ramipril during the trial or vice versa . We advised participants to maintain all aspects of their lifestyle throughout the trial and requested them to refrain from exercise , smoking , and caffeine for 24 hours before all testing . On the morning of testing , patients rested in a supine position for 15 minutes in a quiet room before the measurements . We assessed blood pressure , ABI , walking distance , duplex ultrasounds of leg arteries , and the Walking Impairment Question naire ( WIQ ) scores before and after both interventions . We advised patients about potential side effects and requested that they report any adverse event to the study coordinator . All patients performed a treadmill exercise test at a speed of 3.2 km/h and a grade of 12 % ( 5 ) , and we recorded pain-free walking time ( time to onset of claudication pain ) and maximum walking time . In our study , all patients reached a maximal level of claudication pain that limited exercise during the grade d treadmill test . The WIQ was developed and vali date d against treadmill walking and is used to evaluate limitations in community-based walking ability ( 6 ) . The WIQ assessed walking distance , speed , and stair-climbing ability , using a weighted st and ardized formula and returning a summary score between 0 % and 100 % ( 6 , 7 ) . Statistical Analyses All analysts were blinded to treatment assignment , and an independent investigator double-checked all measurement calculations and data base entries . The study was powered to detect a 180-second change in maximum walking time with ramipril , assuming a st and ard deviation of 250 seconds ( = 0.05 [ 2-sided ] ; power , 86 % ) . We compared 24-week changes from baseline in pain-free walking time , maximum walking time , and WIQ scores between treatments by using an analysis of covariance model with terms for treatment and baseline value as the analysis end points . We log-transformed the WIQ data to achieve a normal distribution before analysis . We conducted all statistical analyses by using Stata software , version 8.2 ( Stata Corp. , College Station , Texas ) . We expressed normally distributed data as means ( SDs ) or 95 % CIs and non-normally distributed data as medians ( ranges ) . A P value less 0.05 was deemed to be significant . No data were missing for any clinical variable measured in our study . Role of the Funding Sources This work was funded by the National Health and Medical Research Council of Australia . Aventis Pharma Pty . Ltd. provided ramipril ( Tritace ) and matching placebo capsules but provided no other funding for the study or to the investigators . The funding sources had no role in the design , conduct , or reporting of the study or in the decision to su bmi t the manuscript for publication . Results This article has been retracted . See Notice of Retraction . The ramipril and placebo groups were similar in age , other cardiovascular risk factors , medication use , and PAD severity , as evidence d by clinical symptoms ( walking times ) , WIQ scores , and resting ABI ( Table ) . No patient was taking cilostazol or pentoxifylline . On duplex ultrasonography , 6 of 40 patients had a superficial femoral artery occlusion ( 2 placebo patients and 4 ramipril patients ) , and the remaining patients had stenotic disease in the superficial femoral artery . Only 25 % of patients were taking antiplatelet or lipid-lowering therapy . No adverse events were reported . Table . Baseline Characteristics AnkleBrachial Index Ramipril  significantly increased ABI both at rest ( change with placebo , 0.05 mm Hg [ SD , 0.04 ] ; change with ramipril , 0.07 mm Hg [ SD , 0.08 ] ; P < 0.001 ) and after exercise ( change with placebo , 0.04 mm Hg [ SD , 0.05 ] ; change with ramipril , 0.08 mm Hg [ SD , 0.14 ] ; P < 0.001 ) . At rest , this increase was due to reduction in brachial systolic blood pressure with ramipril treatment ( 0.85 mm Hg [ SD , 1.57 ] vs. 5.05 mm Hg [ SD , 2.33 ] ; P < 0.001 ) rather than an increase in limiting leg pressure ( 0.75 mm Hg [ SD , 1.71 ] vs. 0.15 mm Hg [ SD , 1.27 ] ; P= 0.26 ) . After exercise , both a reduction in brachial pressure ( change with placebo , 0.30 mm Hg [ SD , 2.45 ] ; change with ramipril , 6.80 mm Hg [ SD , 6.07 ] ; P < 0.001 ) and an increase in limiting leg pressure ( change with placebo , 5.40 mm Hg [ SD , 7.56 ] ; change with ramipril , 7.10 mm Hg [ SD , 4.59 ] ; P < 0.001 ) contributed to the increase in ABI . Treadmill Test After adjustment for the baseline pain-free walking time , mean pain-free walking time after ramipril treatment was 227 seconds ( 95 % CI , 175 seconds to 278 seconds ; P < 0.001 ) longer than after placebo treatment ( Figure 2 ) . Similarly , maximum walking time significantly improved over the 24-week treatment period by 451 seconds ( CI , 367 seconds to 536 seconds ; P < 0.001 ) in the ramipril group after adjustment for baseline values ( Figure 2 ) . The lack of change observed over the 24-week treatment period in the placebo group ( change in mean walking time , 10 seconds [ SD , 9 ] [ CI , 14 seconds to 6 seconds ] ; P < 0.001 ) may reflect both the advanced age of participants and the fact that they all had limiting infrainguinal disease , which would probably give more reproducible treadmill data than aortoiliac disease . In addition , we asked patients to maintain all aspects of their lifestyle throughout the trial . Figure 2 . Effect of ramipril on maximum treadmill walking times . Walking Impairment Question naire Ramipril improved WIQ median distance score from 5 % ( range , 1 % to 39 % ) to 21 % ( range , 12 % to 58 % ) ( P < 0.001 ) , speed score from 3 % ( range , 3 % to 39 % ) to 18 % ( range , 8 % to 50 % ) ( P < 0.001 ) , and stair-climbing score from 17 % ( range , 4 % to 80 % ) to 67 % ( range , 38 % to 88 % ) ( P < 0.001 ) . Duplex Ultrasonography Volume flow was unaltered in the limiting leg at the stenotic site . However , ramipril significantly increased volume flow in the common femoral artery proximal to the site of stenosis in both the limiting leg ( change with placebo , 0.014 L/min [ SD , 0.022 ] ; change with ramipril , 0.017 L/min [ SD , 0.034 ] ; P= 0.008 ) and the nonlimiting leg ( change with placebo , 0.006 L/min [ SD , 0.041 ] ; change with ramipril , 0.019 L/min [ SD , 0.019 ] ; P= 0.035 ) . Discussion This article has been retracted . See Notice of Retraction . Our study shows that OBJECTIVE The purpose of the study was to examine the effects of a 12-month exercise program on lower limb mobility ( temporal-spatial gait parameters and gait kinematics ) , walking performance , peak physiological responses , and physical activity levels in individuals with symptoms of intermittent claudication due to peripheral arterial disease ( PAD-IC ) . METHODS Participants ( n = 21 ) with an appropriate history of PAD-IC , ankle-brachial pressure index ( ABI ) < 0.9 in at least one leg and a positive Edinburgh claudication question naire response were prospect ively recruited . Participants were r and omly allocated to either a control PAD-IC group ( CPAD-IC )  ( n = 11 ) that received st and ard medical therapy and a treatment PAD-IC group ( TPAD-IC ) ( n = 10 ) , which also took part in a 12-month supervised exercise program . A further group of participants ( n = 11 ) free of PAD ( ABI > 0.9 ) and who were non-regular exercisers were recruited from the community to act as age and mass matched controls ( CON ) . Lower limb mobility was determined via two-dimensional video motion analysis . A grade d treadmill test was used to assess walking performance and peak physiological responses to exercise . Physical activity levels were measured via a 7-day pedometer recording . Differences between groups were analyzed via repeated measures analysis of variance ( ANOVA ) . RESULTS The 12-month supervised exercise program had no significant effect on lower limb mobility , peak physiological responses , or physical activity levels in TPAD-IC compared with CPAD-IC participants . However , the TPAD-IC participants demonstrated significantly greater walking performance ( 171 % improvement in pain free walking time and 120 % improvement in maximal walking time compared with baseline ) . CONCLUSION The results of this study confirm that a 12-month supervised exercise program will result in improved walking performance , but does not have an impact on lower limb mobility , peak physiological responses , or physical activity levels of PAD-IC patients Background : Although only a small percentage of patients with peripheral arterial disease ( PAD ) have claudication , many more suffer from atypical leg symptoms . Purpose : This pilot trial evaluated a risk-factor modification program to improve walking ability in patients with PAD and leg symptoms other than intermittent claudication . Methods : Patients 18 years or older with an ankle-brachial index ( ABI ) of 0.50 to 0.89 completed a baseline assessment of current walking ability , physical activity level , health-related quality of life , glycosylated hemoglobin values , and fasting lipid profiles . Patients were r and omized to usual care ( control group ) versus usual care plus an educational intervention on risk-factor management ( intervention group ) . We compared functional outcomes between and within groups using the Student ’s t test and control and intervention group outcomes at 12 weeks using analysis of covariance with the baseline value as the covariate . Results : We r and omized 50 patients into two treatment arms . There was no difference in the mean age of patients in each group . At baseline , mean ABI for the control versus the intervention group was 0.72 ( SD=0.10 ) and 0.75 ( SD=0.10 ) , respectively , and mean stair-climbing values did not differ between groups . At 12 weeks , mean stair-climbing values were 40.2 ( SD=30.2 ) for the control and 61.2 ( SD=32.8 ) for the intervention group . The difference in adjusted mean walking distance between groups at 12 weeks was not significant . Analysis of covariance associated assignment to the intervention versus the control arm with a significant increase at 12 weeks in the ABI ( p=.008 ) and stair-climbing ability ( p=.02 ) . Conclusions : Patients in the intervention group improved objective measures of blood flow and reported stair-climbing ability Although intercellular adhesion molecule-1 ( ICAM-1 ) and vascular cell adhesion molecule-1 ( VCAM-1 ) play a relevant role in atherosclerosis , little is known about the prognostic impact of their soluble forms ( s ) in patients with peripheral arterial disease ( PAD ) . The aim of this prospect i ve study was to verify whether plasma levels of sICAM-1 and sVCAM-1 predict cardiovascular risk in PAD , and improve the prognostic value of the ankle/brachial index ( ABI ) alone . Accordingly , plasma levels of sICAM-1 and sVCAM-1 , and the ABI were measured in 75 PAD patients who were monitored for a mean of 24+/-13 months . Twenty-two ( 29.3 % ) patients had a cardiovascular event ( 15 coronary , 3 cerebrovascular and 4 peripheral events ) . Plasma levels of sVCAM-1  were 618+/-258 ng/mL in patients with and 496+/-164 ng/mL in those without an event ( p=0.016 ) . The corresponding sICAM-1 values were 344+/-239 ng/mL and 275+/-99 ng/mL ( p=0.079 ) . The cardiovascular event rate was higher in patients with sVCAM-1 levels above the median than in those with sVCAM-1 below the median ( p=0.0027 by log rank test ) . Independent predictors of events were sVCAM-1 levels above the median ( p=0.005 ) and an ABI below the median ( p=0.001 ) . Amongst patients with ABI below the median , the occurrence of sVCAM-1 above the median was associated with a 3.4-fold increase in risk ( 95 % CI 1.308 to 9.573 , p=0.013 ) . In conclusion , increased plasma levels of sVCAM-1  have a negative prognostic impact in PAD and improve the predictive value of ABI , which is currently the most powerful risk indicator in these patients BACKGROUND The purpose of this study was to determine whether treatment with granulocyte colony-stimulating factor ( G-CSF ) , which mobilizes endothelial progenitor cells from bone marrow , can safely improve the clinical outcomes of patients with atherosclerotic peripheral artery disease ( PAD ) . METHODS AND RESULTS Thirty-nine patients with intractable PAD were r and omly assigned to 3 groups : a negative control group ( n=12 ) treated with conventional drug therapy ; a positive control group ( n=13 ) treated with conventional drug therapy plus bone marrow transplantation ( BMT ) ; and a G-CSF group ( n=14 ) treated with conventional therapy plus subcutaneous injection of 2 - 5 microg/kg of recombinant human G-CSF once daily for 10 days . One month after treatment , subjective symptoms improved significantly in the G-CSF and BMT groups . Ankle-brachial pressure index and transcutaneous oxygen pressure increased significantly in the BMT and G-CSF groups , but no such improvements were seen in the group receiving conventional therapy alone . CONCLUSIONS G-CSF improves the clinical signs and symptoms of patients with intractable PAD to the same degree as BMT does . This noninvasive treatment may thus represent a useful new approach to managing the disease OBJECTIVES Our aim was to evaluate the possible association between homocysteine levels and peripheral arterial disease ( PAD ) in a population -based study of Japanese-Brazilians . MATERIAL S AND METHODS This cross-sectional study was derived from a population -based survey on the prevalence of diabetes and associated diseases conducted in Japanese-Brazilians . A total of 1330 male and female subjects aged > or=30 years were su bmi tted to clinical examination and laboratory procedures including homocysteine measurement . The ankle-brachial index ( ABI ) was calculated ; subjects with ABI values < 0.9 were diagnosed with PAD . The evaluable population included 1008 subjects .  Logistic regression was used taking PAD as the dependent variable . RESULTS Mean age of the population was 56.5 years and overall prevalence of PAD was 20 % . A worse cardiovascular profile was found in male patients , including significantly higher homocysteine levels ( 11.9+/-1.8 vs. 9.1+/-1.1micromol/L , p<0.001 ) . Men with PAD had higher prevalence rates of hyperhomocysteinemia compared to women ( 22.7 % vs 7.6 % ) . Univariate analysis showed an odds ratio of hyperhomocysteinemia for PAD of 1.51 [ 1.02 - 2.25 ] in men and 1.69 [ 1.06 - 2.68 ] in women . After adjustment for other cardiovascular risk factors , higher levels of homocysteine were only significantly related to PAD in men . CONCLUSION In a Japanese-Brazilian population , elevated levels of homocysteine are associated with PAD in men . Prospect i ve studies are necessary to confirm this finding OBJECTIVE To establish associations between leg strength and mortality in men and women with lower extremity peripheral arterial disease ( PAD ) . METHODS This was an observational , prospect i ve study of 410 men and women with PAD aged 55 and older recruited from Chicago-area medical centers and followed for a mean of 60 months . The participants were followed for a mean of 60.0 months . Isometric knee extension , knee flexion , hip extension , and hip flexion were measured at baseline . Primary outcomes were all-cause and cardiovascular disease mortality . Cox proportional hazards models were used to assess relations between leg strength and all-cause and cardiovascular disease mortality among men and women , adjusting for age , race , comorbidities , physical activity , smoking , body mass index , and the ankle brachial index . RESULTS Among the 246 male participants , poorer baseline strength for knee flexion ( P trend = .029 ) , knee extension ( P trend = .010 ) , and hip extension ( P trend = .013 ) were each associated independently with higher all-cause mortality . Poorer strength for knee flexion ( P trend = .042 ) and hip extension ( P trend = .029 ) were associated with higher cardiovascular mortality . Compared with those in the fourth ( best ) baseline knee flexion quartile , hazard ratios for all-cause and cardiovascular disease mortality among men in the first ( poorest ) knee flexion quartile were 2.23 ( 95 % confidence interval [ CI ] , 1.02 - 4.87 ; P = .045 ) and 4.20 ( 95 % CI , 1.12 - 15.79 ; P = .044 ) , respectively . No significant associations of leg strength and all-cause mortality were identified among women . CONCLUSIONS Poorer leg strength is associated with increased mortality in men , but not women , with PAD . Future study is needed to determine whether interventions that increase leg strength improve survival in men with PAD BACKGROUND Patients with peripheral arterial disease ( PAD ) are at an increased risk of cardiovascular mortality and morbidity and thus are an excellent group in whom to evaluate the feasibility and the effect of an aggressive multifactorial intervention on atherosclerotic vascular disease risk factors . The Arterial Disease Multiple Intervention Trial ( ADMIT ) was design ed to determine the efficacy , safety , and compliance of an multifactorial therapy on selected atherosclerotic disease risk factors in patients with PAD . METHODS By a 2 x 2 x 2 factorial design , eligible participants ( N = 468 ) were r and omly assigned to low-dose warfarin , antioxidant vitamins , and niacin or its corresponding placebo , and followed up for 1 year . All participants were encouraged to use aspirin . Pravastatin was added to the drug regimen for those who needed to reduce LDL cholesterol to recommended levels . RESULTS Niacin increased HDL cholesterol levels by 30 % , with the majority of effect achieved at a dosage of 500 mg twice daily . Warfarin had an anticoagulant effect . The antioxidant vitamins result ed in a significant increase in vitamin E , C , and beta-carotene plasma levels . Overall , compliance was high and few adverse effects were reported . CONCLUSIONS ADMIT demonstrates that it is both feasible and safe to modify multiple atherosclerotic disease risk factors effectively with intensive combination therapy in patients with PAD 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 PURPOSE The purpose was to investigate in a large , r and omized , double-blinded , placebo-controlled trial , whether antibiotic treatment can prevent progression of peripheral arterial disease ( PAD ) . MATERIAL AND METHODS Five hundred and seven patients were included ; all patients had an established diagnosis of PAD . Their mean age was 66 years ( 36 - 85 ) , and 59 % were males . Patients were r and omized to Roxithromycin 300 mg daily for 28 days .  Baseline investigations were ankle blood pressure , ankle-brachial blood pressure index ( ABPI ) , walking distance , C. pneumoniae serology , cholesterol and medical history . Follow-up was performed every 6 months . Primary events were defined as death , peripheral revascularization and major lower limb amputation . Secondary events were thrombosis , stroke , transient cerebral ischaemic attack and myocardial infa rct ion . Change in ABPI was also investigated . Data were analyzed mainly by Cox regression and linear regression . RESULTS Included patients with PAD were r and omized . Two patients withdrew . Of the remaining , 248 received roxithromycin  and 257  placebo . In the treatment group 55 % were seropositive and 53 % in the placebo group . Mean follow-up was 2.1 years ( range 0.06 - 5.1 years ) . In the placebo group , 26 died and 80 primary events occurred in total . In the treatment group , 28 died and 74 primary events were observed . The hazard ratio of death was 1.13 ( 95 % CI : 0.68 ; 1.90 ) , and of primary events 0.92 ( 95 % CI : 0.67 ; 1.26 ) . Also on secondary events and ABPI changes , no significant differences were found . CONCLUSION Long-term treatment with roxithromycin is ineffective in preventing death , amputation , peripheral revascularization , myocardial infa rct ion , stroke , transient cerebral ischaemic attack , thrombosis and decline in ABPI in patients with an established diagnosis of PAD BACKGROUND The prevalence and clinical significance of orthostatic hypertension  ( OHT ) remain largely undetermined in hypertensive patients . This study investigated the association of OHT and  orthostatic hypotension ( OH )  with cardiovascular disease ( CVD ) and target organ damage ( TOD ) in hypertensive patients . METHODS A cross-sectional study was conducted in 4,711 hypertensives and 826 normotensives , aged 40 - 75 years . OHT was defined as an increase in systolic blood pressure ( SBP ) of > or = 20 mm Hg , and OH was defined as either a reduction in SBP of at least 20 mm Hg or a reduction in diastolic BP ( DBP ) of at least 10 mm Hg during the first 3 min after st and ing . RESULTS Hypertension was only independently associated with a risk of OHT . After controlling for age , sex , and other confounders , OH was associated with peripheral artery disease ( PAD ) ( odds ratio ( OR ) 1.49 , 95 % confidence interval ( CI ) 1.15 - 1.89 , P < 0.01 ) , left ventricular hypertrophy ( LVH ) ( OR 1.48 , 95 % CI 1.12 - 1.93 , P < 0.001 ) , coronary artery disease ( CAD ) ( OR 1.71 , 95 % CI 1.12 - 2.61 , P < 0.01 ) , and stroke ( OR 1.72 , 95 % CI 1.19 - 2.34 , P < 0.01 ) , but OHT was only associated with PAD ( OR 1.36 , 95 % CI 1.05 - 1.81 , P < 0.05 ) and stroke ( OR 1.76 , 95 % CI 1.27 - 2.26 , P < 0.01 ) . The adjusted OR for PAD , predicted by the quintiles of the orthostatic SBP changes , showed a J-shaped relationship in untreated hypertensive patients , as was also the case for LVH in hypertensive women . CONCLUSIONS OH is associated with CV risk ; the associations of OHT with TOD and stroke in hypertensive patients still need to be confirmed in prospect i ve studies BACKGROUND Simplified contrast-enhanced ultrasound ( CEUS ) can be used to evaluate muscle perfusion in peripheral arterial disease ( PAD ) . Here , we report its diagnostic accuracy for detecting symptomatic PAD . Additionally , we hypothesize that the extent of collateral formation is reflected by CEUS . METHODS Ultrasound contrast agent was injected into an antecubital vein of 58 control subjects and 52 symptomatic PAD patients and its appearance in the calf muscle was evaluated . Interreader variability was tested using 118 raw data films . Arterial collateralization of PAD patients was assessed by angiographic imaging . RESULTS PAD patients showed a significantly longer median time to peak intensity ( TTP , 36.9s ) than control subjects ( 19.4s , p<0.001 ) with longer TTPs in advanced PAD stages . The area under the receiver operating characteristic curve was 0.942 and the mean TTP difference between two blinded readers was 0.28s . A TTP cut off at 30.5s was associated with 91 % positive predictive value . PAD patients with good collateralization showed a significantly shorter TTP ( 34.1s ) than patients with poor collateralization ( 44.0 s , p=0.008 ) but not a higher ankle-brachial index ( ABI ) . CONCLUSIONS CEUS accurately displays perfusion deficits of the calf muscle in symptomatic PAD patients . The degree of arterial collateralization is reflected by CEUS and not by ABI OBJECTIVES Among persons with lower extremity peripheral artery disease ( PAD ) , we determined whether objective measures of walking performance predict mortality independently of the ankle brachial index ( ABI ) . BACKGROUND The ability of office-based functional performance measures to predict mortality in patients with PAD is unknown . METHODS Participants were 444 persons with PAD followed prospect ively for 4.8 years . The 6-min walk and 4-m walks at usual and fastest pace were measured at baseline . Cox proportional hazard models were used to assess relations between baseline measures of lower extremity performance with mortality , adjusting for confounders . RESULTS One hundred twenty-seven patients ( 28.6 % ) died during follow-up . Adjusting for age , gender , race , comorbidities , ABI , and other confounders , participants in the poorest baseline quartile of 6-min walk performance had significantly increased total mortality ( hazard ratio [ HR ] 2.36 [ 95 % confidence interval ( CI ) 1.33 to 4.18 ] ) and cardiovascular mortality ( HR 5.59 [ 95 % CI 1.97 to 15.9 ] ) compared with the best quartile of baseline performance . Participants in the poorest baseline quartile of normal-paced 4-m walking speed had significantly increased total mortality ( HR 1.86 [ 95 % CI 1.06 to 3.29 ] ) and cardiovascular mortality ( HR 2.55 [ 95 % CI 1.01 to 6.46 ] ) compared with the best quartile of baseline performance . CONCLUSIONS This study demonstrates for the first time that performance-based measures , which can be administered in an office setting , provide prognostic information regarding mortality in persons with PAD beyond that provided by the ABI OBJECTIVE Data sets regarding patients with abdominal aortic aneurysm ( AAA ) have almost universally been restricted to single geographic regions . We aim ed to obtain data on the risk factor profile and cardiovascular ( CV ) co-morbidity among multi-ethnic patients with known AAA in the global REACH ( REduction of Atherothrombosis for Continued Health ) Registry . METHODS The REACH Registry is an international , prospect i ve , observational out-patient registry enrolling out- patients > /=45 years of age with established coronary artery disease ( CAD ) , cerebrovascular disease ( CVD ) or peripheral arterial disease ( PAD ) or with at least three atherothrombotic risk factors . This report includes observations pertaining to 68,236 out- patients enrolled in 44 countries . MAIN OUTCOME MEASURES Gender , ethnic origin , CV risk factors , established atherosclerotic disease ( CAD , CVD and PAD ) at baseline , and CV outcome events at 1-year were compared in patients with and without AAA . RESULTS An AAA was reported in 1722 ( 2.5 % ) of 68,236 out- patients enrolled in the REACH Registry . Older age ( 73 + /- 8 vs 68 + /- 10 , P < .0001 ) , male gender ( 81 % vs 63 % , P < .0001 ) , White ethnicity ( 79 % vs 67 % , P < .0001 ) and a history of smoking ( 81 % vs 55 % , P < .0001 ) were independently related to the diagnosis of AAA . There was a weaker association with hypertension or hypercholesterolemia , and an inverse relation with diabetes . Fatal and non-fatal coronary and cerebrovascular event rates were not different between the AAA and non-AAA cohorts , but individuals with AAA suffered increased rates of other cardiovascular deaths ( 1.39 % vs 0.94 % , P = .0135 ) , hospitalizations for atherothrombotic events ( 14.1 % vs 9.3 % , P < .0001 ) due to increased rates of revascularization procedures , and new or worsening PAD ( 3.7 % vs 1.3 % , P < .0001 ) at 1-year follow-up . CONCLUSION This study , the largest published to date , presents the CV risk profile and outcome of patients with an established diagnosis of AAA from a cohort of patients with either overt manifestations of CV disease or multiple risk factors , and further defines these patients in a multi-ethnic , global context 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 The " obesity paradox " is defined as an inverse association of good health , survival and obesity . Usually in healthy persons the more obese you are the more metabolic complications you have ; however , thin patients with chronic obstructive pulmonary disease ( COPD ) have more cardiovascular complications and a higher mortality rate . OBJECTIVES To explore whether atherosclerosis and peripheral artery disease ( PAD ) contribute to the higher morbidity and mortality of patients with COPD . METHODS This prospect i ve study included 87 patients with chronic COPD who were treated in the pulmonary outpatient clinic ; all signed a consent form before enrollment . We documented their  lung function ( FEV1 % ) , body mass index ( BMI ) and ankle brachial index ( ABI ) . The primary endpoints were to find an association between atherosclerosis and BMI in patients with COPD , and between atherosclerosis and severity of lung disease . RESULTS Average ABI was 1.01 + /- 0.20 , BMI was 29.33 + /- 7.48 kg/m2 , and the abdominal circumference was 107.34 + /- 18.87 cm . A positive correlation was found between BMI and ABI ( P=0.001 ) and between abdominal circumference and ABI ( P=0.000 ) . Patients with peripheral artery disease were older ( 73.6 + /- 11.5 vs. 68.1 + /- 11.6 years old , P= 0.04 ) , were thinner ( average BMI 25.5 + /- 6.2 vs. 31.06 + /- 7.3 , P= 0.001 ) , and had a lower abdominal circumference ( 97.7 + /- 18.3 vs. 111.7 + /- 17.5 cm , P=0.001 ) . No such difference was observed for years of smoking . Male PAD patients with COPD had a lower BMI ( 25.2 + /- 5.6 vs. 29.9 + /- 7.4 , P = 0.016 ) , and their abdominal circumference was smaller ( 96.1 + /- 18.0 vs. 110.2 + /- 16.5 cm , P=0.004 ) . Female PAD patients with COPD had a lower BMI ( 26.3 + /- 8.2 vs. 33.1 + /- 7.0 , P=0.045 ) , but their abdominal circumference was not different from females without PAD ( 102.0 + /- 19.7 vs. 114.0 + /- 19.4 cm , P=0.162 ) . Patients with PAD had a worse lung disease ( FEV1 % 34 + /- 8 % vs. 45 + /- 16 % , P=0.01 ) . During the 1 year of follow-up five patients died : two PAD patients due to acute myocardial infa rct ion and three non-PAD patients died from pulmonary insufficiency ( two patients ) and pulmonary emboli ( one patient ) . DISCUSSION We found that COPD patients with PAD were older and thinner and had a lower abdominal circumference and a more progressive lung disease . Extensive atherosclerosis in patients with COPD may partly explain the " obesity paradox " observed in patients with COPD The extent and clinical significance of stem and progenitor cell ( SPC ) increases in response to lower-extremity ischemia in people with peripheral artery disease ( PAD ) are unclear . We compared changes in SPC levels immediately following a treadmill exercise test between individuals with and without PAD . Among participants with PAD , we determined whether more severe PAD was associated with greater increases in SPCs following treadmill exercise-induced lower-extremity ischemia . We measured SPC levels in 25 participants with PAD and 20 without PAD  before and immediately after a treadmill exercise test .  Participants with PAD , compared to participants without PAD , had greater increases in CD34+CD45dim ( + 0.08±0.03 vs −0.06±0.04 , p=0.008 ) , CD34+CD45dimCD133 + ( + 0.08±0.05 vs −0.08±0.04 , p=0.014 ) , CD34+CD45dimCD31 + ( + 0.10±0.03 vs −0.07±0.04 , p=0.002 ) , and CD34+CD45dimALDH+ SPCs ( + 0.18±0.07 vs −0.05±0.08 , p=0.054 ) measured as a percentage of all white blood cells . Among participants with PAD , those with any increases in the percent of SPCs immediately after the treadmill exercise test compared to those with no change or a decrease in SPCs had lower baseline ankle – brachial index values ( 0.65±0.17 vs 0.90±0.19 , p=0.004 ) and shorter treadmill times to onset of ischemic leg symptoms ( 2.17±1.54 vs 5.25±3.72 minutes , p=0.012 ) . In conclusion , treadmill exercise-induced lower-extremity ischemia is associated with acute increases in circulating SPCs among people with PAD . More severe PAD is associated with a higher prevalence of SPC increases in response to lower-extremity ischemia . Further prospect i ve study is needed to establish the prognostic significance of ischemia-related increases in SPCs among patients with PAD AIM Peripheral arterial disease ( PAD ) , particularly critical limb ischemia ( CLI ) , is a severe cause of amputation and mortality . More than 50 % of diabetic patients with CLI die within four to five years . The development of novel stem cell therapies may bring new hope to these patients . We aim ed to assess the efficacy of autologous bone marrow cell therapy for treating CLI using a meta- analysis . METHODS We search ed the literature in PubMed , the Cochrane Central Registry of Controlled Trials , the Elsevier data base and EBSCO for trials of autologous cell therapy in patients with severe PAD published before October 30 , 2013 . We chose objective clinical endpoints to assess the efficacy of therapy in the meta- analysis , including changes in the ankle-brachial index ( ABI ) , transcutaneous oxygen tension ( TcO2 ) , pain scale ( 0 - 10 scale ) and amputation-free survival ( AFS ) . RESULTS Thirty-one articles reporting clinical trials involving a total of 1,214 patients treated with bone marrow stem cell-based therapy  were collected for the meta- analysis , in which the r and omized controlled trials ( RCTs ) and other trials ( non- RCTs ) were classified into two groups . Regarding the efficacy  of stem cell therapy  , the ABI showed significant increases ( P＜0.05 ) at 12 , 24 and 48 weeks after therapy in the non- RCT and RCT groups , but not after four to eight weeks in the non- RCT group . The TcO2 values also increased in the RCT group at four to eight weeks after therapy and 24 weeks after therapy ( P＜0.001 ) and in the non- RCT group at four to eight weeks after therapy ( P= 0.01 ) , although no significant increases were observed in the RCT group at 12 weeks after therapy or the non- RCT group at 24 weeks after therapy . Meanwhile , pain was significantly reduced ( P＜0.05 ) at four to eight weeks and 24 weeks after therapy in both the non- RCT and RCT groups , but not at four to eight weeks or 12 weeks after therapy in the RCT group . In addition , the long-term clinical trials demonstrated that the AFS rate improved after therapy with bone marrow stem cells ( one-year AFS , P＜0.00001 ; three-year AFS , P=0.0003 ) . CONCLUSIONS The present results suggest that autologous bone marrow stem cells have an advantageous therapy effect in PAD patients who are not eligible for revascularization Background / Aims : Recent data have addressed the issue of higher levels of homocysteine ( Hcy ) and endothelin-1 ( ET-1 ) in end-stage renal disease ( ESRD ) that may be considered an independent predictor for cardiovascular disease . The prevalence of peripheral arterial disease ( PAD ) in patients with ESRD has been reported to be relevant , highlighting its clinical importance . We aim ed to explore the therapeutic role of propionyl-L-carnitine ( PLC ) in hemodialysis patients with PAD by measuring ankle/brachial index ( ABI ) , ET-1 and Hcy . Design : R and omized , double-blind , placebo-controlled trial . Methods : Sixty-four patients on hemodialysis with chronic renal insufficiency and PAD were assigned to receive either intravenous PLC ( 600 mg ) or placebo 3 times weekly for 12 months . The ABI and plasma levels of ET-1 and Hcy were measured at baseline , 6 and 12 months . Results : In the PLC-treated group , progressive increases in ABI were observed , while in the placebo group the reverse trend was seen . Highly significant and progressive reductions in plasma levels of ET-1 and Hcy , compared to baseline , were also seen in the PLC-treated group . Conclusions : Hemodynamic flow , endothelial profile and Hcy levels were ameliorated by the administration of PLC in hemodialysis patients with ESRD and PAD Beneficial effects of aggressive lipid-lowering with high-dose atorvastatin ( 80 mg/day ) have been demonstrated in patients with coronary and cerebrovascular disease . The impact of such a therapy in patients with peripheral arterial disease ( PAD ) is less known so far . Here we studied the effects of high-dose atorvastatin on brachial artery endothelial function , common carotid intima-media thickness ( IMT ) and local progression of PAD in these patients . One hundred of 500 patients screened with documented PAD were r and omly assigned to receive 80 mg of atorvastatin daily for six months or to continue on conventional medical treatment .  Ninety-six percent of patients in the control group were on st and ard statin treatment . High resolution B-mode ultrasonography was used to study brachial artery flow-mediated dilation ( FMD ) , IMT and ankle-brachial index ( ABI ) at baseline and at six months . FMD and IMT at baseline and at six months were 4.1 ( 0.06 - 8.6 ) versus 5.0 ( 0.76 vs. 8.1 ) % , p = 0.96 , and 0.76 ( 0.66 - 0.82 ) versus 0.73 ( 0.63 - 0.81 ) mm , p = 0.41 , respectively , in the atorvastatin group , and 2.66 ( -1.9 - 6.9 ) versus 3.65 (0.0 - 8.6)% , p = 0.02 , and 0.78 ( 0.71 - 0.90 ) versus 0.77 ( 0.70 - 0.90 ) mm , p = 0.48 , in the control group . ABI at baseline and at six months was not different in either group . LDL cholesterol was reduced from 2.53 ( 2.21 - 3.28 ) to 1.86 ( 1.38 - 2.29 ) mM ( p < 0.0001 ) in the atorvastatin group , whereas levels remained stable in the control group [ 2.38 ( 1.94 - 3.16 ) vs. 2.33 ( 1.82 - 2.84 ) mM , p = 0.61 ] . Major adverse cardiovascular events occurred in 2.1 % in the atorvastatin group and 1.9 % in the control group ( p = 0.61 ) . In conclusion , in this pilot trial aggressive lipid-lowering with 80 mg of atorvastatin daily for six months had no effect on brachial artery FMD in patients with PAD . IMT and ABI were also similar in patients with and without high-dose atorvastatin at six months 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 Objectives : Cilostazol improves walking in patients with peripheral arterial disease ( PAD ) . We hypothesized that cilostazol reduces diabetic complications in PAD patients . Methods : Diabetic PAD patients were prospect ively recruited to a r and omized double-blinded , placebo-controlled trial , using cilostazol 100 mg twice a day . Clinical assessment included ankle-brachial index , arterial compliance , peripheral transcutaneous oxygenation , treadmill walking distance and vali date d quality of life ( QoL ) question naires . Biochemical analyses included glucose and lipid profiles . All tests were at baseline , 6 , and 24 weeks . Results : 26 diabetic PAD patients ( 20 men ) were recruited .  Cilostazol improved absolute walking distance at 6 and 24 weeks ( 86.4 % vs. 14.1 % , P = .049 ; 143 % vs. 23.2 % , P = .086 ) . Arterial compliance and lipid profiles improved as did some QoL indices for cilostazol at 6 and 24 weeks . Blood indices were similar at baseline and at follow-up points for both treatment groups . Conclusions : Cilostazol is a well-tolerated and efficacious treatment , which improves claudication distances in diabetic PAD patients with further benefits in arterial compliance , lipid profiles , and BACKGROUND Patients with lower extremity peripheral artery disease ( PAD ) are at increased risk of major adverse cardiovascular events ( MACE ) and major adverse limb events ( MALE ) . There is limited information on the prognosis of patients who experience MALE . OBJECTIVES Among participants with lower extremity PAD , this study investigated : 1 ) if hospitalizations , MACE , amputations , and deaths are higher after the first episode of MALE compared with patients with PAD who do not experience MALE ; and 2 ) the impact of treatment with low-dose rivaroxaban and aspirin compared with aspirin alone on the incidence of MALE , peripheral vascular interventions , and all peripheral vascular outcomes over a median follow-up of 21 months . METHODS We analyzed outcomes in 6,391 patients with lower extremity PAD who were enrolled in the COMPASS ( Cardiovascular Outcomes for People Using Anticoagulation Strategies ) trial . COMPASS was a r and omized , double-blind placebo-controlled study of low-dose rivaroxaban and aspirin combination or rivaroxaban alone compared with aspirin alone . MALE was defined as severe limb ischemia leading to an intervention or major vascular amputation . RESULTS A total of 128 patients experienced an incident of MALE . After MALE , the 1-year cumulative risk of a subsequent hospitalization was 61.5 % ; for vascular amputations , it was 20.5 % ; for death , it was 8.3 % ; and for MACE , it was 3.7 % . The MALE index event significantly increased the risk of experiencing subsequent hospitalizations ( hazard ratio [ HR ] : 7.21 ; p < 0.0001 ) , subsequent amputations ( HR : 197.5 ; p < 0.0001 ) , and death ( HR : 3.23 ; p < 0.001 ) . Compared with aspirin alone , the combination of rivaroxaban 2.5 mg twice daily and aspirin lowered the incidence of MALE by 43 % ( p = 0.01 ) , total vascular amputations by 58 % ( p = 0.01 ) , peripheral vascular interventions by 24 % ( p = 0.03 ) , and all peripheral vascular outcomes by 24 % ( p = 0.02 ) . CONCLUSIONS Among individuals with lower extremity PAD , the development of MALE is associated with a poor prognosis , making prevention of this condition of utmost importance . The combination of rivaroxaban 2.5 mg twice daily and aspirin significantly lowered the incidence of MALE and the related complications , and this combination should be considered as an important therapy for patients with PAD . ( Cardiovascular Outcomes for People Using Anticoagulation Strategies [ COMPASS ] ; NCT01776424 ) With regard to oral contraceptives , much research has concentrated on venous thrombosis and on the coronary and cerebral forms of atherosclerotic disease , while peripheral arterial disease ( PAD ) has received little attention . In this case-control study , we assessed oral contraceptive use and the risk of PAD in young women using a population -based case-control study . The women were 18 - 49 years of age , and had been admitted to a collaborating hospital between January 1990 and October 1995 , and had a diagnosis of PAD . Participants were patients with PAD ( n = 152 ) , and control women ( n = 925 ) , identified by r and om digit dialing . The diagnosis of PAD was based almost exclusively on intra-arterial angiography . Patients and control subjects filled out the same structured question naire , which included questions on  medical history , cardiovascular risk factors , and contraceptive use .  The adjusted odds ratio for PAD in women using any type of oral contraceptives vs. no use , was 3.8 ( 95 % CI 2.4 - 5.8 ) . When first generation oral contraceptive use was compared with no use , the odds ratio was 8.7 ( 95 % CI 3.6 - 21.3 ) . For second and third generation oral contraceptives , the adjusted odds ratios ( compared with non-users ) were 2.6 ( 95 % CI 1.4 - 4.9 ) and 3.0 ( 95 % CI 1.4 - 6.6 ) , respectively . This is the first study on oral contraceptive use and PAD in humans . All types of oral contraceptives were associated with an increased risk of PAD Background —Endothelial dysfunction plays a key role in atherogenesis . We prospect ively investigated the impact of noninvasive measurement of endothelial function on cardiovascular risk in peripheral arterial disease ( PAD ) . The study was specially aim ed at assessing whether brachial artery flow-mediated dilation ( FMD ) added to the predictive value of  ankle-brachial pressure index  ( ABPI ) . Methods and Results —Of 131 patients monitored for a mean of 23±10 months , 18 had a coronary event , 12 a cerebrovascular event , and 9 a peripheral event .  The median FMD was lower in patients with an event than in those without ( 5.8 % versus 7.6 % , P < 0.05 ) , whereas vasodilation to nitroglycerin was similar in the two groups . The cardiovascular event rate was higher in patients with FMD below the median versus those with FMD above the median ( P < 0.001 by log-rank test ) . In a Cox proportion hazard model , independent predictors of events were FMD below the median ( P < 0.01 ) , ABPI below the median ( P < 0.01 ) , and previous stroke ( P < 0.02 ) . Similar results were obtained when peripheral events were excluded from the analysis . Below-median ABPI and FMD combined was more accurate in predicting risk ( relative risk [ RR ] 13.0 ; 95 % CI , 3.0 to 56.2 ; P < 0.01 ) than ABPI ( RR , 6.4 ; 95 % CI , 1.4 to 29.1 ; P < 0.02 ) and FMD ( RR , 4.8 ; 95 % CI , 1.1 to 23.3 ; P < 0.05 ) alone . Conclusions —A low brachial artery FMD is an independent predictor of cardiovascular risk in patients with PAD and adds to the prognostic value of ABPI , which is currently the most powerful prognostic indicator in PAD OBJECTIVES To assess the efficacy of whole-body progressive resistance training ( PRT ) as a treatment for the symptoms of peripheral arterial disease ( PAD ) in older adults . DESIGN R and omized controlled pilot trial . SETTING University clinical weight training facility in Sydney , Australia . PARTICIPANTS Twenty-two older adults with symptomatic PAD . INTERVENTIONS The efficacy of supervised whole-body high-intensity PRT ( H-PRT ) with low-intensity nonprogressive resistance training ( L-RT ) and a usual care control group that performed unsupervised walking for 6 months was compared . MEASUREMENTS Pilot outcome measures included 6-minute walk ( 6 MW ) outcomes , body composition , dynamic muscle strength and endurance , and performance-based tests of function . RESULTS Mean age was 71.1 ± 7.2 . Mean ankle brachial index was 0.55 ± 0.13 .  Exercise adherence was similar in all groups ( P = .29 ) . H-PRT ( n = 8) improved total 6MW distance ( mean difference ( MD ) 62.6 ± 58.0 m , P = .02 ) significantly more than L-RT ( n = 7 ; MD=-48.2 ± 67.6 m ) and controls ( n = 7 ; MD=-9.9 ± 52.9 m ) . Change in 6MW onset of claudication was significantly and independently related to change in bilateral calf endurance ( correlation coefficient ( r ) = 0.65 , P = .03 ) , and change in 6MW distance was significantly and independently related to change in bilateral hip extensor endurance ( r = 0.71 , P = .02 ) in all groups . CONCLUSION H-PRT  significantly improved 6MW ability in older adults with intermittent claudication from PAD , whereas L-RT and unsupervised walking did not . Improvement in walking ability was significantly related to improvements in bilateral calf and hip extensor endurance , supporting further investigations targeted at musculoskeletal impairment in this cohort OBJECTIVE To determine the risk factors for peripheral arterial disease ( PAD ) in a diabetic population and to examine whether different levels of these risk factors might explain why diabetic subjects have an increased risk of PAD compared with normal glucose tolerance subjects . RESEARCH DESIGN AND METHODS There were 1,592 men and women aged 55 - 74 years selected at r and om from the age-sex registers of 11 general practice s in Edinburgh , Scotl and . Subjects underwent a comprehensive medical examination , including assessment for PAD  ( intermittent claudication on World Health Organization question naire or major asymptomatic disease on noninvasive testing ) and a glucose tolerance test . RESULTS Of the subjects , 288 ( 18.7 % ) were found to have diabetes or impaired glucose tolerance ( IGT ) . The prevalence of PAD was greater in those with diabetes/IGT ( 20.6 % ) compared with those with normal glucose tolerance ( 12.5 % ) ( odds ratio [ OR ] 1.64 , 95 % CI 1.17 - 2.31 ) . Among the diabetes/IGT group , mean levels of smoking , systolic blood pressure , and triglycerides were higher in subjects with PAD than in those without PAD ( P < or = 0.05 ) . Mean levels of systolic blood pressure and plasma triglycerides were also higher in diabetic subjects than in nondiabetic subjects with PAD ( P < or = 0.05 ) . In multivariate analysis , those with diabetes/IGT no longer had a significantly higher risk of PAD after adjusting separately for systolic blood pressure ( OR 1.22 , 95 % CI 0.85 - 1.73 ) and plasma triglycerides ( OR 1.26 , 95 % CI 0.89 - 1.79 ) . Simultaneous adjustment for both systolic blood pressure and triglycerides reduced the risk of PAD among diabetic subjects to 1.11 ( 95 % CI 0.78 - 1.58 ) . CONCLUSIONS Increased mean levels of triglycerides and systolic blood pressure may help to explain the higher prevalence of PAD in diabetic subjects compared with that in normal glucose tolerance subjects Objective We explored the efficacy of intravenous therapy with propionyl L-carnitine in patients with both peripheral arterial disease ( PAD ) and chronic renal insufficiency requiring haemodialysis . Methods The trial was a r and omised , double-blind , placebo-controlled trial . Sixty-four patients on haemodialysis ( 32 per treatment arm ) with chronic renal insufficiency and PAD were assigned to receive either intravenous propionyl L-carnitine 600 mg or placebo 3 times weekly for 12 months . The main outcome measures were the ankle/brachial index ( ABI ) , plasma malondialdehyde ( MDA ) and 4-hydroxynonenal ( 4-HNE ) concentrations , and the plasma nitrite/nitrate ratio ( NO2/NO3 ) ; these were measured at baseline and at 6 and 12 months . Results Significant increases in ABI were observed in the propionyl L-carnitine group , whereas in the placebo group the reverse trend was seen . In patients treated with propionyl L-carnitine , significant progressive decreases were seen in plasma MDA , 4-HNE and the NO2/NO3 ratio from baseline . In the placebo-treated group , only weakly significant or no differences were seen . Conclusion Intravenous administration of propionyl L-carnitine to haemodialysis patients with PAD improves both haemodynamic flow and the oxidative profile ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle – brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute C and esartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease : Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A R and omized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Sc and inavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Sc and inavian Cardiac Outcomes Trial — Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : C And esartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease — EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy C and esartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease  EXPLOR : Amlodipine – Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine – Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infa rct ion in 52 Countries INVEST : INternational VErapamil SR/T Tr and olapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention : an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : r and omized controlled trials RF : risk factor ROADMAP : R and omized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker C and esartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly : Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan R and omised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospect i ve Diabetes Study VADT : Veterans ' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization # # # 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension ( ESH ) and the European Society of Cardiology BACKGROUND In this prospect i ve study we evaluated the relationship between thromboxane B2 ( TXB2 ) , prostacyclin ( PGI2 ) and lactate concentrations , and the improvement of walking abilities and endothelial function in patients with peripheral artery disease ( PAD ) undergoing a supervised treadmill training program ( STTP ) .  METHODS A total of fifty-nine patients with stable intermittent claudication were included into a 12-week long STTP .  Changes in blood pressure , biochemical parameters , ankle/brachial index ( ABI ) , flow-mediated dilatation ( FMD ) , maximal walking time ( MWT ) and pain-free walking time ( PFWT ) were assessed before and after STTP . Additional baseline and post-STTP measurements were taken for blood lactate , and TXB2 and PGI2 urinary derivatives before and after maximal exercise ( ME ) . RESULTS The MWT improved significantly after STTP by 91 % ( p<0.0001 ) and PFWT by 97 % ( p<0.0001 ) . Also , ABI values improved significantly after STTP in all patient groups and was more pronounced in those with longer MWT at baseline . FMD values increased by 45 % ( p<0.0001 ) after STTP . Urinary 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-PGF1α concentration tend to decrease after STTP and their ratio remained unchanged . Lactate levels did not change after the treadmill training program . Hs-CRP and fibrinogen concentration decreased significantly after STTP only in patients with longer MWT at baseline-fourth quartile . CONCLUSIONS STTP in patients with PAD showed significantly improved walking abilities and endothelial function . Lactate production , TXB2 release , and PGI2 release are not directly correlated with improvement of endothelial function and walking abilities . Patients with better-walking abilities at baseline derive greater clinical and metabolic benefits from STTP BACKGROUND Serum C-reactive protein ( CRP ) has proven to be an independent marker of the extent of atherosclerosis in patients with coronary , cerebrovascular , and peripheral arterial disease . In this prospect i ve observational study , we wanted to assess the relationship between serum CRP and extent of disease transversely and longitudinally in time , as well as future cardiovascular complications in patients with peripheral arterial disease ( PAD ) . Hypothesizing that CRP not only is a marker of but also actively participates in atherogenesis , we explored the possibility of CRP production by femoral atherosclerotic plaques . METHODS  Serum CRP  was measured as highly sensitive ( hsCRP ) in 387 patients with PAD attending the vascular clinic of a university and 2 affiliated teaching hospitals .  Serum hsCRP  was related to the ankle-brachial pressure index ( ABPI ) as an indication of severity of disease at inclusion and at 12 months ' follow-up and to future events ( death and coronary , cerebral , and peripheral arterial events ) . In femoral plaques , the production of CRP was analyzed with reverse transcription-polymerase chain reaction , and CRP plaque localization was assessed with immunostaining on serial tissue sections with antibodies toward CRP , smooth muscle cells , T cells , and macrophages . RESULTS The hsCRP ( average + /- SD ) was 3.26 + /- 2.41 mg/L. Serum hsCRP showed a correlation with baseline and 12-month follow-up ABPI ( Spearman rank correlation ; P < .05 for both correlations ) . When the patients were divided into three equally sized groups according to baseline serum hsCRP , the ABPI at baseline and at 12 months decreased significantly from the low- to the high-hsCRP group ( baseline ABPI : 0.70 , 0.65 , and 0.57 , P < .01 ; 12-month follow-up ABPI : 0.78 , 0.70 , and 0.65 , P < .01 ) . These associations persisted after correction for conventional risk factors . Furthermore , serum hsCRP was related to the combined end point " death and /or any cardiovascular event " ( log-rank test ; P = .04 ) during a median 24-month follow-up period . Reverse transcription-polymerase chain reaction analysis showed CRP production in 4 of 14 femoral plaques . CRP was detected in all femoral plaques , but not in healthy brachial arteries . Immunoreactivity for CRP was observed in smooth muscle cells , macrophages , and T cells . CONCLUSIONS Serum hsCRP was related to the severity of PAD , showing a relation to future hemodynamic function and cardiovascular events in PAD patients . In addition to coronary plaques , aneurysmal aortas , and failed venous coronary bypasses , femoral plaques also produce CRP , thus illustrating that the production of CRP may represent a universal response to vascular injury and suggesting that vascular CRP may contribute to plaque development OBJECTIVE To examine whether 3 months of lipoic acid ( LA ) supplementation improved walking tolerance and delayed claudication pain onset in peripheral arterial disease ( PAD ) . DESIGN R and omized , double-blind , controlled study . SETTING General Clinical Research Center . SUBJECTS Twenty-eight ( 28 ) participants ( 15 men , 13 women ) with PAD ( ankle brachial index range 0.9 - 0.4 , mean age 73.2 + /- 1.6 years ) . INTERVENTION LA ( 600 mg/day ) or placebo for 3 months . OUTCOME MEASURES Walking tolerance was assessed by 6-minute walk test distance , 4-meter walk time , initial claudication pain time ( ICT ) and distance ( ICD ) , and peak claudication pain . Serum was assessed for inflammation ( C-reactive protein [ CRP ] ) and oxidative stress ( lipid hydroperoxides ) as potential mechanisms for changes in walking tolerance . RESULTS ICT increased 34.4 % and 15 % , ICD was reduced by 40.5 % and 18 % , and peak claudication pain ratings were reduced by 93 % and 7 % in LA and placebo groups , respectively . Although the improvements in peak pain and ICT achieved significance within the LA group ( both p<0.05 ) , the interactions of group by time were not found to be significant ( p>0.05 ) . Oxidative stress and CRP measures were not different between groups by month 3 ( p>0.05 ) . There were no serious side-effects associated with the LA . CONCLUSIONS LA may confer pain relief during exercise . However , longer and larger trials are warranted to determine long-term effects of LA alone or combined with other interventions on PAD symptoms BACKGROUND Patients with peripheral arterial disease ( PAD ) have high rates of cardiovascular morbidity and mortality , including that caused by associated coronary heart disease and cerebrovascular disease . Previous studies have shown that coagulation parameters are altered in PAD and that altered coagulation may play a critical role in the susceptibility to cardiovascular complications in PAD . It is therefore important to assess the effect of secondary prevention measures on coagulation in patients with PAD . The Arterial Disease Multiple Intervention Trial ( ADMIT ) , a multicenter , r and omized , placebo-controlled trial , was conducted to determine the feasibility of a combined lipid-modifying , antioxidant , and antithrombotic treatment regimen in patients with PAD . The objective of this study was to assess the effect of the ADMIT interventions on coagulation . METHODS ADMIT participants were r and omly assigned to low-dose warfarin , niacin , and antioxidant vitamin cocktail or corresponding placebos in a 2 x 2 x 2 factorial design . Specialized coagulation studies were performed in a subset of 80 ADMIT participants at baseline and after 12 months of treatment . RESULTS Low-dose warfarin ( 1 to 4 mg/d ) result ed in a significant decrease in factor VIIc ( P < .001 ) and in plasma F1.2 ( P = .001 ) . Unexpectedly , niacin treatment also result ed in significant decrease in both fibrinogen ( 48 mg/dL ; P < .001 ) and F1.2 ( P = .04 ) . von Willebr and factor increased after antioxidant vitamin treatment ( P = .04 ) . CONCLUSIONS A regimen of low-dose warfarin effectively modifies coagulation in patients with PAD . Niacin also favorably modifies fibrinogen and plasma F1.2 . Niacin , in addition to its lipid effects , modifies abnormal coagulation factors that accompany PAD Tertatolol is a noncardioselective beta-blocker without intrinsic sympathomimetic activity . In a preliminary 3-month open study , it was shown that T was devoid of any atherogenic effect since HDL-cholesterol ( HDL-C ) and apoprotein levels did not change for 3 months of therapy . To investigate the long-term effects of tertatolol on the lipid profile and its safety in hypertensive patients with peripheral arterial disease ( PAD ) , a 9-month , r and omized , double-blind , parallel group study was carried out in 40 patients .  Tertatolol 5 mg once daily was compared with metoprolol 200 mg once daily . If BP was not controlled after 2 months , a vasodilatator agent , dihydralazine , was added at the lowest dose required to control BP ( diastolic BP < 90 mm Hg ) . Lipoprotein fractions and apoproteins were assayed before ( M0 ) and after 2 , 6 and 9 months of therapy . At the same occasions , peripheral arterial disease ( PAD ) was evaluated on exercise tests carried out on a treadmill and on the regional blood flow measured in the ankle arteries by the Doppler technique . Four patients were not eligible for analysis . In the tertatolol group , 1 patient with a normal BP , and 2 patients who dropped out , 1 because of persistent nausea and 1 because of personal reasons . In the metoprolol group , 1 patient refused to take dihydralazine . In the 35 fully documented patients , BP control was achieved in both groups . The mean reductions in supine systolic/diastolic BP were 31.4/14.6 and 34.7/17.1 mm Hg in the tertatolol and metoprolol groups , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS 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 The relationship between reproductive health disorders and lifestyle factors in middle-aged and older men is not clear . The aim of this study is to describe lifestyle and biomedical associations as possible causes of erectile dysfunction ( ED ) , prostate disease ( PD ) , lower urinary tract symptoms ( LUTS ) and perceived symptoms of and rogen deficiency ( pAD ) in a representative population of middle-aged and older men , using the Men in Australia Telephone Survey ( MATeS ) . Methods A representative sample ( n = 5990 ) of men aged 40 + years , stratified by age and State , was contacted  by r and om selection of households , with an individual response rate of 78 % . All men participated in a 20-minute computer-assisted telephone interview exploring general and reproductive health . Associations between male reproductive health disorders and lifestyle and biomedical factors were analysed using multivariate logistic regression ( odds ratio [ 95 % confidence interval ] ) . Variables studied included age , body mass index , waist circumference , smoking , alcohol consumption , physical activity , co-morbid disease and medication use for hypertension , high cholesterol and symptoms of depression . Results Controlling for age and a range of lifestyle and co-morbid exposures , sedentary lifestyle and being underweight was associated with an increased likelihood of ED ( 1.4 [ 1.1 - 1.8 ] ; 2.9 [ 1.5 - 5.8 ] , respectively ) and pAD ( 1.3 [ 1.1 - 1.7 ] ; 2.7 [ 1.4 - 5.0 ] , respectively . Diabetes and cardiovascular disease were both associated with ED , with hypertension strongly associated with LUTS and pAD . Current smoking ( inverse association ) and depressive symptomatology were the only variables independently associated with PD . All reproductive disorders showed consistent associations with depression ( measured either by depressive symptomatology or medication use ) in both age-adjusted and multivariate analyses . Conclusion A range of lifestyle factors , more often associated with chronic disease , were significantly associated with male reproductive health disorders . Education strategies directed to improving general health may also confer benefits to male reproductive health 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 The aim of the present study was to evaluate whether beta blockade presents a risk of intermittent claudication and how it affects the walking capacity and lower limb haemodynamics in patients with intermittent claudication . The study was divided into six parts : A case-control study with 55 pairs , cases with hypertension and intermittent claudication and controls with hypertension only , matched for age , sex , place of residence , and time of examination , all without coronary heart disease , which is a known confounding factor . An open controlled study on the effect of withdrawal of beta blockade on walking capacity of 28 patients with intermittent claudication . A placebo-controlled double-blind crossover study on the effect of antihypertensive treatment on the walking capacity of 14 patients with intermittent claudication . Three placebo-controlled double-blind crossover studies on the effect of propranolol , metoprolol , pindolol , labetalol , and /or methyldopa on calf blood flow in 34 hypertensive subjects without peripheral arterial disease and in altogether 21 patients with intermittent claudication .  Walking capacity was measured on a treadmill . Calf blood flow was measured with strain gauge plethysmography by the venous occlusion technique . The case-control comparison showed that beta blockers were used as often by patients with intermittent claudication as by controls . Walking capacity increased during the first month of the open controlled study irrespective of whether the beta blockade was withdrawn or continued . There was no difference in this respect between the various types of beta blockers . Antihypertensive treatment with metoprolol or methyldopa did not affect walking capacity . Resting calf blood flow was unaffected by propranolol or metoprolol , regardless of the presence or absence of peripheral arterial disease , as well as by pindolol , labetalol , or methyldopa in patients with intermittent claudication . During reactive hyperaemia , propranolol and metoprolol reduced flow in patients without peripheral arterial disease . Propranolol also reduced hyperaemic blood flow in the limb with less or no symptoms in patients with intermittent claudication . None of the active drugs decreased the hyperaemic flow consistently in the limb with the stronger symptoms . In a comparison of haemodynamic effects between the drugs , calf blood flow at rest was higher after pindolol than after propranolol and hyperaemic flow of the better limb was higher after pindolol than after propranolol and labetalol . ( ABSTRACT TRUNCATED AT 400 WORDS
However , lack of data specifically examining outcomes in PAD patients should not detract from the overwhelming evidence on the benefit of treating hypertension and lowering blood pressure
BACKGROUND Peripheral arterial disease ( PAD ) causes considerable morbidity and mortality .
Hypertension is a risk factor for PAD .
Treatment for hypertension must be compatible with the symptoms of PAD .
Controversy regarding the effects of beta-adrenoreceptor blockade for hypertension in patients with PAD has led many physicians to stop prescribing beta-adrenoreceptor blockers .
Little is known about the effects of other classes of anti-hypertensive drugs in the presence of PAD .
This is the second up date of a Cochrane review first published in 2003 .
OBJECTIVES To determine the effects of anti-hypertensive drugs in patients with both raised blood pressure and symptomatic PAD in terms of the rate of cardiovascular events and death , symptoms of claudication and critical leg ischaemia , and progression of atherosclerotic PAD as measured by ankle brachial index ( ABI ) changes and the need for revascularisation ( reconstructive surgery or angioplasty ) or amputation .