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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 ) Background : The PCSK9 ( proprotein convertase subtilisin/kexin type 9 ) inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER trial ( Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk ) . We investigated the efficacy and safety of evolocumab in patients with peripheral artery disease ( PAD ) as well as the effect on major adverse limb events . Methods : FOURIER was a r and omized trial of evolocumab versus placebo  in 27 564 patients with atherosclerotic disease on statin therapy followed for a median of 2.2 years . Patients were identified as having PAD at baseline if they had intermittent claudication and an ankle brachial index of < 0.85 , or if they had a prior peripheral vascular procedure . The primary end point was a composite of cardiovascular death , myocardial infa rct ion , stroke , hospital admission for unstable angina , or coronary revascularization . The key secondary end point was a composite of cardiovascular death , myocardial infa rct ion , or stroke . An additional outcome of interest was major adverse limb events defined as acute limb ischemia , major amputation , or urgent peripheral revascularization for ischemia . Results : Three thous and six hundred forty-two patients ( 13.2 % ) had PAD ( 1505 with no prior myocardial infa rct ion or stroke ) . Evolocumab significantly reduced the primary end point consistently in patients with PAD ( hazard ratio [ HR ] 0.79 ; 95 % confidence interval [ CI ] , 0.66–0.94 ; P=0.0098 ) and without PAD ( HR 0.86 ; 95 % CI , 0.80–0.93 ; P=0.0003 ; Pinteraction=0.40 ) . For the key secondary end point , the HRs were 0.73 ( 0.59–0.91 ; P=0.0040 ) for those with PAD and 0.81 ( 0.73–0.90 ; P<0.0001 ) for those without PAD ( Pinteraction=0.41 ) . Because of their higher risk , patients with PAD had larger absolute risk reductions for the primary end point ( 3.5 % with PAD , 1.6 % without PAD ) and the key secondary end point ( 3.5 % with PAD , 1.4 % without PAD ) . Evolocumab reduced the risk of major adverse limb events in all patients ( HR , 0.58 ; 95 % CI , 0.38–0.88 ; P=0.0093 ) with consistent effects in those with and without known PAD . There was a consistent relationship between lower achieved low-density lipoprotein cholesterol and lower risk of limb events ( P=0.026 for the beta coefficient ) that extended down to < 10 mg/dL. Conclusions : Patients with PAD are at high risk of cardiovascular events , and PCSK9 inhibition with evolocumab significantly reduced that risk with large absolute risk reductions . Moreover , lowering of low-density lipoprotein cholesterol with evolocumab reduced the risk of major adverse limb events . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifier : NCT01764633 Background Peripheral 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 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 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 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 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 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 ) BACKGROUND Sero-epidemiological and experimental studies suggest that Chlamydia pneumoniae infections play an important role in the development of atherosclerosis . Clinical trials have shown contradictory results regarding the efficacy of antibiotics to prevent atherosclerosis-related complications in patients with coronary artery disease . Our aim was to study the effect of a short course of azithromycin on the incidence of cardiovascular events and peripheral vascular function in patients with stable peripheral arterial disease ( PAD ) . PATIENTS AND METHODS Five hundred and nine PAD- patients were r and omised to receive either a 3-day course of azithromycin ( 500 mg daily ) or placebo , with 2 years of follow-up . C. pneumoniae serology was determined at baseline . Clinical endpoints were death , coronary events ( myocardial infa rct ion , unstable angina , and /or coronary revascularization procedures ) , cerebral events ( stroke , TIA , and /or carotid endarterectomy ) and peripheral arterial complications ( increased PAD-symptoms with decreased ankle-brachial index ( ABPI , 0.1-point decrease after 12 months ) , and /or peripheral revascularization procedures ) . RESULTS Five hundred and nine patients ( 160 women ) with an atherosclerotic risk factor profile were r and omised , 257 patients to azithromycin and 252 to placebo .  Four hundred and forty nine patients ( 88 % ) had intermittent claudication and 60 ( 12 % ) had critical limb ischemia . By 24-month follow up , 182 patients ( 36 % ) developed 252 complications ( 45 deaths , 34 coronary events , 34 cerebral events and 139 peripheral arterial complications ) . C. pneumoniae IgA-titres were associated with the development of cardiovascular events . Nevertheless , the number of complications ( 131 in the azithromycin group vs. 121 in the placebo group ) and the number of patients that developed complications ( 98 ( 38 % ) in the azithromycin vs. 84 ( 33 % ) in the placebo group ) was comparable in both treatment groups . Life table analysis showed no effect of azithromycin on survival or ABPI . CONCLUSION A short-term course of azithromycin offers no benefits for survival or ankle pressure in PAD- patients Background — 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 AIM Nitroglycerin-mediated vasodilatation ( NMD ) provides insight into the NTG-induced bioactivity of smooth muscle . It is plausible that in dysfunctional smooth muscle cells , the response to nitroglycerin may become blunted . The relationship between impaired brachial artery NMD and subsequent cardiovascular events is not well established . METHODS We examined brachial artery flow-mediated dilatation ( FMD ) and NMD using ultrasound in 93 subjects ( 71±7 years , including 26 with peripheral artery disease ( PAD ) , 37 with aortic aneurysms , 10 with PAD complicated with aneurysms , and 20 without evident arterial disease ) . Brachial artery responses to hyperemia and nitroglycerin were measured every minute after cuff deflation and nitroglycerin administration . Time courses of vasodilatation were assessed and maximal FMD and NMD were measured . RESULTS The time courses in response to NTG were sigmoidal and maximal diameter reached 7.2±1.6 minutes after NTG was administered sublingually . The mean FMD was 2.3±2.0 % and the mean NMD was 17.6±7.1 % . Subjects were prospect ively followed for an average of 47±13 months . Eighteen subjects had an event during follow-up ; events included myocardial infa rct ion ( five ) , unstable angina pectoris ( four ) , stroke ( two ) , aortic dissection ( one ) , ruptured aortic aneurysm ( three ) , symptomatic abdominal aortic aneurysm ( two ) , and lower limb ischemia requiring revascularization ( one ) . NMD and FMD were significantly lower in subjects with events than in those without an event . In a Cox proportional-hazards model , lower FMD as well as lower NMD independently predicted future cardiovascular events . CONCLUSION Brachial artery nitroglycerin-mediated vasodilatation may add information to conventional risk stratification OBJECTIVE Determine the efficacy of a home-based walking intervention to improve walking ability and quality of life in people with diabetes and peripheral arterial disease ( PAD ) . RESEARCH DESIGN AND METHODS We conducted a r and omized , controlled , single-blind trial within university-affiliated clinics in our local community . We r and omized 145 participants ( 45 women ) with diabetes and PAD to our intervention — a 6-month behavioral intervention targeting levels of readiness to engage in routine walking for exercise — versus attention control . Our primary outcome was 6-month change in maximal treadmill walking distance . Secondary outcomes included 3-month change in maximal walking distance , lower limb function ( i.e. , walking impairment scores ) , quality of life ( Medical Outcomes Short Form Survey ) , exercise behaviors , depressive symptoms , and self-efficacy at 3 and 6 months . RESULTS The mean age of participants was 66.5 ( SD 10.1 ) years . Intervention and control groups did not differ significantly in 6-month change in maximal treadmill walking distance ( average [ SE ] 24.5 [ 19.6 ] meters vs. 39.2 [ 19.6 ] meters ; P = 0.60 ) . Among secondary outcomes , for the intervention and control groups , respectively , average walking speed scores increased by 5.7 [ 2.2 ] units and decreased by 1.9 [ 2.8 ] units ( P = 0.03 ) ; the mental health quality of life subscale score increased by 3.2 [ 1.5 ] and decreased by 2.4 [ 1.5 ] units ( P = 0.01 ) . CONCLUSIONS A home-based walking intervention did not improve walking distance but did improve walking speed and quality of life in people with diabetes and PAD . Clinicians should consider recommending home-based walking therapy for such patients OBJECTIVES The Heart Protection Study ( HPS ) provides an opportunity to assess directly the effects of cholesterol-lowering therapy on major vascular events ( defined as myocardial infa rct ion , coronary death , stroke , or revascularization ) in patients with peripheral arterial disease ( PAD ) . In addition , the effects on peripheral vascular events ( ie , non-coronary revascularization , aneurysm repairs , major amputations or PAD deaths ) can be assessed . METHODS 6748 UK adults with PAD and 13,788 other high-risk participants were r and omly allocated to receive 40 mg simvastatin daily or matching placebo , yielding an average LDL cholesterol difference of 1.0 mmol/L ( 39 mg/dL ) during a mean of 5 years . RESULTS For participants with PAD , allocation to simvastatin was associated with a highly significant 22 % ( 95 % CI 15 - 29 ) relative reduction in the rate of first major vascular event following r and omisation ( 895 [ 26.4 % ] simvastatin-allocated vs 1101 [ 32.7 % ] placebo-allocated ; P < .0001 ) , which was similar to that seen among the other high-risk participants . The absolute reduction in first major vascular event was 63 ( SE 11 ) per 1000 patients with PAD and 50 ( SE 7 ) per 1000 without pre-existing PAD . Overall , among all participants , there was a 16 % ( 5 - 25 ) relative reduction in the rate of first peripheral vascular event following r and omisation ( 479 [ 4.7 % ] simvastatin vs 561 [ 5.5 % ] placebo ) , largely irrespective of baseline LDL cholesterol and other factors . This effect chiefly reflects a 20 % ( 8 - 31 ) relative reduction in non-coronary revascularization procedures ( 334 [ 3.3 % ] vs 415 [ 4.0 % ] ; P = .002 ) . CONCLUSION HPS demonstrates the benefits of cholesterol-lowering statin therapy in patients with PAD , regardless of their presenting cholesterol levels and other presenting features . Allocation to 40 mg simvastatin daily reduces the rate of first major vascular events by about one-quarter , and that of peripheral vascular events by about one-sixth , with large absolute benefits seen in participants with PAD because of their high vascular risk . Consequently , statin therapy should be considered routinely for all patients with PAD 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 The purpose of this study was to examine the effects of a 12month exercise program on lower limb movement variability in patients with peripheral arterial disease ( PAD ) . Participants ( n=21 ) with an appropriate history of PAD and intermittent claudication ( IC ) volunteered for this study and were r and omly allocated to either a control group ( CPAD-IC ) ( n=11 ) , which received normal medical therapy and a treatment group ( TPAD-IC ) ( n=10 ) , which received normal medical therapy treatment and a 12month supervised exercise program . All participants underwent 2D joint angular kinematic analysis during normal walking to assess lower limb movement variability and walking speed . Between-group differences were analyzed via mixed measures ANOVA . The 12month supervised exercise program made no significant impact on the lower limb movement variability or walking speed of the TPAD-IC group as determined by either intralimb joint coordination or single joint analysis techniques . Long term supervised exercise programs do not appear to influence the lower limb movement variability of PAD-IC patients 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 AIMS Patients with diabetes are at excessive risk of mortality and cardiovascular morbidity . Previous studies suggest that aspirin may be less effective in diabetic patients . In this multi-centre , r and omized , double blind trial picotamide , a dual inhibitor of thromboxane A2 synthase and receptor , was compared with aspirin for the prevention of mortality and major cardiovascular events in diabetics with peripheral arterial disease ( PAD ) . METHODS AND RESULTS A total of 1209 adults aged 40 - 75 years with type 2 diabetes and PAD were r and omized to receive picotamide ( 600 mg bid ) or aspirin ( 320 mg od ) for 24 months . The cumulative incidence of the 2 years overall mortality was significantly lower amongst patients who received picotamide ( 3.0 % ) than in those who received aspirin ( 5.5 % ) with a relative risk ratio for picotamide versus aspirin of 0.55 ( 95 % CI : 0.31 - 0.98 % ) . Events were reported in 43 patients ( 7.1 % ) on picotamide and 53 ( 8.7 % ) on aspirin . The combined endpoint of mortality and morbidity had a slightly lower incidence in the picotamide group but this difference did not reach statistical significance . CONCLUSION Picotamide is significantly more effective than aspirin in reducing overall mortality in type 2 diabetic patients with associated PAD Cardiovascular disease mortality rates have decreased in men during the past 20 years , but have steadily increased in women . In the United States , > 500,000 women die of coronary artery disease ( CAD ) every year . Although many factors can influence an individual 's risk for CAD , some factors are unique to women , including reproductive status . Menopause is associated with significant elevations in serum cholesterol levels and a 3-fold increase in the risk of CAD . It has been suggested that these changes result from a reduction in the level of estrogen . However , recent data from prospect i ve clinical trials have not found any evidence that hormone replacement therapy protects against cardiovascular disease . On the other h and , several studies have shown that , in women , lipid lowering with statin therapy can reduce coronary events . On the strength of these findings , the Beyond Endorsed Lipid Lowering with Electron-Beam Computed Tomography Scanning ( BELLES ) trial-a 1-year , multicenter , r and omized , double-blind , parallel-group study -has been specifically design ed to determine the benefits of aggressive statin therapy on the progression of atherosclerosis in postmenopausal women OBJECTIVES To evaluate whether lipid-lowering therapy with xuezhikang reduces the risk of coronary events and total mortality in patients with coronary heart disease ( CHD ) aged 65 and older . DESIGN Subgroup analysis of the China Coronary Secondary Prevention Study , a r and omized , double-blind , placebo-controlled , clinical trial . SETTING Sixty-six hospitals in China . PARTICIPANTS A total of 1,445 patients , aged 65 to 75 , were chosen from 4,780 patients with a history of myocardial infa rct ion . INTERVENTION The patients were r and omized to the xuezhikang ( n=735 ) or the placebo ( n=710 ) group and followed for a mean of 4 years . MEASUREMENTS The primary endpoint was recurrent coronary events ; the secondary endpoint was all-cause mortality and other clinical events , including adverse effects . RESULTS Elderly patients were at greater risk for coronary events , death from coronary events , all-cause mortality , and malignancies than younger patients .  Xuezhikang therapy reduced the incidence of coronary events 36.9 % ( P=.001 ) , death from coronary heart disease 31.0 % ( P=.04 ) , all-cause mortality 31.9 % ( P=.01 ) , stroke 44.1 % ( P=.04 ) , the need for a percutaneous coronary intervention or coronary artery bypass graft 48.6 % ( P=.07 ) , and malignancies 51.4 % ( P=.03 ) . Based on the treatment of elderly patients with xuezhikang for an average of 4 years , the number needed to treat ( NNT ) to prevent one coronary event , one coronary death , and one mortality due to all causes was estimated to be 18 , 33 , and 23 , respectively . In a like manner , the estimated NNT to prevent one coronary event , one coronary death , and one mortality due to all causes in younger patients was 23 , 82 , and 51 , respectively . There was not a significantly greater number of adverse effects in the xuezhikang group than in the placebo group . CONCLUSION This is the first study demonstrating that treatment with xuezhikang capsules is safe and effective for the secondary prevention of CHD in older Chinese people Peripheral arterial disease ( PAD ) is associated with major cardiovascular morbidity and mortality . Abnormalities in nitric oxide metabolism due to excess of the NO synthase inhibitor asymmetric dimethylarginine ( ADMA ) may be pathogenic in PAD . We explored the association between ADMA levels and markers of atherosclerosis , function , and prognosis .  A total of 133 patients with symptomatic PAD were enrolled .  Ankle — brachial index ( ABI ) , walking time , vascular function measures ( arterial compliance and flow-mediated vasodilatation ) and plasma ADMA level  were assessed for each patient at baseline . ADMA correlated inversely with ABI ( r = —0.238 , p = 0.003 ) and walking time ( r = —0.255 , p = 0.001 ) , independent of other vascular risk factors . We followed up 125 ( 94 % ) of our 133 initial subjects with baseline measurements ( mean 35 months ) . Subjects with ADMA levels in the highest quartile ( > 0.84 μmol/l ) showed a significantly greater occurrence of a major adverse cardiovascular event ( MACE ) compared to those with ADMA levels in the lower three quartiles ( p = 0.001 ) . Cox proportional-hazards regression analysis revealed that ADMA was a significant predictor of MACE , independent of other risk factors including age , sex , blood pressure , smoking history , diabetes and ABI ( hazard ratio = 5.1 , p < 0.001 ) . Measures of vascular function , such as compliance , flow-mediated vasodilatation ( FMVD ) and blood pressure , as well as markers of PAD severity , including ABI and walking time , were not predictive . In conclusion , circulating levels of ADMA correlate independently with measures of disease severity and major adverse cardiovascular events . Agents that target this pathway may be useful for this patient population . Clinical Trial Registration — URL : http:// www . clinical trials.gov . Unique identifier : Background —Atherosclerosis is increasingly considered to be a chronic inflammatory process . We examined whether genetic variants of the toll-like receptor 4 ( TLR4 ) , which are correlated with impaired innate immunity and with progression of carotid atherosclerosis , are also associated with coronary atherosclerosis and predict the risk of cardiovascular events . Methods and Results —Two polymorphisms of the TLR4 gene ( Asp299Gly and Thr399Ile ) were determined in 655 men with angiographically documented coronary atherosclerosis . All patients participated in a prospect i ve cholesterol-lowering trial evaluating the effect on coronary artery disease and were r and omly assigned to either pravastatin or placebo for 2 years . There were no significant differences between genetically defined subgroups with respect to baseline risk factors , treatment , or in-trial changes of lipid , lipoprotein , or angiographic measurements . Genotype was not associated with progression of atherosclerosis . In the pravastatin group , 299Gly carriers had a lower risk of cardiovascular events during follow-up than noncarriers ( 2.0 % versus 11.5 % , P = 0.045 ) . Among noncarriers , pravastatin reduced the risk of cardiovascular events from 18.1 % to 11.5 % ( P = 0.03 ) , whereas among 299Gly carriers this risk was strikingly reduced from 29.6 % to 2.0 % ( P = 0.0002 , P = 0.025 for interaction ) . Conclusions —Among symptomatic men with documented coronary artery disease , the TLR4 Asp299Gly polymorphism was associated with the risk of cardiovascular events . This variant also modified the efficacy of pravastatin  in preventing cardiovascular events , such that carriers of the variant allele had significantly more benefit from pravastatin treatment BACKGROUND AND METHODS The effect of intensive lipid-lowering therapy on coronary atherosclerosis among men at high risk for cardiovascular events was assessed by quantitative arteriography . Of 146 men no more than 62 years of age who had apolipoprotein B levels greater than or equal to 125 mg per deciliter , documented coronary artery disease , and a family history of vascular disease , 120 completed the 2 1/2-year double-blind study , which included arteriography at base line and after treatment . Patients were given dietary counseling and were r and omly assigned to one of three treatments : lovastatin ( 20 mg twice a day ) and colestipol ( 10 g three times a day ) ; niacin ( 1 g four times a day ) and colestipol ( 10 g three times a day ) ; or conventional therapy with placebo ( or colestipol if the low-density lipoprotein [ LDL ] cholesterol level was elevated ) . RESULTS The levels of LDL and high-density lipoprotein ( HDL ) cholesterol changed only slightly in the conventional-therapy group ( mean changes , -7 and + 5 percent , respectively ) , but more substantially among patients treated with lovastatin and colestipol ( -46 and + 15 percent ) or niacin and colestipol ( -32 and + 43 percent ) . In the conventional-therapy group , 46 percent of the patients had definite lesion progression ( and no regression ) in at least one of nine proximal coronary segments ; regression was the only change in 11 percent . By comparison , progression ( as the only change ) was less frequent among patients who received lovastatin and colestipol ( 21 percent ) and those who received niacin and colestipol ( 25 percent ) , and regression was more frequent ( lovastatin and colestipol , 32 percent ; niacin and colestipol , 39 percent ; P less than 0.005 ) . Multivariate analysis indicated that a reduction in the level of apolipoprotein B ( or LDL cholesterol ) and in systolic blood pressure , and an increase in HDL cholesterol correlated independently with regression of coronary lesions . Clinical events ( death , myocardial infa rct ion , or revascularization for worsening symptoms ) occurred in 10 of 52 patients assigned to conventional therapy , as compared with 3 of 46 assigned to receive lovastatin and colestipol and 2 of 48 assigned to receive niacin and colestipol ( relative risk of an event during intensive treatment , 0.27 ; 95 percent confidence interval , 0.10 to 0.77 ) . CONCLUSIONS In men with coronary artery disease who were at high risk for cardiovascular events , intensive lipid-lowering therapy reduced the frequency of progression of coronary lesions , increased the frequency of regression , and reduced the incidence of cardiovascular events 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 Coronary heart disease , hypertension , and dyslipidemia are highly prevalent and commonly coexist in people who are middle-aged and older . Previous data suggested that lowering cholesterol concentrations in individuals at high risk of cardiovascular disease improved clinical outcomes . Xuezhikang , a partial extract of red yeast rice containing statin , has a marked impact on lipids . The purpose of this study , therefore , was to evaluate the impact of Xuezhikang on reducing cardiovascular events and mortality in elderly Chinese hypertensive patients with a history of myocardial infa rct ion ( MI ) enrolled in the Chinese Coronary Secondary Prevention Study . In this r and omized trial , 1530 elderly hypertensive patients ( > or = 65-years-old ) with previous MI were assigned either to placebo ( n = 758 ) or to Xuezhikang ( n = 772 ) daily for an average of 4.5 years . The primary endpoint was recurrent coronary events ; the secondary endpoint was all-cause mortality and other clinical events , including adverse effects . There were 68 cases of coronary events ( 8.8 % ) detected in the Xuezhikang group and 108 cases ( 14.3 % ) in the placebo group ( 38.2 % risk reduction by Xuezhikang therapy ) . Death from coronary heart disease ( CHD ) totaled 49 cases in the Xuezhikang group ( 6.4 % ) and 68 cases in the placebo group ( 9.0 % ) , indicating that Xuezhikang significantly decreased the risk of CHD death by 29.2 % . Our study demonstrated that Xuezhikang therapy could effectively and safely reduce cardiovascular events and all-cause death in Chinese elderly hypertensive patients with previous MI . This finding may have an important implication for the treatment of elderly hypertensive patients with CHD Background : 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 A line of epidemiological studies suggests that the accumulation of coronary risk factors promotes the progression of coronary atherosclerosis . Recent clinical studies showed that aggressive low-density lipoprotein ( LDL ) cholesterol-lowering therapy using statins could regress coronary atheroma and reduce major cardiovascular events . Additionally , therapy that controlled amlodipine-based blood pressure reduced major cardiovascular events in patients with hypertension compared with an atenolol-based regimen . An open-label r and omized multicenter study is primarily planned to evaluate the changes in coronary atheroma volume using intravascular ultrasonography 18–24 months after intensive lowering of LDL-cholesterol and blood pressure compared with a st and ard therapy indicated by current guidelines in Japanese patients with coronary artery disease ( CAD ) . The secondary endpoints include changes in serum lipid levels , inflammatory markers , glucose markers and blood pressure .  In total , 100 subjects with CAD who are undergoing percutaneous coronary intervention will be tested . The MILLION study will provide new evidence and therapeutic st and ards for the prevention of CAD in Japanese patients by controlling both LDL-C levels and blood pressure OBJECTIVES To investigate the effects of a 24-week program of upper- and lower-limb aerobic exercise training on walking performance in patients with symptomatic peripheral arterial disease ( PAD ) and to study the mechanisms that could influence symptomatic improvement . METHODS After approval from the North Sheffield Local Research Ethics Committee , 104 patients ( median age , 69 years ; range , 50 to 85 years ) with stable PAD were r and omized into an upper- or lower-limb aerobic exercise training group ( UL-Ex or LL-Ex ) , or to a nonexercise training control group . Training was performed twice weekly for 24 weeks at equivalent relative exercise intensities . An incremental arm- and leg-crank test ( ACT and LCT ) to maximum exercise tolerance was performed before and at 6 , 12 , 18 , and 24 weeks of the intervention to determine peak oxygen consumption ( VO(2 ) ) . Walking performance , defined as the claudicating distance ( CD ) and maximum walking distance ( MWD ) achieved before intolerable claudication pain , was assessed at the same time points by using a shuttle-walk protocol . Peak blood lactate concentration , Borg ratings of perceived exertion ( RPE ) and pain category ratio ( CR-10 ) were recorded during all assessment s. RESULTS CD and MWD increased over time ( P < .001 ) in both training groups . At 24 weeks , CD had improved by 51 % and 57 % , and MWD had improved by 29 % and 31 % ( all P < .001 ) in the UL-Ex and LL-Ex groups , respectively . An increase in peak heart rate at MWD in the UL-Ex group ( 109 + /- 4 vs 115 + /- 4 beats/min ; P < .01 ) and LL-Ex group ( 107 + /- 3 vs 118 + /- 3 beats/min ; P = .01 ) was accompanied by an increase in the amount of pain experienced in both groups ( P < .05 ) , suggesting that exercising patients could tolerate a higher level of cardiovascular stress and an increased intensity of claudication pain before test termination after training . Patients assigned to exercise training also showed an increase in LCT peak VO2 at the 24-week time point in relation to baseline ( P < .01 ) and control patients ( P < .01 ) , whereas ACT peak VO2 was only improved in the UL-Ex group ( P < .05 ) . CONCLUSIONS Our results suggest that a combination of physiologic adaptations and improved exercise pain tolerance account for the improvement in walking performance achieved through upper-limb aerobic exercise training in patients with PAD . Furthermore , that both arm- and leg-crank training could be useful exercise training modalities for improving cardiovascular function , walking performance , and exercise pain tolerance in patients with symptomatic PAD BACKGROUND HMG CoA reductase inhibitors ( or statins ) , a new class of lipid-lowering compounds , have raised expectations for more widespread use than that of the older lipid-lowering drugs . Not only are they more effective in lowering LDL cholesterol , but they are better tolerated as well . No data exist concerning the effect of statins on early carotid atherosclerosis and clinical events in men and women who have moderately elevated LDL cholesterol levels but are free of symptomatic cardiovascular disease . METHODS AND RESULTS Lovastatin ( 20 to 40 mg/d ) or its placebo was evaluated in a double-blind , r and omized clinical trial with factorial design along with warfarin ( 1 mg/d ) or its placebo . This report is limited to the lovastatin component of the trial . Daily aspirin ( 81 mg/d ) was recommended for everyone . Enrollment included 919 asymptomatic men and women , 40 to 79 years old , with early carotid atherosclerosis as defined by B-mode ultrasonography and LDL cholesterol between the 60th and 90th percentiles . The 3-year change in mean maximum intimal-medial thickness ( IMT ) in 12 walls of the carotid arteries was the primary outcome ; change in single maximum IMT and incidence of major cardiovascular events were secondary outcomes . LDL cholesterol fell 28 % , from 156.6 mg/dL at baseline to 113.1 mg/dL at 6 months ( P < .0001 ) , in the lovastatin groups and was largely unchanged in the lovastatin-placebo groups . Among participants not on warfarin , regression of the mean maximum IMT was seen after 12 months in the lovastatin group compared with the placebo group ; the 3-year difference was statistically significant ( P = .001 ) . A larger favorable effect of lovastatin was observed for the change in single maximum IMT but was not statistically significant ( P = .12 ) . Five lovastatin-treated participants suffered major cardiovascular events -- coronary heart disease mortality , nonfatal myocardial infa rct ion , or stroke -- versus 14 in the lovastatin-placebo groups ( P = .04 ) . One lovastatin-treated participant died , compared with eight on lovastatin-placebo ( P = .02 ) . CONCLUSIONS In men and women with moderately elevated LDL cholesterol , lovastatin reverses progression of IMT in the carotid arteries and appears to reduce the risk of major cardiovascular events and mortality . Results from ongoing large-scale clinical trials may further establish the clinical benefit of statins BACKGROUND Vascular diseases , such as carotid artery stenosis ( CAS ) , abdominal aortic aneurysm ( AAA ) , and peripheral arterial occlusive disease ( PAD ) of the lower limb , are common in elderly men . These diseases have not been thoroughly reported in Eastern countries as well as in Western countries . We compare the prevalence rates in Korea with previous reports , and evaluate correlations between known risk factors and these conditions in this population . MATERIAL S AND METHODS From November 2008 to December 2012 , elderly men ( ≥65 years ) were r and omly referred from the Incheon Federation of the Korean Senior Citizens ' Association , which is one of the major organizations representing retired individuals in Korea .  CAS was defined as ≥50 % of internal CAS , AAA was defined as ≥3 cm aortic diameter , and PAD of the lower limb was defined as an ankle brachial index ≤0.9 . RESULTS The average age was 72.14 ± 5.15 years .  CAS  was detected in 116 subjects ( 7.2 % ) , AAA  was detected in 52 subjects ( 3.2 % ) , and PAD was detected in 79 subjects ( 4.9 % ) . On multivariate analysis , octogenarian status and coronary artery disease were significantly associated with CAS and current smoking was significantly associated with PAD ( P < 0.001 ) . CONCLUSIONS The Korean prevalence rates of CAS and PAD in this study are similar to previous reports . The prevalence of AAA in Korea is lower compared with western reports , but higher than previous Asian reports . It is presently necessary to conduct major clinical studies throughout Asian countries to prepare for a rapid increase in the prevalence of major vascular diseases in Asia OBJECTIVES This study sought to determine whether patients with peripheral arterial disease ( PAD ) experience different reductions in ischemic event and increases in bleeding events with extended duration dual antiplatelet therapy versus those without PAD . BACKGROUND Patients with PAD have increased ischemic and bleeding risks after coronary stenting . METHODS The DAPT ( Dual Antiplatelet Therapy ) study r and omized 11,648 patients free from ischemic and bleeding events 12 months after coronary stenting to continued thienopyridine plus aspirin therapy for an additional 18 months versus aspirin therapy alone . The effects of continued thienopyridine on myocardial infa rct ion ( MI ) or stent thrombosis , major adverse cardiovascular and cerebrovascular events ( death , MI , or stroke ) and bleeding ( GUSTO [ Global Utilization of t-PA and Streptokinase for Occluded Coronary Arteries ] moderate or severe ) were assessed among those with versus without PAD . RESULTS Among 11,648 r and omized patients , 649 ( 5.57 % ) had PAD . Between 12 and 30 months , r and omized patients with PAD had higher rates of MI/stent thrombosis ( 6.03 % vs. 2.92 % ; p < 0.001 ) , major adverse cardiovascular and cerebrovascular events ( 11.65 % vs. 4.62 % ; p < 0.001 ) , and bleeding ( 4.86 % vs. 1.74 % ; p < 0.001 ) . Continued thienopyridine versus placebo was associated with consistent treatment effects for MI/stent thrombosis ( with PAD , HR : 0.63 ; 95 % CI : 0.32 to 1.22 ; without PAD , HR : 0.53 ; 95 % CI : 0.42 , 0.66 ; interaction p = 0.631 ) , major adverse cardiovascular and cerebrovascular events ( with PAD , HR : 1.06 ; 95 % CI : 0.67 to 1.67 ; without PAD , HR : 0.70 ; 95 % CI : 0.59 to 0.84 ; interaction p = 0.103 ) , and bleeding ( with PAD , HR , 1.82 ; 95 % CI : 0.87 to 3.83 ; without PAD , HR : 1.66 ; 95 % CI : 1.23 to 2.24 ; interaction p = 0.811 ) . CONCLUSIONS Among patients undergoing coronary stenting , those with PAD have more ischemic and bleeding events versus those without PAD . Extended duration dual antiplatelet therapy is associated with consistent ischemic benefit and bleeding harm among patients with and without PAD Summary Background Amputations in people with type 2 diabetes mellitus substantially impair their quality of life and impose high costs on health-care systems . Our aim was to assess the effect of fenofibrate on amputation events in a large cohort of patients with type 2 diabetes . Methods In the Fenofibrate Intervention and Event Lowering in Diabetes ( FIELD ) study , 9795 patients aged 50–75 years with type 2 diabetes were r and omly assigned by computer-generated r and omisation sequence to receive fenofibrate 200 mg per day ( n=4895 ) or matching placebo ( n=4900 ) for 5 years ' duration . Information about non-traumatic amputation — a prespecified tertiary endpoint of the study —was routinely gathered . Clinicians who were masked to treatment allocation adjudicated amputations as minor or major ( below or above the ankle , respectively ) . Amputations were also classified on the basis of whether or not large-vessel disease was present in the limb , to distinguish those related to large-artery atherosclerosis from those predominantly related to microvascular disease . Analysis was by intention to treat ( ITT ) . The FIELD study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N64783481 . Findings All 9795 patients were included in the ITT population . 115 patients had one or more non-traumatic lower-limb amputations due to diabetes .  Previous cardiovascular disease , microvascular disease , previous non-traumatic amputation or skin ulcer , smoking , and longer duration of diabetes were more frequent in patients who had amputations during the trial than in those who had other cardiovascular events or in those who had neither event ( all p<0·001 for three-way comparison ) . Mean lipid concentrations differed between patients who had on- study amputations and those who had other cardiovascular events or neither event , but by no more than 0·2 mmol/L. The risks of first amputation ( 45 vs 70 events ; hazard ratio [ HR ] 0·64 , 95 % CI 0·44–0·94 ; p=0·02 ) and minor amputation events without known large-vessel disease ( 18 vs 34 events ; 0·53 , 0·30–0·94 ; p=0·027 ) were lower for patients assigned to fenofibrate than for patients assigned to placebo , with no difference between groups in risk of major amputations ( 24 vs 26 events ; 0·93 , 0·53–1·62 ; p=0·79 ) . Interpretation Classic markers of macrovascular and microvascular risk were associated with lower extremity amputations in patients with type 2 diabetes . Treatment with fenofibrate was associated with a lower risk of amputations , particularly minor amputations without known large-vessel disease , probably through non-lipid mechanisms . These findings could lead to a change in st and ard treatment for the prevention of diabetes-related lower-limb amputations . Funding Laboratoires Fournier SA ( now part of Solvay Pharmaceuticals ) and National Health and Medical Research Council of Australia Background : In patients with symptomatic peripheral artery disease with a history of limb revascularization , the optimal antithrombotic regimen for long-term management is unknown . Methods : The EUCLID trial ( Examining Use of Ticagrelor In PAD ) r and omized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily . Patients were enrolled based on an abnormal ankle-brachial index ⩽0.80 or a previous lower extremity revascularization . This analysis focuses on the 7875 ( 57 % ) patients enrolled based on the previous lower extremity revascularization criterion . Patients could not be enrolled within 30 days of most recent revascularization , and patients with an indication for dual antiplatelet therapy were excluded . The primary efficacy end point was a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . The primary safety end point was major bleeding . Results : Patients with a previous revascularization had a mean age of 66 years , 73 % were male , and the median baseline ankle-brachial index was 0.78 . After adjustment for baseline characteristics , patients enrolled based on previous revascularization had similar rates of the primary composite end point ( hazard ratio [ HR ] 1.10 , 95 % confidence interval [ CI ] 0.98–1.23 , P=0.12 ) and statistically significantly higher rates of myocardial infa rct ion ( HR 1.29 , 95 % CI 1.08–1.55 , P=0.005 ) and acute limb ischemia ( HR 4.23 , 95 % CI 2.86–6.25 , P<0.001 ) when compared with patients enrolled based on ankle-brachial index criteria . No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point ( 11.4 % vs 11.3 % ; HR 1.01 , 95 % CI 0.88–1.15 ; P=0.90 ) , all-cause mortality ( 9.2 % vs 9.2 % ; HR 0.99 , 95 % CI 0.86–1.15 ; P=0.93 ) , acute limb ischemia ( 2.5 % vs 2.5 % ; HR 1.03 , 95 % CI 0.78–1.36 ; P=0.84 ) , or major bleeding ( 1.9 % vs 1.8 % ; HR 1.15 , 95 % CI 0.83–1.59 ; P=0.41 ) . The median duration of follow-up was ≈30 months . Conclusions : After adjustment for baseline characteristics , patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infa rct ion and acute limb ischemia , with similar composite rates of cardiovascular death , myocardial infa rct ion , and stroke when compared with patients enrolled based on the ankle-brachial index criterion . No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events . Clinical Trial Registration : URL : http://www . clinical trials.gov . Unique identifier : NCT01732822 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 We sought to determine whether lipid-lowering therapy and antioxidants retard the progression of coronary calcification and prevent atherosclerotic cardiovascular disease ( ASCVD ) events . BACKGROUND The electron beam computed tomography-derived coronary calcium score predicts coronary disease events . Small , uncontrolled studies suggest that vigorous lipid-lowering therapy slows progression of coronary calcification and prevents coronary artery disease events , but controlled , scientific demonstration of these effects is lacking . METHODS We conducted a double-blind , placebo-controlled r and omized clinical trial of atorvastatin 20 mg daily , vitamin C 1 g daily , and vitamin E ( alpha-tocopherol ) 1,000 U daily , versus matching placebos in 1,005 asymptomatic , apparently healthy men and women age 50 to 70 years with coronary calcium scores at or above the 80th percentile for age and gender . All study participants also received aspirin 81 mg daily . Mean duration of treatment was 4.3 years . RESULTS Treatment reduced total cholesterol by 26.5 % to 30.4 % ( p < 0.0001 ) , low-density lipoprotein cholesterol by 39.1 % to 43.4 % ( p < 0.0001 ) , and triglycerides by 11.2 % to 17.0 % ( p < or = 0.02 ) but had no effect ( p = 0.80 ) on progression of coronary calcium score ( Agatston method ) . Treatment also failed to significantly reduce the primary end point , a composite of all ASCVD events ( 6.9 % vs. 9.9 % , p = 0.08 ) . Event rates were related to baseline calcium score ( pre-specified analysis ) and may have been reduced in a subgroup of participants with baseline calcium score > 400 ( 8.7 % vs. 15.0 % , p = 0.046 [ not a pre-specified analysis ] ) . CONCLUSIONS Treatment with alpha-tocopherol , vitamin C , and low doses of atorvastatin ( 20 mg once daily ) did not affect the progression of coronary calcification . Treatment may have reduced ASCVD events , especially in subjects with calcium scores > 400 , but these effects did not achieve conventional levels of statistical significance Importance Patients with concomitant peripheral arterial disease ( PAD ) experience worse cardiovascular outcomes after percutaneous coronary intervention ( PCI ) . Objective To assess the efficacy and safety of prolonged ( 24 months ) vs short ( ≤6 months ) dual antiplatelet therapy ( DAPT ) in patients with PAD undergoing PCI . Design , Setting , and Participants This sub analysis of the r and omized Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study ( PRODIGY ) trial assessed unselected patients from tertiary care hospitals with stable coronary artery disease or acute coronary syndromes with or without concomitant PAD from December 2006 to December 2008 . Data analysis was performed from January 7 to April 4 , 2016 . Interventions Percutaneous coronary intervention . Main Outcomes and Measures Rates of the primary efficacy end point , composite of death , myocardial infa rct ion , or cerebrovascular accidents , and occurrence of the key safety end point , a composite of Bleeding Academic Research Consortium type 2 , 3 , or 5 . Results This analysis comprised 246 and 1724 patients with and without PAD , respectively . In the patients with PAD , mean ( SD ) age was 73.2 ( 9.2 ) in the prolonged group and 75.7 ( 8.7 ) years in the short DAPT group , and 97 ( 82.2 % ) were male in the prolonged group and 92 ( 71.9 % ) were male in the short DAPT group . In the patients without PAD , mean ( SD ) age was 67.1 ( 11.2 ) years in the prolonged group and 66.8 ( 11.3 ) years in the short DAPT group , and 667 ( 76.8 % ) were male in the prolonged group and 655 ( 76.6 % ) were male in the short DAPT group . Status of PAD was associated with a higher risk of death and ischemic events ( hazard ratio [ HR ] , 2.80 ; 95 % CI , 2.05 - 3.83 ; P < .001 ) . Prolonged vs short DAPT conveyed a lower risk of the primary efficacy end point in patients with PAD ( 19 [ 16.1 % ] vs 35 [ 27.3 % ] ; HR , 0.54 ; 95 % CI , 0.31 - 0.95 ; P = .03 ) but not in patients without PAD ( 81 [ 9.3 % ] vs 63 [ 7.4 % ] ; HR , 1.28 ; 95 % CI , 0.92 - 1.77 ; P = .15 ) , with positive interaction ( P = .01 ) . The risk of definite or probable stent thrombosis was significantly lower in patients with PAD treated with prolonged compared with short DAPT ( HR , 0.07 ; 95 % CI , 0 - 1.21 ; P = .01 ) . Bleeding Academic Research Consortium type 2 , 3 , or 5 bleeding occurred in 6 patients with PAD ( 5.2 % ) receiving prolonged DAPT relative to 8 ( 6.9 % ) of those receiving short DAPT ( HR , 0.77 ; 95 % CI , 0.27 - 2.21 ; P = .62 ) , with a significant interaction ( P = .04 ) compared with patients without PAD . Conclusions and Relevance Peripheral artery disease confers a poor prognosis in patients undergoing PCI in the setting of stable coronary artery disease or acute coronary syndromes . Prolonged DAPT lowers the risk of ischemic events with no apparent bleeding liability in this high-risk group . Trial Registration clinical trials.gov Identifier : NCT00611286 BACKGROUND The majority of cardiovascular events and deaths attributable to both raised blood pressure and dyslipidaemia occur in subjects with relatively " normal " blood pressure and lipid levels respectively . The study was design ed to evaluate the potential benefits of cholesterol lowering in the primary prevention of coronary heart disease in hypertensive subjects with average and below average levels of serum cholesterol . MATERIAL AND METHODS Out of 19 342 hypertensive subjects ( aged 40 - 79 ) who were initially r and omized to one of two antihypertensive treatment strategies in the Anglo-Sc and inavian Cardiac Outcomes Trial ( ASCOT ) , 10 305 subjects with total cholesterol levels < or = 6.5 mmol/L were additionally r and omized to either 10 mg atorvastatin or placebo . The primary endpoint was non-fatal myocardial infa rct ion or fatal coronary heart disease . RESULTS The lipid arm of the study was prematurely stopped after a median follow-up period of 3.3 years . One hundred events occurred in those r and omized to atorvastatin compared to 154 events in those receiving placebo , a 36 % relative risk reduction ( p = 0.0005 ) in the primary endpoint . Among secondary and tertiary endpoints , stroke was reduced with 27 % ( p = 0.02 ) . There was a non-significant 13 % reduction in total mortality . Non-cardiovascular mortality was similar in the two treatment limbs of the trial . After three years of follow-up , atorvastatin lowered total serum cholesterol by 1.1 mmol/L compared with placebo . INTERPRETATION Treatment with 10 mg atorvastatin o.d . in hypertensive patients at moderate risk gives a significant risk reduction of coronary heart disease , independent of baseline level of total cholesterol 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 Numerous r and omized , double-blind , placebo-controlled studies and observational studies have shown that statins reduce mortality and major cardiovascular events in older high-risk persons with hypercholesterolemia . The Heart Protection Study showed that statins reduced mortality and major cardiovascular events in high-risk persons regardless of the initial level of serum lipids , age , or gender . The up date d National Cholesterol Education Program III guidelines state that in very high-risk persons , a serum low-density lipoprotein ( LDL ) cholesterol level of < 70 mg/dl ( 1.8 mmol/l ) is a reasonable clinical strategy for moderately high-risk persons ( 2 or more risk factors and a 10-year risk for coronary artery disease of 10 % to 20 % ) , and the serum LDL cholesterol should be reduced to < 100 mg/dl ( 2.6 mmol/l ) . When LDL cholesterol-lowering drug therapy is used to treat high-risk persons or moderately high-risk persons , the serum LDL cholesterol should be reduced by at least 30 % to 40 % . The serum LDL cholesterol should be decreased to less than 160 mg/dl in persons at low risk for cardiovascular disease . Addition of other lipid-lowering drugs to statin therapy has not been demonstrated to further reduce cardiovascular events and mortality 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 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 BACKGROUND Cardiovascular disease ( CVD ) is the leading cause of death , and principal reason for the large difference in life expectancy between indigenous Māori and the non-indigenous population in New Zeal and . CVD guidelines recommend that people who are at high risk or who have had previous CVD should be offered aspirin , blood pressure lowering and lipid lowering therapies . However , prescribing and adherence rates are low and CVD events remain high . AIM To assess whether a medication strategy using a fixed dose combination pill ( ' polypill ' ) could improve prescribing and adherence to recommended medications , lower blood pressure and improve lipids compared with current care over 12 months . METHODS IMProving Adherence using Combination Therapy ( IMPACT ) is an open-label r and omised controlled trial comparing a once-daily polypill containing four preventive medications with usual care .  Six hundred participants who have had previous CVD events or are at high risk of CVD will be enrolled , including 300 Māori . Participants are identified , enrolled and prescribed either the polypill or current medications at their usual primary health care practice , with medications ( including the polypill ) dispensed through local community pharmacies . The polypill contains 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril and either 12.5 mg hydrochlorothiazide or 50 mg atenolol . Primary outcomes are adherence to guidelines -recommended medications and changes in systolic blood pressure and low density lipoprotein at 12 months . Secondary outcomes include other lipids , medication dispensing , barriers to adherence , CVD and other serious adverse events , quality of life and prescriber acceptability . The trial is registered with the Australian New Zeal and Clinical Trial Registry ( ACTRN12606000067572 ) 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 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 Background Recent evidence on the use of statin therapy indicates the potential for ultra-low levels of LDL-C to provide greater protection from recurrent coronary heart disease events . Guidelines for the treatment of lipid disorders were revised to indicate that an LDL-C treatment goal of 70 mg/dl was optional ( NCEP ATPIII ) . In these same guidelines , low levels of HDL-C are also suggested but not specifically proscribed as a target of therapy . Recently ARBITER 2 ( Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 2 ) has provided the first evidence of the potential of raising HDL-C with extended release niacin when added to statin monotherapy in secondary prevention . However , whether this approach would be superior to a strategy in which lower concentrations of LDL-C are targeted is unknown . Material s and methods ARBITER 6-HALTS ( HDL and LDL Treatment Strategies ) will be a r and omized , parallel group , open-label study comparing HDL-C and LDL-C focused strategies of lipid treatments for their effects on atherosclerosis . Up to 400 subjects will be assigned to either  intensified LDL-C lowering therapy with ezetimibe or HDL-C raising therapy with extended-release niacin . The primary endpoint is the mean change in the intima-media thickness of the common carotid artery after 14 months . Secondary endpoints include the change in lipid values and lipid subfractions , drug discontinuation due to adverse effects , change in quality of life , and a composite endpoint consisting of all major adverse cardiovascular events . Conclusion ARBITER 6-HALTS will guide clinicians on whether a lipid treatment strategy of raising HDL-C or further LDL-C reduction is superior in the secondary prevention of coronary heart disease 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 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 BACKGROUND Cholesterol-lowering therapy with statins has been reported to reduce the morbidity and mortality of cardiovascular diseases . This study aim ed to investigate the effects of combined application of extended-release niacin and atorvastatin on lipid profile modification and the risks of adverse events in patients with coronary artery disease . METHODS Consecutive 108 patients with coronary artery disease and serum total cholesterol ( TC ) > or = 3.5 mmol/L were r and omized into two groups : group A using atorvastatin and group B using extended-release niacin ( niacin ER ) and atorvastatin .  Plasma lipid profile , glucose , and adverse events were assessed at the hospitalization , and 6 and 12 months after treatment . In addition , clinical cardiovascular events were evaluated after 12 months of treatment . RESULTS The levels of TC , low density lipoprotein cholesterol ( LDL-C ) were significantly decreased ( P < 0.05 ) in groups A and B , but the levels of high density lipoprotein cholesterol ( HDL-C ) and ApoA increased by 29.36 % and 40.81 % respectively after 12 months of treatment in group B ( P < 0.01 ) . The medications were generally well tolerated in the two groups . No significant difference of adverse events was found between the two groups ( group A : 3.2 % vs group B 5.1 % , P > 0.05 ) . CONCLUSIONS Combined use of extended-release niacin with atorvastatin was superior to atorvastatin monotherapy alone in lipid profile regulation . Combination therapy with niacin ER and atorvastatin was well tolerated and safe in patients with coronary artery disease The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial ( ALLHAT ) provides a unique opportunity to compare the long-term relative safety and efficacy of angiotensin-converting enzyme inhibitor and calcium channel blocker – initiated therapy in older hypertensive individuals . Patients were r and omized to amlodipine ( n=9048 ) or lisinopril ( n=9054 ) . The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infa rct ion , analyzed by intention-to-treat . Secondary outcomes included all-cause mortality , stroke , combined cardiovascular disease ( CVD ) , end-stage renal disease ( ESRD ) , cancer , and gastrointestinal bleeding . Mean follow-up was 4.9 years .  Blood pressure control was similar in nonblacks , but not in blacks . No significant differences were found between treatment groups for the primary outcome , all-cause mortality , ESRD , or cancer . Stroke rates were higher on lisinopril in blacks ( RR=1.51 , 95 % CI 1.22 to 1.86 ) but not in nonblacks ( RR=1.07 , 95 % CI 0.89 to 1.28 ) , and in women ( RR=1.45 , 95 % CI 1.17 to 1.79 ) , but not in men ( RR=1.10 , 95 % CI 0.92 to 1.31 ) . Rates of combined CVD were higher ( RR=1.06 , 95 % CI 1.00 to 1.12 ) because of higher rates for strokes , peripheral arterial disease , and angina , which were partly offset by lower rates for heart failure ( RR=0.87 , 95 % CI 0.78 to 0.96 ) on lisinopril compared with amlodipine .  Gastrointestinal bleeds and angioedema were higher on lisinopril . Patients with and without baseline coronary heart disease showed similar outcome patterns . We conclude that in hypertensive patients , the risks for coronary events are similar , but for stroke , combined CVD , gastrointestinal bleeding , and angioedema are higher and for heart failure are lower for lisinopril-based compared with amlodipine-based therapy . Some , but not all , of these differences may be explained by less effective blood pressure control in the lisinopril arm OBJECTIVE To investigate the effect of intensive lipid lowering with high-dose atorvastatin on the incidence of major cardiovascular events compared with low-dose atorvastatin in patients with coronary artery disease and type 2 diabetes , with and without chronic kidney disease ( CKD ) . PATIENTS AND METHODS Following 8 weeks ' open-label therapy with atorvastatin ( 10 mg/d ) , 10,001 patients with coronary artery disease were r and omized to receive double-blind therapy with either 80 mg/d or 10 mg/d of atorvastatin between July 1 , 1998 , and December 31 , 1999 . Of 1501 patients with diabetes , renal data were available for 1431 . Patients with CKD were defined as having a baseline estimated glomerular filtration rate ( eGFR ) below 60 mL/min per 1.73 m2 , using the Modification of Diet in Renal Disease equation . RESULTS After a median follow-up of 4.8 years , 95 ( 17.4 % ) of 546 patients with diabetes and CKD experienced a major cardiovascular event vs 119 ( 13.4 % ) of 885 patients with diabetes and normal eGFRs ( hazard ratio [ HR ] , 1.32 ; 95 % confidence interval [ CI ] , 1.00 - 1.72 ; P<.05 ) . Compared with 10 mg of atorvastatin , 80 mg of atorvastatin reduced the relative risk of major cardiovascular events by 35 % in patients with diabetes and CKD ( 20.9 % [ 57/273 ] vs 13.9 % [ 38/273 ] ; HR , 0.65 ; 95 % CI , 0.43 - 0.98 ; P=.04 ) and by 10 % in patients with diabetes and normal eGFR ( 14.1 % [ 62/441 ] vs 12.8 % [ 57/444 ] ; HR , 0.90 ; 95 % CI , 0.63 - 1.29 ; P=.56 ) . The absolute risk reduction in patients with diabetes and CKD was substantial , yielding a number needed to treat of 14 to prevent 1 major cardiovascular event over 4.8 years . Both treatments were well tolerated . CONCLUSION Patients with diabetes , stable coronary artery disease , and mild to moderate CKD experience marked reduction in cardiovascular events with intensive lipid lowering , in contrast to previous observations in patients with diabetes and end-stage renal disease . TRIAL REGISTRATION clinical trials.gov identifier : NCT00327691 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 — Lipoprotein(a ) ( Lp(a ) ) hyperlipoproteinemia is a major risk factor for cardiovascular disease , which is not affected by treatment of other cardiovascular risk factors . This study sought to assess the effect of chronic lipoprotein apheresis ( LA ) on the incidence of cardiovascular events in patients with progressive cardiovascular disease receiving maximally tolerated lipid-lowering treatment . Methods and Results — In a prospect i ve observational multicenter study , 170 patients were investigated who commenced LA because of Lp(a)-hyperlipoproteinemia and progressive cardiovascular disease . Patients were characterized regarding plasma lipid status , lipid-lowering drug treatment , and variants at the LPA gene locus . The incidence rates of cardiovascular events 2 years before ( y-2 and y-1 ) and prospect ively 2 years during LA treatment ( y+1 , y+2 ) were compared . The mean age of patients was 51 years at the first cardiovascular event and 57 years at the first LA  . Before LA  , mean low-density lipoprotein cholesterol and Lp(a ) were 2.56±1.04 mmol·L−1 ( 99.0±40.1 mg·dL−1 ) and Lp(a ) 3.74±1.63 µmol·L−1 ( 104.9±45.7 mg·dL−1 ) , respectively . Mean annual rates for major adverse coronary events declined from 0.41 for 2 years before LA to 0.09 for 2 years during LA ( P<0.0001 ) . Event rates including all vascular beds declined from 0.61 to 0.16 ( P<0.0001 ) . Analysis of single years revealed increasing major adverse coronary event rates from 0.30 to 0.54 ( P=0.001 ) for y-2 to y-1 before LA , decline to 0.14 from y-1 to y+1 ( P<0.0001 ) and to 0.05 from y+1 to y+2 ( P=0.014 ) . Conclusions — In patients with Lp(a)-hyperlipoproteinemia , progressive cardiovascular disease , and maximally tolerated lipid-lowering medication  , LA effectively lowered the incidence rate of cardiovascular events . Clinical Trial Registration — URL : https://drks-neu.uniklinik-freiburg.de . Unique identifier : DRKS00003119 OBJECTIVES This study was design ed to evaluate the effect of pravastatin on progression of coronary atherosclerosis and ischemic events in patients with coronary artery disease and mild to moderate hyperlipidemia . BACKGROUND Few clinical trial data support the use of lipid-lowering therapy in patients with coronary artery disease and mild to moderate elevations in cholesterol levels . METHODS Four hundred eight patients ( mean age 57 years ) with coronary artery disease and low density lipoprotein ( LDL ) cholesterol > or = 130 mg/dl ( 3.36 mmol/liter ) but < 190 mg/dl ( [ 4.91 mmol/liter ] ) despite diet were r and omized in a 3-year study to receive pravastatin or placebo .  Atherosclerosis progression was evaluated by quantitative coronary arteriography . RESULTS Baseline mean LDL cholesterol was 164 mg/dl ( 4.24 mmol/liter ) . Pravastatin decreased total and LDL cholesterol and triglyceride levels by 19 % , 28 % and 8 % , respectively , and increased high density lipoprotein cholesterol by 7 % ( p < or = 0.001 vs. placebo for all lipid variables ) . Progression of atherosclerosis was reduced by 40 % for minimal vessel diameter ( p = 0.04 ) , particularly in lesions < 50 % stenosis at baseline . There was a consistent although not statistically significant effect on mean diameter and percent diameter stenosis . There were also fewer new lesions in those assigned pravastatin ( p < or = 0.03 ) . Myocardial infa rct ion was reduced during active treatment ( 8 in the pravastatin group , 17 in the placebo group ; log-rank test , p < or = 0.05 ; 60 % risk reduction ) , with the benefit beginning to emerge after 1 year . CONCLUSIONS In patients with coronary artery disease and mild to moderate cholesterol elevations , pravastatin reduces progression of coronary atherosclerosis and myocardial infa rct ion . The time course of event reduction increases the potential for a relatively rapid decrease in the clinical manifestations of coronary artery disease with lipid lowering OBJECTIVE Statins are powerful lipid-lowering drugs that have been proved effective in the prevention of coronary artery disease , clearly reducing the risk of mortality and cardiovascular events . Whether hyperlipidemic patients undergoing coronary artery bypass grafting profit from the lipid-lowering beneficial effects of statins is as yet uncertain . We sought to determine whether preoperative statin therapy may have an effect on outcome among hyperlipidemic patients undergoing coronary artery bypass grafting .  METHODS From January 2000 through March 2006 , prospect ively recorded clinical data from 3346 consecutive patients undergoing isolated first-time elective coronary artery bypass grafting  were analyzed for major adverse cardiac events and all-cause in-hospital mortality . Of these , 167 patients had preoperative statin-untreated hyperlipidemia ( group 1 ) , 2592 had statin-treated hyperlipidemia ( group 2 ) , and 587 had statin-untreated normolipidemia ( group 3 ) . RESULTS Risk-adjusted multivariate logistic regression analysis revealed statin-treated hyperlipidemia ( odds ratio , 0.42 ; 95 % confidence interval , 0.26 - 0.69 ; P = .0007 ) and statin-untreated normolipidemia ( odds ratio , 0.42 ; confidence interval , 0.26 - 0.69 ; P = .0007 ) to be independently associated with reduced in-hospital major adverse cardiac events but not with in-hospital mortality . To further control for selection bias , a computed propensity score matching based on 14 major preoperative risk factors was performed . After propensity matching , conditional logistic regression analysis confirmed statin-treated hyperlipidemia and statin-untreated normolipidemia to be strongly related to reduced in-hospital major adverse cardiac events ( odds ratio , 0.41 ; 95 % confidence interval , 0.24 - 0.71 [ P = .0013 ] and odds ratio , 0.23 ; 95 % confidence interval , 0.11 - 0.48 [ P = .0001 ] ) but not with in-hospital mortality ( odds ratio , 1.18 ; 95 % confidence interval , 0.36 - 3.87 [ P = .79 ] and odds ratio , 1.10 ; 95 % confidence interval , 0.32 - 4.41 [ P = .80 ] ) after coronary artery bypass grafting surgery . CONCLUSIONS Hyperlipidemic , but not normolipidemic , patients have an increased risk for in-hospital major adverse cardiac events and therefore clearly benefit from preoperative statin therapy before coronary artery bypass grafting surgery Background We investigated in a longitudinal , multicenter , cohort study whether combined lipid apheresis and lipid-lowering medication can reduce extremely high levels of lipoprotein(a ) ( Lp[a ] ) and thus prevent major adverse coronary events ( MACE ) more efficaciously than lipid-lowering medication alone . Methods Eligible patients had coronary artery disease and Lp(a ) levels ≥2.14 µmol/l ( 95th percentile ) . All patients received lipid-lowering medications alone until maximally tolerated doses were no longer effective , followed by combined lipid apheresis and lipid-lowering medication . The rates of the primary outcome , MACE , were recorded for both periods . Results A total of 120 patients were included . The mean duration of lipid-lowering therapy alone was 5.6±5.8 years , and that of apheresis was 5.0±3.6 years . Median Lp(a ) concentration was reduced from 4.00 µmol/l to 1.07 µmol/l with apheresis treatment ( P<0.0001 ) ; the corresponding mean annual MACE rate per patient was 1.056 versus 0.144 ( P<0.0001 ) . Conclusions Lowering of Lp(a ) levels by apheresis was efficacious and safe , and we recommend this therapy for patients in whom maximally tolerated doses of medication alone have failed to control coronary artery disease-associated events 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 Patients with intermittent claudication carry a high risk for cardiovascular complications . The TransAtlantic Inter-Society Consensus ( TASC ) Group estimated a five-year overall mortality of 30 % for these patients , the majority dying from cardiovascular causes . We investigated whether this evaluation is still applicable in nowadays patients . We therefore prospect ively followed 255 male patients with intermittent claudication from the CAVASIC Study during 7 years for overall mortality , vascular morbidity and mortality and local PAD outcomes . Overall mortality reached 16.1 % ( n = 41 ) . Most patients died from cancer ( n = 20 ) . Half of patients ( n = 22 ; 8.6 % ) died within the first five years . Incident cardiovascular events were observed among 70 patients ( 27.5 % ) , 54 ( 21.2 % ) during the first five years . Vascular mortality was low with 5.1 % ( n = 13 ) for the entire and 3.1 % for the first five years of follow-up . Prevalent coronary artery disease did not increase the risk to die from all or vascular causes . PAD symptoms remained stable or improved in the majority of patients ( 67 % ) . In summary , compared to TASC , the proportion of cardiovascular events did not markedly decrease over the last two decades . Vascular mortality , however , was low among our population . This indicates that nowadays patients more often survive cardiovascular events and a major number dies from cancer OBJECTIVES The goal of this study was to examine the prospect i ve association between oxidation-specific biomarkers , primarily oxidized phospholipids ( OxPL ) on apolipoprotein B-100-containing lipoproteins ( OxPL/apoB ) and lipoprotein ( a ) [ Lp(a ) ] , and risk of peripheral artery disease ( PAD ) . We examined , as secondary analyses , indirect measures of oxidized lipoproteins , including autoantibodies to malondialdehyde-modified low-density lipoprotein ( MDA-LDL ) and apolipoprotein B-100 immune complexes ( ApoB-IC ) . BACKGROUND Biomarkers to predict the development of PAD are lacking . OxPL circulate in plasma , are transported by Lp(a ) , and deposit in the vascular wall and induce local inflammation . METHODS The study population included 2 parallel nested case-control studies of 143 men within the Health Professionals Follow-up Study ( 1994 to 2008 ) and 144 women within the Nurses ' Health Study ( 1990 to 2010 ) with incident confirmed cases of clinical ly significant PAD , matched 1:3 to control subjects . RESULTS Levels of OxPL/apoB were positively associated with risk of PAD in men and women : pooled relative risk : 1.37 , 95 % confidence interval : 1.19 to 1.58 for each 1-SD increase after adjusting age , smoking , fasting status , month of blood draw , lipids , body mass index , and other cardiovascular disease risk factors . Lp(a ) was similarly associated with risk of PAD ( pooled adjusted relative risk : 1.36 ; 95 % confidence interval : 1.18 to 1.57 for each 1-SD increase ) . Autoantibodies to MDA-LDL and ApoB-IC were not consistently associated with risk of PAD . CONCLUSIONS OxPL/apoB were positively associated with risk of PAD in men and women . The major lipoprotein carrier of OxPL , Lp(a ) , was also associated with risk of PAD , reinforcing the key role of OxPL in the pathophysiology of atherosclerosis mediated by Lp(a ) The use of lipid-lowering drugs is now established clinical practice . However , not all patient categories have been covered in the l and mark studies ( 4S , WOSCOPS and CARE ) , leaving the arena open for widely differing opinions . Dyslipidoemia in patients with diabetes mellitus and arteriosclerotic disease of the aorta , limb arteries or carotid arteries should be corrected . The benefit remains unproven for patients with coronary artery disease and normal lipid levels , and for the elderly .  Omega-3 supplements are approved in Norway for hypertriglyceridoemia , but clinical benefit has not been established for this treatment , in contrast to treatment with gemfibrosil . Hormone replacement therapy for postmenopausal women effectively lowers LDL cholesterol levels and the results of r and omised studies with clinical endpoints are awaited . The rapid effect ( within six months ) of lowered cholesterol on coronary events suggests that starting treatment during middle age is adequate for many patients , except for those with familial hyperlipidemias Objective : The aim of this study was to evaluate the effectiveness of a supervised exercise program ( SEP ) plus at home nonsupervised exercise therapy ( non-SET ) on functional status , quality of life ( QoL ) and hemodynamic response in post-lower-limb bypass surgery patients . Results : One hundred and seventeen patients were r and omized to an intervention ( n = 57 ) or a control group ( n = 60 ) . A new individual SEP was design ed for patients with peripheral arterial disease ( PAD ) and applied to the studied subjects of the intervention group who also continued non-SET at home , whereas those assigned to the control group received just usual SEP according to a common cardiovascular program . The participants of the study were assessed by a 6-min walking test ( 6 MWT ) , an ankle-brachial index ( ABI ) , and the Medical Outcomes Study Short Form-36 ( SF-36 ) of QoL at baseline , at 1 and 6 months after surgery . A significant improvement was observed in the walked distance in the intervention group after 6 months compared with the control group ( p < 0.001 ) . The intervention group had significantly higher QoL score in the physical and mental component of SF-36 ( p < 0.05 ) . Conclusions : A 6-month application of the new SEP and non-SET at home has yielded significantly better results in walking distance and QoL in the intervention group than in the controls Background Do the benefits of intensive lipid-lowering therapy seen in symptomatic patients extend to high-risk subjects who have never had symptoms ? Methods and ResulsOf 120 men completing the FATS trial , 91 were symptomatic and 29 asymptomatic . All had apolipoprotein B 2125 mg/dL , a positive family history , and coronary atherosclerosis . All were counseled in diet and r and omized to intensive therapy : colestipol 10 g TID plus either niacin 1 g QID or lovastatin 20 mg BID or to conventional therapy : placebos , or colestipol if low-density lipoprotein cholesterol was elevated . End points included quantitative arteriographic disease change and clinical events over a 2.5-year interval . At baseline , symptomatic and asymptomatic patients had comparable risk profiles , but proximal stenosis severity averaged 36 % for symptomatic and 23 % for asymptomatic patients ( P<.001 ) . Among the 91 symptomatic patients , those in the intensive group experienced definite ( .101%S ) proximal lesion progression less frequently than conventional ( 24 % of intensive versus 48 % of conventional ) and definite regression more frequently ( 36 % of intensive versus 15 % of conventional ) ( P=.009 ) . Similarly , among the 29 asymptomatic patients , 19 % of intensive versus 38 % of conventional had progression and 31 % of intensive versus 0%1 of conventional , regression ( P=.04 ) . Ischemia on baseline exercise tolerance testing was associated with significantly greater proximal disease progression among the asymptomatic patients . Clinical cardiovascular events ( death , infa rct ion , or revascularization ) occurred in 10 of 38 symptomatic patients originally assigned to conventional therapy , compared with 5 of 76 symptomatic patients assigned to intensive ( P<.01 ) ; no asymptomatic patient had an event . ConcluionsAsymptomatic subjects with this high-risk profile have less coronary disease at baseline than comparable symptomatic patients , and they have an excellent short-term clinical prognosis . However , asymptomatic subjects are indistinguishable from symptomatic patients in terms of their arterial disease progression with conventional therapy and their regression with intensive . These findings may justify an active treatment strategy in such subjects , particularly those with provokable ischemia 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 Background — Clinical trials have demonstrated that , compared with placebo , intensive statin therapy reduces ischemia in patients with acute coronary syndromes and in patients with stable coronary artery disease . However , no studies to date have assessed intensive versus moderate statin therapy in older patients with stable coronary syndromes . Methods and Results — A total of 893 ambulatory coronary artery disease patients ( 30 % women ) 65 to 85 years of age with ≥1 episode of myocardial ischemia that lasted ≥3 minutes during 48-hour ambulatory ECG at screening were r and omized to atorvastatin  80 mg/d or pravastatin  40 mg/d and followed up for 12 months . The primary efficacy parameter ( absolute change from baseline in total duration of ischemia at month 12 ) was significantly reduced in both groups at month 3 and month 12 ( both P<0.001 for each treatment group ) with no significant difference between the treatment groups . Atorvastatin-treated patients experienced greater low-density lipoprotein cholesterol reductions than did pravastatin-treated patients , a trend toward fewer major acute cardiovascular events ( hazard ratio , 0.71 ; 95 % confidence interval , 0.46 , 1.09 ; P=0.114 ) , and a significantly greater reduction in all-cause death ( hazard ratio , 0.33 ; 95 % confidence interval , 0.13 , 0.83 ; P=0.014 ) . Conclusions — Compared with moderate pravastatin therapy , intensive atorvastatin therapy was associated with reductions in cholesterol , major acute cardiovascular events , and death in addition to the reductions in ischemia observed with both therapies . The contrast between the therapies ’ differing efficacy for major acute cardiovascular events and death and their nonsignificant difference in efficacy for reduction of ischemia suggests that low-density lipoprotein cholesterol – lowering thresholds for ischemia and major acute cardiovascular events may differ . The Study Assessing Goals in the Elderly ( SAGE ) demonstrates that older men and women with coronary artery disease  benefit from intensive statin therapy 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
Lipid-lowering therapy is effective in reducing cardiovascular mortality and morbidity in people with PAD .
It may also improve local symptoms .
Until further evidence on the relative effectiveness of different lipid-lowering agents is available , use of a statin in people with PAD and a blood cholesterol level > /=3.5 mmol/litre is most indicated
BACKGROUND Lipid-lowering therapy is recommended for secondary prevention in people with coronary artery disease .
It may also reduce cardiovascular events and /or local disease progression in people with lower limb peripheral arterial disease ( PAD ) .
OBJECTIVES To assess the effects of lipid-lowering therapy on all-cause mortality , cardiovascular events and local disease progression in patients with PAD of the lower limb .