Cardioprotective medication is associated with improved survival in patients with peripheral arterial disease. High prevalence of peripheral arterial disease in hypertensive patients: the Evaluation of Ankle-Brachial Index in Hungarian Hypertensives screening program Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic Peripheral Artery Disease Microalbuminuria and peripheral arterial disease are independent predictors of cardiovascular and all-cause mortality, especially among hypertensive subjects: five-year follow-up of the Hoorn Study. Peripheral Arterial Disease as an Independent Predictor for Excess Stroke Morbidity and Mortality in Primary-Care Patients: 5-Year Results of the getABI Study Low-Density Lipoprotein Cholesterol Lowering With Evolocumab and Outcomes in Patients With Peripheral Artery Disease: Insights From the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) Effects of chronic administration of selective betablockers on peripheral circulation of the lower limbs in patients with essential hypertension. Using ankle-brachial index to detect peripheral arterial disease: prevalence and associated risk factors in a random population sample. Screening of unrecognized peripheral arterial disease (PAD) using ankle-brachial index in high cardiovascular risk patients free from symptomatic PAD. Ten Year Mortality in Different Peripheral Arterial Disease Stages: A Population Based Observational Study on Outcome. Outcomes Among Hypertensive Patients With Concomitant Peripheral and Coronary Artery Disease: Findings From the INternational VErapamil-SR/Trandolapril STudy Rationale and design of the Arterial Disease Multiple Intervention Trial (ADMIT) pilot study. Intensive Blood Pressure Control Reduces the Risk of Cardiovascular Events in Patients With Peripheral Arterial Disease and Type 2 Diabetes Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension Can long-term antibiotic treatment prevent progression of peripheral arterial occlusive disease? A large, randomized, double-blinded, placebo-controlled trial. Distribution of ankle—brachial index and the risk factors of peripheral artery disease in a multi-ethnic Asian population Presentations of major peripheral arterial disease and risk of major outcomes in patients with type 2 diabetes: results from the ADVANCE-ON study
OBJECTIVES We sought to investigate the effect of cardiac medication on long-term mortality in patients with peripheral arterial disease ( PAD ) . BACKGROUND Peripheral arterial disease is associated with increased cardiovascular morbidity and mortality . Treatment guidelines recommend aggressive management of risk factors and lifestyle modifications . However , the potential benefit of cardiac medication in patients with PAD remains ill defined . METHODS In this prospect i ve observational cohort study , 2,420 consecutive patients ( age , 64 + /- 11 years , 72 % men ) with PAD ( ankle-brachial index < or = 0.90 ) were screened for clinical risk factors and cardiac medication . Follow-up end point was death from any cause . Propensity scores for statins , beta-blockers , aspirin , angiotensin-converting enzyme ( ACE ) inhibitors , calcium channel blockers , diuretics , nitrates , coumarins , and digoxin were calculated . Cox regression models were used to analyze the relation between cardiac medication and long-term mortality . RESULTS Medical history included diabetes mellitus in 436 patients ( 18 % ) , hypercholesterolemia in 581 ( 24 % ) , smoking in 837 ( 35 % ) , hypertension in 1,162 ( 48 % ) , coronary artery disease in 1,065 ( 44 % ) , and a history of heart failure in 214 ( 9 % ) . Mean ankle-brachial index was 0.58 ( + /-0.18 ) . During a median follow-up of eight years , 1,067 patients ( 44 % ) died . After adjustment for risk factors and propensity scores , statins ( hazard ratio [ HR ] 0.46 , 95 % confidence interval [ CI ] 0.36 to 0.58 ) , beta-blockers ( HR 0.68 , 95 % CI 0.58 to 0.80 ) , aspirins ( HR 0.72 , 95 % CI 0.61 to 0.84 ) , and ACE inhibitors ( HR 0.80 , 95 % CI 0.69 to 0.94 ) were significantly associated with a reduced risk of long-term mortality . CONCLUSIONS On the basis of this observational longitudinal study , statins , beta-blockers , aspirins , and ACE inhibitors are associated with a reduction in long-term mortality in patients with PAD Aims : Peripheral arterial disease ( PAD ) can be diagnosed in asymptomatic stage , measuring ankle-brachial index ( ABI ) . Low ABI is an indicator of increased cardiovascular risk and its inclusion to traditional risk factors can improve risk prediction . The objective of the present cross-sectional part of our large-scale , multicenter , observational study was to evaluate the prevalence of PAD in a large cohort of hypertensive patients . Methods and results : A total of 21 892 hypertensive men and women ( 9162 men ; mean age 61.45 years ) were included in our prospect i ve study in hypertension clinics . Clinical history , physical examination , and blood analysis were taken , and the ABI was measured with the Doppler method in all patients . The prevalence of PAD ( ABI ⩽0.9 ) was 14.4 % . In 15.6 % of the patients an ABI of 0.91–0.99 , and in 9.4 % of the patients high ABI ( > 1.3 ) was measured . In the low , moderate , high , and very high Systematic Coronary Risk Evaluation risk groups , the prevalence of low ABI was 8.1 , 11.1 , 16.3 , and 26 % , respectively . The prevalence of PAD was lower in hypertensive patients achieving their blood pressure target ( 9.6 vs. 16.8 % ; P < 0.001 ) . Conclusions : Asymptomatic PAD was highly prevalent in the studied hypertensive population . The use of ABI screening may improve cardiovascular risk prediction . Optimal blood pressure goal values in PAD patients and cardiovascular morbidity/mortality data will be evaluated after the 5-year long prospect i ve phase of the Evaluation of Ankle-Brachial Index in Hungarian Hypertensives program Background — 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 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 : There is controversial evidence with regard to the significance of peripheral arterial disease ( PAD ) as an indicator for future stroke risk . We aim ed to quantify the risk increase for mortality and morbidity associated with PAD . Methods : In an open , prospect i ve , noninterventional cohort study in the primary care setting , a total of 6,880 unselected patients ≧65 years were categorized according to the presence or absence of PAD and followed up for vascular events or deaths over 5 years . PAD was defined as ankle-brachial index ( ABI ) < 0.9 or history of previous peripheral revascularization and /or limb amputation and /or intermittent claudication . Associations between known cardiovascular risk factors including PAD and cerebrovascular mortality/events were analyzed in a multivariate Cox regression model . Results : During the 5-year follow-up [ 29,915 patient-years ( PY ) ] , 183 patients had  a stroke ( incidence per 1,000 PY : 6.1 cases ) . In  patients with PAD  ( n = 1,429 ) compared to those without PAD ( n = 5,392 ) , the incidence of all stroke types st and ardized per 1,000 PY , with the exception of hemorrhagic stroke , was about doubled ( for fatal stroke tripled ) . The corresponding adjusted hazard ratios were 1.6 ( 95 % confidence interval , CI , 1.1–2.2 ) for total stroke , 1.7 ( 95 % CI 1.2–2.5 ) for ischemic stroke , 0.7 ( 95 % CI 0.2–2.2 ) for hemorrhagic stroke , 2.5 ( 95 % CI 1.2–5.2 ) for fatal stroke and 1.4 ( 95 % CI 0.9–2.1 ) for nonfatal stroke . Lower ABI categories were associated with higher stroke rates . Besides high age , previous stroke and diabetes mellitus , PAD was a significant independent predictor for ischemic stroke . Conclusions : The risk of stroke is substantially increased in PAD patients , and PAD is a strong independent predictor for stroke Background : 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 This paper summarizes the results of two studies carried out to evaluate the effects of the cardioselective betablockers atenolol , acebutolol and metoprolol on peripheral circulation of the lower limbs . The 1st study was a double dummy double blind cross over placebo controlled trial carried out for 13 weeks to evaluate the effects of acebutolol ( 600 mg/die ) and metoprolol ( 300 mg/die ) , two cardioselective betablockers , on peripheral haemodynamics in patients suffering from mild to moderate hypertension . The 2nd study was a placebo controlled trial on the effects of atenolol ( 100 mg/day ) on haemodynamics at the calf carried out for 8 weeks in patients suffering from essential to severe moderate hypertension , part of which aged over 65 years and affected by arteriosclerosis obliterans of the lower limbs , stage I and II according to Fontaine 's classification .  Calf blood flow in basal condition ( R.F. ) and after ischemic stimulus ( P.F. ) was evaluated by strain gauge plethysmography ; basal ( B.V.R. ) and minimal ( M.V.R. ) vascular resistances at the calf by the ratio between M.B.P./R.F. and M.B.P./P.F. respectively , Windsor 's index ( W.I. ) by ultrasound . Neither the patients with hypertension only nor the elderly hypertensive suffering from arteriosclerosis obliterans of the lower limbs showed changes in R.F. and P.F. , in B.V.R. and M.V.R. and in W.I. after chronic treatment with cardioselective beta-blockers . Many patients --about 17 % of all patients , and 40 % of arteriopathics -- in the two trials had cold h and s and feet . These studies suggest that chronic administration of selective beta-blockers does not exert unfavourable effects on muscular blood flow at the calf in patients with hypertension with or without arteriosclerosis obliterans of the lower limbs at I and II stage . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND AND AIM The ankle-brachial index ( ABI ) is being used increasingly to diagnose peripheral arterial disease ( PAD ) that predicts cardiovascular morbidity and mortality . The aim of this study is to determine the prevalence of PAD  and associated risk factors in a Spanish r and om population sample of age > or = 40 . METHODS AND RESULTS PAD is defined as an ABI<0.9 in either leg . 784 participants of age > or = 40 were r and omly selected in a Spanish province . 55.4 % of them were female . The prevalence of PAD in this sample was 10.5 % ( 95 % confidence interval ( CI ) 8.4 - 12.8 ) ; 9.7 % in females and 11.4 % in males . In logistic regression analyses , adjusted for age and gender , smoking per 10 pack-years ( odds ratio ( OR ) 1.40 , 95 % CI 1.23 - 1.58 ) , hypertension ( OR 1.85 , 95 % CI 1.05 - 3.28 ) , hypercholesterolemia ( OR 1.76 , 95 % CI 1.04 - 2.98 ) , and diabetes ( OR 1.80 , 95 % CI 1.04 - 3.11 ) were positively associated with prevalent PAD . More than 91 % of persons with PAD had one or more cardiovascular disease risk factors . CONCLUSIONS We conclude that in our study hypertension , hypercholesterolemia , diabetes mellitus and smoking are associated with PAD . The majority of individuals with PAD had at least one important cardiovascular risk factor advanced enough to be considered eligible for an aggressive treatment OBJECTIVE To determine the utility of  ankle-brachial index ( ABI )  in screening for unrecognized peripheral arterial disease ( PAD ) . Although PAD is a consistent predictor of cardiovascular morbidity and mortality , it is often under-diagnosed and under-treated . METHODS In this prospect i ve , observational , real-life , epidemiologic study ( ELLIPSE ) the prevalence of  PAD ( ABI < 0.9 )  was calculated in 2146 asymptomatic patients > or = 55 years of age who were at high cardiovascular risk and who were hospitalized in departments of cardiology , diabetology , geriatrics , internal medicine , or neurology in metropolitan France .  Univariate and multivariate analyses were performed to identify PAD risk factors . The discriminatory power of the model was evaluated by calculating the area under the curve ( AUC ) of the receiver operating characteristic curve . RESULTS The ABI was < 0.9 in 41.1 % of patients . In the multivariate analysis , absence of > or = 1 pulse ( odds ratio [ OR ] , 2.18 ; 95 % confidence interval [ CI ] , 1.81 to 2.63 ; P < .0001 ) , arterial bruit ( OR , 1.92 ; 95%CI , 1.34 to 2.75 ; P < .0004 ) , previous non-Q-wave myocardial infa rct ion ( OR , 1.50 ; 95%CI , 1.08 to 2.08 ; P = .02 ) , regular smoking ( OR , 1.49 ; 95%CI , 1.22 to 1.80 ; P < .0001 ) , age > or = 81 years ( OR , 1.45 ; 95%CI , 1.15 to 1.82 ; P = .001 ) , creatinine clearance < 60 mL/min ( OR , 1.33 ; 95%CI , 1.08 to 1.63 ; P = .008 ) , and treated hypertension ( OR , 1.28 ; 95%CI , 1.03 to 1.59 ; P = .03 ) were significantly associated with PAD . Although risk increased with the number of variables , the model , based on clinical symptoms and on medical history parameters , was not discriminatory ( AUC = 0.66 ) . On average , physicians took 15 minutes to perform the ABI test . CONCLUSIONS The high prevalence of asymptomatic PAD in this patient population suggests that ABI should systematic ally be performed in high-risk hospitalized patients to ensure that appropriate secondary prevention programs are initiated 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 Hypertension is a common risk factor for peripheral arterial disease ( PAD ) . Guidelines suggest treating PAD patients to a blood pressure < 130/80 mm Hg ; therefore , our objective was to explore whether attainment of this target blood pressure is associated with improved outcomes . We performed a post hoc analysis of the INternational VErapamil-SR/Tr and olapril STudy , a r and omized clinical trial , which included hypertensive patients with concomitant PAD and coronary artery disease . There were 2699 PAD patients followed for a mean of 2.7 years ( 60 970 patient-years ) . The primary outcome , all-cause death , nonfatal myocardial infa rct ion , or nonfatal stroke , occurred in 16.3 % of PAD patients versus 9.2 % without PAD ( adjusted hazard ratio : 1.26 [ 95 % CI : 1.13 to 1.40 ] ; P<0.0001 ) . The primary outcome occurred least frequently among PAD patients treated to an average systolic blood pressure of 135 to 145 mm Hg and an average diastolic blood pressure of 60 to 90 mm Hg . PAD patients displayed a J-shape relationship with systolic blood pressure and the primary outcome , although individuals without PAD did not . PAD patients may require a different target blood pressure than those without PAD 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 —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 Isolated systolic hypertension is an important risk factor for cardiovascular disease and results primarily from elastic artery stiffening . Although various drug therapies are used to lower peripheral blood pressure ( BP ) in patients with isolated systolic hypertension , the effects of the 4 major classes of antihypertensive agents on central BP , pulse pressure ( PP ) amplification , and arterial stiffness in this condition are not clear . Fifty-nine patients over the age of 60 years with untreated isolated systolic hypertension ( systolic BP ≥140 mm Hg and diastolic BP ≤90 mm Hg ) were r and omly assigned to receive 1 of the following 4 antihypertensive agents : perindopril , atenolol , lercanidipine , or bendrofluazide  . BP was measured using a mercury sphygmomanometer , and augmentation index and carotid-femoral ( aortic ) pulse wave velocity were measured at baseline , after 2 weeks of placebo therapy , and at the end of 10 weeks of active therapy . Peripheral systolic BP and peripheral PP were reduced similarly after treatment with all 4 classes of drug . However , central PP was only reduced significantly by perindopril , lercanidipine , and bendrofluazide , whereas atenolol had no effect . Lercanidipine reduced the augmentation index , whereas atenolol increased it . Aortic pulse wave velocity was not changed by any of the drugs . In summary , despite similar reductions in peripheral systolic and PPs with the 4 classes of drug , changes in central pressure and augmentation index varied . Because central PP and increased wave reflections are considered important risk factors in patients with isolated systolic hypertension , the choice of therapy may be influenced by these findings in the future 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 Peripheral artery disease ( PAD ) is a manifestation of systemic atherosclerosis and is associated with increased cardiovascular morbidity and mortality . We describe the prevalence and risk factors of PAD in a multi-ethnic Asian population ( Chinese , Malays and Indians ) in Singapore . The Singapore Prospect i ve Study Program recruited 4132 individuals between 2004 and 2006 in which the ankle — brachial index ( ABI ) was measured using the  Smartdop ™ 20EX bi-directional blood flow detector . PAD was defined as ≤ 0.9 and a high ABI > 1.4 , with ABI 1.11—1.20 as reference . The mean age ( SD ) of individuals in the study was 49.9 ( 11.8 ) years , with 51.8 % females . PAD was present in 4.3 % of the population and a high ABI ( > 1.4 ) was rare . Malays and Indians had a higher risk ( especially in females ) . Compared to those with an ABI between 1.11 and 1.20 , those with PAD were more likely to be of Malay and Indian ethnicity , female sex , with higher systolic blood pressure and pulse pressure , with increased prevalence of diabetes mellitus , hypertension , albuminuria and renal impairment , and with a past history of stroke . In conclusion , in this large multi-ethnic Asian population , we document the distribution and risk factor associations for PAD . PAD shows an ethnic distribution similar to that of coronary artery disease in Singapore , with differences in sex distribution . Apart from traditional vascular risk factors , pulse pressure , renal impairment and a past history of stroke are important determinants of PAD Background 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 )
However , lack of data specifically examining outcomes in PAD patients should not detract from the overwhelming evidence on the benefit of treating hypertension and lowering blood pressure
BACKGROUND Peripheral arterial disease ( PAD ) causes considerable morbidity and mortality .
Hypertension is a risk factor for PAD .
Treatment for hypertension must be compatible with the symptoms of PAD .
Controversy regarding the effects of beta-adrenoreceptor blockade for hypertension in patients with PAD has led many physicians to stop prescribing beta-adrenoreceptor blockers .
Little is known about the effects of other classes of anti-hypertensive drugs in the presence of PAD .
This is the second up date of a Cochrane review first published in 2003 .
OBJECTIVES To determine the effects of anti-hypertensive drugs in patients with both raised blood pressure and symptomatic PAD in terms of the rate of cardiovascular events and death , symptoms of claudication and critical leg ischaemia , and progression of atherosclerotic PAD as measured by ankle brachial index ( ABI ) changes and the need for revascularisation ( reconstructive surgery or angioplasty ) or amputation .