Presentations of major peripheral arterial disease and risk of major outcomes in patients with type 2 diabetes: results from the ADVANCE-ON study Mortality and Vascular Morbidity in Older Adults With Asymptomatic Versus Symptomatic Peripheral Artery Disease Major Adverse Limb Events and Mortality in Patients With Peripheral Artery Disease: The COMPASS Trial. 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. Leg strength predicts mortality in men but not in women with peripheral arterial disease. Mortality over four years in SHEP participants with a low ankle-arm index. Prognostic value of functional performance for mortality in patients with peripheral artery disease. Peripheral Arterial Disease as an Independent Predictor for Excess Stroke Morbidity and Mortality in Primary-Care Patients: 5-Year Results of the getABI Study Picotamide, a combined inhibitor of thromboxane A2 synthase and receptor, reduces 2-year mortality in diabetics with peripheral arterial disease: the DAVID study. Ankle-brachial index and the incidence of cardiovascular events in the Mediterranean low cardiovascular risk population ARTPER cohort Serum concentrations of L-arginine and L-homoarginine in male patients with intermittent claudication: a cross-sectional and prospective investigation in the CAVASIC Study. Ten Year Mortality in Different Peripheral Arterial Disease Stages: A Population Based Observational Study on Outcome. Cognitive-behavioral treatment of women's body-image dissatisfaction. Progenitor cell release plus exercise to improve functional performance in peripheral artery disease: the PROPEL Study. The Group Oriented Arterial Leg Study (GOALS) to improve walking performance in patients with peripheral arterial disease. Distribution of ankle—brachial index and the risk factors of peripheral artery disease in a multi-ethnic Asian population Effect of niacin, warfarin, and antioxidant therapy on coagulation parameters in patients with peripheral arterial disease in the Arterial Disease Multiple Intervention Trial (ADMIT). Unsupervised Exercise and Mobility Loss in Peripheral Artery Disease: A Randomized Controlled Trial Ischemia-related changes in circulating stem and progenitor cells and associated clinical characteristics in peripheral artery disease 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 Screening of unrecognized peripheral arterial disease (PAD) using ankle-brachial index in high cardiovascular risk patients free from symptomatic PAD. Using ankle-brachial index to detect peripheral arterial disease: prevalence and associated risk factors in a random population sample.
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 — Our aim was to assess the mortality and vascular morbidity risk of elderly individuals with asymptomatic versus symptomatic peripheral artery disease ( PAD ) in the primary care setting . Methods and Results — This prospect i ve cohort study included 6880 representative unselected patients ≥65 years of age with monitored follow-up over 5 years . According to physician diagnosis , 5392 patients had no PAD , 836 had asymptomatic PAD ( ankle brachial index < 0.9 without symptoms ) , and 593 had symptomatic PAD ( lower-extremity peripheral revascularization , amputation as  a  result  of PAD , or intermittent claudication symptoms regardless of ankle brachial index ) . The risk of symptomatic compared with asymptomatic PAD patients was significantly increased for the composite of all-cause death or severe vascular event ( myocardial infa rct ion , coronary revascularization , stroke , carotid revascularization , or lower-extremity peripheral vascular events ; hazard ratio , 1.48 ; 95 % confidence interval , 1.21 to 1.80 ) but not for all-cause death alone ( hazard ratio , 1.13 ; 95 % confidence interval , 0.89 to 1.43 ) , all-cause death/myocardial infa rct ion/stroke ( excluding lower-extremity peripheral vascular events and any revascularizations ; hazard ratio , 1.18 ; 95 % confidence interval , 0.92 to 1.52 ) , cardiovascular events alone ( hazard ratio , 1.20 ; 95 % confidence interval , 0.89 to 1.60 ) , or cerebrovascular events alone ( hazard ratio , 1.33 ; 95 % confidence interval , 0.80 to 2.20 ) . Lower ankle brachial index categories were associated with increased risk . PAD was a strong factor for the prediction of the composite end point in an adjusted model . Conclusions — Asymptomatic PAD diagnosed through routine screening in the offices of primary care physicians carries a high mortality and /or vascular event risk . Notably , the risk of mortality was similar in symptomatic and asymptomatic patients with PAD and was significantly higher than in those without PAD . In the primary care setting , the diagnosis of PAD has important prognostic value BACKGROUND 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 ) Microalbuminuria ( MA ) is associated with increased  cardiovascular and all-cause mortality .  It has been proposed that MA reflects generalized atherosclerosis and may thus predict mortality . To investigate this hypothesis , we studied the associations between , on the one h and , MA and peripheral arterial disease ( PAD ) , a generally accepted marker of generalized atherosclerosis , and , on the other h and , cardiovascular and all-cause mortality in an age- , sex- , and glucose tolerance-stratified sample ( n=631 ) of a population -based cohort aged 50 to 75 years followed prospect ively for 5 years . At baseline , the  albumin-to-creatinine ratio ( ACR ) was measured in an overnight spot urine sample ; MA was defined as ACR > 2.0 mg/mmol . PAD was defined as an ankle-brachial pressure index below 0.90 and /or a history of a peripheral arterial bypass or amputation . After 5 years of follow-up , 58 subjects had died ( 24 of cardiovascular causes ) . Both MA and PAD were associated with a 4-fold increase in cardiovascular mortality . After adjusting for age , sex , diabetes mellitus , hypertension , levels of total and HDL-cholesterol and triglyceride , body mass index , smoking habits , and preexistent ischemic heart disease , the relative risks ( RR ) ( 95 % confidence intervals ) were 3.2 ( 1.3 to 8.1 ) for MA and 2.4 ( 0.9 to 6.1 ) for PAD . When both MA and PAD were included in the multivariate analysis , the RRs were 2.9 ( 1.1 to 7.3 ) for MA and 2.0 ( 0.7 to 5.7 ) for PAD . MA and PAD were both associated with an about 2-fold increase in all-cause mortality . The RRs of all-cause mortality associated with MA and PAD were about 4 times higher among hypertensive than among normotensive subjects . We conclude that both MA and PAD are associated with an increased risk of cardiovascular mortality . MA and PAD are mutually independent risk indicators . The associations of MA and PAD with all-cause mortality are somewhat weaker . They are more pronounced in the presence of hypertension than in its absence . These data suggest that MA affects mortality risk through a mechanism different from generalized atherosclerosis OBJECTIVE To 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 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 OBJECTIVES Among persons with lower extremity peripheral artery disease ( PAD ) , we determined whether objective measures of walking performance predict mortality independently of the ankle brachial index ( ABI ) . BACKGROUND The ability of office-based functional performance measures to predict mortality in patients with PAD is unknown . METHODS Participants were 444 persons with PAD followed prospect ively for 4.8 years . The 6-min walk and 4-m walks at usual and fastest pace were measured at baseline . Cox proportional hazard models were used to assess relations between baseline measures of lower extremity performance with mortality , adjusting for confounders . RESULTS One hundred twenty-seven patients ( 28.6 % ) died during follow-up . Adjusting for age , gender , race , comorbidities , ABI , and other confounders , participants in the poorest baseline quartile of 6-min walk performance had significantly increased total mortality ( hazard ratio [ HR ] 2.36 [ 95 % confidence interval ( CI ) 1.33 to 4.18 ] ) and cardiovascular mortality ( HR 5.59 [ 95 % CI 1.97 to 15.9 ] ) compared with the best quartile of baseline performance . Participants in the poorest baseline quartile of normal-paced 4-m walking speed had significantly increased total mortality ( HR 1.86 [ 95 % CI 1.06 to 3.29 ] ) and cardiovascular mortality ( HR 2.55 [ 95 % CI 1.01 to 6.46 ] ) compared with the best quartile of baseline performance . CONCLUSIONS This study demonstrates for the first time that performance-based measures , which can be administered in an office setting , provide prognostic information regarding mortality in persons with PAD beyond that provided by the ABI 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 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 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 High serum concentrations of l-arginine and l-homoarginine increase nitric oxide ( NO ) availability and thereby improve endothelial function . Information about the association of these markers with peripheral arterial disease ( PAD ) and related outcomes is sparse . METHODS l-arginine , its metabolites and l-homoarginine were analyzed in the CAVASIC Study including 232 male patients diagnosed with intermittent claudication and 246 age- and diabetes-matched controls . After the baseline investigation PAD patients were prospect ively followed ( median 7 years ) . The association of these markers with symptomatic PAD at baseline , incident cardiovascular events and all-cause mortality was assessed . RESULTS At baseline each increase of ln-l-homoarginine and l-arginine by one st and ard deviation was associated with symptomatic PAD : OR=0.75 , 95%CI 0.59 - 0.96 , P=0.02 and OR=1.36 , 95%CI 1.07 - 1.73 , P=0.01 , respectively ( both models adjusted for ln-CRP , GFR , HDL cholesterol , and current smoking ) . Only l-arginine remained significant after additional adjustment for ln-NT-proBNP and hs-cTnT : OR=1.49 , P=0.002 . In the Cox regression analysis elevated ln-l-homoarginine significantly reduced the risk to die ( n=38 ) even independent from ln-NT-proBNP and hs-cTnT : HR=0.59 , 95%CI 0.41 - 0.84 , P=0.004 . l-arginine was significantly predicting incident cardiovascular events ( n=65 ) : HR=1.68 , 95%CI 1.35 - 2.10 , P < 0.001 . CONCLUSIONS This study in male patients with intermittent claudication and age- and diabetes-matched controls showed an association of l-homoarginine and l-arginine with PAD . During follow-up , l-arginine was associated with incident cardiovascular events probably due to its primary role in NO metabolism and impact on endothelial integrity . l-homoarginine was related to all-cause mortality implying a broader role in metabolic processes besides endothelial function 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 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 Functional impairment , functional decline , and mobility loss are major public health problems in people with lower extremity peripheral artery disease ( PAD ) . Few medical therapies significantly improve walking performance in PAD . We describe methods for the PROgenitor cell release Plus Exercise to improve functionaL performance in PAD ( PROPEL ) Study , a r and omized controlled clinical trial design ed to determine whether granulocyte-macrophage colony stimulating factor ( GM-CSF ) combined with supervised treadmill walking exercise improves six-minute walk distance more than GM-CSF alone , more than supervised treadmill exercise alone , and more than placebo plus attention control in participants with PAD , respectively . PROPEL Study participants are r and omized to one of four arms in a 2 by 2 factorial design . The four study arms are GM-CSF plus supervised treadmill exercise , GM-CSF plus attention control , placebo plus supervised exercise therapy , or placebo plus attention control . The primary outcome is change in six-minute walk distance at 12-week follow-up . Secondary outcomes include change in brachial artery flow-mediated dilation ( FMD ) , change in maximal treadmill walking time , and change in circulating CD34 + cells at 12-week follow-up . Outcomes are also measured at six-week and six-month follow-up . Results of the PROPEL Study will have important implication s for underst and ing mechanisms of improving walking performance and preventing mobility loss in the large and growing number of men and women with PAD People with lower extremity peripheral artery disease ( PAD ) have greater functional impairment and faster functional decline than those without PAD . We describe methods for the Group Oriented Arterial Leg Study ( GOALS ) , an ongoing r and omized controlled clinical trial design ed to determine whether a Group-Mediated Cognitive Behavioral ( GMCB ) intervention improves functional performance in PAD participants , compared to a health education control condition . In GOALS , PAD participants were r and omized to either an intervention or a health education control condition in a parallel design . Both conditions consist of weekly group sessions with other PAD participants . In the intervention , cognitive behavioral techniques are used to assist participants in setting and adhering to home-based walking exercise goals . Participants are encouraged to walk for exercise at home at least 5 days/week . In the control condition , participants receive lectures on health-related topics . After 6 months of on-site weekly sessions , participants are transitioned to telephone follow-up for another 6 months . Participants in the intervention are asked to continue home walking exercise .  The primary outcome is change in six-minute walk performance between baseline and six-month follow-up . Secondary outcomes include change in six-minute walk performance at 12-month follow-up , and change in treadmill walking performance , the Walking Impairment Question naire , quality of life , and physical activity at six and 12-month follow-up . In conclusion , if our group-mediated cognitive behavioral intervention is associated with improved walking performance in individuals with PAD , results will have major public health implication s for the large and growing number of people with 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 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 Few medical therapies improve lower extremity functioning in people with lower extremity peripheral artery disease ( PAD ) . Among people with PAD , we studied whether a group-mediated cognitive behavioral intervention promoting home-based unsupervised exercise prevented mobility loss and improved functional performance compared to control . Methods and Results One hundred ninety-four PAD participants were r and omized . During months 1 to 6 , the intervention group met weekly with other PAD participants and a facilitator . Group support and self-regulatory skills were used to help participants adhere to walking exercise . Ninety-percent of exercise was conducted at or near home . The control group attended weekly lectures . During months 6 to 12 , each group received telephone contact only . Primary outcomes have been reported . Here we compare changes in exploratory outcomes of mobility loss ( the inability to climb a flight of stairs or walk one-quarter mile without assistance ) , walking velocity , and the Short Physical Performance Battery . Compared to controls , fewer participants r and omized to the intervention experienced mobility loss at 6-month follow-up : 6.3 % versus 26.5 % , P=0.002 , odds ratio=0.19 ( 95 % CI=0.06 to 0.58 ) and at 12-month follow-up : 5.2 % versus 18.5 % , P=0.029 , odds ratio=0.24 ( 95 % CI=0.06 to 0.97 ) . The intervention improved fast-paced 4-m walking velocity at 6-month follow-up ( P=0.005 ) and the Short Physical Performance Battery at 12-month follow-up ( P=0.027 ) , compared to controls . Conclusions In exploratory analyses , a group-mediated cognitive behavioral intervention promoting unsupervised walking exercise prevented mobility loss and improved functioning at 6- and 12-month follow-up in PAD patients . Clinical Trial Registration URL : http:// clinical trials.gov . Unique identifier : NCT00693940 The extent and clinical significance of stem and progenitor cell ( SPC ) increases in response to lower-extremity ischemia in people with peripheral artery disease ( PAD ) are unclear . We compared changes in SPC levels immediately following a treadmill exercise test between individuals with and without PAD . Among participants with PAD , we determined whether more severe PAD was associated with greater increases in SPCs following treadmill exercise-induced lower-extremity ischemia . We measured SPC levels in 25 participants with PAD and 20 without PAD  before and immediately after a treadmill exercise test .  Participants with PAD , compared to participants without PAD , had greater increases in CD34+CD45dim ( + 0.08±0.03 vs −0.06±0.04 , p=0.008 ) , CD34+CD45dimCD133 + ( + 0.08±0.05 vs −0.08±0.04 , p=0.014 ) , CD34+CD45dimCD31 + ( + 0.10±0.03 vs −0.07±0.04 , p=0.002 ) , and CD34+CD45dimALDH+ SPCs ( + 0.18±0.07 vs −0.05±0.08 , p=0.054 ) measured as a percentage of all white blood cells . Among participants with PAD , those with any increases in the percent of SPCs immediately after the treadmill exercise test compared to those with no change or a decrease in SPCs had lower baseline ankle – brachial index values ( 0.65±0.17 vs 0.90±0.19 , p=0.004 ) and shorter treadmill times to onset of ischemic leg symptoms ( 2.17±1.54 vs 5.25±3.72 minutes , p=0.012 ) . In conclusion , treadmill exercise-induced lower-extremity ischemia is associated with acute increases in circulating SPCs among people with PAD . More severe PAD is associated with a higher prevalence of SPC increases in response to lower-extremity ischemia . Further prospect i ve study is needed to establish the prognostic significance of ischemia-related increases in SPCs among patients with PAD 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 OBJECTIVE To determine the utility of  ankle-brachial index ( ABI )  in screening for unrecognized peripheral arterial disease ( PAD ) . Although PAD is a consistent predictor of cardiovascular morbidity and mortality , it is often under-diagnosed and under-treated . METHODS In this prospect i ve , observational , real-life , epidemiologic study ( ELLIPSE ) the prevalence of  PAD ( ABI < 0.9 )  was calculated in 2146 asymptomatic patients > or = 55 years of age who were at high cardiovascular risk and who were hospitalized in departments of cardiology , diabetology , geriatrics , internal medicine , or neurology in metropolitan France .  Univariate and multivariate analyses were performed to identify PAD risk factors . The discriminatory power of the model was evaluated by calculating the area under the curve ( AUC ) of the receiver operating characteristic curve . RESULTS The ABI was < 0.9 in 41.1 % of patients . In the multivariate analysis , absence of > or = 1 pulse ( odds ratio [ OR ] , 2.18 ; 95 % confidence interval [ CI ] , 1.81 to 2.63 ; P < .0001 ) , arterial bruit ( OR , 1.92 ; 95%CI , 1.34 to 2.75 ; P < .0004 ) , previous non-Q-wave myocardial infa rct ion ( OR , 1.50 ; 95%CI , 1.08 to 2.08 ; P = .02 ) , regular smoking ( OR , 1.49 ; 95%CI , 1.22 to 1.80 ; P < .0001 ) , age > or = 81 years ( OR , 1.45 ; 95%CI , 1.15 to 1.82 ; P = .001 ) , creatinine clearance < 60 mL/min ( OR , 1.33 ; 95%CI , 1.08 to 1.63 ; P = .008 ) , and treated hypertension ( OR , 1.28 ; 95%CI , 1.03 to 1.59 ; P = .03 ) were significantly associated with PAD . Although risk increased with the number of variables , the model , based on clinical symptoms and on medical history parameters , was not discriminatory ( AUC = 0.66 ) . On average , physicians took 15 minutes to perform the ABI test . CONCLUSIONS The high prevalence of asymptomatic PAD in this patient population suggests that ABI should systematic ally be performed in high-risk hospitalized patients to ensure that appropriate secondary prevention programs are initiated BACKGROUND 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
No significant associations were found for hip flexion strength , WIQ distance score , or WIQ speed score with mortality .
CONCLUSIONS A number of lower extremity performance measures are prognostic markers for mortality in PAD and may be useful clinical tools for identifying patients at higher risk of death .
BACKGROUND Peripheral artery disease ( PAD ) is associated with impaired mobility and a high rate of mortality .
The aim of this systematic review was to investigate whether reduced lower extremity performance was associated with an increased incidence of  cardiovascular and all-cause mortality in people with PAD .