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Abstract: Background: Lower extremity peripheral arterial disease (PAD) is a coronary heart disease (CHD) risk equivalent. Selected studies have demonstrated less intense risk factor management and diminished mobility in individuals with PAD as compared to individuals with clinical recognized CHD. However, comparable data have not been reported from a nationally representative population. Objectives: To assess the prevalence, treatment, and control of cardiovascular risk factors among individuals with PAD as defined by an ankle-brachial index (ABI) <0.90 (but without recognized CHD) as compared with individuals with recognized CHD (but without PAD). A second objective was to evaluate the diagnostic accuracy of measures of walking dysfunction to identify individuals with PAD. Design, setting, and participants: We analyzed data from 7571 participants aged 40 or older who participated in the National Health and Nutrition Examination Survey (NHANES) 1999–2004, a nationally representative cross-sectional survey of the U.S. population. Results: The prevalence of PAD without CHD was 4.1% (95% CI 3.6–4.5) compared to 7.9% (7.1, 8.9) for CHD (without PAD). Hypertension prevalence was similar, but treatment and control rates were lower among individuals with PAD compared to CHD (treatment: 69% vs. 84%, p <0.001; control: 50% vs. 63%, p =0.01). Treatment of hypercholesterolemia was lower among individuals with PAD (54% vs. 79%, p <0.001) but control was similar (83% vs. 85%, p =0.78). Diabetes awareness, treatment, and control did not differ between the two groups. Walking mobility limitations were specific, but insensitive, for the identification of individuals with PAD. Conclusion: PAD in the absence of clinically recognized CHD is under-treated and poorly controlled in the general U.S. population. Leg symptoms are not adequate to identify individuals with PAD, who are at high risk of ischemic events. [Copyright &y& Elsevier]

Background and aims Traditional glycemic markers, fasting glucose and hemoglobin A1c (HbA1c), predict incident peripheral artery disease (PAD). However, it is unknown whether nontraditional glycemic markers, fructosamine, glycated albumin, and 1,5-anhydroglucitol, are associated with PAD and whether these glycemic markers demonstrate particularly strong associations with severe PAD, critical limb ischemia (CLI). Methods We quantified the associations of these five glycemic markers with incident PAD (hospitalizations with PAD diagnosis or leg revascularization) in 11,634 ARIC participants using Cox regression models. Participants were categorized according to diabetes diagnosis and clinical cut-points of glycemic markers (nontraditional glycemic markers were categorized according to percentiles corresponding to the HbA1c cut-points). Results Over a median follow-up of 20.7 years, there were 392 cases of PAD (133 were CLI with tissue loss). HbA1c was more strongly associated with incident PAD than fasting glucose, with adjusted hazard ratios (HR) 6.00 (95% CI, 3.73–9.66) for diagnosed diabetes with HbA1c ≥ 7% and 3.53 (2.39–5.22) for no diagnosed diabetes with HbA1c ≥ 6.5% compared to no diagnosed diabetes with HbA1c <5.7%. Three nontraditional glycemic markers demonstrated risk gradients intermediate between HbA1c and fasting glucose and their risk gradients were substantially attenuated after adjusting for HbA1c. All glycemic markers consistently demonstrated stronger associations with CLI than PAD without CLI ( p for difference <0.02 for all glycemic markers). Conclusions Nontraditional glycemic markers were associated with incident PAD independent of fasting glucose but not necessarily HbA1c. Our results also support the importance of glucose metabolism in the progression to CLI. [ABSTRACT FROM AUTHOR]

Background and aims Most prior studies investigating the association of lower extremity peripheral artery disease (PAD) with physical function were small or analyzed selected populations (e.g., patients at vascular clinics or persons with reduced function), leaving particular uncertainty regarding the association in the general community. Methods Among 5262 ARIC participants (age 71–90 years during 2011–2013), we assessed the cross-sectional association of ankle-brachial index (ABI) with the Short Physical Performance Battery (SPPB) score (0–12), its individual components (chair stands, standing balance, and gait speed) (0–4 points each), and grip strength after accounting for potential confounders, including a history of coronary disease, stroke, or heart failure. Results There were 411 participants (7.8%) with low ABI ≤0.90 and 469 (8.9%) participants with borderline low ABI 0.91–1.00. Both ABI ≤0.90 and 0.91–1.00 were independently associated with poor physical function (SPPB score ≤6) compared to ABI 1.11–1.20 (adjusted odds ratio 2.10 [95% CI 1.55–2.84] and 1.86 [1.38–2.51], respectively). The patterns were largely consistent across subgroups by clinical conditions (e.g., leg pain or other cardiovascular diseases), in every SPPB component, and for grip strength. ABI >1.3 (472 participants [9.0%]), indicative of non-compressible pedal arteries, was related to lower physical function as well but did not necessarily reach significance. Conclusions In community-dwelling older adults, low and borderline low ABI suggestive of PAD were independently associated with poorer systemic physical function compared to those with normal ABI. Clinical attention to PAD as a potential contributor to poor physical function is warranted in community-dwelling older adults. [ABSTRACT FROM AUTHOR]

Background and aims Low 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with peripheral artery disease (PAD). Prevalence of low 25(OH)D and PAD differ between whites and blacks. However, these associations have not been studied prospectively or in a population based cohort. We tested the hypothesis that low 25(OH)D is associated with greater risk of incident PAD in white and black adults. Methods 25(OH)D was measured in serum collected at ARIC visit 2 (1990–1992). We followed 11,789 ARIC participants free of PAD at visit 2 through 2011 for incident PAD events. 25(OH)D (ng/mL) was categorized as deficient (<20), insufficient (20 to <30) or sufficient (≥30). PAD was defined by an ankle brachial index (ABI) of <0.9 at ARIC visits 3 or 4 or a hospital diagnosis with an ICD-9 code indicating PAD during follow-up. Analysis used multivariable-adjusted Cox proportional hazards regressions. Results Over a mean follow-up of 17.1 years, 1250 incident PAD events were identified. 22% of whites and 61% of blacks were 25(OH)D deficient. After adjustment for demographic characteristics, the hazard ratio (95% CI) of PAD in participants with deficient versus sufficient 25(OH)D was 1.49 (1.26, 1.76). Inclusion of BMI, physical activity, and smoking status attenuated the association [1.25 (1.06, 1.48)]. The association between 25(OH)D and PAD was qualitatively stronger in blacks ( p for interaction = 0.20). Conclusions Deficient 25(OH)D was associated with increased risk of PAD in black and white participants. Whether treatment of low vitamin D through supplementation or modest sunlight exposure prevents PAD is unknown. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate systemic and limb ischemic event rates of PAD patients with prior leg amputation and determine predictors of adverse outcomes. Methods: The REduction of Atherothrombosis for Continued Health (REACH) Registry provided a prospective multinational cohort of 7996 outpatients with PAD enrolled from primary medical clinics in 44 countries in 2003–2004. 1160 patients (14.5%) had a prior leg amputation at any level. Systemic (myocardial infarction [MI], stroke, cardiovascular death) and limb (angioplasty, surgery, amputation) ischemic event rates were determined in a 3-year follow-up. Results: PAD patients with leg amputations on entry had a 5-fold higher rate of a subsequent amputation (12.4% vs. 2.4%, P <.001), lower rate of peripheral angioplasty (8.3% vs. 10.7%, P =.005), and similar rates of surgical revascularization procedures compared with PAD patients without amputation. A nearly 2-fold increase in rates of cardiovascular death (14.5% vs. 7.7%, P <.001) and all-cause mortality (21.8% vs. 12.6%, P <.001) and an increase in the composite outcome of MI, stroke, cardiovascular death, or hospitalization (48.7% vs. 40.0%, P <.001) were noted. Recent (≤1 year) amputation was associated with higher rates of worsening PAD, subsequent lower extremity surgical revascularization procedures, re-amputation, non-fatal MI, and the composite outcome, including hospitalization. Adverse systemic and limb ischemic outcomes were similar regardless of amputation level. Conclusions: Individuals with a history of leg amputations have markedly elevated rates of systemic and limb-related outcomes. PAD patients with recent ischemic amputation have the highest risk of adverse events. A history of “minor” ischemic amputation may confer an identical systemic risk as “major” leg amputation. [Copyright &y& Elsevier]

Abstract: Background: The clinical significance of a high ankle-brachial index (ABI), defined by the associated risk factor burden and ischemic risk, is largely unknown. Methods: Using data from the Atherosclerosis Risk in Communities Study, we categorized 14,777 participants into normal (ABI between 0.9 and 1.3) and high ABI groups (ABI>1.3, >1.4, and >1.5) and compared the risk factor profile and CVD event rates of the normal ABI group to each high ABI group. Results: The prevalence of high ABI was 5.5% for ABI>1.3, 1.2% for ABI>1.4, and 0.37% for ABI>1.5. Compared with participants with a normal ABI, those with ABI>1.3 had a lower prevalence of hypertension and current smoking. The ABI>1.3 group had a greater mean body mass index, but was characterized by fewer pack years of smoking and lower systolic and diastolic blood pressures than the normal ABI group. The prevalence of diabetes, left ventricular hypertrophy, claudication, and coronary heart disease and mean values of fibrinogen, factor VIII activity, von Willebrand factor, lipoprotein (a), and carotid and popliteal intimal-medial thickness were similar between the two ABI groups. The risk factor profiles of the ABI>1.4 and >1.5 groups were also not statistically significantly different from that of the normal ABI group. Over a mean follow-up time of 12.2 years, the age, sex, and race-adjusted CVD event rates per 1000 person years were 8.1 in the normal ABI group, 7.6 in the ABI>1.3 group, 7.6 in the ABI>1.4 group, and 7.4 in the ABI>1.5 group. The CVD event rates of the high ABI groups were similar to that of the normal ABI group. Conclusion: Individuals with a high ABI are not characterized by a more adverse atherosclerosis risk factor profile and do not suffer greater CVD event rates than those with a normal ABI. [Copyright &y& Elsevier]

Abstract: Background:: Some risk factors for peripheral arterial disease (PAD) have been identified, but little information is available on PAD risk factors in individuals with diabetes. Methods:: Using data from the Atherosclerosis Risk in Communities (ARIC) Study, we assessed the relation of traditional and non-traditional risk factors with the risk of PAD in 1651 participants with diabetes, but not PAD, at baseline. Incident PAD was defined as an ankle–brachial index (ABI)&#60;0.9 assessed at regular examinations; hospital discharge codes for PAD, amputation, or leg revascularization; or claudication assessed by annual questionnaire. Results:: Over a mean of 10.3 years of follow-up, 238 persons developed incident PAD identified, yielding a PAD event rate of 13.9 per 1000 person years. Adjusted for sex, age, race, and center, the risk of developing PAD was increased 1.87-fold (95% confidence interval (95% CI): 1.36–2.57) in persons who were current smokers versus non-smokers, 2.27-fold (95% CI: 1.57–3.26) for baseline coronary heart disease (CHD) versus no baseline CHD, and 1.75-fold (95% CI: 1.18–2.60) for the highest quartile versus lowest quartile of triglycerides. We found no evidence of an association with other blood lipids or hypertension. Compared with the lowest quartiles, comparably-adjusted relative risks for the highest quartiles were 1.60 (95% CI: 1.10–2.33) for waist-to-hip ratio, 2.52 (95% CI: 1.70–3.73) for fibrinogen, 1.70 (95% CI: 1.17–2.47) for factor VIII, 1.73 (95% CI: 1.18–2.54) for von Willebrand factor, 2.15 (95% CI: 1.43–3.24) for white blood cell count, 1.81 (95% CI: 1.19–2.74) for serum creatinine, 0.55 (95% CI: 0.37–0.83) for serum albumin, and 2.73 (95% CI: 1.77–4.22) for carotid intima-media thickness. Persons who had a prior history of diabetes and were taking insulin had a relative risk of 1.97 (95% CI: 1.35–2.87) for future PAD events, compared with those with newly identified diabetes at baseline. In our final multivariable model, current smoking, prevalent CHD, elevated fibrinogen and carotid IMT, and a prior history of diabetes with insulin treatment were independently associated with greater PAD incidence. Conclusion:: These markers might be useful to identify individuals with diabetes at particular risk for PAD. [Copyright &y& Elsevier]

Abstract: Objectives: To examine differences in risk factor (RF) management between peripheral artery disease (PAD) and coronary artery (CAD) or cerebrovascular disease (CVD), as well as the impact of RF control on major 1-year cardiovascular (CV) event rates. Methods: The REACH Registry recruited >68000 outpatients aged ≥45 years with established atherothrombotic disease or ≥3 RFs for atherothrombosis. The predictors of RF control that were evaluated included: (1) patient demographics, (2) mode of PAD diagnosis, and (3) concomitant CAD and/or CVD. Results: RF control was less frequent in patients with PAD (n =8322), compared with those with CAD or CVD (but no PAD, n =47492) [blood pressure; glycemia; total cholesterol; smoking cessation (each P <0.001)]. Factors independently associated with optimal RF control in patients with PAD were male gender (OR=1.9); residence in North America (OR=3.5), Japan (OR=2.5) or Latin America (OR=1.5); previous coronary revascularization (OR=1.3); and statin use (OR=1.4); whereas prior leg amputation was a negative predictor (OR=0.7) (P <0.001). Optimal RF control was associated with fewer 1-year CV ischemic symptoms or events. Conclusions: Patients with PAD do not achieve RF control as frequently as individuals with CAD or CVD. Improved RF control is associated with a positive impact on 1-year CV event rates. [Copyright &y& Elsevier]