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In people without lower extremity peripheral artery disease (PAD), mitochondrial DNA copy number declines with aging, and this decline is associated with declines in mitochondrial activity and functional performance. However, whether lower extremity ischemia is associated with lower mitochondrial DNA copy number and whether mitochondrial DNA copy number is associated with the degree of functional impairment in people with PAD is unknown. In people with and without PAD, age 65 years and older, we studied associations of the ankle-brachial index (ABI) with mitochondrial DNA copy number and associations of mitochondrial DNA copy number with functional impairment. Calf muscle biopsies were obtained from 34 participants with PAD (mean age: 73.5 years (SD 6.4), mean ABI: 0.67 (SD 0.15), mean 6-minute walk distance: 1191 feet (SD 223)) and 10 controls without PAD (mean age: 73.1 years (SD 4.7), mean ABI: 1.14 (SD 0.07), mean 6-minute walk distance: 1387 feet (SD 488)). Adjusting for age and sex, lower ABI values were associated with higher mitochondrial DNA copy number, measured in relative copy number (ABI

Screening for asymptomatic peripheral artery disease (aPAD) with the ankle-brachial index (ABI) test is hypothesized to reduce disease progression and cardiovascular (CV) events by identifying individuals who may benefit from early initiation of medical therapy. Using a Markov model, we evaluated the cost effectiveness of initiating medical therapy (e.g. statin and ACE-inhibitor) after a positive ankle-brachial index (ABI) screen in 65-year-old patients. We modeled progression to symptomatic PAD (sPAD) and CV events with and without ABI screening, evaluating differences in costs and quality-adjusted life years (QALYs). The cost of the ABI test, physician visit, new medication, CV events, and interventions for sPAD were incorporated in the model. We performed sensitivity analysis on model variables with uncertainty. Our model found an incremental cost of US $338 and an incremental QALY of 0.00380 with one-time ABI screening, resulting in an incremental cost-effectiveness ratio (ICER) of $88,758/QALY over a 35-year period. The variables with the largest effects in the ICER were aPAD disease prevalence, cost of monthly medication after a positive screen and 2-year medication adherence rates. Screening high-risk populations, such as tobacco users, where the prevalence of PAD may be 2.5 times higher, decreases the ICER to $24,092/QALY. Our analysis indicates the cost effectiveness of one-time screening for aPAD depends on prevalence, medication costs, and adherence to therapies for CV disease risk reduction. Screening in higher-risk populations under favorable assumptions about medication adherence results in the most favorable cost effectiveness, but limitations in the primary data preclude definitive assessment of cost effectiveness.

Little is known about the prognostic significance of specific characteristics of magnetic resonance imaging (MRI) measured plaque in the superficial femoral artery (SFA). Associations of MRI-measured plaque quantity, lumen area, and plaque composition in the SFA with subsequent mobility loss were studied in people with lower extremity peripheral artery disease (PAD). Participants with an ankle-brachial index (ABI) < 1.00 were identified from Chicago medical centers and underwent direct visualization of atherosclerotic plaque in the SFA using MRI. Participants were followed annually for up to 4 years. Mobility loss was defined as becoming unable to walk up and down a flight of stairs or walk one-quarter of a mile without assistance among participants without mobility impairment at baseline. Analyses adjusted for age, sex, race, comorbidities, ABI, physical activity, and other confounders. Of 308 PAD participants without baseline mobility impairment, 100 (32.5%) developed mobility loss during follow-up. Compared to the lowest mean plaque area tertile at baseline, participants in the highest (worst) plaque area tertile had a higher rate of mobility loss (hazard ratio (HR) = 2.08, 95% confidence interval (CI) = 1.14-3.79, p = 0.018). Compared to the highest mean lumen area tertile, the smallest (worst) mean lumen area tertile was associated with greater mobility loss (HR = 2.18, 95% CI = 1.20-3.96, p = 0.011). Neither lipid rich necrotic core nor calcium in the SFA were associated with mobility loss. In conclusion, greater plaque quantity and smaller lumen area in the proximal SFA, but not lipid rich necrotic core or calcium, were associated with higher mobility loss in people with PAD.

We studied whether slower community walking speed and whether greater time spent lying down or sleeping were associated with higher mortality in people with lower extremity peripheral artery disease (PAD). Participants with an ankle-brachial index (ABI) < 0.90 were identified from Chicago medical centers. At baseline, participants reported their usual walking speed outside their home and the number of hours they spent lying down or sleeping per day. Cause of death was adjudicated using death certificates and medical record review. Analyses were adjusted for age, sex, race, comorbidities, ABI, and other confounders. Of 1314 PAD participants, 189 (14.4%) died, including 63 cardiovascular disease (CVD) deaths. Mean follow-up was 34.9 months ± 18.1. Relative to average or normal pace (2-3 miles/hour), slower walking speed was associated with greater CVD mortality: no walking at all: hazard ratio (HR) = 4.17, 95% confidence interval (CI) = 1.46-11.89; casual strolling (0-2 miles/hour): HR = 2.24, 95% CI = 1.16-4.32; brisk or striding (>3 miles/hour): HR = 0.55, 95% CI = 0.07-4.30. These associations were not significant after additional adjustment for the six-minute walk. Relative to sleeping or lying down for 8-9 hours, fewer or greater hours sleeping or lying down were associated with higher CVD mortality: 4-7 hours: HR = 2.08, 95% CI = 1.06-4.05; 10-11 hours: HR = 4.07, 95% CI = 1.86-8.89; ⩾ 12 hours: HR = 3.75, 95% CI = 1.47-9.62. These associations were maintained after adjustment for the six-minute walk. In conclusion, slower walking speed outside the home and less than 8 hours or more than 9 hours lying down per day are potentially modifiable behaviors associated with increased CVD mortality in patients with PAD.

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(+)CD45(dim) (+0.08±0.03 vs -0.06±0.04, p=0.008), CD34(+)CD45(dim)CD133(+) (+0.08±0.05 vs -0.08±0.04, p=0.014), CD34(+)CD45(dim)CD31(+) (+0.10±0.03 vs -0.07±0.04, p=0.002), and CD34(+)CD45(dim)ALDH(+) 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 prospective study is needed to establish the prognostic significance of ischemia-related increases in SPCs among patients with PAD.

The article focuses on an introduction of guidelines by the American Heart Association (AHA) and the American College of Cardiology (ACC) for treatment of patients with lower extremity peripheral artery disease (PAD). It states association of PAD with significant mortality along with quality of life (QoL) impairment in the U.S. It mentions initiation of diagnostic testing for PAD through ankle-brachial index (ABI) tests.

Peripheral artery disease (PAD) is associated with poor health status (symptoms, functioning, quality of life (QOL)). Whether sex differences exist in PAD-specific health status is unknown. In patients presenting to a specialty clinic with new-onset or recent exacerbation of PAD, we examined sex differences as assessed by the Peripheral Artery Questionnaire (PAQ). The Patient-centered Outcomes Related to TReatment Practices in Peripheral Arterial Disease: Investigating Trajectories (PORTRAIT) study is a multicenter, international prospective study of patients with new or worsening PAD symptoms. Baseline characteristics and mean PAQ scores were compared among women (n=481) and men (n=793) before they underwent treatment. The independent association of sex with health status was assessed with multivariable linear regression. As compared with men, women were less often Caucasian, married and employed, and more often lacking health insurance, living alone (36.2% vs 23.6%, p<0.001), had depression and avoided care due to cost (17.0% vs 12.3%, p=0.018). Women and men were of a similar age and education level, and had similar ankle-brachial index (ABI) values (0.7 ± 0.2 in both groups, p=0.052). Female sex was independently associated with lower PAQ scores on all domains (physical functioning adjusted mean difference of -8.40, p<0.001; social functioning adjusted mean difference of -6.8, p<0.001; QOL adjusted mean difference of -6.7, p<0.001), although no differences were observed in treatment satisfaction (adjusted mean difference -0.20, p=0.904). Despite similar ABIs, women presenting with symptoms of PAD had poorer PAD-specific functioning as compared with men, impacting all major health status domains, independent of socio-economic and clinical characteristics. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine if galectin-3 levels were different between participants with peripheral artery disease (PAD) and controls, and to describe its relationship with markers of early atherosclerosis. Sixty participants were recruited into two groups: a PAD group (n=31), ankle–brachial index (ABI) ⩽0.90 and a normal ABI group (n=29), ABI 1.0–1.4. PAD participants were older (68.6 vs 61.8 years, p=0.037), more commonly men (68% vs 38%, p=0.02), and with more cardiovascular risk factors (p<0.001). Galectin-3 was 22% higher in PAD participants (mean±SD: 17.6±4.7 vs 14.4±4.1 ng/mL, p<0.01). The odds ratio for galectin-3 in PAD to be 1 ng/mL higher than the participants with normal ABI was 1.19, after adjusting by age and gender (p=0.014). High-sensitivity C-reactive protein (hs-CRP) and homeostatic model assessment (HOMA) were positively associated with galectin-3 in the age- and gender-adjusted model, while arterial elasticity and microalbuminuria were not. In conclusion, galectin-3 levels were higher in participants with PAD. [ABSTRACT FROM AUTHOR]

We sought to evaluate whether case ascertainment using administrative health data would be a feasible way to identify peripheral artery disease (PAD) patients from the community. Subjects’ ankle–brachial index (ABI) scores from two previous prospective observational studies were linked with International Classification of Diseases (ICD) and Canadian Classification of Interventions (CCI) codes from three administrative databases from April 2002 to March 2012, including the Alberta Inpatient Hospital Database (ICD-10-CA/CCI), Ambulatory Care Database (ICD-10-CA/CCI), and the Practitioner Payments Database (ICD-9-CM). We calculated diagnostic statistics for putative case definitions of PAD consisting of individual code or sets of codes, using an ABI score ⩽ 0.90 as the gold standard. Multivariate logistic regression was performed to investigate additional predictive factors for PAD. Different combinations of diagnostic codes and predictive factors were explored to find out the best algorithms for identifying a PAD study cohort. A total of 1459 patients were included in our analysis. The average age was 63.5 years, 66% were male, and the prevalence of PAD was 8.1%. The highest sensitivity of 34.7% was obtained using the algorithm of at least one ICD diagnostic or procedure code, with specificity 91.9%, positive predictive value (PPV) 27.5% and negative predictive value (NPV) 94.1%. The algorithm achieving the highest PPV of 65% was age ⩾ 70 years and at least one code within 443.9 (ICD-9-CM), I73.9, I79.2 (ICD-10-CA/CCI), or all procedure codes, validated with ABI < 1.0 (sensitivity 5.56%, specificity 99.4% and NPV 84.6%). In conclusion, ascertaining PAD using administrative data scores was insensitive compared with the ABI, limiting the use of administrative data in the community setting. [ABSTRACT FROM AUTHOR]

Proximal claudication is secondary to ischemia caused by peripheral artery disease (PAD), whereas proximal pseudo-claudication is secondary to other disease processes such as hip arthritis, spinal stenosis, neuropathy, and so forth. The differentiation between the two can be challenging. Exercise transcutaneous oxygen pressure measurement (exercise-TcPO2) allows noninvasive detection of flow-reducing lesions in the proximal arteries and tributaries of the lower extremity arterial tree. We present the first case report in the United States using an exercise-TcPO2 algorithm. A 71-year-old diabetic patient with proximal left-sided and right-calf claudication with indeterminate ankle-brachial indices underwent an exercise-TcPO2 study before and after endovascular intervention. Four TcPO2 probes were placed: one at chest level (reference probe), one on each buttock, and one on the symptomatic calf. The Delta from Resting Oxygen Pressure (DROP) index was calculated at each probe site using a previously validated protocol. Proximal left- and right-calf ischemia were confirmed by the initial exercise-TcPO2, and, after endovascular treatment of the left iliac artery lesion, improvements in proximal exercise-TcPO2 values were found. These data suggest that exercise-TcPO2 can be useful in PAD evaluation in patients with non-compressible arteries and/or proximal claudication. [ABSTRACT FROM PUBLISHER]