Background and aims There is a demand for longitudinal studies that use both objective and subjective measures of physical activity to investigate the association of physical activity with the change in carotid intima-media thickness (CIMT). In order to investigate such association, we conducted an 8-year follow-up study that used both objective and subjective measures of physical activity. Methods This cohort study used subsamples of the ongoing Korean Genome and Epidemiology Study (KoGES). Included participants were between 49 to 79 years of age at baseline. Exclusion criteria included incomplete assessments of pedometer/accelerometer, international physical activity questionnaire (IPAQ), and baseline CIMT. Participants with a history of cardiovascular diseases were further excluded. Linear regression models were used for the main analysis. Age differences were assessed by stratifying the participants into < 60 years and ≥ 60 years. Results After removing excluded participants, 835 participants were included in the final analysis (age, 59.84 ± 6.53 years; 326 (39.04%) males). 453 participants were < 60 years and 382 participants were ≥ 60 years. The daily total step count was inversely associated with the percent change in overall CIMT over 8-years (β = -0.015, standard error = 0.007, P = 0.034). This association was present among participants in the < 60-year-old group (β = -0.026, standard error = 0.010, P = 0.006), but not among participants in the ≥ 60-year-old group (β = -0.010, standard error = 0.011, P = 0.38). Conclusions The findings suggest that taking preemptive actions of increasing physical activity may prevent the incidence of atherosclerosis.

INTRODUCTION Patients with peripheral artery disease (PAD) suffer from severe exercise intolerance and accelerated rates of functional decline, resulting, in part, from significant endothelial cell dysfunction and the consequent impairment in leg blood flow. Unfortunately, few non‐invasive therapeutic interventions have been shown to ameliorate the microvascular dysfunction in patients with PAD. Repeated exposure to heat therapy (HT) improves endothelial function in sedentary young individuals, but the effects of this therapy on vascular function in patients with PAD remain poorly defined. The objective of the present study was to test the hypothesis that 8 weeks of home‐based leg HT would improve leg vascular function in patients with symptomatic PAD. METHODS Thirty‐four patients with symptomatic PAD (66 ± 8 years, ankle‐brachial index: 0.68 ± 0.12) were randomized into one of two groups: home‐based leg HT (HT, n=18) or a control treatment (CON, n=16). Patients in both groups were provided with identical water‐circulating trousers and a portable heating pump and were asked to apply the therapy daily (7 days/week, 90 min per session) for 8 consecutive weeks. The pump issued to participants circulated water through the trousers at 43ºC in the HT group and 33ºC in the control group. Laser‐Doppler flowmetry was used to measure red blood cell flux, an index of skin blood flow, during local skin heating to 39°C for 40 min, followed by 43ºC for 20 min. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux divided by mean arterial pressure and expressed as a percentage of maximal vasodilation (%CVCmax). Calf skeletal muscle perfusion was assessed using arterial spin labeling magnetic resonance imaging (MRI) following circulatory occlusion of the thigh for 5 min. RESULTS Five participants were either withdrawn prior to study completion or failed to complete the 8‐week follow‐up visit. The remaining 29 participants were included in the final analysis (CON: n=14, HT: n=15). Two participants from CON and 4 from HT were unable to undergo the MRI scans. At baseline, local skin heating to 39ºC increased %CVCmax to 55.8 ± 12.9% in CON and 52.5 ± 18.7% in the HT group. The change from baseline to 8 weeks in %CVCmax was similar between CON and HT (CON: ‐2.6 ± 13.9%, HT: ‐0.7 ± 16.3%, p=0.74). Peak calf blood flow during reactive hyperemia was comparable between groups at baseline (CON: 48.0 ± 24.6 ml/min/100g, HT: 43.8 ± 20.4 ml/min/100g, p=0.76). The change from baseline to 8 weeks in peak calf perfusion was also similar between CON and HT (CON: ‐4.8±21.9 ml/min/100g, HT: ‐2.8±11.0 ml/min/100g, p=0.84). CONCLUSION Eight weeks of home‐based leg HT does not improve leg vascular function in patients with symptomatic PAD.

Introduction Near infrared spectroscopy (NIRS) is a potentially valuable tool to examine disease severity and the effects of therapeutic interventions on microvascular leg oxygenation in patients with peripheral artery disease (PAD). However, multiple factors can confound the interpretation of NIRS signals and therefore limit its clinical applicability, including adipose tissue thickness (ATT) and skin melanin content. We tested the hypothesis that the changes in the concentration of oxygenated [oxy‐Hb+Mb] and deoxygenated [deoxy‐Hb+Mb] hemoglobin + myoglobin would be reduced in the calf of black PAD patients during exercise when compared to white patients. Similarly, we hypothesized that patients with a thicker calf ATT would exhibit a lower change in oxy[Hb+Mb] and deoxy[Hb+Mb] during exercise relative to patients with low ATT. Methods Twenty‐four participants with a history of exertional calf pain (18 males, 6 females, 67±7 years; ankle‐brachial index: 0.6±0.1) were asked to complete two graded tests on the treadmill. The protocol consisted of a constant walking speed of 2 mph and progressive increases in grade of 2% every 2 min. The NIRS device was secured to the skin over the medial gastrocnemius muscle of the most symptomatic leg. Oxy[Hb+Mb] and deoxy[Hb+Mb] were measured continuously at rest and during exercise. The final 20‐s averages of stages 1, 2 and peak exercise were utilized for analysis. Magnetic resonance imaging of the calf was used to measure ATT. The average ATT among all individuals (7±3 mm) was used to divide participants into ‘low’ (n=12) or ‘high’ (n=12) ATT groups. A three‐way repeated measures analysis of variance was used to evaluate the effects of skin color, ATT, and stage of the treadmill test (i.e. stage 1, stage 2, peak walking time) on the changes from baseline in calf oxy[Hb+Mb] and deoxy[Hb+Mb]. Results Seven participants were black and the remaining 17 were white. The average ATT at the medial gastrocnemius site was 4±1 mm in the low ATT group and 9±2 mm in the high ATT group. A significant interaction was observed between skin color, ATT, and exercise stage for the change from baseline in oxy[Hb+Mb] (p=0.049). Post‐hoc testing revealed that among white participants, the change in oxy[Hb+Mb] during exercise was significantly lower in the high ATT group when compared to the low ATT group (p=0.039). Among black participants, the change in calf oxy[Hb+Mb] was similar between high and low ATT (p=0.57). There was a trend for a main effect of ATT on the changes in deoxy[Hb+Mb] during exercise (p=0.1), but the main effects of skin color (p=0.2) and the interaction between skin color, ATT, and exercise stage (p=0.5) were not significant. Conclusions In conclusion, the changes in NIRS‐derived calf oxy[Hb+Mb] during exercise are impacted by both skin color and ATT in patients with symptomatic PAD.

Few non-invasive therapies currently exist to improve functional capacity in people with lower extremity peripheral artery disease (PAD). The goal of the present study was to test the hypothesis that unsupervised, home-based leg heat therapy (HT) using water-circulating trousers perfused with warm water would improve walking performance in patients with PAD. Symptomatic PAD patients were randomized into either leg HT (n=18) or a sham treatment (n=16). Patients were provided with water-circulating trousers and a portable pump and were asked to apply the therapy daily (7 days/week, 90 min per session) for 8 weeks. The primary study outcome was the change from baseline in 6-minute walk distance at 8-week follow-up. Secondary outcomes included the claudication onset-time, peak walking time, peak pulmonary oxygen consumption and peak blood pressure during a graded treadmill test, resting blood pressure, the ankle-brachial index, post-occlusive reactive hyperemia in the calf, cutaneous microvascular reactivity and perceived quality of life. Of the 34 participants randomized, 29 completed the 8-week follow-up. The change in 6-minute walk distance at the 8-week follow-up was significantly higher (p=0.029) in the group exposed to HT as compared to the sham-treated group (Sham: median: -0.9; 25%,75% percentiles: -5.8,14.3; HT: median: 21.3; 25%,75% percentiles: 10.1,42.4, p=0.029). There were no significant differences in secondary outcomes between the HT and sham group at 8-week follow-up. The results of this pilot study indicate that unsupervised, home-based leg HT is safe, well-tolerated and elicits a clinically meaningful improvement in walking tolerance in patients with symptomatic PAD.