Inorganic nitrate supplementation improves exercise tolerance and calf vascular function in patients with peripheral artery disease

Peripheral artery disease (PAD) is an atherosclerotic disease that is associated with poor vascular function, walking impairment, and reduced quality of life. Land-based exercise therapy (LBET) is frequently recommended to improve walking and reduce symptoms. Recently, evidence has suggested that heated-water exercise therapy (HWET) is an effective intervention for PAD. However, the efficacy of LBET versus HWET in PAD patients had not been elucidated. Therefore, we sought to compare effects of LBET with HWET on cardiovascular function, exercise tolerance, physical function, and body composition in PAD patients. PAD patients ( n = 53) were recruited and randomly assigned to a LBET group ( n = 25) or HWET group ( n = 28). The LBET group performed treadmill walking, whereas the HWET group performed walking in heated water for 12 wk. Leg (legPWV) and brachial-to-ankle arterial stiffness (baPWV), blood pressure (BP), ankle-brachial index (ABI), 6-min walking distance (6MWD), claudication onset time (COT), physical function, and body composition were assessed before and after 12 wk. There were significant group-by-time interactions ( P < 0.05) for legPWV, BP, 6MWD, COT, body composition, and resting metabolic rate (RMR). Both groups significantly reduced ( P < 0.05) legPWV, BP, and body fat percentage, and HWET measures were significantly lower than LBET measures. Both groups significantly increased 6MWD, COT, and RMR, and HWET group measures were significantly greater than LBET measures. A time effect was noted for baPWV reduction in both groups ( P < 0.05). These results suggest that both LBET and HWET improve cardiovascular function, exercise tolerance, and body composition, and HWET showed considerably greater improvements compared with LBET in patients with PAD. NEW & NOTEWORTHY The results of this study reveal for the first time that although land-based exercise therapy is effective for reducing arterial stiffness and blood pressure in patients with peripheral artery disease (PAD), heated-water exercise therapy demonstrates greater benefits on vascular function. The greater improvements in muscular strength, time to onset of claudication, and exercise tolerance after heated-water exercise therapy may have clinical implications for improving quality of life in patients with PAD. The heated-water exercise therapy intervention demonstrated relatively higher exercise training adherence (∼88%) compared with the land-based exercise intervention (∼81%).

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Impacts of Aqua Aerobic Exercise on Vascular Health and Exercise Tolerance in Patients With Peripheral Artery Disease

Case Medical Research ◽

10.31525/ct1-nct03849300 ◽

2019 ◽

Author(s):

Keyword(s):

Aerobic Exercise ◽

Peripheral Artery Disease ◽

Exercise Tolerance ◽

Vascular Health ◽

Peripheral Artery ◽

Artery Disease

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Abstract 11: Effects of Canakinumab in Patients With Peripheral Artery Disease

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.11 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Kerry S Russell ◽

Denise Yates ◽

Andrea Feller ◽

Tianke Wang ◽

Ping Chen ◽

...

Keyword(s):

Peripheral Artery Disease ◽

Vascular Function ◽

Cardiovascular Events ◽

Ankle Brachial Index ◽

Unmet Need ◽

Walking Distance ◽

Plaque Progression ◽

Peripheral Artery ◽

Plaque Volume ◽

Artery Disease

Background: Peripheral artery disease (PAD) affects 8.5 million people in the US. PAD patients are at high risk for cardiovascular events, and their quality of life is often significantly impaired by decreased mobility. Interleukin-1β (IL-1β) may play an important role in this disease by promoting inflammatory responses that drive atherosclerotic plaque progression and impair vascular function. We sought to test whether interruption of IL-1β signaling would improve patient mobility and decrease plaque progression in the lower extremities. Methods: 38 patients (mean age 65; 71% male) with symptomatic PAD (confirmed by ankle-brachial index) were randomized 1:1 to receive Canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. Plaque volume in the superficial femoral artery (SFA) was assessed serially using 3.0T MRI. Mobility was assessed serially using the 6-minute walk test (maximum and pain-free walking distance). Results: Canakinumab was safe and well-tolerated. 12 patients discontinued (8 placebo, 4 Canakinumab). MRI data (from 31 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA at either time point in placebo-treated patients; nor was there a change in plaque volume in the Canakinumab-treated group. There was a serial and significant improvement in placebo-adjusted maximum and pain-free walking distance observed as early as 3 months after treatment with Canakinumab (58-meter improvement over placebo in pain-free distance at 3 months, P=0.01). Two placebo-treated patients required peripheral vascular interventions due to progression of disease; however, no Canakinumab-treated patients required revascularization during the study. Canakinumab decreased markers of systemic inflammation (IL-6 and hsCRP). Conclusions: Treatment with Canakinumab may improve maximum and pain-free walk distance in patients with symptomatic PAD. In conjunction with results soon to be reported for the CANTOS trial of Canakinumab for secondary prevention of cardiovascular events, additional studies may provide support that inhibition of IL-1β signaling can improve symptoms and function in this patient population with high unmet need.

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Eight weeks of nitrate supplementation improves blood flow and reduces the exaggerated pressor response during forearm exercise in peripheral artery disease

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00015.2018 ◽

2018 ◽

Vol 315 (1) ◽

pp. H101-H108 ◽

Cited By ~ 9

Author(s):

Nicholas T. Kruse ◽

Kenichi Ueda ◽

William E. Hughes ◽

Darren P. Casey

Keyword(s):

Blood Flow ◽

Peripheral Artery Disease ◽

Pressor Response ◽

Treated Group ◽

Moderate Intensity ◽

Peripheral Artery ◽

Pressor Responses ◽

Nitrate Supplementation ◽

Artery Disease ◽

Forearm Exercise

Peripheral artery disease (PAD) is characterized by a reduced blood flow (BF) and an elevated blood pressure (pressor) response during lower extremity exercise. Although PAD is evident in the upper extremities, no studies have determined BF and pressor responses during upper extremity exercise in PAD. Emerging evidence suggests that inorganic nitrate supplementation may serve as an alternative dietary strategy to boost nitric oxide bioavailability, improving exercising BF and pressor responses during exercise. The present study investigated 1) BF and pressor responses to forearm exercise in patients with PAD ( n = 21) relative to healthy age-matched control subjects ( n = 16) and 2) whether 8 wk of NaNO3 supplementation influenced BF and pressor responses to forearm exercise in patients with PAD. Patients with moderate to severe PAD were randomly assigned to a NaNO3 (1 g/day, n = 13)-treated group or a placebo (microcrystalline cellulose, n = 8)-treated group. Brachial artery forearm BF (FBF; via Doppler) and blood pressure (via finger plethysmography) were measured during mild-intensity (~3.5-kg) and moderate-intensity (~7-kg) handgrip exercise. The absolute change (from baseline) in FBF was reduced (except in the 3.5-kg condition) and BP responses were increased in patients with PAD compared with healthy control subjects in 3.5- and 7-kg conditions (all P < 0.05). Plasma nitrate and nitrite were elevated, exercising (7-kg) ΔFBF was improved (from 141 ± 17 to 172 ± 20 ml/min), and mean arterial pressure response was reduced (from 13 ± 1 to 9 ± 1 mmHg, P < 0.05) in patients with PAD that received NaNO3 supplementation for 8 wk relative to those that received placebo. These results suggest that the BF limitation and exaggerated pressor response to moderate-intensity forearm exercise in patients with PAD are improved with 8 wk of NaNO3 supplementation. NEW & NOTEWORTHY Peripheral artery disease (PAD) results in an exaggerated pressor response and reduced blood flow during lower limb exercise; however, the effect of PAD in the upper limbs has remained unknown. These results suggest that 8 wk of inorganic nitrate supplementation improves the blood flow limitation and exaggerated pressor response to moderate-intensity forearm exercise in PAD.

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Leg heat therapy improves perceived physical function but does not enhance walking capacity or vascular function in patients with peripheral artery disease

Journal of Applied Physiology ◽

10.1152/japplphysiol.00277.2020 ◽

2020 ◽

Vol 129 (6) ◽

pp. 1279-1289

Author(s):

Jacob C. Monroe ◽

Chen Lin ◽

Susan M. Perkins ◽

Yan Han ◽

Brett J. Wong ◽

...

Keyword(s):

Physical Function ◽

Peripheral Artery Disease ◽

Vascular Function ◽

Controlled Study ◽

Peripheral Artery ◽

Walking Capacity ◽

Heat Therapy ◽

Walking Performance ◽

Artery Disease ◽

Potent Vasoconstrictor

This is the first sham-controlled study to investigate the effects of leg heat therapy (HT) on walking performance, vascular function, and quality of life in patients with peripheral artery disease (PAD). Adherence to HT was high, and the treatment was well tolerated. Our findings revealed that HT applied with water-circulating trousers evokes a clinically meaningful increase in perceived physical function and reduces the serum concentration of the potent vasoconstrictor endothelin-1 in patients with PAD.

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