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Passive heat therapy for lowering systolic blood pressure and improving vascular function in mid-life and older adults

被动热疗可降低中年和老年人的收缩压并改善血管功能

基本信息

批准号：
10375083
负责人：
DOUGLAS R SEALS
金额：
$ 65.5万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10375083
关键词：
3-nitrotyrosine Acetylcholine Acute Adult Adverse event Age-Years Aging Antioxidants Aorta Arteries Ascorbic Acid Automobile Driving Biological Assay Biological Availability Biopsy Blood Pressure Blood Vessels Body Temperature Cardiovascular Diseases Carotid Arteries Clinical Clinical Trials Dementia Disease Drops Elderly Endothelial Cells Endothelium Exposure to Guidelines Hour Human Hypertension Immersion Impaired cognition Impairment Individual Infusion procedures Life Style Measures Mediating Medical Molecular Nitric Oxide Oregon Oxidative Stress Pharmacology Pharmacotherapy Physiologic pulse Placebos Plasma Prevalence Production Randomized Reactive Oxygen Species Rest Risk Factors Safety Serious Adverse Event Serum Signal Transduction Stroke Temperature Therapeutic Therapeutic heat application Translations Umbilical vein Universities Vascular Diseases Vascular Endothelium Vasodilator Agents Water Woman age group age related angiogenesis arterial stiffness blood pressure reduction brachial artery cardiovascular disorder risk cardiovascular risk factor clinical application clinical practice clinical research site comorbidity design effectiveness evaluation endothelial dysfunction exposed human population follow-up high risk population improved in vivo indexing insight lifestyle intervention men microvesicles middle age novel oxidized low density lipoprotein pilot trial preservation rectal response young adult

项目摘要

Project Summary Age-related increases in systolic blood pressure (SBP) and vascular dysfunction are major factors driving cardiovascular diseases (CVD) in “mid-life” (50-64 years) and older (65+) (ML/O) adults. Much of the elevated CVD risk occurs in ML/O adults with casual (resting) SBP in the “elevated” (120-129 mmHg) and stage 1 hypertension (130-139 mmHg) ranges and is associated with: a) impaired endothelial function (decreased brachial artery flow-mediated dilation [FMDBA]); and b) stiffening of the large elastic arteries (increased carotid- femoral pulse wave velocity [CFPWV], i.e., aortic stiffness, and carotid artery β-stiffness index), all mediated by excess reactive oxygen species (ROS)-related oxidative stress, which reduces nitric oxide (NO) bioavailability. Current guidelines recommend that SBP in these ranges be treated with lifestyle strategies for ~3 months prior to considering drug therapy. We have shown in healthy young adults that passive heat therapy (hot water immersion to raise core temperature from ~37.0 to 38.5-39.0°C) is safe and may improve SBP and vascular function. We recently completed a small pilot trial (n=23) in ML/O adults and found that 30 sessions of heat therapy over ~10 weeks was safe/well-tolerated, reduced casual SBP (~10 mmHg) and ambulatory 24- h SBP (~6 mmHg), increased FMDBA and NO bioavailability, and reduced CFPWV, carotid β-stiffness and vascular oxidative stress. Exposing endothelial cells in culture to serum obtained from subjects after (vs. before) heat therapy suppressed basal ROS production and increased acetylcholine-stimulated NO production, indicating that changes in “circulating factors” may, at least in part, transduce the CV benefits of heat therapy. As the required next step in translation of passive heat therapy to eventual clinical practice, we propose a larger, properly powered, randomized, sham-controlled, parallel group design, single-site clinical trial to assess the efficacy, safety, underlying mechanisms, and potential lasting effects of passive heat therapy (36 x 60-min sessions over ~12 weeks) vs. sham (thermoneutral water immersion) for decreasing casual and 24-h SBP and improving vascular function in ML/O men and women with elevated SBP/stage 1 hypertension. To determine before, after passive heat therapy vs. sham (control), and after 4 and 12 weeks of follow-up: Aim 1: Casual (resting) and 24-h BP. Safety, tolerability, and implementation feasibility will also be assessed. Aim 2: Vascular endothelial function (FMDBA) and aortic (CFPWV) and carotid (β-stiffness index) stiffness. Aim 3: a) Oxidative stress-related suppression of FMDBA (acute increase in FMDBA in response to a supra- therapeutic infusion of the ROS scavenger, vitamin C); b) markers of oxidative stress, pro-oxidant signaling, and antioxidant defenses in endothelial cells obtained from clinical endovascular biopsy; c) abundance and content of circulating microvesicles (MVs); and d) NO bioavailability, ROS production, and NO-mediated angiogenesis (functional assay of NO bioavailability) in cultured endothelial cells exposed to 1) intact plasma, 2) MV-depleted plasma, or 3) isolated MVs collected from subjects before vs. after heat therapy or sham.

项目总结