GENETICS, EXERCISE AND BLOOD PRESSURE IN HYPERTENSIVES

高血压患者的遗传、运动和血压

• 批准号: 2858455
• 负责人: Leslie I. Katzel
• 金额: $ 11.68万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2858455
• 关键词: aerobic exercise; aging; blood lipoprotein metabolism; blood pressure; cardiovascular function; clinical research; clinical trials; echocardiography; familial hypertension; gene environment interaction; genetic polymorphism; genetic susceptibility; genotype; glucose clamp technique; glucose metabolism; heart rate; human old age (65+); human subject; human therapy evaluation; hypertension; nuclear magnetic resonance spectroscopy; peptidyl dipeptidase A; psychological stressor; psychophysiology; ultrasound blood flow measurement; weight loss

A Ph.D. biophysics from Johns Hopkins University (JHU), a MD from the University of Maryland (UMSOM), with postdoctoral clinical and research training in gerontology at JHU and NIA/GRC, and a NIA KO8 with postdoctoral clinical and research training in gerontology prepared the candidate for an academic career in gerontology. The candidate, an Associate Professor of Medicine at the UMSOM has 10 years of experience performing patient oriented research into the effects of weight loss and aerobic exercise training (AEX) on lipoprotein and glucose metabolism, and cardiovascular function in older men and women. The candidate directs clinical research at the BVAMC GRECC, is PI on a VA Merit Review grant, and co-PI on the UMSOM Pepper Center. The candidate has mentored 17 trainees in patient oriented research. Receipt of this K24 award will provide the candidate additional protected time for research and mentoring of gerontology MD fellows, postdoctoral Ph.D. fellows, and other trainees in patient oriented clinical investigations. The candidate's long term goal is to establish a nationally recognized center of excellence for research into gene-environment interactions and their influence on the prevention and treatment of cardiovascular diseases (CVD) in the elderly. Research: Prior studies demonstrate that the angiotensin converting enzyme (ACE) DD gene variant present in 25-30 percent of the population increases the risk for hypertension, stroke and cardiovascular disease. The study hypothesis is that in older hypertensive individuals, the ACE DD polymorphism will blunt the beneficial effects of AEX on BP, lipoprotein and glucose metabolism, and cardiovascular function compared to individuals with the ACE ID and II genotypes. This hypothesis will be tested in a clinical trial that will compare the effects of 6 months of AEX on BP, the BP response to mental stress (cardiovascular reactivity), metabolic function (lipoproteins, glucose clamp) and endothelial function in older hypertensives with the ACE DD versus ACE ID and II genotypes. Trainees will participate in all aspects of this research and learn how to design and implement clinical investigations that enhance our knowledge of gene-environmental interactions in moderating the effectiveness of AEX in lowering BP, and in improving metabolic and cardiovascular function in older hypertensive patients. This research may lead to targeted lifestyle and pharmacologic therapies based on genotype to treat hypertension and CVD in older patients.

约翰霍普金斯大学(JHU)生物物理学博士，马里兰大学(UMSOM)医学博士，在JHU和NIA/GRC接受老年学博士后临床和研究培训，以及NIA KO8博士后老年学临床和研究培训，为候选人在老年学学术生涯做好准备。这位候选人是UMSOM的医学副教授，拥有10年的以患者为导向的研究经验，研究减肥和有氧运动(AEX)对老年男性和女性脂蛋白和葡萄糖代谢以及心血管功能的影响。候选人在BVAMC GRECC指导临床研究，是退伍军人事务部功绩审查拨款的PI，以及UMSOM Pepper Center的联合PI。这位候选人已经指导了17名以患者为导向的研究实习生。获得这一K24奖项将为候选人提供额外的保护时间，用于研究和指导老年学医学博士研究员、博士后研究员和其他以患者为导向的临床研究实习生。候选人的长期目标是建立一个国家认可的卓越研究中心，研究基因与环境的相互作用及其对老年人心血管疾病(CVD)预防和治疗的影响。研究：先前的研究表明，25%-30%的人群中存在血管紧张素转换酶(ACE)DD基因变异，会增加患高血压、中风和心血管疾病的风险。研究假设是，在老年高血压患者中，与具有ACE ID和II基因的人相比，ACE DD多态将削弱AEX对血压、脂蛋白和葡萄糖代谢以及心血管功能的有益影响。这一假设将在一项临床试验中得到验证，该试验将比较6个月的AEX对具有ACE DD和ACE ID和II基因的老年高血压患者的血压、对精神压力(心血管反应性)、代谢功能(脂蛋白、葡萄糖钳)和内皮功能的影响。受训者将参与这项研究的所有方面，并学习如何设计和实施临床研究，以增强我们对基因-环境相互作用的了解，从而调节AEX在降低血压方面的有效性，并改善老年高血压患者的代谢和心血管功能。这项研究可能导致基于基因型的有针对性的生活方式和药物治疗，以治疗老年患者的高血压和心血管疾病。