Assessing Functional Arterial Stiffness in Older Hypertensive Veterans

评估老年高血压退伍军人的功能性动脉僵硬度

• 批准号: 10595488
• 负责人: Adam D Gepner
• 金额: --
• 依托单位: WM S. MIDDLETON MEMORIAL VETERANS HOSP
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10595488
• 关键词: Activities of Daily Living; Acute; Age; Aging; Antihypertensive Agents; Arteries; Biological Markers; Biomechanics; Blood Pressure; Blood Vessels; Blood flow; Cardiology; Cardiovascular Diseases; Cardiovascular system; Caring; Cessation of life; Cladribine; Clinical Research; Clinical Trials Design; Collaborations; Collagen; Communities; Control Groups; Cross-Sectional Studies; Data; Deposition; Diagnosis; Educational Curriculum; Elastin; Elderly; Endothelium; Event; Exercise; Exercise Physiology; Fright; Functional disorder; Funding; Future; Geriatrics; Goals; Guidelines; Health system; Home; Human; Hypertension; Individual; Injury; Intervention; Knowledge; Laboratories; Link; Liquid substance; Measures; Mechanics; Mentors; Mentorship; Multi-Ethnic Study of Atherosclerosis; Myocardial Infarction; National Heart, Lung, and Blood Institute; Nature; Nitroglycerin; Participant; Pathology; Patients; Pattern; Pharmaceutical Preparations; Pharmacology Study; Pharmacotherapy; Physical Function; Physiology; Polypharmacy; Property; Prospective Studies; Quality of life; Recommendation; Regimen; Reproducibility; Research; Research Personnel; Rest; Risk; Scientist; Specialist; Stress; Stress Tests; Stroke; Structure; Sublingual drug administration; System; Techniques; Testing; Training; Training Activity; Vasodilator Agents; Veterans; Wages; age related; arterial stiffness; blood pressure control; blood pressure medication; blood pressure reduction; cardiovascular disorder risk; care coordination; career; cooking; exercise capacity; hypertension control; hypertension treatment; hypertensive; improved; multidisciplinary; normal aging; novel; older patient; overtreatment; primary care clinic; randomized, clinical trials; recruit; response; sex; side effect; skills; telehealth; tool

This is the second resubmission of a CSR&D CDA-2 proposal to provide five years of research and salary support to Adam Gepner, MD. The CDA will prepare him to become an independent VA geriatric cardiovascular disease investigator with clinical research expertise in geriatric cardiology, exercise physiology, arterial pathophysiology. This application combines clearly defined training activities, continuous collaboration with a multidisciplinary mentorship committee, and a novel research plan. Dr. Gepner proposes to non-invasively measure acute changes in arterial stiffness parameters to identify older Veterans with greater “arterial reserve” - the ability of the arteries to rapidly respond to changes in blood flow and pressure with stress and then rapidly return to baseline. The central hypothesis is that arterial reserve, determined by change in arterial stiffness measures following acute exercise or administration of sublingual nitroglycerin, will be greater in non- hypertensives and those with controlled blood pressure than in those with poorly controlled blood pressure. His proposal aligns with VA priorities because undertreatment of hypertension is well-recognized in the VA system. Dr. Gepner hopes to provide new tools to personalize hypertensive care by identifying individuals that can tolerate more aggressive blood pressure treatment goals thereby reducing adverse cardiovascular disease (CVD) events. Resting arterial stiffness predicts future CVD events, is tightly linked with blood pressure, and progresses most rapidly in older individuals with poorly controlled hypertension. Arterial stiffness is dynamic and responds acutely to both exercise and administration of antihypertensive medications. The arterial response to exercise and blood pressure medications is variable in older individuals, likely due to differences in arterial reserve. The primary scientific objective of this CDA is to investigate acute changes in arterial stiffness parameters with exercise and nitroglycerin administration in participants with varying degrees of blood pressure control and those without hypertension. Three specific aims will be pursued in a prospective study of 180 ambulatory, community dwelling, Veterans ≥60 years old who will be recruited from the Care Coordination Home Telehealth Network (CCHT) and Madison VA primary care clinics: Aims 1 and 2 are to determine if changes in arterial stiffness parameters following 1) exercise and 2) acute blood pressure reduction with short-acting sublingual nitroglycerin are associated with differences in baseline blood pressure control in older hypertensive Veterans and compared to a non-hypertensive age- and sex-matched non-hypertensive control group. Aim 3 is to determine associations between exercise capacity and changes arterial stiffness parameters among older hypertensive Veterans to ensure that the effects of lower blood pressure do not negatively impact functional capacity. Dr. Gepner will complete didactic training focusing on clinical trial design and conduct. He also will gain expertise in exercise physiology, fluid dynamics and the biomechanical properties arteries. He will participate in a structured curriculum to improve his skills as a geriatric cardiovascular specialist to improve care for older Veterans. Dr. Gepner’s primary mentor is Dr. Cindy Carlsson, a VA clinician-investigator with expertise in geriatrics and CVD biomarkers. Secondary mentors include Dr. Dane Cook, an exercise scientist and the Director of the Human Exercise Lab, which will allow for hands-on training in exercise physiology; Dr. Naomi Chesler, an expert in the mechanical aspects of arterial stiffness and Dr. Sanjay Asthana, the director of the Madison VA GRECC. Successful completion of the proposed research will provide a framework for understanding changes in arterial stiffness in older Veterans with hypertension and allow Dr. Gepner to build his own VA laboratory to study age-related vascular physiology. Unmasking how these changes impact antihypertensive goals and medication tolerability are imperative in older Veterans and will provide a platform for Dr. Gepner’s next career step, to apply for MERIT funding to test the effects of specific antihypertensive treatment intensities and to derive novel targets for antihypertensive treatment in Veterans with difficult to control blood pressure.

这是CSR＆D CDA-2提案的第二次重新提议，以提供五年的研究和薪水 支持医学博士亚当·格普纳（Adam Gepner）。 CDA将使他成为独立的VA老年心血管 疾病研究者具有老年心脏病学临床研究专业知识，运动生理学，动脉 病理生理学。该应用程序结合了明确定义的培训活动，与 多学科心态委员会和一个新颖的研究计划。 Gepner博士提出非侵入性的建议 测量动脉刚度参数的急性变化，以识别具有更大“动脉储备”的老年退伍军人 - 动脉快速响应血流和压力压力的变化，然后迅速响应的能力 返回基线。中心假设是由动脉刚度变化决定的动脉储备 在非 - 高血压和血压受控的患者比血压控制不良的患者。他的 提案与VA优先级保持一致，因为在VA系统中，高血压的不足是众所周知的。 Gepner博士希望通过识别可以 容忍更具侵略性的血压治疗目标，从而减少不良心血管疾病 （CVD）事件。休息伪像未来的CVD事件，与血压紧密相关， 在高血压控制较差的老年人中，进展最快。动脉刚度是动态的， 对运动和给药的抗高血压药物的敏锐反应。动脉反应 老年人的运动和血压药物可变，可能是由于动脉差异 预订。该CDA的主要科学目标是研究动脉刚度的急性变化 具有不同程度血压的参与者的运动和硝酸甘油给药的参数 控制和没有高血压的人。在180的前瞻性研究中将追求三个具体目标 卧床，社区住宅，退伍军人≥60岁，将从护理协调之家招募 远程医疗网络（CCHT）和麦迪逊VA初级保健诊所：目标1和2是确定是否发生变化 1）锻炼和2）急性血压降低，短效 舌下硝酸甘油与较早高血压的基线血压控制差异有关 退伍军人与非高血压年龄和性别匹配的非高血压对照组进行了比较。 AIM 3是 确定锻炼能力和变化较老的动脉僵硬参数之间的关联 高血压退伍军人，以确保降低血压的影响不会对功能产生负面影响 容量。 Gepner博士将完成专注于临床试验设计和行为的教学培训。他也会收获 运动生理学，流体动力学和生物力学特性动脉方面的专业知识。他将参加 一种结构化的课程，可提高他作为老年心血管专家的技能，以改善老年人的护理 退伍军人。 Gepner博士的主要心理是辛迪·卡尔森（Cindy Carlsson） 老年病和CVD生物标志物。次要导师包括运动科学家丹恩·库克（Dane Cook）博士 人类运动实验室，该实验室将允许进行运动生理的动手培训； Naomi Chesler博士，一个 麦迪逊弗吉尼亚州麦迪逊主任Sanjay Asthana博士的机械方面的专家Sanjay Asthana博士 Grecc。成功完成拟议的研究将为理解变化提供一个框架 在高血压的老年退伍军人中，在动脉僵硬中，允许Gepner博士建立自己的VA实验室 研究与年龄相关的血管生理学。揭示这些变化如何影响降压目标和 老年退伍军人必须使用药物耐受性，并将为Gepner博士的下一个职业提供一个平台 步骤，申请绩效资金以测试特定的降压治疗强度的影响并得出 难以控制血压的退伍军人的降压治疗的新目标。