Assessing Functional Arterial Stiffness in Older Hypertensive Veterans

这是第二次重新提交CSR&D CDA-2提案，以提供五年的研究和工资 Adam Gepner，MD。CDA将为他成为一名独立的VA老年心血管 具有老年心脏病学、运动生理学、动脉 病理生理学该应用程序将明确定义的培训活动、持续协作与 多学科指导委员会，和一个新的研究计划。Gepner博士建议以非侵入性的方式 测量动脉硬度参数的急性变化，以识别具有更大“动脉储备”的老年退伍军人 - 动脉对血流和压力变化迅速作出反应的能力， 回到基线。中心假设是由动脉硬度变化决定的动脉储备 急性运动或舌下含服硝酸甘油后的措施，将在非 高血压患者和血压控制良好的患者的血压水平高于血压控制不佳的患者。他 该提案与VA优先事项一致，因为VA系统已充分认识到高血压治疗不足。 博士Gepner希望提供新的工具，通过识别可以个性化高血压护理的个人， 耐受更积极的血压治疗目标，从而减少不良心血管疾病 (CVD)事件静息动脉硬度可预测未来的CVD事件，与血压密切相关， 进展最快的老年人与控制不佳的高血压。动脉僵硬是动态的， 对运动和服用抗高血压药物都有急性反应。动脉对 运动和血压药物在老年人中是可变的，可能是由于动脉血管的差异， 保护区该CDA的主要科学目的是研究动脉僵硬度的急性变化 不同程度血压参与者运动和硝酸甘油给药的参数 对照组和无高血压组。在一项180人的前瞻性研究中，将追求三个具体目标 将从护理协调之家招募的门诊、社区居住、≥60岁的退伍军人 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 1）运动和2）短效降压后的动脉硬度参数 舌下含服硝酸甘油与老年高血压患者基线血压控制差异相关 并与年龄和性别匹配的非高血压对照组进行比较。目标3是 确定老年人运动能力和动脉硬度参数变化之间的关系， 高血压退伍军人，以确保降低血压的影响不会产生负面影响的功能 容量Gepner博士将完成以临床试验设计和实施为重点的教学培训。他也将获得 运动生理学、流体动力学和动脉生物力学特性方面的专业知识。他将参加 一个结构化的课程，以提高他的技能，作为一个老年心血管专家，以改善护理老年人 老兵Gepner博士的主要导师是Cindy Carlsson博士，她是一名退伍军人管理局的临床研究员， 老年病学和CVD生物标志物。二级导师包括Dane Cook博士，一位运动科学家和主任 人类运动实验室，这将允许在运动生理学动手培训;纳奥米切斯勒博士，一个 动脉硬化机械方面的专家和麦迪逊退伍军人事务部主任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 在患有高血压的老年退伍军人的动脉硬化中，并允许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， 药物耐受性在老年退伍军人中至关重要，并将为Gepner博士的下一个职业生涯提供平台 步骤，申请MERIT资助，以测试特定抗高血压治疗强度的效果，并获得 血压难以控制的退伍军人降压治疗的新靶点。

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.