Assessing Functional Arterial Stiffness in Older Hypertensive Veterans

这是第二次重新提交CSR&D CDA-2提案，提供五年的研究和工资 支持亚当·盖普纳，医学博士。CDA将为他成为一名独立的退伍军人老年心血管医生做好准备 在老年心脏病学、运动生理学、动脉方面具有临床研究专长的疾病研究员 病理生理学。此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，以及一个新颖的研究计划。Gepner博士建议以非侵入性方式 测量动脉僵硬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 -动脉在应激状态下对血流和压力的变化迅速做出反应的能力，然后迅速 返回到基线。中心假设是动脉储备，由动脉僵硬的变化决定 在急性运动或舌下服硝酸甘油后采取的措施，将在非 高血压患者和血压控制良好的患者比血压控制不佳的患者更容易患病。他的 建议与退伍军人管理局的优先事项一致，因为退伍军人管理局系统中对高血压治疗不足的认识很好。 Gepner博士希望提供新的工具，通过识别能够 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。静息动脉僵硬预测未来的心血管事件，与血压密切相关，以及 进展最快的是高血压控制不佳的老年人。动脉僵硬是动态的 对运动和服用降压药都有敏锐的反应。动脉的反应 运动和降压药物在老年人中是不同的，可能是由于动脉的不同 保留。这项CDA的主要科学目标是研究动脉僵硬的急性变化。 不同程度血压受试者运动和服用硝酸甘油的参数 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 流动的，社区居住，退伍军人≥60岁，将从护理协调之家招募 远程医疗网络(CCHT)和弗吉尼亚州麦迪逊初级保健诊所：目标1和2旨在确定 1)运动和2)短效急性降压后的动脉僵硬参数 舌下含服硝酸甘油与老年高血压患者基线血压控制的差异相关 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 在老年人中确定运动能力和动脉僵硬参数变化之间的关系 高血压退伍军人确保降低血压的效果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实施的教学培训。他也会从中获益 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 提高他作为老年心血管专家的技能以改善对老年人的护理的有条理的课程 退伍军人。Gepner博士的主要导师是Cindy Carlsson博士，一位退伍军人管理局的临床医生兼调查员，在 老年病和心血管疾病生物标记物。二级导师包括运动科学家戴恩·库克博士和主任 人类运动实验室的内奥米·切斯勒博士，该实验室将允许进行运动生理学的动手培训。 动脉僵硬的机械方面的专家和麦迪逊退伍军人事务部主任桑杰·阿萨纳博士 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中的动脉僵硬，并允许Gepner博士建立自己的VA实验室 学习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 老年退伍军人对药物的耐受性是必不可少的，这将为格普纳博士的下一步职业生涯提供一个平台 步骤，申请优秀资助，以测试特定降压治疗强度的效果，并推导出 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.