ACES - ACE inhibitors Combined with Exercise for hypertensive Seniors

摘要 该项目的目的是进行随机对照试验(RCT)，以确定是否选择 抗高血压药物影响功能状态和其他心血管危险因素的变化 在患有高血压的老年人中。功能状态，由身体性能的测量确定， 是预测老年人心血管结果的重要指标。功能受损的老年人 经历更多心血管事件，接受心脏手术的风险更高，患心血管疾病相关风险更高 死亡比功能更强的同龄人更多。患有高血压的老年人经历了功能加速下降， 目前，体育锻炼是防止这种下降的主要策略。然而，功能性的 对运动的反应是高度多变的，而且似乎受到降压药类型的影响 用药(S)控制血压。初步证据表明，与其他第一批相比- 系列降压药、血管紧张素转换酶(ACE)抑制剂增强运动衍生 改善老年高血压患者的功能状态。这项随机对照试验将检验这一假设。久坐不动 65岁有功能障碍和高血压的男性和女性将从两个地点招募 参加一项为期36周的干预研究。参赛者将被随机分配到三个一线之一 抗高血压药物：(1)血管紧张素转换酶抑制剂培哚普利，(2)AT1受体拮抗剂氯沙坦，或(3) 噻嗪类利尿剂氢氯噻嗪。所有参与者还将参加有组织的有氧运动 干预。主要目的是确定与氯沙坦和羟基喜树碱相比，培哚普利是否能改善自我 有节奏的步速。第二个目的是确定培哚普利对a)运动能力的相对影响， B)体重和成分，以及c)心血管风险的循环指数。在探索性分析中， 收集骨骼肌活组织标本，以评估研究药物对骨骼肌指标的影响。 血管生成。这项研究有望区分FDA批准的三种降压药的有益效果 临床相关人群中新出现的心血管危险因素的药物治疗。因此，这项研究已经 在处方中迅速影响临床实践指南的重要意义 向数百万美国人提供降压药。

ABSTRACT The purpose of this project is to conduct a randomized, controlled trial (RCT) to determine if choice of antihypertensive medication influences changes in functional status and other cardiovascular risk factors among older persons with hypertension. Functional status, determined by measures of physical performance, is an important predictor of cardiovascular outcomes in older adults. Seniors with compromised function experience more CV events, have a higher risk of undergoing cardiac surgery and higher risk of CVD-related death than higher-functioning peers. Seniors with hypertension experience accelerated declines in function, and presently physical exercise is the primary strategy for preventing this decline. However, functional responses to exercise are highly variable and appear to be influenced by the type of antihypertensive medication(s) utilized to control blood pressure. Preliminary evidence suggests that, compared to other first- line antihypertensive agents, angiotensin converting enzyme (ACE) inhibitors enhance exercise-derived improvements in functional status among hypertensive seniors. This RCT will test this hypothesis. Sedentary men and women > 65 years of age with functional limitations and hypertension will be recruited from two sites to participate in a 36 week intervention study. Participants will be randomly assigned to one of three first-line antihypertensive agents: (1) the ACE inhibitor perindopril, (2) AT1 receptor antagonist losartan, or (3) the thiazide diuretic hydrochlorothiazide. All participants will also participate in a structured aerobic exercise intervention. The primary aim is to determine if, compared to losartan and HCTZ, perindopril improves self- paced gait speed. The secondary aim is to determine the relative effect of perindopril on a) exercise capacity, b) body mass and composition, and c) circulating indices of cardiovascular risk. In exploratory analyses, skeletal muscle biopsies will be collected to evaluate the influence of study drugs on indices of skeletal muscle angiogenesis. This study is expected to differentiate beneficial effects of three FDA-approved antihypertensive medications on an emerging cardiovascular risk factor in a clinically-relevant population. Thus the study has important implications for expeditiously influencing clinical practice guidelines in the prescription of antihypertensive drugs to millions of Americans.