Hypertension and Antihypertensive Therapy in Elderly Women

描述（由申请人提供）：高血压是全球范围内影响超过5000万美国人的主要公共卫生问题。它是导致冠状动脉疾病、心力衰竭、中风和肾脏疾病的靶器官损伤的主要危险因素。大型流行病学调查显示，老年女性患高血压的人数多于男性。性别的这种特殊作用是否基于同样特殊的病理生理，从而使降压治疗的选择“个性化”，并改善对治疗的反应，目前尚不清楚。本研究计划的主要目的是确定久坐老年人（即65岁）高血压的性别差异机制，并确定运动训练联合降压药物治疗对老年女性是否有效。利用微神经造影、多普勒超声和血压计等创新技术，Specific Aim 1将检验老年高血压女性交感神经活动增强的假设。将进行自主神经功能测试；将比较老年正常血压和高血压男性和女性的交感神经反应、血管收缩能力、交感神经传导转化为血管阻力和压力反射功能；特异性目的2将检验老年高血压女性脑室动脉硬化比男性更突出的假设。比较正常血压和高血压男性和女性的脉搏波速度、动态收缩动脉弹性、主动脉增压压和指数、动脉总顺应性、心脏大小和主动脉脉动尺寸；特异性目的3将验证长期运动训练计划联合抗高血压药物治疗比单独药物治疗对高血压老年人更有效的假设，并且对运动训练的反应在性别之间存在差异。参加特异性Aim 1和2研究的患者将被随机分配到单独药物治疗[氯沙坦（AT1受体拮抗剂）和氢氯噻嗪（利尿剂），Hyzaar加接触控制的组合]或运动训练（Hyzaar加运动训练）6个月，治疗后将重复使用特异性Aim 1和2中采用的相同方案，结果将在组间和性别之间进行比较。在这个项目完成后，我们将获得关于与年龄和性别相关的高血压的性质、抗高血压治疗的选择以及老年高血压男性和女性对治疗的反应的新的和临床上重要的信息。我们将确定老年人高血压和抗高血压治疗中性别差异的潜在机制，这可能会为这一特殊患者群体带来更有效的治疗。

DESCRIPTION (provided by applicant): Hypertension is a major public health problem worldwide affecting over 50 million Americans. It is a major risk factor for target organ damage resulting in coronary artery disease, heart failure, stroke, and kidney disease. Large epidemiological surveys have shown that more elderly women than men have hypertension. Whether this specific effect of sex is grounded in equally specific pathophysiology which could "personalize" the selection of antihypertensive therapy and improve the response to treatment is unknown. The primary goal of this research proposal is to determine the mechanisms underlying sex differences in hypertension in sedentary seniors (i.e., =65 years old), and to determine whether exercise training in combination with antihypertensive drug treatment is effective in elderly women. Using the innovative techniques of microneurography, Doppler ultrasound, and tonometry, Specific Aim 1 will test the hypothesis that sympathetic neural activity is augmented in elderly hypertensive women. Autonomic function tests will be performed; sympathetic neural responses, vasoconstrictor capability, transduction of sympathetic traffic into vascular resistance, and baroreflex function will be compared in elderly normotensive and hypertensive men and women; Specific Aim 2 will test the hypothesis that ventricular-arterial stiffening is more prominent in elderly hypertensive women than men. Pulse wave velocity, dynamic systolic arterial elastance, aortic artery augmentation pressure and index, total arterial compliance, cardiac size, and aortic pulsative dimensions will be compared between normotensive and hypertensive men and women; Specific Aim 3 will test the hypothesis that a long-term exercise training program in combination with antihypertensive drug treatment is more effective than pharmacologic therapy alone in hypertensive seniors, and the responses to exercise training differ between sexes. Patients enrolled in Specific Aim 1 and 2 studies will be assigned randomly either to drug treatment alone [a combination of losartan (AT1 receptor antagonist) and hydrochlorothiazide (diuretic), Hyzaar plus contact control] or to exercise training (Hyzaar and exercise training) for 6 months, the same protocols employed in Specific Aim 1 and 2 will be repeated after treatment, and results will be compared among groups and between sexes. Upon completion of this project, we will have obtained novel and clinically important information regarding the nature of hypertension associated with aging and sex, the selection of antihypertensive therapy, and the responses to treatment in elderly hypertensive men and women. We will identify the mechanisms underlying sex differences in hypertension and antihypertensive therapy in seniors, which may lead to more effective therapies for this particularly patient population. PUBLIC HEALTH RELEVANCE High blood pressure is a major public health problem worldwide affecting over 50 million Americans and resulting in heart disease, stroke, and kidney disease. It has been found that more elderly women than men have high blood pressure, but the mechanisms are completely unknown and whether the treatment should differ in older male and female patients is unclear. The primary goal of this project is to address these important issues. Results obtained will provide novel insights into the mechanisms for sex differences in high blood pressure in the elderly, the selection of treatment, and the responses to treatment in this patient population.