Hypertension and Antihypertensive Therapy in Elderly Women

老年妇女的高血压和抗高血压治疗

• 批准号: 7910596
• 负责人: QI FU
• 金额: $ 41.36万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7910596
• 关键词: Address; Adverse effects; Affect; Aftercare; Age; Aging; American; Antihypertensive Agents; Arteries; Attenuated; Baroreflex; Blood Pressure; Blood Volume; Body mass index; Breathing; Cardiac; Cardiovascular system; Congestive Heart Failure; Coronary Arteriosclerosis; Data; Development; Diastolic blood pressure; Dimensions; Diuretics; Doppler Ultrasound; Elderly; Elderly woman; Enrollment; Epidemiologic Studies; Epidemiology; Essential Hypertension; Exercise; Female; Functional disorder; Goals; Heart Diseases; Heart failure; High Prevalence; Human; Hydrochlorothiazide; Hypertension; Insulin Resistance; Kidney Diseases; Laboratories; Lead; Losartan; Losartan/Hydrochlorothiazide; Magnetic Resonance Imaging; Measures; Medical; Myocardial; Natural History; Nature; Organ; Pathogenesis; Patients; Pharmaceutical Preparations; Physiologic pulse; Play; Population; Protocols documentation; Public Health; Pulse Pressure; Race; Randomized; Reporting; Research Proposals; Resistance; Risk; Risk Factors; Role; Selection for Treatments; Sex Characteristics; Sex Preselection; Stroke; Surveys; Techniques; Testing; Training; Training Programs; Valsalva Maneuver; Vascular resistance; Vasoconstrictor Agents; Vasomotor; Ventricular; Woman; age related; arterial stiffness; blood pressure regulation; effective therapy; evidence base; heart dimension/size; human old age (65+); hypertension treatment; improved; indexing; innovation; insight; male; men; middle age; neuromechanism; neuroregulation; normotensive; novel; patient population; pressure; public health relevance; receptor; relating to nervous system; research study; response; sedentary; sex; tonometry; trafficking; treatment response

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.

描述（由申请人提供）：高血压是全球一个主要的公共卫生问题，影响了超过5000万美国人。它是目标器官损伤的主要危险因素，导致冠状动脉疾病，心力衰竭，中风和肾脏疾病。大型流行病学调查表明，年纪大的女性比男性多。性别的这种特定作用是否基于同样具体的病理生理学，可以“个性化”降压治疗的选择并改善对治疗的反应。这项研究建议的主要目的是确定久坐的老年人（即= 65岁）高血压的性别差异的机制，并确定与降压药治疗结合的运动训练是否对老年妇女有效。使用微功能学，多普勒超声和分解的创新技术，特定的目标1将检验以下假设：老年高血压女性增强了交感神经活动。将进行自主功能测试；同情神经反应，血管收缩能力，交感神经交通转变为血管抗性以及将在老年人和高血压的男性和女性中进行比较；具体目标2将检验以下假设：老年高血压女性中心室 - 动脉僵硬比男性更为突出。脉搏波速度，动态收缩动脉弹性，主动脉动脉增强压力和指数，总动脉依从性，心脏大小和主动脉搏动性维度将在正常的男性和高血压男性和高血压之间进行比较；具体目标3将检验以下假设：长期运动训练计划与降压药治疗相结合比仅在高血压老年人中仅比药理治疗更有效，并且男女之间对运动训练的反应不同。参加特定目标1和2研究的患者将单独分配给药物治疗[Losartan（AT1受体拮抗剂）和氢氯噻嗪（利尿剂），Hyzaar Plus接触对照的组合，或进行运动训练（Hyzaar和运动训练）（HYZAAR和运动训练）6个月，在6个月中，在特定的AIM和2中进行了相同的治疗方法，并重复进行1个对等级进行比较。该项目完成后，我们将获得有关与衰老和性别相关的高血压性质，降压治疗的选择以及对老年高血压男性和女性治疗的反应的新颖和临床上重要的信息。我们将确定老年人高血压和降压治疗中性别差异的基本机制，这可能会导致对这一特别患者人群的更有效的疗法。 公共卫生相关性 高血压是全球主要的公共卫生问题，影响了超过5000万美国人 并导致心脏病，中风和肾脏疾病。已经发现更多的年长妇女 比男性具有高血压，但是机制是完全未知的，是否 老年男性和女性患者的治疗应有不同。该项目的主要目标是解决这些重要问题。获得的结果将提供有关老年人高血压性别差异机制的新见解，治疗的选择以及对 该患者人群的治疗。