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: 8115122
• 负责人: QI FU
• 金额: $ 40.7万
• 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 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8115122
• 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，老年妇女患高血压的人数多于男子。性别的这种特异性效应是否基于同样特异的病理生理学，从而可以“个性化”选择抗高血压治疗并改善对治疗的反应尚不清楚。这项研究提案的主要目标是确定久坐老年人高血压性别差异的潜在机制（即，=65岁），并确定运动训练联合抗高血压药物治疗是否对老年女性有效。利用显微神经造影术、多普勒超声和眼压测量等创新技术，《特定目标1》将检验老年高血压妇女交感神经活动增强的假设。将进行自主神经功能测试;将在老年血压正常和高血压男性和女性中比较交感神经反应、血管收缩能力、交感神经流量到血管阻力的转导以及压力反射功能;具体目标2将检验以下假设：老年高血压女性的心室-动脉硬化比男性更突出。将比较血压正常和高血压男性和女性之间的脉搏波速度、动态收缩期动脉弹性、主动脉扩张压力和指数、总动脉顺应性、心脏大小和主动脉搏动尺寸;具体目标3将检验以下假设：在老年高血压患者中，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更有效，对运动训练的反应也因性别而异。入选特定目标1和2研究的患者将被随机分配至单独药物治疗组[氯沙坦联合（AT 1受体拮抗剂）和氢氯噻嗪（利尿剂），海捷亚加接触控制]或运动训练（Hyzaar和运动训练）6个月，治疗后将重复特定目标1和2中采用的相同方案，并将结果进行组间和性别间比较。完成本项目后，我们将获得新的和临床上重要的信息，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的治疗反应。我们将确定老年人高血压和抗高血压治疗的性别差异的机制，这可能会导致对这一特殊患者群体更有效的治疗。 公共卫生相关性 高血压是一个主要的公共卫生问题，在世界范围内影响超过5000万美国人 导致心脏病中风和肾病据发现， 男性比男性有高血压，但机制是完全未知的， 老年男性和女性患者的治疗应有所不同尚不清楚。本项目的主要目标是解决这些重要问题。研究结果将为老年人高血压的性别差异机制、治疗方法的选择以及对高血压的反应提供新的见解。 该患者群体的治疗。

项目成果

Relationship between sympathetic baroreflex sensitivity and arterial stiffness in elderly men and women.

• DOI: 10.1161/hypertensionaha.111.176560
• 发表时间: 2012-01
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Okada Y;Galbreath MM;Shibata S;Jarvis SS;VanGundy TB;Meier RL;Vongpatanasin W;Levine BD;Fu Q
• 通讯作者: Fu Q

Response to creatine kinase and pressor response to orthostatic tolerance.

对肌酸激酶的反应和对直立耐受的升压反应。

• DOI: 10.1161/hypertensionaha.111.00713
• 发表时间: 2013
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Okada,Yoshiyuki;Galbreath,MMelyn;Jarvis,SaraS;Bivens,TiffanyB;Vongpatanasin,Wanpen;Levine,BenjaminD;Fu,Qi
• 通讯作者: Fu,Qi

Integrative Blood Pressure Response to Upright Tilt Post Renal Denervation.

肾去神经支配后直立倾斜的综合血压反应。

• DOI: 10.1093/ajh/hpx018
• 发表时间: 2017
• 期刊: American journal of hypertension
• 影响因子: 3.2
• 作者: Howden,ErinJ;East,Cara;Lawley,JustinS;Stickford,AbigailSL;Verhees,Myrthe;Fu,Qi;Levine,BenjaminD
• 通讯作者: Levine,BenjaminD

Left ventricular remodeling and arterial afterload in older women with uncontrolled and controlled hypertension.

• DOI: 10.1097/gme.0000000000001046
• 发表时间: 2018-05
• 期刊: Menopause (New York, N.Y.)
• 作者: Yoo JK;Okada Y;Best SA;Parker RS;Hieda M;Levine BD;Fu Q
• 通讯作者: Fu Q

Greater resting muscle sympathetic nerve activity reduces cold pressor autonomic reactivity in older women, but not older men.

较大的静息肌肉交感神经活动会降低老年女性的冷加压自主神经反应，但不会降低老年男性的冷升压自主神经反应性。

• DOI: 10.1152/ajpregu.00231.2022
• 发表时间: 2023
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Akins,JohnD;Okada,Yoshiyuki;Hendrix,JosephM;Vongpatanasin,Wanpen;Fu,Qi
• 通讯作者: Fu,Qi