AGE ASSOCIATED CHANGES IN VASCULAR STIFFNESS PROPERTIES

血管硬度特性与年龄相关的变化

• 批准号: 6288698
• 负责人: Edward G Lakatta
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6288698
• 关键词: adult human (21+); aerobic exercise; aging; angiocardioultrasonography; arteriosclerosis; blood pressure; body composition; cardiovascular disorder epidemiology; carotid artery; clinical research; hormone therapy; human subject; myocardium; pulse pressure wave; sex hormones; somatotropin; vascular resistance

SUMMARY OF WORK The ultimate goals of this project are to determine how arterial stiffness properties influence myocardial structure and function and contribute to cardiovascular morbidity and mortality. A. We have examined the contribution of arterial stiffness to left ventricular (LV)mass in 695 men and 616 women from Taiwan. In both sexes, the major predictors of LV mass were systolic blood pressure, body surface area and age; AGI ntributed minimally to LV mass in either sex. B. To determine whether growth hormone or sex steroid supplementation ameliorates arterial stiffness properties in older adults with deficiencies of these substances, we are measuring pulse wave velocity and AGI in men and women aged 65 years and older, before and after hormonal replacement. C. We are testing the hypothesis that 1-2 years of home-based aerobic exercise training can reduce arterial stiffness in the multicenter NIH-sponsored Activities Counseling Trial of 810 subjects 35-75 years old. D. To determine whether aerobic exercise training can reduce the elevated arterial stiffness of older heart failure patients, we will measure arterial stiffness and peak VO2 before and after a 3 month program of aerobic training. E. A multicenter study to determine whether arterial stiffness is an independent risk factor for cardiovascular events in elderly free- living persons has been initiated. F. Follow-up measurements of arterial stiffness on endurance trained older men and their sedentary age peers, initially studied in 1989-1991 have been obtained to determine whether chronic endurance training attenuates the normal age- associated increase in arterial stiffness. G. Arterial stiffness will be measured in the Pittsburgh, PA site for the Cardiovascular Health Study. Long-term follow-up of this cohort will allow us to examine the prognostic significance of arterial stiffness in an older population. H. The relationship between arterial stiffness and some newly discovered hormones involved in sodium and blood pressure regulation (plasma ouabain-like factor and marinobufagenin)is being examined in BLSA subjects across a large age and blood pressure range. I. We have recently discovered, in cross-sectionsl studies, estrogen replacement therapy (ERT) in postmenopausal women reduced BP and the age-associated increase in arterial stiffness and that the addition of progestins to ERT may reduce these beneficial effects. ERT has been found also to reduce longitudinal changes in SBP, even if ERT users presented higher Sbp levels than non-ERT users. The reduction of the longitudinal increase in SBP exerted by ERT was more pronounced in older postmenopausal women, and in those with lighter BMI. J. We are attempting to identify genetic factors contributing to exaggerated arterial stiffness and arterial intima -medial thickness in a Sardinian population (a founder population, relatively genetically homogenous compared to outbred populations) and to deterine whether these factors enhance the predictive accuracy for overall cardiovascular risk, when added to standard cardiovascular risk profile. - Human Subjects

工作摘要该项目的最终目标是确定动脉僵硬度特性如何影响心肌结构和功能以及心血管发病率和死亡率。答：我们检查了台湾 695 名男性和 616 名女性的动脉僵硬度对左心室 (LV) 质量的影响。对于男女来说，左心室质量的主要预测因素是收缩压、体表面积和年龄。无论性别，AGI 对 LV 质量的影响都很小。 B. 为了确定补充生长激素或性类固醇是否可以改善缺乏这些物质的老年人的动脉僵硬度，我们正在测量 65 岁及以上男性和女性在激素替代前后的脉搏波速度和 AGI。 C. 我们正在 NIH 资助的多中心活动咨询试验中对 810 名 35-75 岁受试者进行的多中心活动咨询试验中测试这一假设，即 1-2 年的家庭有氧运动训练可以减少动脉僵硬度。 D. 为了确定有氧运动训练是否可以降低老年心力衰竭患者升高的动脉僵硬度，我们将在 3 个月的有氧训练计划之前和之后测量动脉僵硬度和峰值摄氧量。 E. 已经启动了一项多中心研究，以确定动脉僵硬度是否是老年自由生活者心血管事件的独立危险因素。 F. 最初于 1989-1991 年进行研究，对接受过耐力训练的老年男性及其久坐年龄的同龄人的动脉僵硬度进行了后续测量，以确定长期耐力训练是否会减弱与年龄相关的动脉僵硬度的正常增加。 G. 动脉硬度将在宾夕法尼亚州匹兹堡的心血管健康研究中心进行测量。对这一队列的长期随访将使我们能够检查老年人群中动脉僵硬度的预后意义。 H. 动脉硬化与一些新发现的涉及钠和血压调节的激素（血浆哇巴因样因子和海蟾蜍配基）之间的关系正在大年龄和血压范围内的 BLSA 受试者中进行检查。 I. 我们最近在横断面研究中发现，绝经后妇女的雌激素替代疗法 (ERT) 可降低血压和与年龄相关的动脉僵硬度增加，并且在 ERT 中添加孕激素可能会降低这些有益效果。研究发现 ERT 还可以减少 SBP 的纵向变化，即使 ERT 用户的 Sbp 水平高于非 ERT 用户。 ERT 引起的收缩压纵向增加的减少在老年绝经后女性和体重指数较轻的女性中更为明显。 J. 我们正在尝试确定撒丁岛人群（创始人群，与远交人群相比在遗传上相对同质）中导致动脉僵硬度和动脉内膜中层厚度夸大的遗传因素，并确定这些因素是否提高了整体心血管疾病的预测准确性风险，当添加到标准心血管风险概况中时。 - 人类受试者