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

工作总结该项目的最终目标是确定动脉僵硬特性如何影响心肌结构和功能，并有助于心血管发病率和死亡率。答：我们已经检查了来自台湾的695名男性和616名女性的动脉刚度对左心室（LV）肿块的贡献。在这两个性别中，LV质量的主要预测因子是收缩压，身体表面积和年龄。在任何性别中，Agi ntrib in to lv质量最少。 B.确定生长激素或性类固醇补充剂是否可以改善这些物质缺乏的老年人的动脉僵硬特性，我们正在测量65岁以上的男性和女性在激素替代之前和之后的脉搏波速度和AGI。 C.我们正在检验以下假设：1 - 2年的家庭有氧运动训练可以减少810名受试者35-75岁的受试者的多中心赞助活动咨询试验中的动脉僵硬。 D.为了确定有氧运动训练是否可以减少较老的心力衰竭患者的动脉僵硬，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和峰值VO2。 E.一项多中心研究，旨在确定动脉僵硬是否是老年自由生活人员心血管事件的独立危险因素。 F.最初在1989年至1991年进行了研究的耐力老年男性及其久坐的年龄同龄人对动脉僵硬的随访测量，以确定慢性耐力训练是否减轻了正常年龄相关的动脉僵硬。 G.将在宾夕法尼亚州匹兹堡的宾夕法尼亚州进行心血管健康研究中测量动脉僵硬。该队列的长期随访将使我们能够检查老年人群中动脉僵硬的预后意义。 H.在较大的年龄和血压范围内，正在检查动脉僵硬与血压调节（等离子体ouabain样因子和Marinobufagenin）的一些新发现的激素之间的关系。 I.最近，在绝经后妇女的跨区域研究中，雌激素替代疗法（ERT）降低了BP和与年龄相关的动脉僵硬度的增加，并且增加孕激素以降低ERT可能会降低这些有益作用。即使ERT用户的SBP水平高于非ERT用户，也发现ERT也被发现减少SBP的纵向变化。 ERT施加的SBP纵向增加的减少在绝经后妇女以及BMI较轻的妇女中更为明显。 J.我们试图确定遗传因素有助于萨迪尼亚人群中夸张的动脉僵硬和动脉内膜厚度（创始人人群，相对遗传同质的人群与近亲种群相比相对遗传同质），并降低这些因素是否会增强对标准心脏病风险型的总体心血管风险的预测准确性，并增加标准的心脏病风险的整体风险。 - 人类主题