AGE ASSOCIATED CHANGES IN VASCULAR STIFFNESS PROPERTIES

工作总结本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，并导致心血管发病率和死亡率。我们研究了695名台湾男性和616名女性的动脉僵硬对左心室(LV)质量的影响。在男女中，收缩压、体表面积和年龄是预测左心室重量的主要因素；无论男女，AGI对左心室重量的影响最小。B.为了确定补充生长激素或性类固醇是否能改善这些物质缺乏的老年人的动脉僵硬特性，我们测量了65岁及以上的男性和女性在激素替代前后的脉搏波速度和AGI。在NIH赞助的810名35-75岁受试者的多中心活动咨询试验中，我们正在验证这样的假设，即1-2年的家庭有氧运动训练可以减少动脉僵硬。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硬度和峰值VO2。E.一项多中心研究已经启动，以确定动脉僵硬是否是老年人自由生活人群心血管事件的独立危险因素。对-1991年首次研究的耐力训练的老年男性及其同龄人的动脉僵硬进行了跟踪测量，以确定慢性耐力训练是否减弱了正常年龄相关的动脉僵硬增加。动脉硬度将在宾夕法尼亚州匹兹堡的心血管健康研究现场进行测量。对这一队列的长期随访将使我们能够检验动脉僵硬在老年人群中的预后意义。H.在BLSA受试者中，正在研究动脉僵硬与一些新发现的与钠和血压调节有关的激素(血浆哇巴因样因子和MarinoBufagenin)之间的关系，这些激素涉及的年龄和血压范围很大。I.我们最近在横断面研究中发现，绝经后妇女接受雌激素替代疗法(ERT)可以降低血压和与年龄相关的动脉僵硬增加，在ERT中加入孕激素可能会减少这些有益的影响。已经发现，即使ERT患者的SBP水平高于非ERT患者，ERT也可以减少SBP的纵向变化。ERT对SBP纵向升高的抑制作用在年龄较大的绝经后妇女和BMI较轻的妇女中更为明显。J.我们正试图确定导致撒丁岛人群(创始人人群，与近亲交配人群相比，遗传上相对同质)动脉僵硬和动脉内膜中层厚度的遗传因素，并确定当这些因素加入标准的心血管风险谱时，是否提高了对总体心血管风险的预测准确性。-人类科目

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