AGE, RACE, SEX AND AORTIC STIFFNESS--GENETIC MARKERS

描述：(改编自《调查者摘要》)衰老影响血管 细胞功能和动脉壁组成/结构 血管僵硬及其作为高血压危险因素的潜在作用 老年人心血管疾病的发病率和死亡率。年龄相关血管 僵硬与收缩期血的进行性增加相称。 压力、动脉粥样硬化、基质重构、冠心病和最终的心肌梗死。受损的 血液纤溶会引发早期纤维蛋白沉积，动脉粥样硬化， CAD，以及与CAD相关的血管硬度，导致 动脉粥样硬化血栓形成--闭塞事件。CAD风险因素与 通过改变表达和/或改变血液纤溶活性 一种或多种纤溶蛋白的活性。这些蛋白质发挥作用 在冠状动脉粥样硬化性心脏病相关的动脉基质重塑和 因此，与年龄相关的CAD相关的血管僵硬也是如此。这个 这项拟议研究的总体目标是确定身份识别 纤溶蛋白的特定基因类型或基因组合 与可识别的风险因素或风险因素相关 各组分(即HTG-VLDL、Lp[a]、胰岛素、同型半胱氨酸)可同时 确定动脉粥样硬化/冠心病的综合致病风险类别 以及与年龄相关的CAD相关的主动脉僵硬。这项病例对照研究 将在1,640名受试者中进行种族/性别混合 冠状动脉造影术可识别的冠心病(&gt；50%狭窄，820例)和非冠心病 (冠状动脉正常)或冠心病症状(820名对照)。具体研究 将包括以下内容：征聘病例/控制人员(目标1)； 慢性前列腺炎患者PA1-1和u-PA基因突变位点的鉴定 促进通过聚合酶链式反应进行更具成本效益的基因分析(目标2)； 急性淋巴细胞白血病患者主动脉僵硬量/程度的测定 病例/对照，使用多普勒超声(脉搏波速度)(目标3)； 纤溶蛋白基因分型的测定(限制性片段长度 多态，RFLP)(AIM 4)和纤溶蛋白抗原/活性， 包括Lp(A)和同型半胱氨酸水平在病例/对照来源的血液中 样本(目标5)；最后，多因素决定和 年龄相关的冠心病相关的主动脉僵硬的统计分析(目标6)。 调查人员表示，从这些研究中收集的结果将 鉴定新的纤溶蛋白基因型别作为环境因子 CAD的风险，并进一步帮助识别风险增加的个人 年龄相关的CAD相关的主动脉僵硬，导致心血管疾病 发病率和死亡率。

DESCRIPTION: (Adapted from Investigator's Abstract) Aging affects vascular cell function and arterial wall composition/structure which contributes to vascular stiffness and its underlying role as a risk factor for cardiovascular morbidity and mortality in the elderly. Age-related vascular stiffness is commensurate with a progressive increase in systolic blood pressure, atherosclerosis, matrix remodeling, CAD and eventual MI. Impaired blood fibrinolysis will initiate early fibrin deposition, atherogenesis, CAD, and CAD-associated vascular stiffness, resulting in atherothrombotic-occlusive events. CAD risk factors are associated with impaired blood fibrinolytic activity by altering the expression and/or activity of one or more of the fibrinolytic proteins. These proteins play an essential role in CAD-associated arterial matrix remodeling and consequentially also age-related CAD-associated vascular stiffness. The overall goal of this proposed study is to determine whether identification of specific genotypes or genotypic combinations of fibrinolytic proteins in conjunction with identifiable risk factors or risk factor-associated components (i.e., HTG-VLDL, Lp[a], insulin, homocysteine) may simultaneously identify categories of combined pathogenetic risk for atherosclerosis/CAD and age-related CAD-associated aortic stiffness. This case-control study will be carried out with a racial/gender mix of 1,640 subjects with angiographically identifiable CAD (>50% stenosis, 820 cases) and without CAD (normal coronary arteries) or CAD symptoms (820 controls). Specific studies will include the following: recruitment of cases/controls (Aim 1); identification of the mutation sites in the PA1-1 and u-PA genes to facilitate more cost-effective genotype analysis by PCR (Aim 2); determination of the amount/degree of aortic stiffness in all cases/controls, using Doppler ultrasound (pulse wave velocity) (Aim 3); determination of fibrinolytic protein genotypes (restriction fragment length polymorphisms, RFLPs) (Aim 4) and fibrinolytic protein antigen/activity, including Lp(a) and homocysteine levels, in case/control-derived blood samples (Aim 5); and finally, the multifactorial determination and statistical analysis of age-related CAD-associated aortic stiffness (Aim 6). The investigators state that the results gleaned from these studies will identify new fibrinolytic protein genotypes as mediators of environmental risk for CAD and further help to identify individuals at increased risk for age-related CAD-associated aortic stiffness, resulting in cardiovascular morbidity and mortality.