Age Associated Changes in Structural and Functional Vasc

血管结构和功能的年龄相关变化

• 批准号: 6969621
• 负责人: Samer Najjar
• 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/6969621
• 关键词: age difference; aging; angiography; antihypertensive agents; atherosclerosis; cardiovascular disorder chemotherapy; cardiovascular disorder epidemiology; cardiovascular disorder risk; cardiovascular function; cardiovascular imaging /visualization; carotid artery; clinical trials; congestive heart failure; coronary disorder; human subject; human therapy evaluation; hypertension; longitudinal human study; magnetic resonance imaging; noninvasive diagnosis; patient oriented research; pulse pressure wave; tomography; vascular resistance; vasomotion; age difference; aging; angiography; antihypertensive agents; atherosclerosis; cardiovascular disorder chemotherapy; cardiovascular disorder epidemiology; cardiovascular disorder risk; cardiovascular function; cardiovascular imaging /visualization; carotid artery; clinical trials; congestive heart failure; coronary disorder; human subject; human therapy evaluation; hypertension; longitudinal human study; magnetic resonance imaging; noninvasive diagnosis; patient oriented research; pulse pressure wave; tomography; vascular resistance; vasomotion

The overall goals of this project are to characterize the determinants of vascular structure and function, and evaluate their effects on cardiovascular morbidity and mortality 1. Increased aortic pulse wave velocity (aPWV) has been associated with mortality in clinical but not general populations. Aortic PWV was measured at baseline in 2488 older adults. Over an average of 4.6 years of follow-up, 265 deaths occurred with 111 categorized as cardiovascular in cause. Higher aortic aPWV quartile was associated with both total mortality (P = 0.010) and CV mortality (P=.006), independent of age, gender, race, SBP, known CV disease, creatinine, cholesterol and smoking. Thus, among a generally healthy, well-functioning, community dwelling population, aPWV, a marker of arterial stiffness, is associated with higher total mortality and CV mortality specifically. 2. In order to investigate the hypothesis that the age-associated changes in cardiovascular structure and function represent the mechanism through which increased age exerts its deleterious effects on cardiovascular morbidity and mortality, and to test the related hypothesis that physiologic vascular properties explain the chronologic age-associated increased risk of atherosclerosis, we plan to evaluate traditional as well as novel measures of vascular properties, and examine how they relate to non-invasive assessments of atherosclerosis. This will be performed in 300 BLSA subjects as well as individuals with known absence of coronary artery disease and patients with known premature coronary artery disease. A research and development contract has been awarded to procure novel non-invasive imaging tools such as electron beam computed tomography, vascular magnetic resonance imaging, and vascular magnetic resonance angiography (Project Officer, S. Najjar). 3. Isolated systolic hypertension (ISH) is the dominant form of hypertension in older individuals, and is associated with a significant increase in cardiovascular morbidity and mortality. But the factors underlying the increased risk of ISH have not been fully elucidated. Since alterations in vascular structure and function are increasingly recognized as potent predictors of adverse events, we investigated the cardiovascular changes associated with ISH. 447 Taiwanese subjects over the age of 50 and with DBP<90 mmHg, were classified into a normotensive group (NT, SBP<140 mmHg) and an untreated ISH group (SBP>140 mmHg). The NT group was on average 5 years younger than the ISH (62+/-8 and 67+/-7 years, p<0.05). As expected SBP and PP were significantly higher in the ISH group. Furthermore, we found that a number of vascular structural and functional parameters were significantly greater in the ISH group than in the NT group. Thus, ISH is not isolated , but rather is associated with accelerated alterations in a host of cardiovascular structural and functional parameters. The increased risk associated with ISH may, in part, be mediated through these alterations, some of which have already been established as risk factors for cardiovascular diseases independent of blood pressure. 4. Hypertension (HTN) is generally considered a risk factor for arterial stiffening because chronically increased blood pressure determines structural and functional changes in arterial walls. However, arterial stiffening may also predispose to the development of HTN. We therefore evaluated whether arterial stiffening predicts the development of HTN in normotensive healthy adults. Pulse wave velocity (PWV), a non-invasive index of arterial stiffness, was measured in 364 volunteers from the Baltimore Longitudinal Study of Aging who were normotensive at baseline. After a mean follow-up of 5.1+/-2.9 years, 75 subjects (21%) developed HTN. Variables that were significantly associated with the development of HTN included older age, higher PWV, body mass index, systolic blood pressure, diastolic blood pressurre, and triglycerides, and lower HDL cholesterol. Beacuse of a significant interaction between age and PWV, we examined younger (age<50 years) and older age groups separately. We found that in healthy normotemsive younger, but not older, adults, higher arterial stiffness is an independent predictor of future HTN. Thus, screening for arterial stiffening may identify a subset of normotenisve younger individuals at increased risk for developing HTN, in whom early interventions may be indicated. 5. Intimal medial thickness (IMT) and vascular stiffness have been shown to be independent predictors of adverse cardiovascular events. The metabolic syndrome (MS) is defined as the clustering of 3 or more of the cardiovascular risk factors of dysglycemia, hypertension, dyslipidemia, and obesity. We evaluated whether the clustering of multiple components of the MS has a greater impact on these vascular parameters than individual components of the MS in 471 participants from the Baltimore Longitudinal Study on Aging who were without clinical cardiovascular disease and not on antihypertensive therapy. MS was an independent predictor of increased carotid IMT and stiffness, and conferred a disproportionate increase in carotid IMT (16%) and stiffness (32%,) compared to controls even after taking into account each individual component of the MS. This suggests that the components of the MS interact to synergistically impact vascular thickness and stiffness. Future studies should examine whether the excess cardiovascular risk associated with the MS is, in part, mediated through the amplified alterations in these vascular properties (J Am Coll Cardiol. 2004;43(8):1388-95).

该项目的总体目标是表征血管结构和功能的决定因素，并评估其对心血管发病率和死亡率的影响1。增加的主动脉脉冲波速度（APWV）与临床但一般人群中的死亡率有关。在2488名老年人的基线时测量主动脉PWV。在平均4。6年的随访中，有265例死亡发生，有111例被归类为心血管。较高的主动脉APWV四分位数与总死亡率（P = 0.010）和CV死亡率（P = .006）有关，独立于年龄，性别，种族，SBP，已知CV疾病，肌酐，胆固醇和吸烟。因此，在通常健康，功能良好的，社区居住的人群中，APWV是动脉僵硬的标志，与较高的总死亡率和CV死亡率有关。 2. In order to investigate the hypothesis that the age-associated changes in cardiovascular structure and function represent the mechanism through which increased age exerts its deleterious effects on cardiovascular morbidity and mortality, and to test the related hypothesis that physiologic vascular properties explain the chronologic age-associated increased risk of atherosclerosis, we plan to evaluate traditional as well as novel measures of vascular properties, and examine how they与动脉粥样硬化的非侵入性评估有关。这将在300名BLSA受试者以及已知缺乏冠状动脉疾病和已知过早冠状动脉疾病的患者的个体中进行。已经授予了一项研究与开发合同，用于购买新颖的非侵入性成像工具，例如电子束计算机断层扫描，血管磁共振成像和血管磁共振血管造影（Project S. Najjar）。 3。分离的收缩期高血压（ISH）是老年人中高血压的主要形式，与心血管发病率和死亡率的显着增加有关。但是，ISH风险增加的因素尚未完全阐明。由于血管结构和功能的改变越来越被认为是不良事件的有效预测指标，因此我们研究了与ISH相关的心血管变化。 447名台湾受试者50岁以上，DBP <90 mmHg被分为正常的组（NT，SBP <140 mmHg），而未经处理的ISH组（SBP> 140 mmHg）分为。 NT组平均比ISH小5年（62 +/- 8和67 +/- 7年，p <0.05）。正如预期的那样，ISH组的SBP和PP明显更高。此外，我们发现ISH组的许多血管结构和功能参数明显大于NT组。因此，ISH不是孤立的，而是与许多心血管结构和功能参数中的加速变化有关。与ISH相关的风险增加可能部分是通过这些改变来介导的，其中一些变化已经被确定为独立于血压的心血管疾病的危险因素。 4。高血压（HTN）通常被认为是动脉僵硬的危险因素，因为长期升高的血压决定了动脉壁的结构和功能变化。但是，动脉僵硬也可能易于HTN的发展。因此，我们评估了动脉僵硬是否预测了正常健康的成年人中HTN的发展。脉冲波速度（PWV）是一种无创的动脉刚度指数，在巴尔的摩纵向研究的364名志愿者中测量了基线时正常衰老的衰老纵向研究。在平均随访为5.1 +/- 2。9年后，有75名受试者（21％）发展了HTN。与HTN的发展显着相关的变量包括年龄较大，PWV，体重指数，收缩压，舒张血压，舒张血压和甘油三酸酯以及较低的HDL胆固醇。 BeaCuse在年龄与PWV之间存在显着相互作用，我们分别检查了年龄较大（年龄<50岁）和年龄段。我们发现，在健康的正常人较年轻而不是年龄较大的成年人中，较高的动脉僵硬是未来HTN的独立预测指标。因此，对动脉僵硬的筛查可能会鉴定出一个正常分离的年轻个体的子集，患有HTN的风险增加，其中可能会表明早期干预措施。 5。内侧厚度（IMT）和血管刚度已显示为不良心血管事件的独立预测指标。代谢综合征（MS）定义为3个或更多的患者性血糖，高血压，血脂异常和肥胖的心血管危险因素的聚类。我们评估了在巴尔的摩纵向研究的471名参与者中，MS的多个组成部分的聚类对这些血管参数的影响是否比没有临床性心血管疾病而不是对抗高血管治疗的471名参与者更大。 MS是颈动脉IMT和刚度增加的独立预测指标，即使考虑到MS的每个单独成分，也相比，颈动脉IMT（16％）和刚度（32％）的较差不成比例。这表明MS的成分相互作用，以协同影响血管厚度和刚度。未来的研究应检查与MS相关的过量心血管风险是否部分通过这些血管特性的扩增变化介导（J Am CollCardiol。2004; 43（8）：1388-95）。