Cardiac MR of Subclin CVD: Impact of Age

Subclin CVD 的心脏 MR：年龄的影响

• 批准号: 6657288
• 负责人: WARREN J MANNING
• 金额: $ 81.71万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6657288
• 关键词: acute phase protein; age difference; atherosclerosis; bioimaging /biomedical imaging; cardiovascular disorder diagnosis; cardiovascular disorder epidemiology; cardiovascular imaging /visualization; clinical research; diagnosis design /evaluation; disease /disorder proneness /risk; early diagnosis; family genetics; heart imaging /visualization /scanning; human genetic material tag; human subject; magnetic resonance imaging

DESCRIPTION (Verbatim from the Applicant's Abstract): Coronary heart disease and stroke are leading causes of mortality for men and women in the United States. Our current understanding of the pathogenesis of and the risk factors for cardiovascular disease (CVD) is derived largely from prospective studies of clinically overt disease. Unfortunately, clinical risk factors for CVD defined by these methods fail to predict a large proportion of CVD events, and some subjects at high clinical risk fail to develop overt disease. Subclinical disease precedes clinical events by years/decades but is difficult to quantify. For example, left ventricular hypertrophy (LVH) and aortic atherosclerosis are strong predictors of CVD events, but are difficult to accurately non-invasively quantify, especially among the elderly and overweight subjects (both growing populations in the U.S.). MRI perrnits accurate assessment of cardiac anatomy/function and subclinical aortic atherosclerosis. The underlying hypothesis of this proposal is that subclinical CVD is a precursor to overt CVD, and that MRI measures of subclinical aortic and cardiac anatomic disease are superior for the characterization of risk as compared with current measures of risk factors as well as more conventional imaging (e.g., carotid ultrasound, echo). Longitudinal/time-averaged indexes of all established risk factors for CVD have been collected in the Framingham Heart Study (FHS). These time-averaged indexes are stronger predictors of clinical CVD than single measures. In a Pilot study of 312 FHS Offspring subjects, MRI measures of LV mass were successfully acquired in a larger proportion of subjects than echo, and MR evidence of LVH and subclinical aortic disease correlated more strongly (than echo and carotid ultrasound measures) with these time-averaged indexes. Application of MRI methods in the FHS offers an opportunity to identify subclinical atherosclerosis and LVH in this well-characterized cohort and to relate these data with conventional imaging measures already acquired in this cohort. Importantly, the near-concurrent acquisition of brain MRI/neuropsychologic examination in the same FHS cohort offer the unique contemporaneous opportunity to examine subclinical cerebrovascular disease with MRI indexes of subclinical atherosclerosis. We propose to expand our Pilot study to perform heart and thoracic/abdominal aorta MRI studies in 2400 FHS participants to allow for identification of individual CVD risk factors for subclinical atherosclerosis. These population-based data will extend our knowledge of the distribution and severity of atherosclerosis in adult men and women and their relations to existing echo, carotid ultrasound and brain MRI measures. This study provides the rare opportunity to examine associations of quantitative MRI measures of aortic atherosclerosis and LVH with both cross-sectional and time-averaged measures of individual atherosclerotic risk factors (e.g., blood pressure, cigarette smoking, and cholesterol) and with novel inflammatory markers (e.g., C-reactive protein, MCP-1). Further, because the FHS consists of hundreds of sibships for which a DNA repository has been established, we propose to determine the heritability of MRI indexes of atherosclerosis and LVH, laying the groundwork for future genetic studies.

描述（逐字研究来自申请人的摘要）：冠状动脉疾病 中风是统一男女死亡的主要原因 国家。我们当前对发病机理和风险因素的理解 对于心血管疾病（CVD），主要源于前瞻性研究 临床上明显的疾病。不幸的是，定义的CVD的临床风险因素 通过这些方法无法预测大部分的CVD事件，有些 高临床风险的受试者无法发展出明显的疾病。亚临床 疾病先于临床事件，数年/几十年，但很难量化。 例如，左心室肥大（LVH）和主动脉粥样硬化是 CVD事件的强烈预测指标，但难以准确地非侵入性 量化，尤其是在老年人和超重主题中（都在增长 在美国的人口）。 MRI Perrnits对心脏的准确评估 解剖学/功能和亚临床主动脉粥样硬化。基础 该提议的假设是亚临床CVD是公开的先驱 CVD，以及亚临床主动脉和心脏解剖疾病的MRI测量 与当前措施相比，风险的表征优越 风险因素以及更常规的成像（例如，颈动脉超声波， 回声）。 CVD的所有已建立风险因素的纵向/时间平均指数 被收集在弗雷明汉心脏研究（FHS）中。这些时间平均的索引 比单一措施比临床CVD的预测更强。在试点研究中 在312名FHS后代受试者中，LV质量的MRI度量已成功 比Echo的受试者比例更大，LVH的MR证据 亚临床主动脉疾病的相关性更强（比Echo和Carotid 超声措施）这些时间平均索引。 MRI的应用 FHS中的方法提供了一个识别亚临床的机会 在这个良好的人群中，动脉粥样硬化和LVH并将其联系起来 该队列中已经获得的传统成像措施的数据。 重要的是，大脑MRI/神经心理学的近交流 在同一FHS队列中的检查提供了独特的同期机会 用亚临床的MRI指数检查亚临床脑血管疾病 动脉粥样硬化。 我们建议扩大我们的试点研究以进行心脏和胸痛/腹部 主动脉MRI研究在2400名FHS参与者中允许识别 亚临床动脉粥样硬化的单个CVD风险因素。这些 基于人群的数据将扩展我们对分布的了解和 成年男女动脉粥样硬化的严重程度及其与他们与 现有的回声，颈动脉超声和脑MRI测量。这项研究提供 难得的机会检查定量MRI测量的关联 主动脉动脉粥样硬化和LVH具有横截面和时间平均 单个动脉粥样硬化危险因素的度量（例如，血压， 吸烟和胆固醇）以及新颖的炎症标记（例如， C反应蛋白，MCP-1）。此外，因为FHS由数百个 已经建立了DNA存储库的sibships，我们建议 确定动脉粥样硬化和LVH的MRI指数的遗传力 未来遗传研究的基础。