Cardiac MR of Subclin CVD: Impact of Age

描述（来自申请人摘要的逐字记录）：冠心病 和中风是美国男性和女性死亡的主要原因， States.我们目前对该病的发病机制和危险因素的认识 心血管疾病（CVD）的主要来源于前瞻性研究， 临床上明显的疾病。不幸的是，CVD的临床风险因素定义 这些方法不能预测大部分CVD事件， 处于高临床风险的受试者不能发展明显的疾病。亚临床 疾病先于临床事件发生数年/数十年，但难以量化。 例如，左心室肥大（LVH）和主动脉粥样硬化是 CVD事件的强预测因子，但难以准确地非侵入性 量化，特别是在老年人和超重的受试者中（两者都在增长 美国的人口）。MRI能准确评估心脏 解剖/功能和亚临床主动脉粥样硬化。底层 该建议假设亚临床CVD是显性CVD的前兆， CVD和MRI测量亚临床主动脉和心脏解剖疾病 与现行措施相比，在风险表征方面具有上级优势 风险因素以及更常规的成像（例如，颈动脉超声， echo）。 所有已确定的CVD风险因素的纵向/时间平均指数 在心脏病研究（FHS）中收集。这些时间平均指数 是比单一指标更强的临床CVD预测指标。在一项初探性研究中 在312名FHS后代受试者中，成功进行了LV质量的MRI测量 在比超声心动图更大比例的受试者中获得，以及LVH的MR证据 和亚临床主动脉疾病的相关性更强（比回声和颈动脉 超声测量）与这些时间平均指数。MRI应用 FHS中的方法提供了一个机会， 动脉粥样硬化和左室肥厚，并将这些 在该队列中已经采集了常规成像测量的数据。 重要的是，大脑MRI/神经心理学的几乎同时采集 同一FHS队列中的检查提供了独特的同期机会， 亚临床脑血管病的MRI指标 动脉粥样硬化 我们建议将我们的初步研究扩展到心脏和胸/腹 在2400名FHS参与者中进行主动脉MRI研究，以识别 亚临床动脉粥样硬化的个体CVD危险因素。这些 基于人口的数据将扩展我们对分布的了解， 成年男性和女性动脉粥样硬化的严重程度及其与 现有的回声，颈动脉超声和脑MRI措施。这项研究提供 这是一个难得的机会来检查定量MRI测量的相关性， 主动脉粥样硬化和LVH的横截面和时间平均 个体动脉粥样硬化危险因素的测量（例如，血压， 吸烟和胆固醇）和新的炎症标记物（例如， C-反应蛋白，MCP-1）。此外，由于FHS由数百个 已设立DNA储存库的兄弟姊妹，我们建议 测定动脉粥样硬化和左室肥厚MRI指标的遗传度， 为未来的基因研究奠定基础。

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.