Cardiac MR of Subclin CVD: Impact of Age

描述(逐字摘自申请者摘要)：冠心病 中风是美国男性和女性死亡的主要原因 各州。我们目前对糖尿病的发病机制及危险因素的认识 对于心血管疾病(CVD)的研究主要来自于 临床上的显性疾病。不幸的是，心血管疾病的临床危险因素被定义 通过这些方法无法预测很大比例的心血管事件，而且一些 具有高临床风险的受试者不会发展为显性疾病。亚临床 疾病比临床事件早几年或几十年，但很难量化。 例如，左心室肥厚(LVH)和主动脉粥样硬化 心血管事件的强大预测因素，但很难无创地准确预测 量化，特别是在老年人和超重受试者中(两者都在增长 美国的人口)。磁共振成像对心脏的准确评估 解剖/功能与亚临床动脉粥样硬化。潜在的 这一建议的假设是亚临床脑血管病是显性心血管疾病的先兆。 心血管疾病，以及亚临床主动脉和心脏解剖疾病的MRI测量 与当前的措施相比，在表征风险方面更具优势 风险因素以及更传统的成像(例如，颈动脉超声， ECHO)。 所有已确定的心血管疾病危险因素的纵向/时间平均指数 已在《弗雷明翰心脏研究》(FHS)上收集。这些时间平均指数 对临床心血管疾病的预测作用强于单项指标。在一项初步研究中 在312名FHS子代受试者中，MRI测量左室包块成功 与ECHO和左心室肥厚的MR证据相比，在受试者中获得的比例更大 与亚临床主动脉病变的相关性更强(比ECHO和颈动脉 超声测量)与这些时间平均指标。磁共振成像技术的应用 FHS中的方法提供了一个识别亚临床的机会 动脉粥样硬化和左心室肥厚在这一特征良好的队列中的关系 在这个队列中已经获得了使用常规成像方法的数据。 重要的是，几乎同时获得的脑MRI/神经心理学 同一FHS队列中的考试提供了独特的当代机会 亚临床型脑血管病的MRI检查指标 动脉硬化。 我们建议将我们的初步研究扩大到心脏和胸部/腹部 2400名FHS参与者的主动脉MRI研究以允许识别 亚临床动脉粥样硬化的单个心血管危险因素。这些 基于人口的数据将扩展我们对分布和 成年男性和女性动脉粥样硬化的严重程度及其与 现有的超声、颈动脉超声和脑MRI测量。这项研究提供 难得的机会来研究定量MRI测量结果与 横断面和时间平均的主动脉粥样硬化和左心室肥厚 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)和新的炎症标志物(例如， C反应蛋白，MCP-1)。此外，由于FHS由数百名 已经为其建立了DNA存储库的兄弟关系，我们建议 测定蛋鸡动脉粥样硬化和左心室肥厚的MRI指标的遗传度 为未来的基因研究奠定了基础。

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.