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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL070279-02
Application #
6528330
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Bild, Diane
Project Start
2001-09-30
Project End
2005-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
2
Fiscal Year
2002
Total Cost
$770,355
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
Aparicio, Hugo J; Petrea, Rodica E; Massaro, Joseph M et al. (2017) Association of descending thoracic aortic plaque with brain atrophy and white matter hyperintensities: The Framingham Heart Study. Atherosclerosis 265:305-311
Roseman, Daniel A; Hwang, Shih-Jen; Oyama-Manabe, Noriko et al. (2017) Clinical associations of total kidney volume: the Framingham Heart Study. Nephrol Dial Transplant 32:1344-1350
Foppa, Murilo; Arora, Garima; Gona, Philimon et al. (2016) Right Ventricular Volumes and Systolic Function by Cardiac Magnetic Resonance and the Impact of Sex, Age, and Obesity in a Longitudinally Followed Cohort Free of Pulmonary and Cardiovascular Disease: The Framingham Heart Study. Circ Cardiovasc Imaging 9:e003810
Yeon, Susan B; Salton, Carol J; Gona, Philimon et al. (2015) Impact of age, sex, and indexation method on MR left ventricular reference values in the Framingham Heart Study offspring cohort. J Magn Reson Imaging 41:1038-45
Jefferson, Angela L; Beiser, Alexa S; Himali, Jayandra J et al. (2015) Low cardiac index is associated with incident dementia and Alzheimer disease: the Framingham Heart Study. Circulation 131:1333-9
Chuang, Michael L; Gona, Philimon; Hautvast, Gilion L T F et al. (2014) CMR reference values for left ventricular volumes, mass, and ejection fraction using computer-aided analysis: the Framingham Heart Study. J Magn Reson Imaging 39:895-900
Chuang, Michael L; Gona, Philimon; Oyama-Manabe, Noriko et al. (2014) Risk factor differences in calcified and noncalcified aortic plaque: the Framingham Heart Study. Arterioscler Thromb Vasc Biol 34:1580-6
Magnani, Jared W; Yin, Xiaoyan; McManus, David D et al. (2014) Genetic loci associated with atrial fibrillation: relation to left atrial structure in the Framingham Heart Study. J Am Heart Assoc 3:e000616
Hong, Susie N; Gona, Philimon; Fontes, Joao D et al. (2013) Atherosclerotic biomarkers and aortic atherosclerosis by cardiovascular magnetic resonance imaging in the Framingham Heart Study. J Am Heart Assoc 2:e000307
Chuang, Michael L; Gona, Philimon; Hautvast, Gilion L T F et al. (2012) Correlation of trabeculae and papillary muscles with clinical and cardiac characteristics and impact on CMR measures of LV anatomy and function. JACC Cardiovasc Imaging 5:1115-23

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