DESCRIPTION (provided by applicant): In recent years, attention has turned to individuals who have a favorable risk factor profile (low risk; LR) for cardiovascular disease (CVD), defined by no smoking, lack of diabetes, low total cholesterol levels, low blood pressure, and lean body mass index. Compared with individuals with not-LR status, those with LR status in young adulthood/middle age (<50 years) have dramatically reduced risk for development of CVD during their remaining lifespan, substantially greater longevity, and significantly greater health-related quality of life and lower medical costs at older ages (>65 years). It is not known whether individuals with LR status in young adulthood/middle age have similarly low levels of subclinical coronary atherosclerosis (subCAD) and lower left ventricular (LV) mass. Advances in technology currently allow for non-invasive angiographic imaging, which can be combined with sensitive non-invasive assessment of myocardial structure and function using magnetic resonance imaging (MRI). The overall goal of this application is to better define the mechanisms underlying the protection against clinical CVD events associated with LR status in young adulthood. The Chicago Healthy Aging Study (CHAS) is a NHLBI-supported study that will re-examine 1500 individuals aged 65-79 years who were initially examined in 1967-1973; 600 of these CHAS participants were LR and 900 were not-LR at ages 25-44 years. Thus, the CHAS provides a unique opportunity to study the consequences of LR/not-LR status in young adulthood on subCAD and cardiac structure and function, using coronary MR angiography and cardiac MRI. The present application is designed as an ancillary study to the CHAS, and will address the following Specific Aims: 1) To determine the association of LR status at ages 25-44 years with MRI measures of coronary atherosclerosis at ages 65-79 years; 2) To determine the association of LR status at ages 25-44 years with MRI measures of LV mass at ages 65-79 years; and 3) To determine the association of MRI measures of subCAD and LV mass measured at ages 65-79 years with concurrent measures of inflammatory markers, physical functioning, and other measures of subclinical CVD, in the context of LR versus not-LR status at ages 25-44 years. In summary, we will use MRI technology to examine people who were at low risk in young adulthood/middle age and are now 65-79, to determine their burden of subCAD and of elevated LV mass. This research will fill critical gaps in our knowledge of the long-term consequences of LR status, which may ultimately lead to improvements in public health and preventive strategies. PUBLIC HEALTH RELEVANCE: In recent years, attention has turned to individuals who have a favorable risk factor profile (low risk; LR) for coronary artery disease (CAD), defined by no smoking, lack of diabetes, low total cholesterol levels, low blood pressure, and lean body mass index. These individuals have dramatically reduced risk for development of CAD during their remaining lifespan, substantially greater longevity, and significantly greater health-related quality of life and lower medical costs at older ages (>65 years). However, it is not known whether these individuals never develop atherosclerosis, the precursor of CAD, or whether they develop it but it does not convert into clinical events, such as heart attacks. Advances in technology currently allow for imaging of coronary arteries using magnetic resonance imaging (MRI) without having to perform invasive heart catheterization. The overall goal of this application is to better define the mechanisms underlying the long-term protection against clinical CAD events associated with low risk status in young adulthood. We will perform MRI to assess the amount of atherosclerosis in coronary arteries and the size of the heart muscle in a subset (approximately 250) of participants of the Chicago Healthy Aging Study. In summary, we will use MRI technology to examine people who were at low risk in young adulthood/middle age and are now 65-79 years old, to determine their burden of CAD and of problems with heart pumping function. This research will fill critical gaps in our knowledge of the long-term consequences of low risk status, which may ultimately lead to improvements in public health and preventive strategies.

LAY SUMMARY In recent years, attention has turned to individuals who have a favorable risk factor profile (low risk; LR) for coronary artery disease (CAD), defined by no smoking, lack of diabetes, low total cholesterol levels, low blood pressure, and lean body mass index. These individuals have dramatically reduced risk for development of CAD during their remaining lifespan, substantially greater longevity, and significantly greater health-related quality of life and lower medical costs at older ages (>65 years). However, it is not known whether these individuals never develop atherosclerosis, the precursor of CAD, or whether they develop it but it does not convert into clinical events, such as heart attacks. Advances in technology currently allow for imaging of coronary arteries using magnetic resonance imaging (MRI) without having to perform invasive heart catheterization. The overall goal of this proposal is to better define the mechanisms underlying the long-term protection against clinical CAD events associated with low risk status in young adulthood. We will perform MRI to assess the amount of atherosclerosis in coronary arteries and the size of the heart muscle in a subset (approximately 250) of participants of the Chicago Healthy Aging Study. In summary, we will use MRI technology to examine people who were at low risk in young adulthood/middle age and are now 65-79 years old, to determine their burden of CAD and of problems with heart pumping function. This research will fill critical gaps in our knowledge of the long-term consequences of low risk status, which may ultimately lead to improvements in public health and preventive strategies.