Coronary artery disease (CAD) is a major cause of mortality and morbidity in the U.S. Current noninvasive methods to identify individuals with atherosclerosis, such as exercise testing, are often insensitive until plaques have progressed enough to significantly impede blood flow or impair myocardial function. A large number of individuals destined to die suddenly or to experience myocardial infarction will experience no warning symptoms, having only mild non-flow limiting lesions which rupture and cause occlusive clot. Since coronary artery calcification (CAC) can identify individuals with mild, non-flow limiting lesions, CAC is a potent marker of atherosclerosis. The presence of calcium in mild, non-flow limiting lesions is hypothesized to be a predictor of coronary events in asymptomatic adults. Ultrafast Cardiac Computed Tomography (Ultrafast CT) provides a tool to obtain sensitive, noninvasive measures of both the presence and quantity of CAC. We will randomly select 400 males and 400 females from the Rochester Family Heart Study (RFHS) between the ages of 20 and 60 to characterize predictors of CAC among individuals from the general population. We estimate 80% will report no clinical symptoms of CAD.
Aim 1 will establish if age and gender predict CAC in individuals sampled by the RFHS who report no symptoms of CAD.
Aim 2 will establish if measures of lipid metabolism provide additional information in predicting CAC after accounting for variation in age and gender.
Aim 3 will establish if measures of blood pressure, body size, fat distribution, or smoking predict CAC after accounting for variation in age, gender and measures of lipid metabolism.
Aim 4 will establish if the quantity of CAC aggregates in families.
Aim 5 will establish whether the predictors of CAC in asymptomatic individuals differ from predictors in those with symptoms of CAD. Successful completion of these aims will 1) provide estimates of the prevalence of CAC in asymptomatic males and females ages 20 to 60 and 2) establish whether the known predictors of clinically defined CAD also predict CAC in asymptomatic individuals. Utilizing Ultrafast CT to identify individuals in the early stages of CAD is important because preclinical CAD can potentially be treated by risk factor modification, drugs or revascularization. Ultrafast CT will provide the opportunity for studying predictors of atherosclerotic plaques rather than the sequelae of CAD.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL046292-01
Application #
3365387
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1991-04-15
Project End
1995-03-31
Budget Start
1991-04-15
Budget End
1992-03-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Public Health
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Cassidy-Bushrow, Andrea E; Bielak, Lawrence F; Levin, Albert M et al. (2013) Matrix gla protein gene polymorphism is associated with increased coronary artery calcification progression. Arterioscler Thromb Vasc Biol 33:645-51
Cassidy-Bushrow, Andrea E; Bielak, Lawrence F; Sheedy 2nd, Patrick F et al. (2011) Shared genetic architecture in the relationship between adult stature and subclinical coronary artery atherosclerosis. Atherosclerosis 219:679-83
Bielak, Lawrence F; Whaley, Dana H; Sheedy 2nd, Patrick F et al. (2010) Breast arterial calcification is associated with reproductive factors in asymptomatic postmenopausal women. J Womens Health (Larchmt) 19:1721-6
Cassidy-Bushrow, Andrea E; Bielak, Lawrence F; Rule, Andrew D et al. (2009) Hypertension during pregnancy is associated with coronary artery calcium independent of renal function. J Womens Health (Larchmt) 18:1709-16
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Cassidy-Bushrow, Andrea E; Bielak, Lawrence F; Sheedy 2nd, Patrick F et al. (2007) Coronary artery calcification progression is heritable. Circulation 116:25-31
Kullo, Iftikhar J; Malik, A Rauoof; Bielak, Lawrence F et al. (2007) Brachial artery diameter and vasodilator response to nitroglycerine, but not flow-mediated dilatation, are associated with the presence and quantity of coronary artery calcium in asymptomatic adults. Clin Sci (Lond) 112:175-82

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