The epidemic of obesity threatens recent rogress towards reducing the health burden of coronary heart disease (CHD) in the U.S. population. While much is known regarding how obesity and cardio- metabolic risk factors affect the coronary arteries and heart, much remains uncertain. In addition to the fairly rich literature on computed tomography (CT) measures of visceral adipose tissue (VAT), there is mounting evidence that pericardial adipose tissue (PAT), and the epicardial subcompartment (PATepi), is associated with coronary atherosclerosis and cardiac structure-function. CT measures of PAT, PATepi and VAT refine the adiposity phenotype to precise organ-specific measures, compared to weight and body mass index. This project is an ancillary study to NHLBI's Coronary Artery Risk Development in Young Adults (CARDIA), a population-based study that has 25 years of longitudinal data. The long-term objectives of this proposal are to reduce death and disease through a better understanding of obesity and CHD.
Our Specific Aims are: 1) To define the development and natural history of coronary artery calcified (CAC) plaque burden, spotty lesion morphology, and the interrelatedness of the two processes by cardiac CT at three time points over 10 years (2000-2010) in a bi-racial community dwelling population ages 33 to 55 years. 2) To measure PAT and PATepi in the same participants at three time points and perform longitudinal analysis, adjusted for body fatness measures (BMI and waist circumference) and other risk factors, with dependent variables the development, amount, and character of CAC score and spotty plaques by CT and adverse cardiac structure and function measured by echocardiogram. 3) To measure coronary artery remodeling index (RI) in individuals aged 43-55 years with the high-resolution year 25 CT scans and determine the association between RI and PAT, PATepi, VAT (measured by main study), CAC score and spotty lesions, adjusted for body fatness measures (BMI and waist circumference) and other risk factors. Future analysis for prediction of CHD events will be possible by 2015-2020 for aims 1-3. Cardiac CT images, without contrast, will be obtained at standard and high-resolution from a single exposure to measure PAT, PATepi, CAC score, spotty morphology and RI from a 14 second additional scan to the funded abdominal CT. The latter two "high-risk" phenotypes are associated with culprit lesions of the acute coronary syndrome identified by intracoronary ultrasound or at autopsy. This proposal leverages the investment in CARDIA by adding new science related to PAT and its role in coronary atherosclerosis and cardiac structure-function. This project will link 25 years of CARDIA longitudinal data (anthropometric, biomarker, behavioral, psychosocial, nutritional, genetic, CT VAT and cardiac echocardiography) to new phenotypes. Prospectively measuring these phenotypes in 2010-11 will enable future analysis for prediction of clinical CHD events by 2015-20, further strengthening the impact.

Public Health Relevance

Obesity in early life in African American and white dults is a factor in premature heart disease and cardiovascular death. We will leverage an existing study of 5,115 individuals with 25 years of follow-up to make new measurements with CT and echocardiography. We will determine how changes in the fat located around the heart over ten years in adults 33-55 years influences subsequent heart disease.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Kidney, Nutrition, Obesity and Diabetes (KNOD)
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Reis, Jared P
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Wake Forest University Health Sciences
Schools of Medicine
United States
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Allen, Norrina B; Siddique, Juned; Wilkins, John T et al. (2014) Blood pressure trajectories in early adulthood and subclinical atherosclerosis in middle age. JAMA 311:490-7
Reis, Jared P; Loria, Catherine M; Lewis, Cora E et al. (2013) Association between duration of overall and abdominal obesity beginning in young adulthood and coronary artery calcification in middle age. JAMA 310:280-8
Reis, Jared P; Launer, Lenore J; Terry, James G et al. (2013) Subclinical atherosclerotic calcification and cognitive functioning in middle-aged adults: the CARDIA study. Atherosclerosis 231:72-7