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Grant Abstract: Coronary Calcium Score Method and Cardiovascular Disease Events in Two Cohorts

Grant Number: 5R01HL116395-04
PI Name: Criqui
Project Title: Coronary Calcium Score Method and Cardiovascular Disease Events in Two Cohorts

Abstract: In accordance with PA-15-258 (Administrative Supplements for Research on Dietary Supplements), and consistent with the missions of the Office of Dietary Supplements (ODS) to “strengthen knowledge and understanding of dietary supplements by supporting research”, and the National Heart, Lung, and Blood Institute (NHLBI) to “promote the prevention and treatment of heart, lung, and blood diseases”, we propose observational research in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort to determine if use of select dietary supplements is associated with higher coronary artery calcium (CAC) volume or density. Coronary artery calcium (CAC) is a strong predictor of cardiovascular disease (CVD), and contributes significant incremental information beyond standard CVD risk factors to the prediction of future CVD events. However, research by our group (resulting from the parent grant supporting this application) in the MESA cohort demonstrated differential contribution of CAC volume and density scores (vs. CAC measured by Agatston score) to subsequent risk of CVD events. Higher CAC volume (for a given density) was associated with increased risk of CVD events, whereas higher CAC density (for a given volume) was associated with a reduced risk of CVD events. We now propose applying CAC density and volume scoring to learn more about the health effects of dietary supplements, which according to 2011 NHANES data, are used by 67% of US adults. Clinical trials of most dietary supplements have mostly been disappointing, however trials to date have been too short to evaluate interventions that may have a gradual, subtle contribution to the pathophysiology of atherosclerosis, such as small effects on CAC volume and density. Using data available in the MESA cohort, and because over 30% of the US population are reported to use them, we specifically propose evaluating associations between CAC density and volume and use of calcium, vitamin D, vitamin C, vitamin E and omega-3 fatty acids/fish oil supplements (plus explore several others including B vitamins, zinc, magnesium and selenium). We will do so by developing multiple multivariable models to determine if associations exist between CAC volume or density and use of dietary supplements, serially adjusting for basic demographics, dietary intake, traditional risk factors, biomarkers of inflammation, and CVD medications including statins and anti-coagulants. We will also compare mean CAC volume, density and Agatston score between supplement users and non-users, also adjusting for demographics and traditional CVD risk factors. Upon completion, the proposed research will provide insight into the effects of dietary supplements on the pathophysiology of plaque formation, and, if differential effects are measured, will impact the selection of outcome measures in future clinical trials.

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