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Grant Abstract

Grant Number: 5R01HL085710-04
PI Name: MOZAFFARIAN, DARIUSH
Project Title: FATTY ACIDS AND MAJOR CARDIOVASCULAR OUTCOMES

Abstract: With advancing age, the incidence and prevalence of congestive heart failure (CHF), atrial fibrillation (AF), and stroke rise dramatically, producing major burdens of morbidity and mortality. Dietary intakes of n-3 fatty acids and trans-fatty acids influence many cardiovascular disease (CVD) risk factors, including risk factors for CHF, AF, and stroke. However, relations between n-3 and trans-fatty acids and these major CVD endpoints are not well-established. In prior studies, we have demonstrated that reported dietary habits are independently associated with incidence of CVD events in older adults. We have particularly focused on effects of different fish meals and hypothesized that the observed relations with disease risk may be due to n-3 or trans-fatty acids. Estimation of dietary intake of specific fatty acids using diet questionnaires can be challenging. In prior work using case-control designs, we have demonstrated that direct measurement of phospholipid n-3 and trans-fatty acids provides an objective measure of exposure and allows direct investigation of relations between these fatty acids and risk of coronary heart disease. We propose to measure plasma phospholipid fatty acids in stored samples among 4,766 older adults in the Cardiovascular Health Study, a population-based, multicenter cohort study of CVD risk, to investigate prospectively the association between n-3 and trans-fatty acids and incidence of CHF, AF, stroke, and total mortality. Fatty acids will be assessed using plasma stored in 1992, with events prospectively ascertained and adjudicated. For each of these outcomes, we hypothesize that n-3 fatty acids (both seafood and plant-derived) will be associated with lower risk, while trans-fatty acids will be associated with higher risk. As a secondary aim, we will elucidate potential mechanisms for CVD effects by evaluating the relations of these fatty acids with measures of hemodynamics, cardiac structure and function, electrophysiology, insulin sensitivity, inflammation, endothelial function, and obesity. These aims directly address the NIH's goal to investigate the role of nutritional factors for causation or prevention of CHF. The results of this proposed research will be highly relevant to public health, identifying dietary factors which may influence risk of major disease endpoints in older adults, including heart failure, atrial fibrillation, stroke, and death.

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