This application represents a revised competing renewal application of ROl H141993-06 entitled "Polyunsaturated Fats and Primary Cardiac Arrest." During the prior project periods, we demonstrated that 1) modest dietary intake of long-chain n-3 polyunsaturated fatty acids (PUFAs) from seafood (20:5n-3, EPA and 22:6n-3, DHA), measured directly through a questionnaire and indirectly through red-cell membrane fatty acid composition, was associated with a lower risk of primary cardiac arrest (PCA); and, 2) red-cell membrane levels of trans-isomers of linoleic acid (trans-18:2) but not trans-isomers of oleic acid (trans-18:1) were associated with an increased risk of PCA. We now propose to extend our population-based case-control study to determine whether modest dietary intake of the intermediate-chain n-3 PUFA (18:3n-3, ALA), assessed using red-cell membrane fatty acid composition, is associated with a lower risk of PCA, particularly in the setting of low intake of EPA/DHA. We will continue to identify cases of PCA who are attended by paramedics in King County, Washington (through January 2005). Demographically-similar controls will continue to be identified from the same community using random-digit-dialing. Blood specimens from newly identified cases (collected by paramedics in the field) and controls will be analyzed for red-cell membrane levels of ALA and other fatty acids. Spouses of subjects will be interviewed to assess other risk factors, usual saturated fat intake, and recent changes in diet. Analyses will focus on the relation between ALA and risk of PCA in the context of a diet low in EPA/DHA, after adjusting for red-cell membrane linoleic acid and trans-fatty acid levels and other risk factors. To determine whether the association between ALA levels and risk of PCA may result from uncontrolled confounding from other nutrients, we will conduct a dietary intake substudy on newly identified control subjects and assess the relation of red-cell membrane ALA levels with other nutrients, measured using a food frequency questionnaire. The proposed research provides a unique opportunity to examine more fully the role of dietary intake of n-3 PUFAs, particularly ALA, in efforts to reduce PCA, a major component of coronary heart disease mortality in the community.