Red Blood Cell Membrane Alpha-linolenic Acid and the Risk of Sudden Cardiac Arrest

Higher levels of long chain n3 polyunsaturated fatty acids in red blood cell membranes are associated with lower risk of sudden cardiac arrest. Whether membrane levels of alpha-linolenic acid (ALA), a medium chain n3 polyunsaturated fatty acid, show a similar association is unclear. We investigated the association of red blood cell membrane alpha-linolenic acid with sudden cardiac arrest risk in a population based case-control study. Cases, aged 25 to 74 years, were out of hospital sudden cardiac arrest patients, attended by paramedics in Seattle, Washington (n of 265). Controls, matched to cases by age, sex and calendar year, were randomly identified from the community (n of 415). All participants were free of prior clinically diagnosed heart disease. Blood was obtained at the time of cardiac arrest (cases) or at the time of an interview (controls). Higher membrane ALA was associated with a higher risk of sudden cardiac arrest: after adjustment for matching factors and smoking, diabetes, hypertension, education, physical activity, weight, height and total fat intake, the odds ratios corresponding to increasing quartiles of alpha-linolenic acid were 1.7 (95% confidence interval [CI] 1.0 to 3.0), 1.9 (95% CI 1.1 to 3.3), and 2.5 (95% CI 1.3 to 4.8) compared to the lowest quartile. The association was independent of red blood cell levels of long chain n3 fatty acids, trans fatty acids, and linoleic acid. Higher membrane levels of ALA acid are associated with higher risk of sudden cardiac arrest. (Authors abstract)
Sudden cardiac death, also known as out-of-hospital sudden cardiac arrest (SCA), is the leading cause of death from coronary heart disease. Dietary intake of ALA is suggested to reduce risk of cardiac death. Whether membrane levels of ALA are related to SCA risk has received limited attention. Using blood specimens collected by paramedics in the field at the time of cardiac arrest and population-based controls, the investigators reported associations of lower levels of EPA and DHA, and higher levels of trans isomers of linoleic acid (trans 18:2) in red blood cell (RBC) membranes with higher risk of SCA. In this report, the association of red cell membrane ALA and SCA risk, following additional data collection, was examined. In this population-based study, higher levels of ALA in RBC membranes were not associated with a reduction in risk of SCA.  The study results contrast with suggested benefits of dietary ALA shown in several cohort studies. There is limited information on dietary ALA and coronary heart disease events from clinical trials. Dietary ALA has been associated with lower risk of sudden cardiac death in women with high and low intake of DHA and EPA in the Nurses Health Study. The possibility that the association of ALA with higher risk of SCA was restricted to subjects with higher body weight is intriguing.  Further work is needed to confirm the study findings in other populations, and explore whether the association of dietary ALA with SCA is affected by variation in metabolic processes, such as incorporation into membrane phospholipids and conversion to EPA. (Editors comments)