Abstract 13797: The Lipophilic Index of Red Blood Cell Membranes and Risk of Sudden Cardiac Death in Women
Introduction: Fatty acids (FA) are classified based on structural properties (i.e., chain length, saturation, configuration) which may not capture fully their biologic properties. The lipophilic index (LI) is a novel index that summarizes the overall FA profile based on individual FA melting points, which determine FA affinity and membrane fluidity. Because saturates have high and unsaturates have low melting points, greater LI represents potentially decreased membrane fluidity. Changes in cell membrane fluidity may influence predisposition to fatal ventricular arrhythmia and sudden cardiac death (SCD) through changes in cellular electrophysiology.
Methods: To examine whether LI was associated with SCD, we conducted a prospective, nested case-control study among 32,826 women in the Nurses’ Health Study, aged 44-69 at the time of blood draw. Over 22 years, 137 cases of sudden and/or arrhythmic cardiac death were matched to 2 controls on age, ethnicity, smoking status, fasting status and presence of CVD using risk set sampling. The RBC LI was calculated by multiplying the concentration of each FA in the RBC membrane by its melting point and summing across all FA (n=28). Multivariable conditional logistic regression models adjusted for CVD risk factors estimated the relative risk (RR).
Results: Compared to the lowest quartile (Q) of the RBC LI, the RR (95%CI) for SCD were 1.44 (0.69, 3.00) in Q2, 1.63 (0.76, 3.52) in Q3 and 2.64 (1.27, 5.49) in Q4 after accounting for matching factors and potential confounders (P, trend =0.007). These relationships remained significant after adjusting for n-3 FA EPA + DHA (RR Q4 v Q1: 2.29; 95%CI: 1.05, 5.00, P, trend = 0.03) and polyunsaturated:saturated fat ratio (RR Q4 v Q1: 2.85; 95%CI: 1.32, 6.17, P, trend = 0.001). Results were not appreciably altered after adjusting for other FA previously associated with SCD risk, including α-linolenic acid, trans FA, and FA in the de novo lipogenesis pathway. In contrast, the inverse association between RBC n-3 FA and SCD risk was not significant after adjustment for LI.
Conclusions: Higher RBC LI, representative of decreased membrane fluidity, was associated with significantly higher SCD risk. The LI as a summary measure provided additional information beyond individual FA on SCD risk.
Author Disclosures: S.E. Chiuve: None. Q. Sun: None. H. Wu: None. K. De Vito: None. E.L. Ding: None. N.R. Cook: None. C.M. Albert: None.
- © 2014 by American Heart Association, Inc.