Abstract MP001: Plasma Lipophilic Index and Risk of Coronary Heart Disease in US Men

Background: Lipophilicity of fatty acids plays a critical role in modulating the fluidity and function of cellular and lipoprotein membranes that are involved in the etiology of coronary heart disease (CHD). However, no data are available on the relationship between overall fatty acid lipophilicity and risk of CHD. Objective: To examine a novel index of fatty acid lipophilicity in relation to risk of CHD in men. Methods: In a prospective CHD case-control study nested in the Health Professionals Follow-up Study (HPFS), fatty acids in total plasma and erythrocyte membrane were measured by gas-liquid chromatography in 459 CHD cases and 879 matched controls. Plasma lipophilic index (LI) was computed by summing the products between relative density (proportion of total fatty acids) of 21 major fatty acids and their melting points. Erythrocyte LI was derived from 14 fatty acids using the same method. Results: Both plasma and erythrocyte LI summarized a pattern that featured high saturated fatty acids and low polyunsaturated fatty acids. Plasma C24:0, C22:0, C20:0, C23:0, C18:0 (all P <0.0001) were positively and C20:5n–3, C22:6n–3, and C20:4n–6 (all P <0.0001) were inversely associated with plasma LI, and these fatty acids jointly explained ∼71% of plasma LI variation among control participants. Among controls, higher plasma LI was significantly correlated with adverse profiles of CHD risk factors, including elevated levels of triglycerides, C-reactive protein, interlukin-6, and tumor necrosis factor α receptor 1 and 2, and lower level of HDL-cholesterol and adiponectin (all P <0.005). After multivariate adjustment of covariates including age, smoking status, body mass index, and physical activity, plasma LI was significantly associated with increased risk of total CHD: odds ratio (95% confidence interval) was 1.82 (1.16, 2.86; P for trend = 0.016) comparing extreme quintiles. The association was more pronounced for non-fatal myocardial infarction (OR=2.06, 95% CI 1.24, 3.42; P for trend = 0.004) than for fatal CHD (OR=1.04, 95% CI 0.31, 3.55; P for trend = 0.63). The association between erythrocyte LI and risk of CHD was not significant after multivariate adjustment (OR=1.18, 95% CI 0.71, 1.79; P for trend = 0.66). Conclusions: Our data indicate that the novel plasma lipophilic index, which summarizes overall lipophilicity of major fatty acids in plasma, is associated with an increased risk of CHD in men.