Association of plasma fatty acid composition with lower extremity arterial disease: The Atherosclerosis Risk in Communities (ARIC) study

Background and Aim: The fatty acid (FA) composition of plasma cholesterol esters or phospholipids reflects medium-term dietary fat intake and has been associated with coronary heart disease, stroke, and preclinical carotid atherosclerosis. Methods and Results: We examined the association of plasma FA composition with lower extremity arterial disease (LEAD) in 1,534 men and 1,809 women aged 45-64 years who were free of clinical coronary heart disease and stroke, at the Minneapolis center of the Atherosclerosis Risk in Communities (ARIC) Study. FA composition was measured in cholesterol esters and phospholipids using gas-liquid chromatography. LEAD was assessed by a resting ankle-brachial index (ABI), the ratio of ankle systolic blood pressure to brachial systolic pressure, of ≤ 0.95 (approximately the 6th percentile in the entire ARIC population). Compared with men without LEAD, men with LEAD had statistically significantly lower levels of polyunsaturated fatty acids (PUFAs, mainly linoleic acid) and polyunsaturated to saturated FA ratio (P/S), but higher levels of monounsaturated fatty acids (MUFAs, mainly palmitoleic and oleic acids). Saturated fatty acids (SFAs) were slightly, but not statistically significantly higher in men with LEAD than those without the disease. The odds ratio estimate of LEAD for an interquartile increment in phospholipids was 1.12 (95% CI: 0.68-1.86) for SFAs, 1.53 (95% CI: 1.15-2.05) for MUFAs, 0.64 (95% CI: 0.44-0.92) for PUFAs, and 0.68 (95% CI: 0.47-0.99) for P/S, after adjustment for age, plasma LDL-cholesterol and fibrinogen, cigarette smoking, hypertension, diabetes, and dietary vitamin E intake. The magnitude of the associations was similar in plasma cholesterol esters. In women, palmitoleic acid (16:1n7) in both plasma fractions was positively, and phospholipid linoleic acid (18:2n6) was inversely, associated with LEAD. No grouped FAs, however, were statistically significantly associated with LEAD in women after mitltivariate adjustment. Analyses using ABI as a continuous variable were generally consistent with the LEAD findings. Conclusions: Reduced levels of plasma PUFAs and P/S ratio, and elevated levels of plasma MUFAs are associated with lower extremity atherosclerosis, at least in men. This provides further evidence that an atherogenic diet may contribute to LEAD.