Small low-density lipoprotein particles and endothelium-dependent vasodilation in postmenopausal women

Abstract

Low concentrations of estrogen may decrease endothelial function in postmenopausal women. Elevated plasma triglycerides after menopause are frequently associated with a small, dense low-density lipoprotein (LDL) phenotype. Small LDL particles that are more susceptible to oxidation can also inhibit endothelium-dependent vasodilation. The purpose of the present study was to investigate whether hypertriglyceridemia-induced small LDL particles are associated with endothelial dysfunction in postmenopausal women. We studied 15 premenopausal and 41 postmenopausal women. Postmenopausal subjects were divided into those with LDL subclass pattern A (large particles) and those with pattern B (small particles). Plasma lipids, hormones, and diameter and oxidative susceptibility of LDL were measured. Vasodilatory responses of the brachial artery were evaluated by measuring flow-mediated vasodilation (FMD) and nitroglycerin-induced vasodilation (NID). FMD in both postmenopausal groups was significantly lower than in premenopausal women. FMD in subjects with pattern B was significantly smaller than in those with pattern A (4.9 ± 1.9% versus 8.8 ± 3.6%). NID did not differ significantly among the groups. Plasma triglyceride concentrations were higher, lag time for LDL oxidation was shortened, and LDL-derived thiobarbituric acid-reactive substance (TBARS) concentrations were significantly greater in subjects with pattern B than in premenopausal or pattern A subjects. LDL diameter correlated negatively with plasma triglycerides ( r = −0.51) or LDL-derived TBARS ( r = −0.44) and positively with LDL-lag time ( r = 0.66). FMD correlated negatively with LDL-derived TBARS ( r = −0.36) and positively with LDL diameter ( r = 0.44) or LDL-lag time ( r = 0.43). Vascular endothelial dysfunction may be associated with elevated triglyceride-induced small LDL particles that have enhanced oxidative susceptibility in postmenopausal women.