Endothelial dysfunction in men with small LDL particles

Background-It is unknown whether LDL particle size is, independent of other lipids and lipoproteins, associated with endothelial dysfunction in vivo. Methods and Results-We determined in vivo endothelial function in 34 health y men by measuring forearm blood flow responses to intrabrachial artery inf usions of acetylcholine (ACh, an endothelium-dependent vasodilator) and sod ium nitroprusside (an endothelium-independent vasodilator). LDL peak partic le size was measured with gradient gel electrophoresis. Men with small LDL particles (LDL diameter less than or equal to 25.5 nm, n=10) had a 39% lowe r blood flow response to ACh than men with large LDL particles (LDL diamete r >25.5 nm, n=24, blood flow 6.9+/-3.6 versus 11.4+/-5.1 mL/dL.min, P=0.006 ). The groups had comparable LDL cholesterol concentrations (3.9+/-0.6 vers us 3.7+/-1.0 mmol/L, men with small versus large LDL particles), blood pres sure, glucose concentrations, and body mass indexes. LDL size (r=0.45, P=0. 01) but not HDL cholesterol (r=0.31, P=0.09) or triglycerides (r=-0.19, r=0 .30) was significantly correlated with endothelium-dependent vasodilation. Serum triglyceride concentrations and LDL size were inversely correlated (r =-0.44, P=0.01). In multivariate regression analysis, LDL size was the only significant determinant of the ACh-induced increase in blood flow. Sodium nitroprusside-stimulated endothelium-independent vasodilation was similar i n both groups. Conclusions-Small LDL particles are associated with impaired in vivo endoth elial function independent of HDL and LDL cholesterol and triglyceride conc entrations. LDL size may therefore mediate adverse effects of hypertriglyce ridemia on vascular function.