Effect of gemfibrozil ± niacin ± cholestyramine on endothelial function in patients with serum low-density lipoprotein cholesterol levels < 160 mg/dl and high-density lipoprotein cholesterol levels < 40 mg/dl

We studied endothelial function using the brachial artery ultrasound model in 100 subjects from the Armed Forces Regression Study, a placebo- controlled, angiographic regression trial in subjects with normal or modestly elevated low-density lipoprotein (LDL) cholesterol and low levels of high- density lipoprotein (HDL) cholesterol treated for 30 months with gemfibrozil and (if necessary) niacin and/or cholestyramine to raise HDL by 25% and lower LDL to <110 mg/dl. Although the treatment group had highly significant improvements in LDL and HDL cholesterol, there was no difference between the 2 groups in flow-mediated dilation (treatment vs control 6.9 ± 6.5% vs 6.3 ± 7.3%) or nitroglycerin-induced dilation (12.4 ± 9.6% vs 11.9 ± 7.4%, all p = NS). Treatment and control subjects without a history of hypertension had flow-mediated dilation similar to that of a normal reference population (10.6 ± 8.3% vs 8.4 ± 4 5%), whereas subjects with a history of systemic hypertension had markedly impaired flow-mediated dilation that was not significantly improved with treatment (treatment vs control, 6.0 ± 5.5% vs 4.3 ± 5.9%, p = 0.2). Thus, nonhypertensive subjects with angiographic coronary disease and low HDL cholesterol had normal endothelial function in the brachial artery model. Patients with a history of hypertension had marked endothelial dysfunction despite blood pressure treated to normal levels, and this dysfunction is not attenuated by pharmacologic therapy for dyslipidemia.