Lipoprotein(a) Selectively Impairs Receptor-Mediated Endothelial Vasodilator Function of the Human Coronary Circulation

Abstract Objectives. We investigated the influence of lipoprotein(a) [Lp(a)] serum levels on different endothelium-dependent vasodilator stimuli representing different mechanisms of endothelium-dependent vasodilation. Background. Lp(a) is an independent predictor for the development and progression of coronary artery disease. Impairment of endothelium-dependent vasodilation of epicardial arteries has been shown in patients with high levels of Lp(a). Methods. In 108 patients with angiographically normal or minimally diseased coronary vessels, vasomotor responses to acetylcholine, cold pressor testing, increased blood flow and nitroglycerin were assessed. Results. Lp(a) levels ≥30 mg/dl were associated with significant dose-dependent enhancement of the vasoconstrictor response to acetylcholine [receptor-mediated vasodilation, p = 0.002; acetylcholine 10 −6 mol/liter, −29 ± 21% vasoconstriction with Lp(a) levels ≥30 mg/dl vs. −5.6 ± 25% with Lp(a) levels Conclusions. High Lp(a) levels are associated with a selective impairment of vasodilator capacity of receptor-mediated endothelial stimuli. Impaired dilator capacity of the coronary circulation associated with elevated Lp(a) levels may contribute to the pathogenesis of myocardial ischemia in response to trigger mechanisms involving receptor-mediated stimulation such as sympathetic activation.