Influence of plasma lipoprotein(a) levels on coronary vasomotor response to acetylcholine

Abstract

This study was undertaken to examine the influence of plasma lipoprotein(a) [Lp(a)] levels on coronary endothelial vasomotor function. Epidemiologic studies have demonstrated a direct relation between elevated plasma levels of Lp(a) and increased risk of coronary artery disease. Well recognized coronary risk factors are known to affect endothelium-dependent vasomotion; however, the influence of Lp(a) on coronary vasomotor function has not been determined. We used quantitative coronary angiography to measure left anterior descending coronary artery diameter changes produced by intracoronary acetylcholine and isosorbide dinitrate in 30 patients with angiographically normal coronary arteries. Plasma Lp(a) levels were determined with enzyme-linked immunosorbent assay. Vasomotor response to acetylcholine ranged from +13% to -47% in the proximal, from +23% to -53% in the middle and from +13% to -56% in the distal segment of the left anterior descending coronary artery. According to univariate linear regression analysis, Lp(a) had a significant inverse correlation with vasomotor response to acetylcholine: r = 0.47, p < 0.01 in the proximal; r = -0.61, p < 0.001 in the middle; and r = -0.52, p < 0.01 in the distal segment of the left anterior descending coronary artery. By multiple stepwise regression analysis, plasma Lp(a) was the significant predictor of vasomotion in response to acetylcholine in all tested segments (p < 0.01). Elevated Lp(a) levels were associated with impairment of endothelium-dependent vasodilation even when atherosclerotic lesions were not recognizable by angiography. This finding suggests that elevated plasma levels of Lp(a) cause endothelial dysfunction and may contribute in part to later development of atherosclerosis, as shown in epidemiologic studies.