Small Low-Density Lipoprotein Cholesterol Concentration is a Determinant of Endothelial Dysfunction by Peripheral Artery Tonometry in Men

Aim: Endothelial dysfunction is an initial step in the progression of atherosclerosis. Precise measurements of lipoprotein subclass distribution by high-performance liquid chromatography (HPLC) have been established. Here, we investigated the potential associations between lipoprotein subclass cholesterol concentrations and endothelial dysfunction evaluated by digital reactive hyperemia peripheral arterial tonometry (PAT). Methods: We recruited 120 apparently healthy Japanese men. Endothelial function was assessed by digital reactive hyperemia PAT, expressed as the logarithmic-scaled reactive hyperemia index (RHI). Plasma cholesterol concentrations in lipoproteins and their subclasses were determined by HPLC with gel permeation columns. Results: RHI was inversely correlated with age (r = -0.258, p = 0.004), followed by LDL cholesterol (r = -0.236, p = 0.010) and small LDL cholesterol (r = -0.223, p = 0.014). In addition, RHI was significantly inversely associated with heart rate, hemoglobin A1c, total cholesterol, medium LDL cholesterol, apolipoprotein B100, and non-HDL cholesterol. In stepwise multiple regression analysis, age (beta = -0.266, p = 0.024), small LDL cholesterol (beta = -0.213, p = 0.015), and heart rate (beta = -0.183, p = 0.036) were found to be independent determinants of RHI (adjusted R-2 = 0.132, p < 0.001). Conclusions: Small LDL cholesterol concentration was an important, independent determinant of endothelial dysfunction in men.