Impact of high remnant-like lipoproteins on the function of peripheral arterial endothelium in patients with hyperlipidemia and normolipidemia: estimation using Doppler flow analysis

摘要

OBJECTIVES: Cholesterol levels of remnant-like lipoprotein (RLP-cholesterol: RLP-C), which reflect remnant lipoproteins, are associated with coronary arterial endothelial functions and cardiovascular events. The influence of RLP-C on peripheral vascular endothelial functions in patients with hyperlipidemia and normolipidemia was evaluated based on the reactivity of the antecubital artery to acetylcholine (Ach) and isosorbide dinitrate (ISDN) using a Doppler guidewire. METHODS: Protocol 1: Five patients were selected, and the dose-response of the antecubital artery was evaluated by administering Ach (0.5, 5, and 50 micrograms/30 sec) or ISDN (0.025, 0.25, and 2.5 mg/30 sec). An index of vascular reactivity (brachial artery response: BR) was determined by dividing the maximal blood flow velocity after the administration of Ach or ISDN by resting blood flow velocity. Protocol 2: BR was evaluated in 48 patients after administering Ach 50 micrograms or ISDN 2.5 mg. Subsequently, these patients were divided into the following three groups based on early morning RLP-C levels: Group L (n = 11), RLP-C < 2.0 mg/dl (minimal detectable level); Group M (n = 21), 2.0 mg/dl < or = RLP-C < 5.0 mg/dl; and Group H (n = 16), 5.0 mg/dl < or = RLP-C. The factors that regulate BR-Ach 50 micrograms were also evaluated in 34 normolipidemic patients. RESULTS: Protocol 1: BR dose-dependently increased after the administration of Ach and ISDN. Protocol 2: BR-Ach 50 micrograms was significantly less in Group H (3.1 +/- 0.8) than in Groups M (3.8 +/- 0.9, p < 0.03) and L (4.2 +/- 0.9, p < 0.01). However, there were no significant differences in BR-ISDN 2.5 mg between the three groups. Univariate analysis in normolipidemic patients revealed that BR-Ach 50 micrograms was correlated with age (r = -0.355, p < 0.05), RLP-C (r = -0.488, p < 0.01), low-density lipoprotein cholesterol (r = -0.382, p < 0.03), systolic blood pressure (r = -0.354, p < 0.05), and diastolic blood pressure (r = -0.406, p < 0.02). Multivariate analysis using these five factors as independent variables revealed that age, RLP-C, and low-density lipoprotein cholesterol regulated BR-Ach 50 micrograms. CONCLUSIONS: Peripheral vascular endothelial dysfunction may occur in patients with high levels of RLP-C. RLP-C is an independent lipid factor that regulates peripheral vascular endothelial functions even in normolipidemic patients.