普伐他汀降低血浆胆固醇对高胆固醇血症患者前臂动脉功能特性的影响。

Effect of plasma cholesterol reduction by pravastatin on the functional properties of forearm arteries in hypercholesterolemic patients.

作者信息

Baldassarre D, Busnach G, Amato M, Pazzucconi F, Sirtori C R

机构信息

E. Grossi Paoletti Center, Institute of Pharmacological Sciences, University of Milan, Italy.

出版信息

Nutr Metab Cardiovasc Dis. 1999 Jun;9(3):108-17.

PMID:10464783

Abstract

BACKGROUND AND AIM

Since functional properties in the vasculature of hypercholesterolemic subjects are impaired, a six-month pravastatin treatment (20 mg/die) was tested in an open design, on the impaired unstimulated forearm arterial compliance (Un-FAC(AUC)) of 14 asymptomatic type IIa familial hypercholesterolemic patients. In order to evaluate whether FAC(AUC) changes might be related to the extent of cholesterol reduction achieved, this evaluation was carried out in five severely hypercholesterolemic patients, undergoing LDL-apheresis.

METHODS AND RESULTS

Arterial functional properties, i.e. FAC(AUC) responses to glyceryl trinitrate (GTN-FAC(AUC)) and acetylcholine (ACh-FAC(AUC), four patients) and the effects on rest and peak forearm blood flow and vascular resistance were evaluated on the non-dominant arm using plethysmographic methods, that also allow the direct assessment of the non-linear "compliance-blood pressure" curve. Selective LDL-apheresis was performed by using a dextran-sulphate column. Pravastatin effectively lowered plasma total (-16%, p = 0.002) and LDL cholesterol levels (-22%, p = 0.006 vs baseline). Rest and peak flow, basal and post ischemic vascular resistance were not affected as well as Un-FAC(AUC) and GTN-FAC(AUC). However, in the four hypercholesterolemic patients undergoing ACh infusion, there was an improvement in the ACh-FAC(AUC) of borderline statistical significativity (p = 0.056). LDL-apheresis reduced plasma total and LDL cholesterol levels by 55% and 59%, without affecting blood pressure. In this series of five patients Un-FAC(AUC) increased, the Un-FAC(AUC) rise being inversely related to the absolute reduction of plasma total (r = 0.92, p < 0.05) and LDL cholesterol (r = 0.89, p < 0.05) levels.

CONCLUSIONS

In hypercholesterolemic patients a short-term hypocholesterolemic treatment with pravastatin, although able to improve the lipid profile, cannot alter significantly blood flow, vascular resistance, Un-FAC(AUC) and GTN-FAC(AUC). A possible selective improvement in the ACh-receptor-activated signal transduction pathway has been observed and the importance of a drastic reduction of cholesterol concentrations in order to affect the Un-FAC(AUC) is suggested.

摘要

背景与目的

由于高胆固醇血症患者血管的功能特性受损，对14例无症状IIa型家族性高胆固醇血症患者未受刺激的前臂动脉顺应性（Un-FAC(AUC)）进行了一项开放设计的为期6个月的普伐他汀治疗（20mg/日）试验。为了评估FAC(AUC)变化是否可能与所实现的胆固醇降低程度相关，对5例接受低密度脂蛋白分离术的严重高胆固醇血症患者进行了此项评估。

方法与结果

使用体积描记法在非优势臂上评估动脉功能特性，即对硝酸甘油（GTN-FAC(AUC)）和乙酰胆碱（ACh-FAC(AUC)，4例患者）的FAC(AUC)反应以及对静息和峰值前臂血流量及血管阻力的影响，该方法还可直接评估非线性的“顺应性-血压”曲线。使用葡聚糖硫酸酯柱进行选择性低密度脂蛋白分离术。普伐他汀有效降低了血浆总胆固醇（-16%，p = 0.002）和低密度脂蛋白胆固醇水平（-22%，与基线相比p = 0.006）。静息和峰值血流量、基础和缺血后血管阻力以及Un-FAC(AUC)和GTN-FAC(AUC)均未受影响。然而，在4例接受乙酰胆碱输注的高胆固醇血症患者中，ACh-FAC(AUC)有改善，具有临界统计学意义（p = 0.056）。低密度脂蛋白分离术使血浆总胆固醇和低密度脂蛋白胆固醇水平分别降低了55%和59%，且未影响血压。在这5例患者中，Un-FAC(AUC)升高，Un-FAC(AUC)的升高与血浆总胆固醇（r = 0.92，p < 0.05）和低密度脂蛋白胆固醇（r = 0.89，p < 0.05）水平的绝对降低呈负相关。