LOWERING OF HDL(2B) BY PROBUCOL PARTLY EXPLAINS THE FAILURE OF THE DRUG TO AFFECT FEMORAL ATHEROSCLEROSIS IN SUBJECTS WITH HYPERCHOLESTEROLEMIA - A PROBUCOL QUANTITATIVE REGRESSION SWEDISH TRIAL (PQRST) REPORT
LOWERING OF HDL(2B) BY PROBUCOL PARTLY EXPLAINS THE FAILURE OF THE DRUG TO AFFECT FEMORAL ATHEROSCLEROSIS IN SUBJECTS WITH HYPERCHOLESTEROLEMIA - A PROBUCOL QUANTITATIVE REGRESSION SWEDISH TRIAL (PQRST) REPORT
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DOI：
10.1161/01.atv.15.8.1049
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发表时间：
1995-08-01
影响因子：
8.7
通讯作者：
WALLDIUS, G
中科院分区：
文献类型：
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作者：
JOHANSSON, J;OLSSON, AG;WALLDIUS, G
Probucol定量回归瑞典试验（PQRQs）（n = 303）的目的是研究在饮食中加入普罗布考（0.5 g BID）和考来烯胺（8 g BID）是否可以延缓高胆固醇血症（> 6.86 mmol/L）受试者股动脉粥样硬化的进展或诱导其消退。普罗布考在3年的试验期内没有引起退化，这是通过20 cm股动脉段的定量动脉造影管腔体积的变化来估计的。在这份报告中，我们研究了一个代表性的亚组（n = 72）是否降低高密度脂蛋白浓度诱导普罗布考可以解释失败的药物是有效的。我们分析了治疗对HDL颗粒大小亚类的影响。普罗布考降低了HDL（2b）的相对水平，包括最大的HDL颗粒，降低了53%，HDL（2b）的蛋白质浓度降低了67%。HDL中的蛋白质减少主要限于载脂蛋白A-I部分。管腔容积的变化与HDL的变化显著相关，即HDL胆固醇（r = .34，P < .01）、HDL（2）胆固醇（r = .37，P < .01）、HDL（2b）蛋白（r = .44，P < .001）和HDL（2b）相对值（r = .51，P < .001）。分别计算活性组（n = 35）和安慰剂组（n = 37）的相对HDL（2b）分布的相应值也具有显著性（r分别为0.39和0.32;均P <0.05）。药物诱导的相对HDL（2b）浓度变化与动脉粥样硬化变化之间的相关性与甘油三酯浓度变化无关，不能用治疗相互作用解释。HDL（2b）降低与普罗布考浓度高度显著相关。我们认为普罗布考对HDL，特别是HDL（2b）组分的降低作用至少部分解释了为什么该药物不能使股动脉粥样硬化消退。
The aim of the Probucol Quantitative Regression Swedish Trial (PQRST) (n = 303) was to investigate whether probucol (0.5 g BID) added to diet and cholestyramine (8 g BID) could retard progression or induce regression of femoral atherosclerosis in hypercholesterolemic ( > 6.86 mmol/L) subjects. Probucol did not induce regression over the 3-year trial period as estimated by change in lumen volume on quantitative arteriography of a 20-cm segment of the femoral artery. In this report we studied in a representative subgroup (n = 72) whether the reduction in HDL concentrations induced by probucol could explain the failure of the drug to be effective. We analyzed the effects of treatment on HDL particle size subclasses. Probucol lowered the relative level of HDL(2b), comprising the largest HDL particles, by 53% and the protein concentration of HDL(2b) by 67%. The protein reduction in HDL was mainly confined to the apolipoprotein A-I moiety. The change in lumen volume correlated significantly with change in HDL, ie, HDL cholesterol (r = .34, P < .01), HDL(2) cholesterol (r = .37, P < .01), HDL(2b) protein (r = .44, P < .001), and the relative HDL(2b) value (r = .51, P < .001). The corresponding values for relative HDL(2b) distribution calculated on the active (n = 35) and placebo (n = 37) groups separately were also significant (r = .39 and .32, respectively; both P < .05). The correlation between drug-induced change in the relative HDL(2b) concentration and change in atherosclerosis was independent of the alteration in triglyceride concentration and could not be explained by treatment interaction. HDL(2b) lowering was highly significantly correlated to probucol concentration. We suggest that the lowering effects of probucol on HDL and particularly on the HDL(2b) fraction at least in part explain why regression of femoral atherosclerosis was not obtained by the drug.