抄録
We investigated the effect of simvastatin (Simv) on high density lipoprotein cholesterol (HDL-C) in 23 hypercholesterolemic patients who had been pretreated with probucol (Prob). Prob significantly reduced total cholesterol (TC) and HDL-C, but did not significantly decrease low density lipoprotein cholesterol (LDL-C), but additional administration of Simv along with probucol (Prob+Simv) induced further significant decreases in TC and LDL-C as well as a significant reduction in triacylglycerol (TG). Addition of Simv increased HDL-C, but this increase was not significant and HDL-C was still significantly lower than the baseline value. As we have previously reported, Simv tends to decrease high HDL-C. Therefore, we examined its effects in 21 patients with HDL-C less than 81mg/dl; two patients whose HDL-Cs increased up to more than 90mg/dl after treatment with Prob were omitted. In these 21 patients, Simv significantly increased HDLC, though it remained significantly lower than the baseline value. In lipoprot in fractions from 23 patients, Prob significantly reduced VLDL- and HDL-C. Prob+Simv significantly reduced LDL-C and VLDL-TG compared with the baseline or Prob, and significantly reduced HDL-TG compared with the baseline. In apolipoproteins, Prob significantly reduced apoA-I and significantly increased apoE compared with the baseline. Prob+Simv significantly decreased apoB, apoC-II, and apoC-III compared with the baseline or Prob, and significantly decreased apoE which had been elevated by Prob. The addition of Simv increased apoA-I, but the increase was not significant. Prob significantly increased the ratios of (TC-HDL-C)/HDL-C and apoB/apoA-I, atherogenic indices, while the addition of Simv significantly decreased these ratios. Prob significantly decreased the ratio of HDL-C/ apoA-I, while the addition of Simv increased the ratio, abolishing the significant difference from the baseline. The change in HDL-C by addition of Simv was negatively correlated with HDL-C and apoA-I after treatment with Prob, and the changes in HDL-C and VLDL-C by Prob, and positively correlated with LDL-TG after treatment with Prob. In correlation with compositional indices of HDL, the change in HDL-C by Simv was positively correlated with the change in apoA-I, the ratio of apoA-I/apoA-II, and the ratio of HDL-C/apoA-I, and was not correlated with the change in apoA-II. These data indicate that Simv can counter the Prob-induced HDL-C decrease, appearing as if Simv restored the original HDL-C levels disturbed by Prob, if HDL-C was not extremely high. Based on the findings that this Simv-induced increase in HDL-C was associated with decreases in VLDL-lipids and VLDLapolipoproteins and that an increase in HDL2 fraction was implied, we conclude that Simv increased HDL-C by promoting VLDL metabolism. The precise mechanism of this Simv-induced increase in HDL-C remains to be further investigated. Additional-administration of Simv to reduce high serum cholesterol (LDL-C) may be highly useful especially for patients with low HDL C levels.
