Inazu A, Koizumi J, Kajinami K, Kiyohar T, Chichibu K, Mabuchi H
The Second Department of Internal Medicine, School of Medicine, Kanazawa University, Takara-machi, Japan.
Atherosclerosis. 1999 Aug;145(2):405-13. doi: 10.1016/s0021-9150(99)00088-x.
Long-term effects of pravastatin and probucol on serum cholesteryl ester transfer protein (CETP) and xanthoma/xanthelasma size were compared. Twenty-three patients with primary hypercholesterolemia and xanthoma/xanthelasma, including 11 patients with heterozygous familial hypercholesterolemia, were treated with pravastatin (20 mg/day) or probucol (1000 mg/day) for 24 months. Serum CETP levels were measured by sandwich ELISA. In 11 patients (six men and five women, 55 +/- 2 [SE] yr) treated with pravastatin, serum cholesterol levels decreased from 262 +/- 13 to 229 +/- 13 mg/dl during the 24-month treatment period (P = 0.05). Serum HDL cholesterol levels were not changed. Serum CETP levels decreased from 2.5 +/- 0.2 to 2.0 +/- 0.2 microg/ml (-21%, P = 0.002). By contrast, in 12 patients (four men and eight women, 57 +/- 4 year) treated with probucol, serum cholesterol levels did not significantly decrease from 236 +/- 11 to 207 +/- 13 mg/dl. Serum HDL cholesterol levels decreased from 44 +/- 2 to 30 +/- 2 mg/dl (P = 0.009). Serum CETP levels increased from 2.3 +/- 0.1 to 2.8 +/- 0.2 microg/ml (+23%, P = 0.02). Xanthelasma regression was found in two of four patients (50%) each treated with pravastatin and probucol, respectively. In contrast, Achilles' tendon xanthoma regressed in four of five patients (80%) treated with pravastatin, but only in two of five patients (40%) treated with probucol. Patients with xanthoma/xanthelasma regression after 2 years treatment had higher baseline levels of serum CETP than those without regression (2.7 +/- 0.2 microg/ml [n = 9] versus 2.1 +/- 0.2 microg/ml [n = 7], P = 0.05). Serial changes in serum CETP levels during treatment with pravastatin and probucol were discordant, but not related to the degree of xanthoma regression. However, higher level of serum HDL3 cholesterol was an independent factor in the smaller size of Achilles' tendon xanthoma at baseline. In addition, higher levels of serum HDL3 triglyceride on lipid-lowering therapy (6 months) appear to be a common predictor of regression of Achilles' tendon xanthoma in the treatment with either pravastatin or probucol.
比较了普伐他汀和普罗布考对血清胆固醇酯转运蛋白（CETP）及黄色瘤/睑黄瘤大小的长期影响。23例原发性高胆固醇血症合并黄色瘤/睑黄瘤患者，包括11例杂合子家族性高胆固醇血症患者，接受普伐他汀（20mg/天）或普罗布考（1000mg/天）治疗24个月。采用夹心ELISA法测定血清CETP水平。在接受普伐他汀治疗的11例患者（6例男性和5例女性，55±2[标准误]岁）中，24个月治疗期间血清胆固醇水平从262±13降至229±13mg/dl（P=0.05）。血清高密度脂蛋白胆固醇水平未改变。血清CETP水平从2.5±0.2降至2.0±0.2μg/ml（-21%，P=0.002）。相比之下，在接受普罗布考治疗的12例患者（4例男性和8例女性，57±4岁）中，血清胆固醇水平从236±11降至207±13mg/dl，无显著下降。血清高密度脂蛋白胆固醇水平从44±2降至30±2mg/dl（P=0.009）。血清CETP水平从2.3±0.1升至2.8±0.2μg/ml（+23%，P=0.02）。分别接受普伐他汀和普罗布考治疗的4例患者中各有2例（50%）睑黄瘤消退。相比之下，接受普伐他汀治疗的5例患者中有4例（80%）跟腱黄色瘤消退，而接受普罗布考治疗的5例患者中只有2例（40%）消退。治疗2年后黄色瘤/睑黄瘤消退的患者血清CETP基线水平高于未消退者（2.7±（此处原文可能有误，推测为0.2）μg/ml[n=9]对2.1±0.2μg/ml[n=7]，P=0.05）。普伐他汀和普罗布考治疗期间血清CETP水平的系列变化不一致，但与黄色瘤消退程度无关。然而，较高水平的血清HDL3胆固醇是基线时跟腱黄色瘤较小的独立因素。此外，降脂治疗（6个月）时较高水平的血清HDL3甘油三酯似乎是普伐他汀或普罗布考治疗中跟腱黄色瘤消退的共同预测指标。
