Milani M, Cimminiello C, Lorena M, Arpaia G, Soncini M, Bonfardeci G
Medical Department, Sando Prodotti Farmaceutici SpA, Milan, Italy.
Biomed Pharmacother. 1996;50(6-7):269-74. doi: 10.1016/0753-3322(96)84824-4.
Many studies have found that familial hypercholesterolemia, a hyperlipoproteinemia associated with premature atherosclerosis, is characterized by enhanced platelet aggregation. This study was undertaken to measure the urinary excretion of the two main urinary thromboxane B2 (TXB2) metabolites (2, 3-dinor-TXB2 and 11-dehydro-TXB2) in 20 patients affected by familial hypercholesterolemia treated for one month with 40 mg/day of pravastatin (10 patients) in comparison to 10 normocholesterolemic subjects. After a run-in period, the type II A patients showed total cholesterol levels (296 +/- 32 mg/dL) significantly higher (P < 0.001) than those of control subjects (155 +/- 46 mg/dL). The urinary concentrations of 11-dehydro-TXB2 and 2,3-dinor-TXB2 also significantly differed (P < 0.001) between control group (1,463 +/- 1,440 and 386 +/- 447 pg/mg urinary creatinine) and treated patients (3,536 +/- 2,112 and 914 +/- 572 pg/mg urinary creatinine). At baseline there was a positive correlation between total cholesterol (TC) levels and urinary TXB2 metabolite concentrations (2,3-dinor-TXB2 r = 0.61, P < 0.02; 11-dehydro-TXB2, r = 48, P < 0.05), but not between low-density-lipoprotein cholesterol (LDL-C) and the urinary compounds. At the end of a four-week treatment. TC and LDL-C had decreased significantly from the baseline levels, by 27% and 30% in the fluvastatin group (P < 0.01) and by 23% and 31% in the pravastatin group (P < 0.01), with no significant difference between the two groups. After the two treatments with HMG-CoA reductase inhibitors, there was no statistically significant reduction of the urinary metabolite levels. In addition, the positive correlation seen at baseline between TC and TXB2 metabolites was no longer present. In accord with previous studies, we found a significant correlation between TC levels and TXB2 metabolites concentrations in type II A hypercholesterolemic patients. Although, short-term treatment with two statins reduced TC levels, it did not change the thromboxane metabolite excretion.
许多研究发现，家族性高胆固醇血症，一种与早发性动脉粥样硬化相关的高脂蛋白血症，其特征是血小板聚集增强。本研究旨在测量20例家族性高胆固醇血症患者（其中10例患者每天服用40 mg普伐他汀治疗一个月）与10例血脂正常的受试者相比，尿中两种主要的尿血栓素B2（TXB2）代谢产物（2,3-二去甲-TXB2和11-脱氢-TXB2）的排泄情况。在经过一段导入期后，II A型患者的总胆固醇水平（296±32 mg/dL）显著高于对照组（155±46 mg/dL）（P<0.001）。对照组（1463±1440和386±447 pg/mg尿肌酐）与治疗患者（3536±2112和914±572 pg/mg尿肌酐）之间，11-脱氢-TXB2和2,3-二去甲-TXB2的尿浓度也存在显著差异（P<0.001）。在基线时，总胆固醇（TC）水平与尿TXB2代谢产物浓度之间存在正相关（2,3-二去甲-TXB2，r = 0.61，P<0.02；11-脱氢-TXB2，r = 0.48，P<0.05），但低密度脂蛋白胆固醇（LDL-C）与尿中这些化合物之间不存在正相关。在为期四周的治疗结束时，氟伐他汀组的TC和LDL-C较基线水平显著降低，分别降低了27%和30%（P<0.01），普伐他汀组降低了23%和31%（P<0.01），两组之间无显著差异。在使用HMG-CoA还原酶抑制剂进行两种治疗后，尿代谢产物水平没有统计学上的显著降低。此外，基线时TC与TXB2代谢产物之间的正相关不再存在。与先前的研究一致，我们发现II A型高胆固醇血症患者的TC水平与TXB2代谢产物浓度之间存在显著相关性。尽管，两种他汀类药物的短期治疗降低了TC水平，但并未改变血栓素代谢产物的排泄。
