Sakamoto Kenji, Sakamoto Tomohiro, Ogawa Hisao
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Clin Ther. 2006 Jul;28(7):1012-21. doi: 10.1016/j.clinthera.2006.07.001.
Pravastatin has been reported to reduce cardiovascular events and mortality in patients with coronary artery disease (CAD). Hypoadiponectinemia is a known risk factor for CAD.
This study analyzed the effects of shortterm pravastatin treatment on serum lipid and adiponectin concentrations in patients with CAD and hypercholesterolemia.
This was a multicenter, observational pilot study of the effect of 6 months of treatment with pravastatin 10 to 20 mg/d on serum adiponection concentrations in patients with documented CAD and total cholesterol (TC) levels> or =180 mg/dL. Patients from 13 medical centers in Japan were monitored at visits every 4 weeks for assessment of compliance and adverse effects. For the assessment of pravastatin's effects, patients were categorized according to baseline serum adiponectin concentrations: quartile 1 (Q1) = < 4.83 microg/mL; quartile 2 (Q2) = 4.83 to 7.20 microg/mL; (Q4) = > 10.38 microg/mL. The primary end point of the study was the percent change from baseline in adiponectin nectin concentrations at 6 months. Secondary end points were changes in lipids, high-sensitivity C-reactive protein (hsCRP), and glycosylated hemoglobin (HbA1c).
One hundred thirty consecutive patients were enrolled; 11 were excluded and 4 discontinued due to adverse events. Thus, 115 patients were included in the study analyses (83 men, 32 women; mean age, 68 years). No patient had a cardiac event during the 6-month follow-up period. After 6 months of pravastatin treatment, 74 (64.3%) patients had increases in serum adiponectin concentrations. Median (interquartile range) adiponectin concentrations increased significantly from 7.2 (4.8-10.4) mug/mL at baseline to 7.8 (5.4-11.2) microg/mL after 6 months of pravastatin treatment (P<0.001); the mean percent increase from baseline was 16.3%. The percent increase from baseline in serum adiponection concentrations was significantly higher among patients in Q1 (39.3%) compared with those in Q3 (4.5%) and Q4 (6.3%) (P<0.003 and P<0.005, respectively). The relative increase in adiponectin concentrations was significantly correlated with the relative increase in high-density lipoprotein cholesterol (HDL-C) (f=0.47; P<0.001). After 6 months of pravastatin treatment, TC and low-density lipoprotein cholesterol levels had decreased, by 14.6% and 23.3%, respectively, and HDL-C levels had increased by 14.0% (all, P<0.001). The change in triglycerides (-13.3%) was not statistically significant. Serum hsCRP levels were significantly decreased from baseline after 6 months of pravastatin treatment (P<0.001). HbA1c did not change significantly.
In this pilot study in Japanese patients with CAD and hypercholesterolemia, 6 months of treatment with pravastatin 10 to 20mg/d was associated with significant increases in serum adiponectin concentrations.
据报道，普伐他汀可降低冠心病（CAD）患者的心血管事件及死亡率。低脂联素血症是CAD的已知危险因素。
本研究分析了短期普伐他汀治疗对CAD合并高胆固醇血症患者血脂及脂联素浓度的影响。
这是一项多中心观察性试验研究，观察10～20mg/d普伐他汀治疗6个月对确诊CAD且总胆固醇（TC）水平≥180mg/dL患者血清脂联素浓度的影响。来自日本13个医学中心的患者每4周复诊一次，以评估依从性及不良反应。为评估普伐他汀的作用，根据基线血清脂联素浓度对患者进行分类：四分位数1（Q1）=＜4.83μg/mL；四分位数2（Q2）=4.83～7.20μg/mL；四分位数3（Q3）=7.21～10.38μg/mL；四分位数4（Q4）=＞10.38μg/mL。本研究的主要终点是6个月时脂联素浓度相对于基线的变化百分比。次要终点是血脂、高敏C反应蛋白（hsCRP）及糖化血红蛋白（HbA1c）的变化。
连续纳入130例患者；11例因不良事件被排除，4例停药。因此，115例患者纳入研究分析（83例男性，32例女性；平均年龄68岁）。在6个月的随访期内无患者发生心脏事件。普伐他汀治疗6个月后，74例（64.3%）患者血清脂联素浓度升高。脂联素浓度中位数（四分位间距）从基线时的7.2（4.8～10.4）μg/mL显著升高至普伐他汀治疗6个月后的7.8（5.4～11.2）μg/mL（P<0.001）；相对于基线的平均升高百分比为16.3%。Q1组患者血清脂联素浓度相对于基线的升高百分比（39.3%）显著高于Q3组（4.5%）和Q4组（6.3%）（分别为P<0.003和P<0.005）。脂联素浓度的相对升高与高密度脂蛋白胆固醇（HDL-C）的相对升高显著相关（r=±0.47；P<0.001）。普伐他汀治疗6个月后，TC和低密度脂蛋白胆固醇水平分别下降了14.6%和23.3%，HDL-C水平升高了14.0%（均为P<0.001）。甘油三酯的变化（-13.3%）无统计学意义。普伐他汀治疗6个月后，血清hsCRP水平较基线时显著下降（P<0.001）。HbA1c无显著变化。
在这项针对日本CAD合并高胆固醇血症患者的试验研究中，10～20mg/d普伐他汀治疗6个月与血清脂联素浓度显著升高相关。
