阿托伐他汀联合普罗布考对老年冠心病患者造影剂肾病的预防作用

Role of atorvastatin combined with probucol in preventing contrast-induced nephropathy in elderly patients with coronary heart disease

目的探讨阿托伐他汀联合普罗布考对老年冠心病患者经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术后造影剂肾病(contrast-induced nephropathy,CIN)的预防作用及可能机制。方法择期行PCI治疗的老年冠心病患者384例,随机分为阿托伐他汀组、阿托伐他汀+普罗布考组(联合普罗布考组)和阿托伐他汀+联合水化组(联合水化组),每组各128例。3组均给予阿托伐他汀(20mg/次,1次/d)治疗,联合普罗布考组PCI前3~5d给予服用普罗布考片500mg,2次/d;联合水化组于PCI术前12h静脉滴注生理盐水进行水化。分别观察3组PCI术前(治疗前)及PCI术后48h(治疗后)血肌酐(serum creatinine,SCr)、肾小球滤过率估算值(estimated glomerular filtration rate,eGFR)、氧化低密度脂蛋白(oxidized low-density lipoprotein,ox-LDL)、高敏C反应蛋白(high sensitivity C-reactive protein,hs-CRP)水平,记录CIN发生率,并进行比较。结果 3组治疗前SCr、eGFR、ox-LDL、hs-CRP比较差异均无统计学意义(P>0.05);治疗后阿托伐他汀组SCr[(109.8±12.6)μmol/L]高于治疗前[(84.1±7.9)μmol/L](P<0.05),eGFR(62.1±10.1)mL/(min·1.73m^2)低于治疗前[(75.0±5.4)mL/(min·1.73m^2)](P<0.05),联合普罗布考组SCr、eGFR[(96.5±12.6)μmol/L、(72.1±7.7)mL/(min·1.73m2)]及联合水化组SCr、eGFR[(93.4±13.0)μmol/L、(71.2±9.6)mL/(min·1.73m^2)]与治疗前[(89.8±10.1)μmol/L、(78.5±8.1)mL/(min·1.73m2),(86.8±8.4)μmol/L、(76.3±5.4)mL/(min·1.73m^2)]比较差异均无统计学意义(P>0.05);治疗后阿托伐他汀组SCr高于联合普罗布考组和联合水化组(P<0.05),eGFR低于联合普罗布考组和联合水化组(P<0.05),联合普罗布考组与联合水化组SCr、eGFR水平比较差异无统计学意义(P>0.05);治疗后联合普罗布考组ox-LDL[(365.0±101.0)μg/L)]、hs-CRP[(5.7±2.1)mg/L)]低于治疗前[(501.0±75.0)μg/L、(8.7±3.7)mg/L)(P<0.05),阿托伐他汀组[(501.0±126.0)μg/L、(10.9±6.9)mg/L)]和联合水化组[(512.0±130.0)μg/L、(10.4±10.2)mg/L)]与治疗前[(541.0±79.0)μg/L、(10.7±9.6)mg/L,(528.0±84.0)μg/L、(9.8±8.0)mg/L]比较差异无统计学意义(P>0.05);治疗后联合普罗布考组ox-LDL、hs-CRP低于阿托伐他汀组和联合水化组(P<0.05),阿托伐他汀组与联合水化组比较差异无统计学意义(P>0.05);阿托伐他汀组CIN发生率(9.4%)高于联合普罗布考组(3.1%)和联合水化组(3.9%)(P<0.05),联合普罗布考组与联合水化组比较差异无统计学意义(P>0.05)。结论阿托伐他汀联合普罗布考对老年冠心病PCI术后CIN发生有一定预防作用,其机制可能与抗氧化应激有关。

Objective To investigate the effect of atorvastatin plus probucol on preventing contrast-induced nephropathy（CIN）after percutaneous coronary intervention（PCI）in elderly patients with coronary heart disease（CHD）and its possible mechanism.Methods A total of 384 consecutive elderly CHD patients scheduled for PCI were randomly divided into atorvastatin group,atorvastatin＋probucol group and atorvastatin ＋ hydration group,with 128 patients in each group.Besides atorvastatin 20 mg once daily in three groups,atorvastatin＋probucol group received oral administration of probucol 500 mg twice daily 3 to 5 days before PCI,and atorvastatin＋hydration group received intravenous injection of normal saline 12 hours before PCI.The levels of serum creatinine（SCr）,estimated glomerular filtration rate（eGFR）,oxidized low-density lipoprotein（ox-LDL）and high sensitivity C-reactive protein（hs-CRP）were detected before and 48 hours after PCI.The incidence of CIN was recorded and compared.Results There were no significant differences in the levels of SCr,eGFR,ox-LDL and hs-CRP among three groups before PCI.The SCr level was significantly higher,and the eGFR level was significantly lower after PCI（（109.8±12.6）μmol/L,（62.1±10.1）mL/（min·1.73 m2）than that before PCI（（84.1±7.9）μmol/L,（75.0±5.4）mL/（min·1.73 m2））in atorvastatin group（P〈0.05）.No differences were found in the levels of SCr and eGFR both in atorvastatin＋probucol group（（96.5±12.6）μmol/L,（72.1±7.7）mL/（min·1.73 m2）） and atorvastatin ＋ hydration group（（93.4 ± 13.0）μmol/L,（71.2 ±9.6）mL/（min·1.73 m2））after PCI in comparison with those before PCI（（89.8 ± 10.1）μmol/L,（78.5 ±8.1）mL/（min/1.73 m2）;（86.8±8.4）μmol/L,（76.3±5.4）mL/（min/1.73 m2））（P〉0.05）.The SCr level was significantly higher and the eGFR level was significantly lower in atorvastatin group than that in atorvastatin＋probucol group and atorvastatin＋hydration group after PCI（P〈0.05）,and there were no significant differences in the levels of SCr and eGFR between atorvastatin＋probucol group and atorvastatin＋hydration group after PCI（P〉0.05）.The levels of ox-LDL and hs-CRP were significantly lower after PCI in atorvastatin＋probucol group（（365.0±101.0）μg/L,（5.7±2.1）mg/L）than those before PCI（（501.0±75.0）μg/L,（8.7±3.7）mg/L）（P〈0.05）.While no differences were found in the levels of ox-LDL and hs-CRP in both atorvastatin group（（501.0±126.0）μg/L,（10.9±6.9）mg/L）and atorvastatin＋hydration group（（512.0±130.0）μg/L,（10.4±10.2）mg/L）after PCI in comparison with those before PCI（（541.0±79.0）μg/L,（10.7±9.6）mg/L;（528.0±84.0）μg/L,（9.8±8.0）mg/L）（P〉0.05）.The levels of ox-LDL and hs-CRP were significantly lower after PCI in atorvastatin＋probucol group than those in atorvastatin group and atorvastatin＋hydration group（P〈0.05）,and no significant differences were found between atorvastatin group and atorvastatin＋hydration group（P〉0.05）.The incidence of CIN was significantly higher in atorvastatin group（9.4%）than that in atorvastatin＋probucol group（3.1%）and atorvastatin＋hydration group（3.9%）（P〈0.05）,and there was no significant difference between between atorvastatin＋probucol group and atorvastatin＋hydration group（P〉0.05）.Conclusion Atorvastatin plus probucol can reduce the incidence of CIN after PCI in elderly CHD patients,and its protection mechanism may be correlated with the anti-oxidative stress effect.