Athyros Vasilios G, Elisaf Moses, Papageorgiou Athanasios A, Symeonidis Athanasios N, Pehlivanidis Anthimos N, Bouloukos Vasilios I, Milionis Haralambos J, Mikhailidis Dimitri P
Atherosclerosis Unit, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece.
Am J Kidney Dis. 2004 Apr;43(4):589-99. doi: 10.1053/j.ajkd.2003.12.023.
Little is known about the effect of dyslipidemia on serum uric acid (SUA) levels, and less is known about the effect of statin treatment on them. The GREek Atorvastatin and Coronary-heart-disease Evaluation study suggested that a mean atorvastatin dose of 24 mg/d achieves the National Cholesterol Educational Program treatment goals and significantly reduces morbidity and mortality in patients with coronary heart disease (CHD) in comparison to the usual care. Here, we report the time course of SUA levels in usual-care patients undertreated for their dyslipidemia (12% were administered statins) in comparison to structured-care patients treated with atorvastatin in the vast majority (98%).
Mean on-study SUA levels (up to 48 months) were compared with those at baseline by using analyses of variance to assess differences over time within and between treatment groups. Cox multivariate analysis was used to investigate whether changes in SUA levels during the study were clinically relevant.
All patients had normal renal function at baseline; serum creatinine (SCr) levels less than 1.3 mg/dL (<115 micromol/L) and moderately elevated SUA levels (mean, 7.1 +/- 0.9 [SD] mg/dL [425 +/- 52 micromol/L]; upper normal limit, 7.0 mg/dL [415 micromol/L]). Usual-care patients (n = 800) showed an increase in SUA levels by 3.3% ( P < 0.0001). Structured-care patients (n = 800) had an 8.2% reduction in SUA levels ( P < 0.0001). In all patients not administered diuretics (n = 1,407), SUA level changes showed a positive correlation with changes in SCr levels ( r = 0.82; P < 0.0001) and an inverse correlation with estimated glomerular filtration rate ( r = -0.77; P < 0.0001). After adjustment for 19 predictors of all CHD-related events, Cox multivariate analysis involving backward stepwise logistic regression showed a hazard ratio (HR) of 0.89 (95% confidence interval [CI], 0.78 to 0.96; P = 0.03) with every 0.5-mg (30-micromol/L) reduction in SUA level, an HR of 0.76 (95% CI, 0.62 to 0.89; P = 0.001) with every 1-mg (60-micromol/L) reduction, an HR of 1.14 (95% CI, 1.03 to 1.27; P = 0.02) with every 0.5-mg increase, and an HR of 1.29 (95% CI, 1.17 to 1.43; P = 0.001) with every 1-mg increase in SUA levels.
Data suggest that SUA level is an independent predictor of CHD recurrent events. Atorvastatin treatment significantly reduces SUA levels in patients with CHD, thus offsetting an additional factor associated with CHD risk.
关于血脂异常对血清尿酸（SUA）水平的影响知之甚少，而关于他汀类药物治疗对其影响的了解更少。希腊阿托伐他汀与冠心病评估研究表明，阿托伐他汀平均剂量为24mg/d可实现国家胆固醇教育计划的治疗目标，与常规治疗相比，可显著降低冠心病（CHD）患者的发病率和死亡率。在此，我们报告血脂异常治疗不足的常规治疗患者（12%接受他汀类药物治疗）与绝大多数接受阿托伐他汀治疗的结构化治疗患者（98%）的SUA水平随时间的变化情况。
使用方差分析比较研究期间（长达48个月）的平均SUA水平与基线水平，以评估治疗组内和治疗组间随时间的差异。采用Cox多变量分析研究研究期间SUA水平的变化是否具有临床相关性。
所有患者基线时肾功能正常；血清肌酐（SCr）水平低于1.3mg/dL（<115μmol/L），SUA水平中度升高（平均，7.1±0.9[标准差]mg/dL[425±52μmol/L]；正常上限，7.0mg/dL[415μmol/L]）。常规治疗患者（n = 800）的SUA水平升高了3.3%（P < 0.0001）。结构化治疗患者（n = 800）的SUA水平降低了8.2%（P < 0.0001）。在所有未服用利尿剂的患者（n = 1407）中，SUA水平变化与SCr水平变化呈正相关（r = 0.82；P < 0.0001），与估计肾小球滤过率呈负相关（r = -0.77；P < 0.0001）。在对所有冠心病相关事件的19个预测因素进行调整后，涉及向后逐步逻辑回归的Cox多变量分析显示，SUA水平每降低0.5mg（30μmol/L），风险比（HR）为0.89（95%置信区间[CI]，0.78至0.96；P = 0.03）；每降低1mg（60μmol/L），HR为0.76（95%CI，0.62至0.89；P = 0.001）；每升高0.5mg（HR）为1.14（95%CI，1.03至1.27；P = 0.02）；SUA水平每升高1mg，HR为1.29（95%CI，1.17至1.43；P = 0.001）。
数据表明SUA水平是冠心病复发事件的独立预测因素。阿托伐他汀治疗可显著降低冠心病患者的SUA水平，从而抵消与冠心病风险相关的另一个因素。
