Milionis Haralampos J, Kakafika Anna I, Tsouli Sofia G, Athyros Vasilios G, Bairaktari Eleni T, Seferiadis Konstantinos I, Elisaf Moses S
Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.
Am Heart J. 2004 Oct;148(4):635-40. doi: 10.1016/j.ahj.2004.04.005.
Epidemiologic studies have shown that serum uric acid is a risk factor of coronary artery disease. In addition to fenofibrate, there is some evidence that atorvastatin may have a hypouricemic action, but the underlying mechanisms remain speculative.
This randomized trial was conducted to investigate the effects of atorvastatin and simvastatin on uric acid homeostasis in patients treated for primary hyperlipidemia. A total of 180 patients were enrolled; patients were randomly assigned to 40 mg/d of either atorvastatin or simvastatin. Serum lipid and metabolic parameters were measured at baseline and at 6 and 12 weeks of treatment; random urine samples were simultaneously obtained for creatinine, sodium, and uric acid determinations.
Baseline serum uric acid levels correlated positively with the body mass index, serum insulin, creatinine, and triglyceride levels and inversely with serum HDL cholesterol levels. Both statins caused a favorable effect on lipids and a significant decrease in fibrinogen and high-sensitivity CRP levels. However, only atorvastatin reduced serum uric acid levels (from 5.6 +/- 1.7 to 4.9 +/- 1.5 mg/dL, P <.0001) by augmenting its urinary fractional excretion (from 10.4% +/- 7.9% to 12.0% +/- 7.4%, P <.01). In a multivariate logistic regression analysis, the reduction of uric acid levels was independently associated with baseline serum uric acid concentration but not to other variables, including lipid parameters (OR, 1.65; 95% CI, 1.14 to 2.40; P =.008).
Atorvastatin (but not simvastatin) significantly lowered serum uric acid levels. This result may be in favor of a preferable choice of atorvastatin for the treatment of hyperlipidemic patients presenting with hyperuricemia.
流行病学研究表明,血清尿酸是冠状动脉疾病的一个危险因素。除了非诺贝特外,有证据表明阿托伐他汀可能具有降尿酸作用,但其潜在机制仍属推测。
进行这项随机试验以研究阿托伐他汀和辛伐他汀对原发性高脂血症患者尿酸稳态的影响。共纳入180例患者;患者被随机分配接受40mg/d的阿托伐他汀或辛伐他汀治疗。在基线以及治疗6周和12周时测量血脂和代谢参数;同时采集随机尿样用于测定肌酐、钠和尿酸。
基线血清尿酸水平与体重指数、血清胰岛素、肌酐和甘油三酯水平呈正相关,与血清高密度脂蛋白胆固醇水平呈负相关。两种他汀类药物均对血脂产生有益影响,并使纤维蛋白原和高敏C反应蛋白水平显著降低。然而,只有阿托伐他汀通过增加尿酸的尿分数排泄(从10.4%±7.9%增至12.0%±7.4%,P<0.01)降低了血清尿酸水平(从5.6±1.7降至4.9±1.5mg/dL,P<0.0001)。在多变量逻辑回归分析中,尿酸水平的降低与基线血清尿酸浓度独立相关,但与其他变量无关,包括血脂参数(OR,1.65;95%CI,1.14至2.40;P=0.008)。
阿托伐他汀(而非辛伐他汀)显著降低血清尿酸水平。这一结果可能支持在治疗伴有高尿酸血症的高脂血症患者时优先选择阿托伐他汀。