Asberg Anders, Holdaas Hallvard, Jardine Alan G, Edvardsen Cecilie, Hartmann Anders
Laboratory for Renal Physiology, Section of Nephrology, Medical Department, The National Hospital, Oslo, Norway.
Clin Transplant. 2003 Aug;17(4):385-90. doi: 10.1034/j.1399-0012.2003.00063.x.
Cardiovascular risk is greatly increased in renal transplant recipients. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) therapy may reduce cardiovascular risk by improving both dyslipidemia and endothelial function. We therefore performed this study to assess the effect of fluvastatin on endothelial function in renal transplant recipients.
This randomized, placebo-controlled, double-blind designed study investigated the effect of fluvastatin on endothelial function. Thirty-seven recipients received fluvastatin 40 mg/d and 35 received placebo during the first 12 wk following transplantation. All patients initially received cyclosporin A, prednisolone and azathioprine. At the end of treatment, endothelial function was assessed in the forearm skin microvasculature by laser Doppler flowmetry following acetylcholine stimulation. Samples were taken for measurements of serum lipids and vasoactive markers.
There were no differences in endothelial function between fluvastatin recipients and controls, AUCACh was 656 +/- 479 and 627 +/- 518 AU min, respectively (fluv vs. control, p > 0.65). In the placebo limb, total cholesterol and LDL cholesterol increased 22 +/- 12% and 22 +/- 18%, respectively in the first 12 wk following transplantation. The respective values were 18 +/- 13% (p = 0.010) and 34 +/- 19% (p = 0.0013) lower at 12 wk in the fluvastatin treated patients. Plasma ET-1, BigET-1 and urinary excretion of cGMP were not significantly different between treatment groups (p > 0.55).
Although fluvastatin 40 mg/d significantly lowers cholesterol it does not affect endothelial function the first 3 months after renal transplantation. The lack of effect on endothelial function is consistent with a lack of effect on vasoactive substances.
肾移植受者的心血管风险大幅增加。3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂（他汀类药物）治疗可能通过改善血脂异常和内皮功能来降低心血管风险。因此，我们进行了这项研究以评估氟伐他汀对肾移植受者内皮功能的影响。
这项随机、安慰剂对照、双盲设计的研究调查了氟伐他汀对内皮功能的影响。37名受者在移植后的前12周接受40mg/d的氟伐他汀治疗，35名接受安慰剂治疗。所有患者最初均接受环孢素A、泼尼松龙和硫唑嘌呤治疗。治疗结束时，通过乙酰胆碱刺激后用激光多普勒血流仪评估前臂皮肤微血管的内皮功能。采集样本用于测量血脂和血管活性标志物。
氟伐他汀治疗组和对照组的内皮功能无差异，乙酰胆碱刺激后的曲线下面积（AUCACh）分别为656±479和627±518 AU·min（氟伐他汀组与对照组相比，p>0.65）。在安慰剂组，移植后的前12周总胆固醇和低密度脂蛋白胆固醇分别增加了22±12%和22±18%。在氟伐他汀治疗的患者中，12周时相应的值分别低18±13%（p=0.010）和34±19%（p=0.0013）。治疗组之间血浆内皮素-1（ET-1）、大内皮素-1（BigET-1）和尿中环鸟苷酸（cGMP）排泄无显著差异（p>0.55）。
尽管4mg/d的氟伐他汀能显著降低胆固醇，但在肾移植后的前3个月对内皮功能无影响。对内皮功能缺乏影响与对血管活性物质缺乏影响一致。
