Hausberg M, Kosch M, Stam F, Heidenreich S, Kisters K, Rahn K H, Barenbrock M
Department of Internal Medicine D, University of Münster, Münster, Germany.
Kidney Int. 2001 Apr;59(4):1473-9. doi: 10.1046/j.1523-1755.2001.0590041473.x.
Hypercholesterolemia may affect both endothelial function and arterial distensibility (DC). Renal transplant recipients (NTX) exhibit advanced structural and functional alterations of arterial vessel walls. The aim of this double-blind, randomized trial was to evaluate the effects of fluvastatin (FLU) on brachial artery flow-mediated vasodilation (FMD) and DC in hypercholesterolemic NTX.
Eighteen NTX received FLU 40 mg/day and 18 NTX placebo (PLA). Before and after six months of treatment, the brachial artery diameter and DC at rest were measured by a Doppler frequency analysis in the M mode, and then changes in diameter during reactive hyperemia (to assess endothelial-dependent FMD) and after 400 microg sublingual nitroglycerin (to assess endothelium-independent vasodilation-NMD).
FLU, but not PLA, treatment resulted in significant decreases in total (from 288 +/- 10 to 239 +/- 8 mg/dL, P < 0.05) and low-density lipoprotein cholesterol (from 182 +/- 779 to 138 +/- 8 mg/dL, P < 0.05). Blood pressure did not differ between FLU- and PLA-treated patients and was not affected by either treatment. Also, the brachial artery baseline diameter was not different between groups and was not affected by FLU or PLA. Brachial artery flow at rest and during reactive hyperemia as measured by pulsed Doppler did not differ between groups. Brachial artery FMD increased with FLU from 0.23 +/- 0.08 to 0.54 +/- 0.08 mm (P < 0.05), whereas PLA did not alter FMD (0.22 +/- 0.07 vs. 0.14 +/- 0.05 mm at baseline and after six months of PLA treatment, respectively, P = NS). In contrast, NMD did not change significantly with either treatment (0.76 +/- 0.13 vs. 0.83 +/- 0.15 mm at baseline and after 6 months of FLU treatment, respectively, P = NS, and 0.64 +/- 0.09 vs. 0.66 +/- 0.10 mm at baseline and after 6 months of PLA treatment, respectively, P = NS). Also, brachial artery DC was not altered by FLU (6.4 +/- 1.0 vs. 5.8 +/- 0.6 x 10-3/kPa, P = NS) or PLA treatment (5.8 +/- 0.6 vs. 6.8 +/- 0.8 x 10-3/kPa, P = NS).
In hypercholesterolemic NTX, the HMG-CoA reductase inhibitor FLU significantly improves brachial artery FMD as a measure of endothelial function after six months of treatment. In contrast, FLU does not have a beneficial effect on brachial artery DC.
高胆固醇血症可能会影响内皮功能和动脉扩张性(DC)。肾移植受者(NTX)存在动脉血管壁的晚期结构和功能改变。这项双盲随机试验的目的是评估氟伐他汀(FLU)对高胆固醇血症NTX患者肱动脉血流介导的血管舒张(FMD)和DC的影响。
18例NTX患者接受每日40mg氟伐他汀治疗,18例NTX患者接受安慰剂(PLA)治疗。在治疗6个月前后,通过M型多普勒频率分析测量静息状态下的肱动脉直径和DC,然后测量反应性充血期间(以评估内皮依赖性FMD)和舌下含服400μg硝酸甘油后(以评估非内皮依赖性血管舒张-NMD)的直径变化。
氟伐他汀治疗组而非安慰剂治疗组的总胆固醇(从288±10降至239±8mg/dL,P<0.05)和低密度脂蛋白胆固醇(从182±7降至138±8mg/dL,P<0.05)显著降低。氟伐他汀治疗组和安慰剂治疗组患者的血压无差异,且两种治疗均未影响血压。此外,两组间肱动脉基线直径无差异,且不受氟伐他汀或安慰剂影响。两组间通过脉冲多普勒测量的静息和反应性充血期间肱动脉血流无差异。氟伐他汀治疗后肱动脉FMD从0.23±0.08增加至0.54±0.08mm(P<0.05),而安慰剂未改变FMD(基线时为0.22±0.07mm,安慰剂治疗6个月后为0.14±0.05mm,P=无显著性差异)。相比之下,两种治疗对NMD均无显著影响(氟伐他汀治疗6个月后分别为0.76±0.13和0.83±0.15mm,P=无显著性差异;安慰剂治疗6个月后分别为0.64±0.09和0.66±0.10mm,P=无显著性差异)。此外,氟伐他汀(6.4±1.0对5.8±0.6×10-3/kPa,P=无显著性差异)或安慰剂治疗(5.8±0.6对6.8±0.8×10-3/kPa,P=无显著性差异)均未改变肱动脉DC。
在高胆固醇血症NTX患者中,HMG-CoA还原酶抑制剂氟伐他汀在治疗6个月后可显著改善肱动脉FMD,作为内皮功能的一项指标。相比之下,氟伐他汀对肱动脉DC无有益作用。