Tseng Ming-Yuan, Hutchinson Peter J, Turner Carole L, Czosnyka Marek, Richards Hugh, Pickard John D, Kirkpatrick Peter J
Department of Neurosurgery, Addenbrooke's Hospital, University of Cambridge, United Kingdom.
J Neurosurg. 2007 Dec;107(6):1092-100. doi: 10.3171/JNS-07/12/1092.
The authors previously demonstrated that acute pravastatin therapy in patients after aneurysmal subarachnoid hemorrhage (SAH) ameliorates vasospasm-related delayed ischemic neurological deficits. The object of this study was to continue to examine potential mechanisms of these beneficial effects.
Eighty patients with aneurysmal SAH (age range 18-84 years; time to onset 1.8 +/- 1.3 days) were enrolled in a double-blind study and randomized to receive 40 mg of oral pravastatin or placebo daily for as long as 14 days. Daily transcranial Doppler ultrasonography and blood tests every 3 days (including full blood cell counts, coagulation profiles, fasting glucose and lipid profiles, and serum biochemistry) were performed during the trial period.
No significant differences were found in baseline laboratory data between the trial groups. Subsequent measurements during the 14-day trial showed reduced low-density lipoprotein (LDL) cholesterol levels and total/high-density lipoprotein cholesterol ratios between Days 3 and 15 (p < 0.05), and increased D-dimer levels (p < 0.05) on Day 6, in the pravastatin group. Patients who received pravastatin but developed vasospasm had significantly lower baseline LDL cholesterol levels or a less extensive reduction in LDL cholesterol levels (p < 0.05), and greater increases in plasma fibrinogen (p = 0.009) and serum C-reactive protein on Day 3 (p = 0.007), compared with those patients without vasospasm. The reduction in LDL cholesterol levels on Day 3 in the placebo group correlated with the duration of normal cerebral autoregulation on the ipsilateral side of the ruptured aneurysm (p = 0.002).
In addition to functioning through a cholesterol-independent pathway, cerebrovascular protection from acute statin therapy following aneurysmal SAH may also function through cholesterol-dependent mechanisms.
作者之前证明，动脉瘤性蛛网膜下腔出血（SAH）患者接受急性普伐他汀治疗可改善与血管痉挛相关的迟发性缺血性神经功能缺损。本研究的目的是继续探究这些有益作用的潜在机制。
80例动脉瘤性SAH患者（年龄范围18 - 84岁；发病时间1.8±1.3天）纳入一项双盲研究，并随机分组，每天口服40 mg普伐他汀或安慰剂，持续14天。在试验期间，每天进行经颅多普勒超声检查，每3天进行血液检查（包括全血细胞计数、凝血指标、空腹血糖和血脂谱以及血清生化检查）。
试验组之间的基线实验室数据无显著差异。在14天试验期间的后续测量显示，普伐他汀组在第3天至第15天低密度脂蛋白（LDL）胆固醇水平和总胆固醇/高密度脂蛋白胆固醇比值降低（p < 0.05）；在第6天D - 二聚体水平升高（p < 0.05）。接受普伐他汀治疗但发生血管痉挛的患者，与未发生血管痉挛患者相比，其基线LDL胆固醇水平显著更低或LDL胆固醇水平降低幅度更小（p < 0.05），血浆纤维蛋白原升高幅度更大（p = 0.009）以及在第3天血清C反应蛋白升高幅度更大（p = 0.007）。安慰剂组第3天LDL胆固醇水平的降低与破裂动脉瘤同侧正常脑自动调节持续时间相关（p = 0.002）。
除了通过非胆固醇依赖途径发挥作用外，动脉瘤性SAH后急性他汀治疗的脑血管保护作用也可能通过胆固醇依赖机制发挥作用。
