From the Departments of Neurology (D.W., M.L.F., M.H., S.R.M., L.S., B.M.K., D.O.K., C.J.M., J.P.B.), and Environmental Health (R.D.), University of Cincinnati, OH; Division of Neurocritical Care and Emergency Neurology (G.J.F., C.D.A., J.R.), and Hemorrhagic Stroke Research Group (G.J.F., S.M.G., A.M.A., C.D.A., J.R.), Department of Neurology, and Center for Human Genetic Research (G.J.F., C.D.A., J.R.), Massachusetts General Hospital, Boston; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (G.J.F., C.D.A., J.R.); Department of Biostatistical Sciences, Wake Forest University, Winston-Salem, NC (C.D.L.); and Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, OH (J.G.W.).
Stroke. 2013 Nov;44(11):3013-7. doi: 10.1161/STROKEAHA.113.001304. Epub 2013 Sep 5.
Apolipoprotein E (ApoE) genotypes have been associated with lobar intracerebral hemorrhage (ICH). Although statins have been associated with an increased risk of ICH, meta-analyses have not consistently shown a statin-induced risk of ICH. Here, we test whether hypercholesterolemia (HC) and ApoE polymorphisms affect the risk of ICH by statin use.
The Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) study is a prospective, demographically matched case-control study of ICH. A similar study of ICH, Genetic Risks for Medication-Related Hemorrhagic Stroke (GOCHA), was used as a replication cohort. Subjects were classified as normocholesterolemia, HC without statin use, and HC with statin use. Statistical comparisons were performed using Fisher exact test, χ2 tests, and the Breslow-Day test.
The discovery cohort consisted of 558 ICH cases and 1444 controls, and the replication cohort consisted of 1020 ICH cases and 382 controls. The association of lower risk for HC was not attenuated by statin use. Statin use was observed to confer a higher risk for lobar ICH in those carrying ApoE4/E4 and ApoE2/E4 genotypes in both discovery and replication cohorts, and a test for interaction showed a trend towards significance (P=0.11 for statin and ApoE4/E4).
Statin use does not seem to attenuate the association of HC with decreased risk for nonlobar ICH. Our data support a gene-by-drug effect for lobar ICH, but larger sample sizes are needed to confirm the association before any clinical change is warranted.
http://clinicaltrials.gov. Unique identifier: NCT00930280.
载脂蛋白 E（ApoE）基因型与脑叶性脑出血（ICH）有关。尽管他汀类药物与 ICH 风险增加有关，但荟萃分析并未一致显示他汀类药物引起的 ICH 风险。在这里，我们通过他汀类药物的使用来测试高胆固醇血症（HC）和 ApoE 多态性是否影响 ICH 的风险。
遗传和环境风险因素对出血性中风（GERFHS）研究是一项前瞻性、人口匹配的 ICH 病例对照研究。ICH 的类似研究，药物相关出血性中风的遗传风险（GOCHA），被用作复制队列。受试者被分为正常胆固醇血症、无他汀类药物使用的 HC 和使用他汀类药物的 HC。使用 Fisher 精确检验、卡方检验和 Breslow-Day 检验进行统计学比较。
发现队列包括 558 例 ICH 病例和 1444 例对照，复制队列包括 1020 例 ICH 病例和 382 例对照。他汀类药物的使用并没有减弱 HC 风险降低的关联。在携带 ApoE4/E4 和 ApoE2/E4 基因型的个体中，发现他汀类药物的使用与脑叶性 ICH 的风险增加相关，并且在发现和复制队列中，交互作用的检验显示出一种趋势（他汀类药物和 ApoE4/E4 为 P=0.11）。
他汀类药物的使用似乎并没有减弱 HC 与非脑叶性 ICH 风险降低的关联。我们的数据支持脑叶性 ICH 的基因-药物效应，但需要更大的样本量来确认关联，然后才能进行任何临床改变。
