Apolipoprotein E, statins, and risk of intracerebral hemorrhage.

Abstract:

BACKGROUND AND PURPOSE: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. METHODS: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. RESULTS: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). CONCLUSIONS: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. CLINICAL TRIAL REGISTRATION URL:http://clinicaltrials.gov. Unique identifier: NCT00930280.

journal_name

Stroke

journal_title

Stroke

authors

Woo D,Deka R,Falcone GJ,Flaherty ML,Haverbusch M,Martini SR,Greenberg SM,Ayres AM,Sauerbeck L,Kissela BM,Kleindorfer DO,Moomaw CJ,Anderson CD,Broderick JP,Rosand J,Langefeld CD,Woo JG

doi

10.1161/STROKEAHA.113.001304

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

3013-7

issue

11

eissn

0039-2499

issn

1524-4628

pii

STROKEAHA.113.001304

journal_volume

44

pub_type

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