Published Online
on April 15, 2004

A more recent version of this article appeared on June 1, 2004

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Submitted on June 24, 2003
Revised on January 28, 2004
Accepted on February 24, 2004

Hypercholesterolemia, HMG-CoA Reductase Inhibitors, and Risk of Intracerebral Hemorrhage: A Case-Control Study

Daniel Woo MD^*; Brett M. Kissela MD; Jane C. Khoury MS; Laura R. Sauerbeck RN, MS; Mary A. Haverbusch RN, BSN; Jerzy P. Szaflarski MD, PhD; James M. Gebel MD; Arthur M. Pancioli MD; Edward C. Jauch MD; Alexander Schneider MD; Dawn Kleindorfer MD; and Joseph P. Broderick MD

From the Department of Neurology and the Neuroscience Institute (D.W., B.M.K., L.R.S., M.A.H., J.P.S., A.S., D.K., J.P.B.), Department of Environmental Health (J.C.K.), and Department of Emergency Medicine (A.M.P., E.C.J.), University of Cincinnati, Ohio; Department of Neurology (J.G.), University of Louisville, Kentucky.

^* To whom correspondence should be addressed. E-mail: Daniel.woo{at}uc.edu.

Background and Purpose--Several studies have demonstrated an association between hypocholesterolemia and intracerebral hemorrhage (ICH). We tested the hypothesis that hypercholesterolemia or use of HMG-CoA reductase inhibitors (statin) agents, or both, are associated with ICH.

Methods--This study was part of the preplanned midway analysis of an ongoing, population-based, case-control study of the genetic and environmental risk factors of hemorrhagic stroke. Conditional stepwise logistic regression modeling was used to determine if self-reported hypercholesterolemia or statin use, or both, were independent risk factors for ICH.

Results--Between December 1, 1997, and June 30, 2000, 188 cases of ICH and 366 age-, race-, and gender-matched controls were enrolled. Hypercholesterolemia and statin use were less common among cases than controls: 25% versus 38% (P=0.003) and 9% versus 17% (P=0.03), respectively. Hypercholesterolemia with statin use was associated with less risk of ICH (OR=0.30; P=0.0008) in multivariable analysis after controlling for alcohol use, hypertension, previous stroke, first-degree relative with ICH, education level, and apolipoprotein E alleles.

Conclusion--Hypercholesterolemia was associated with a lower risk of ICH. We have not found an increased risk of ICH with the widespread use of statins in our population. Given the lack of cholesterol levels in the current study, further studies are needed to determine if lower cholesterol levels secondary to statin use bear the same risk as low cholesterol levels for ICH.

Key words: stroke • hemorrhage • hypercholesterolemia • HMG-CoA reductase inhibitors • apolipoproteins • risk factors

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