Apolipoprotein E, Statins, and Risk of Intracerebral Hemorrhage
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 poly...
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| Published in | Stroke (1970) Vol. 44; no. 11; pp. 3013 - 3017 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Hagerstown, MD
Lippincott Williams & Wilkins
01.11.2013
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0039-2499 1524-4628 1524-4628 |
| DOI | 10.1161/STROKEAHA.113.001304 |
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| Abstract | 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. |
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| AbstractList | 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. 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.BACKGROUND AND PURPOSEApolipoprotein 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.METHODSThe 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).RESULTSThe 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.CONCLUSIONSStatin 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.CLINICAL TRIAL REGISTRATION URLhttp://clinicaltrials.gov. Unique identifier: NCT00930280. |
| Author | Falcone, Guido J. Sauerbeck, Laura Woo, Jessica G. Woo, Daniel Martini, Sharyl R. Ayres, Alison M. Rosand, Jonathan Greenberg, Steven M. Haverbusch, Mary Langefeld, Carl D. Kissela, Brett M. Flaherty, Matthew L. Kleindorfer, Dawn O. Moomaw, Charles J. Broderick, Joseph P. Deka, Ranjan Anderson, Christopher D. |
| AuthorAffiliation | φ Hemorrhagic Stroke Research Group, Massachusetts General Hospital University of Cincinnati Department of Environmental Health Wake Forest University, Department of Biostatistical Sciences Cincinnati Children’s Hospital Medical Center, Division of Biostatistics and Epidemiology χ Center for Human Genetic Research, Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital γ Program in Medical and Population Genetics, Broad Institute University of Cincinnati Department of Neurology |
| AuthorAffiliation_xml | – name: χ Center for Human Genetic Research, Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital – name: University of Cincinnati Department of Neurology – name: Cincinnati Children’s Hospital Medical Center, Division of Biostatistics and Epidemiology – name: γ Program in Medical and Population Genetics, Broad Institute – name: Wake Forest University, Department of Biostatistical Sciences – name: University of Cincinnati Department of Environmental Health – name: φ Hemorrhagic Stroke Research Group, Massachusetts General Hospital |
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| Keywords | Stroke Nervous system diseases Enzyme Cardiovascular disease Statin derivative Epidemiology Cerebral disorder Vascular disease intracerebral hemorrhage genetics pharmacogenomics Apolipoprotein E Cerebral hemorrhage Central nervous system disease Risk factor Oxidoreductases hydroxymethylgutaryl-CoA reductase inhibitors Cerebrovascular disease Antilipemic agent Reductase apolipoprotein E epidemiology |
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| References | e_1_3_3_6_2 e_1_3_3_5_2 e_1_3_3_8_2 Jacobs DR (e_1_3_3_7_2) 1994; 6 e_1_3_3_17_2 e_1_3_3_9_2 e_1_3_3_16_2 e_1_3_3_19_2 e_1_3_3_18_2 e_1_3_3_13_2 e_1_3_3_24_2 e_1_3_3_12_2 e_1_3_3_23_2 e_1_3_3_15_2 e_1_3_3_14_2 e_1_3_3_25_2 e_1_3_3_2_2 e_1_3_3_20_2 e_1_3_3_4_2 e_1_3_3_11_2 e_1_3_3_22_2 e_1_3_3_3_2 e_1_3_3_10_2 e_1_3_3_21_2 |
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| Snippet | Apolipoprotein E (ApoE) genotypes have been associated with lobar intracerebral hemorrhage (ICH). Although statins have been associated with an increased risk... |
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| SubjectTerms | Aged Apolipoproteins E - genetics Apolipoproteins E - metabolism Biological and medical sciences Case-Control Studies Cerebral Hemorrhage - chemically induced Cerebral Hemorrhage - diagnosis Cerebral Hemorrhage - genetics Drug toxicity and drugs side effects treatment Female Genotype Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects Male Medical sciences Middle Aged Neurology Pharmacology. Drug treatments Prospective Studies Risk Factors Toxicity: nervous system and muscle Vascular diseases and vascular malformations of the nervous system |
| Title | Apolipoprotein E, Statins, and Risk of Intracerebral Hemorrhage |
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