Abstract 117: Apolipoprotein E and use of Statins in Intracerebral Hemorrhage
Background: Apolipoprotein E (ApoE) genotypes have been associated with lobar intracerebral hemorrhage (ICH), and HMG-CoA Reductase Inhibitors (statins) were associated with risk of ICH in a secondary prevention trial. Yet, large meta-analyses of statin use have not consistently identified an increased risk of ICH with statin use. We evaluated whether ApoE genotypes were differentially associated with ICH risk according to statin use.
Methods: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study is a prospective ICH study which recruits cases and controls from the same population. Study physicians adjudicated cases and determined ICH location. Subjects were classified as normocholesterolemia (NC), hypercholesterolemia without statin (HC-NS), and hypercholesterolemia with statin use (HC-S) based on chart review. Genotyping for ApoE (rs429358 and rs7412) was performed using standard methods. Statistical comparisons were performed using Fisher’s exact test and Mantel-Haenszel tests for homogeneity.
Results: From 1997-2008, the study recruited 597 cases of ICH and 1,548 controls. Of these, 26 cases/ 8 controls were excluded for unknown history of hypercholesterolemia, and 13 cases/ 96 controls were excluded for missing ApoE result. Of the 554 cases included, 204 were lobar in location. For non-lobar ICH cases, no significant differences were observed in ApoE genotype and statin use between NC, HC-NS and HC-S cases and controls. However, for lobar ICH, a marked increased risk of ICH was seen in HC-S patients with Apo E4/E4 (OR=4.5; 95% CI 1.3-16; p=0.02) and E2/E4 (OR=11.3; 95%CI 2.0-64; p=0.005), and there was a trend for Apo E2/E3 (OR=2.8; 95% CI 1.1-7.5, p=0.06) compared with Apo E3/E3. Apo E4/E4 did not demonstrate an increased odds of ICH without statin use (OR=1.6; 95% CI 0.27-9.4; p=0.63). The p-value for heterogeneity of odds ratios did not reach statistical significance between the HC-NS vs. HC-S group.
Conclusion: Our data support a gene-by-drug effect for lobar ICH and, if confirmed, may indicate a utility for ApoE genotyping to identify patients who would bear the highest risk of ICH with statin use. However, further study is required to determine if an interaction exists or if the finding is associative.
- © 2012 by American Heart Association, Inc.