Abstract W MP90: APOE Variants are Associated With Increased Risk of Warfarin-Related Intracerebral Hemorrhage
Background: Epsilon (e) variants in the Apolipoprotein E (APOE) gene are well-established risk factors for spontaneous intracerebral hemorrhage (s-ICH). We tested the hypothesis that APOE-e variants are also associated with warfarin-related ICH (w-ICH) and examined interactions between APOE and warfarin.
Methods: Prospective multicenter 2-stage (discovery and replication) study. ICH was classified as lobar and non-lobar based on admission head CT. In the discovery stage, w-ICH cases were matched with warfarin-exposed controls (w-controls). In replication, w-ICH cases were matched with non-warfarin controls (nw-controls). APOE was directly genotyped. Association testing was performed using multivariable logistic regression. Gene-environment interaction between APOE and warfarin was formally tested using a case only approach (combining s-ICH and w-ICH cases).
Results: The discovery stage included 316 w-ICHs (43% lobar and 57% non-lobar) and 355 w-controls. Results are presented in the Table: APOE-e2 was associated with lobar and non-lobar w-ICH, and APOE-e4 was associated with lobar but not with non-lobar w-ICH. In case-only analysis, 885 s-ICHs were combined with w-ICHs (total n=1201) and no evidence of interaction between APOE and warfarin was found (all p>0.20). The replication included 63 w-ICHs (44% lobar and 56% non-lobar) and 990 nw-controls. The distribution of APOE variants was similar in w-controls (discovery) and nw-controls (replication) for both e2 (p=0.81) and e4 (p=0.88). In replication, APOE-e2 and e4 were associated with lobar but not with non-lobar w-ICH.
Conclusions: APOE-e variants constitute strong risk factors for lobar w-ICH. An effect may also exist between APOE-e2 and non-lobar hemorrhages, but given the lack of replication larger sample sizes are required to properly assess this association. APOE exerts its effect independently of warfarin, although power limitations render this absence of interaction preliminary.
Author Disclosures: G.J. Falcone: None. F. Radmanesh: None. H.B. Brouwers: None. L.P. Chitsike: None. W.J. Devan: None. T.W. Battey: None. A. Viswanathan: None. J.N. Goldstein: Consultant/Advisory Board; Modest; CSL Behring. Research Grant; Significant; CSL Behring. S.M. Greenberg: Research Grant; Significant; National Institutes of Health. Consultant/Advisory Board; Significant; Hoffman-Laroche, MRI review committee. D.L. Brown: None. B.B. Worrall: Research Grant; Significant; National Human Genome Research Institute; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute. Other; Significant; Associated editor (Neurology). J.F. Meschia: None. S.L. Silliman: None. M. Selim: Research Grant; Significant; National Institutes of Health. Consultant/Advisory Board; Modest; Daiichi Sankyo. D.L. Tirschwell: None. A. Biffi: None. D. Woo: Research Grant; Significant; NINDS NS 36695. J. Rosand: Research Grant; Significant; National Institutes of Health, American Heart Association. C.D. Anderson: Research Grant; Significant; American Brain Foundation.
- © 2014 by American Heart Association, Inc.