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APOE ? variants increase risk of warfarin-related intracerebral hemorrhage.

ABSTRACT: We aimed to assess the effect of APOE ? variants on warfarin-related intracerebral hemorrhage (wICH), evaluated their predictive power, and tested for interaction with warfarin in causing wICH.This was a prospective, 2-stage (discovery and replication), case-control study. wICH was classified as lobar or nonlobar based on the location of the hematoma. Controls were sampled from ambulatory clinics (discovery) and random digit dialing (replication). APOE ? variants were directly genotyped. A case-control design and logistic regression analysis were utilized to test for association between APOE ? and wICH. A case-only design and logistic regression analysis were utilized to test for interaction between APOE ? and warfarin. Receiver operating characteristic curves were implemented to evaluate predictive power.The discovery stage included 319 wICHs (44% lobar) and 355 controls. APOE ?2 was associated with lobar (odds ratio [OR] 2.46; p < 0.001) and nonlobar wICH (OR 1.67; p = 0.04), whereas ?4 was associated with lobar (OR 2.09; p < 0.001) but not nonlobar wICH (p = 0.35). The replication stage (63 wICHs and 1,030 controls) confirmed the association with ?2 (p = 0.03) and ?4 (p = 0.003) for lobar but not for nonlobar wICH (p > 0.20). Genotyping information on APOE ? variants significantly improved case/control discrimination of lobar wICH (C statistic 0.80). No statistical interaction between warfarin and APOE was found (p > 0.20).APOE ? variants constitute strong risk factors for lobar wICH. APOE exerts its effect independently of warfarin, although power limitations render this absence of interaction preliminary. Evaluation of the predictive ability of APOE in cohort studies is warranted.

SUBMITTER: Falcone GJ

PROVIDER: S-EPMC4176027 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Project description:Background and Purpose- Whether to resume oral anticoagulation treatment after intracerebral hemorrhage (ICH) remains an unresolved question. Previous studies focused primarily on recurrent stroke after ICH. We sought to investigate the association between cardioembolic stroke risk, oral anticoagulation therapy resumption, and functional recovery among ICH survivors in the absence of recurrent stroke. Methods- We conducted a joint analysis of 3 observational studies: (1) the multicenter RETRACE study (German-Wide Multicenter Analysis of Oral Anticoagulation Associated Intracerebral Hemorrhage); (2) the Massachusetts General Hospital ICH study (n=166); and (3) the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage; n=131). We included 941 survivors of ICH in the setting of active oral anticoagulation therapy for prevention of cardioembolic stroke because of nonvalvular atrial fibrillation and without evidence of ischemic stroke and recurrent ICH at 1 year from the index event. We created univariable and multivariable models to explore associations between cardioembolic stroke risk (based on CHA2DS2-VASc scores) and functional recovery after ICH, defined as achieving modified Rankin Scale score of ≤3 at 1 year for participants with modified Rankin Scale score of >3 at discharge. Results- In multivariable analyses, the CHA2DS2-VASc score was associated with a decreased likelihood of functional recovery (odds ratio, 0.83 per 1 point increase; 95% CI, 0.79-0.86) at 1 year. Anticoagulation resumption was independently associated with a higher likelihood of recovery, regardless of CHA2DS2-VASc score (odds ratio, 1.89; 95% CI, 1.32-2.70). We found an interaction between CHA2DS2-VASc score and anticoagulation resumption in terms of association with increased likelihood of functional recovery (interaction P=0.011). Conclusions- Increasing cardioembolic stroke risk is associated with a decreased likelihood of functional recovery at 1 year after ICH, but this association was weaker among participants resuming oral anticoagulation therapy. These findings support, including recovery metrics, in future studies of anticoagulation resumption after ICH.

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APOE ? variants increase risk of warfarin-related intracerebral hemorrhage.

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