Dataset Information

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

Falcone Guido J GJ Radmanesh Farid F Brouwers H Bart HB Battey Thomas W K TW Devan William J WJ Valant Valerie V Raffeld Miriam R MR Chitsike Lennox P LP Ayres Alison M AM Schwab Kristin K Goldstein Joshua N JN Viswanathan Anand A Greenberg Steven M SM Selim Magdy M Meschia James F JF Brown Devin L DL Worrall Bradford B BB Silliman Scott L SL Tirschwell David L DL Flaherty Matthew L ML Martini Sharyl R SR Deka Ranjan R Biffi Alessandro A Kraft Peter P Woo Daniel D Rosand Jonathan J Anderson Christopher D CD

Neurology 20140822 13

<h4>Objective</h4>We aimed to assess the effect of APOE ε variants on warfarin-related intracerebral hemorrhage (wICH), evaluated their predictive power, and tested for interaction with warfarin in causing wICH.<h4>Methods</h4>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 ε variant ...[more]

PMID: 25150286

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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.

Project description:BackgroundCerebral amyloid angiopathy (CAA) is the most common cause of lobar intracerebral hemorrhage (ICH) in the elderly, and its multifocal and recurrent nature leads to high rates of disability and mortality. Therefore, this study aimed to summarize the evidence regarding the recurrence rate and risk factors for CAA-related ICH (CAA-ICH).MethodsWe performed a systematic literature search of all English studies published in PubMed, Embase, Web of Science, Cochrane Library, Scopus, and CINAHL from inception to June 10, 2023. Studies reporting CAA-ICH recurrence rates and risk factors for CAA-ICH recurrence were included. We calculated pooled odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) using a random/fixed-effects model based on the I2 assessment of heterogeneity between studies. Publication bias was assessed using Egger's test.ResultsThirty studies were included in the final analysis. Meta-analysis showed that the recurrence rate of CAA-ICH was 23% (95% CI: 18-28%, I2 = 96.7%). The risk factors significantly associated with CAA-ICH recurrence were: previous ICH (OR = 2.03; 95% CI: 1.50-2.75; I2 = 36.8%; N = 8), baseline ICH volume (OR = 1.01; 95% CI: 1-1.02; I2 = 0%; N = 4), subarachnoid hemorrhage (cSAH) (OR = 3.05; 95% CI: 1.86-4.99; I2 = 0%; N = 3), the presence of cortical superficial siderosis (cSS) (OR = 2.04; 95% CI: 1.46-2.83; I2 = 0%; N = 5), disseminated cSS (OR = 3.21; 95% CI: 2.25-4.58; I2 = 16.0%; N = 6), and centrum semiovale-perivascular spaces (CSO-PVS) severity (OR = 1.67; 95% CI: 1.14-2.45; I2 = 0%; N = 4).ConclusionCAA-ICH has a high recurrence rate. cSAH, cSS (especially if disseminated), and CSO-PVS were significant markers for recurrent CAA-ICH. The onset of ICH in patients with CAA is usually repeated several times, and recurrence is partly related to the index ICH volume. Identifying clinical and neuroimaging predictors of CAA-ICH recurrence is of great significance for evaluating outcomes and improving the prognosis of patients with CAA-ICH.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=400240, identifier [CRD42023400240].

Dataset Information

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

Publications

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

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