Apolipoprotein E Genotype and the Risk of Recurrent Lobar Intracerebral Hemorrhage

O’Donnell, Heather; Rosand, Jonathan; Knudsen, Katherine; Furie, Karen L.; Segal, Alan Z.; Chiu, Rosaleen I.; Ikeda, Deborah; Greenberg, Steven M.

doi:10.1056/nejm200001273420403

Cited by 450 publications

(308 citation statements)

References 31 publications

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“…Some evidence suggests that testing for the apolipoprotein E genotype or detecting cerebral amyloid angiopathy and leukoaraiosis on brain imaging studies might help refine existing prediction rules for hemorrhage. [26][27][28] Future validation of the effectiveness of incorporating such predictors into clinical practice is clearly needed to help improve current risk stratification for intracranial hemorrhage.Our study was strengthened by including the largest number of validated warfarin-related hemorrhages among patients with atrial fibrillation reported to date. Patients were managed using current INR targets, and there was comprehensive assessment of relevant clinical Fang et al…”

mentioning

confidence: 99%

Death and Disability from Warfarin-Associated Intracranial and Extracranial Hemorrhages

Fang

Chang

et al. 2007

The American Journal of Medicine

459

268

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OBJECTIVES-Little is known about the outcomes of patients who have hemorrhagic complications while receiving warfarin therapy. We examined the rates of death and disability resulting from warfarin-associated intracranial and extracranial hemorrhages in a large cohort of patients with atrial fibrillation.METHODS-We assembled a cohort of 13,559 adults with nonvalvular atrial fibrillation and identified patients hospitalized for warfarin-associated intracranial and major extracranial hemorrhage. Data on functional disability at discharge and 30-day mortality were obtained from a review of medical charts and state death certificates. The relative odds of 30-day mortality by hemorrhage type were calculated using multivariable logistic regression.RESULTS-We identified 72 intracranial and 98 major extracranial hemorrhages occurring in more than 15,300 person-years of warfarin exposure. At hospital discharge, 76% of patients with intracranial hemorrhage had severe disability or died, compared with only 3% of those with major extracranial hemorrhage. Of the 40 deaths from warfarin-associated hemorrhage that occurred within 30 days, 35 (88%) were from intracranial hemorrhage. Compared with extracranial hemorrhages, intracranial events were strongly associated with 30-day mortality (odds ratio 20.8 [95% confidence interval, 6.0-72]) even after adjusting for age, sex, anticoagulation intensity on admission, and other coexisting illnesses. CONCLUSIONS-Among anticoagulated patients with atrial fibrillation, intracranialhemorrhages caused approximately 90% of the deaths from warfarin-associated hemorrhage and the majority of disability among survivors. When considering anticoagulation, patients and clinicians need to weigh the risk of intracranial hemorrhage far more than the risk of all major hemorrhages. Atrial fibrillation is the most common clinically significant cardiac arrhythmia and increases the risk for ischemic stroke 4-to 5-fold. 1 Anticoagulation therapy with warfarin can reduce the risk for ischemic stroke by 68% but also increases the risk for major hemorrhagic complications. 2 Clinical decision-making regarding the appropriateness of warfarin therapy for patients with atrial fibrillation has generally relied on balancing the risk of ischemic strokes without warfarin therapy with the risk of all major hemorrhage with warfarin therapy. KeywordsRates of ischemic stroke in patients with atrial fibrillation who are not taking warfarin can be as high as 12% per year, 2,3 and the proportion of patients who have major functional disability after an atrial fibrillation-related ischemic stroke is substantial, as high as 59%. 4 Yet multiple studies demonstrate that patients with atrial fibrillation are frequently not prescribed warfarin despite its benefits in ischemic stroke risk reduction. [5][6][7] The primary deterrent to prescribing warfarin is the fear of inducing life-threatening hemorrhage. 8 Although concerns about hemorrhage prevent many patients from receiving warfarin, there are relatively little data a...

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mentioning

confidence: 99%

Death and Disability from Warfarin-Associated Intracranial and Extracranial Hemorrhages

Fang

Chang

et al. 2007

The American Journal of Medicine

459

268

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“…Studies comparing normal controls against those with pathology positive CAA reveal that both APOE ε2 and ε4 are present in two-thirds of patients with CAA compared to one-fourth of those without. Individuals who have both alleles have an earlier onset of disease and an increased risk of recurrence [16,21,23]. Both APOE ε2 and ε4 are independent risk factors for lobar ICH, however, in the same large-scale genetic association study, APOE ε4 was also found to be associated with deep ICH [24].…”

Section: Cerebral Amyloid Angiopathymentioning

confidence: 92%

“…Cerebral amyloid angiopathy (CAA) is a major risk factor for ICH with a recurrence rate of 10.5% per year [16]. CAA is age dependent, uncommonly occurring in individuals <60 years of age [17].…”

Section: Cerebral Amyloid Angiopathymentioning

confidence: 99%

Treatment Targets in Intracerebral Hemorrhage

Sangha

Gonzales

2011

Neurotherapeutics

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Intracerebral hemorrhage (ICH) imparts a higher mortality and morbidity than ischemic stroke. The therapeutic interventions that are currently available focus mainly on supportive care and secondary prevention. There is a paucity of evidence to support any one acute intervention that improves functional outcome. This chapter highlights current treatment targets for ICH based on the pathophysiology of the disease.

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“…Several risk factors for recurrent ICH have been identified during the years, including older age [130], hypertension [129], lobar ICH location [131], possession of the apolipoprotein E ε2, or ε4 allele [132], and more microbleeds on gradient recalled echo MRI [51]. Of these, hypertension is an important and modifiable risk factor for recurrent hemorrhage.…”

Section: Prevention Of Recurrent Ichmentioning

confidence: 99%