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Apolipoprotein E genotype predicts hematoma expansion in lobar intracerebral hemorrhage.

ABSTRACT: Hematoma volume is the most potent predictor of outcome in spontaneous intracerebral hemorrhage (ICH), and hematoma expansion after hospital presentation occurs in up to 40% of individuals. Among patients with lobar ICH, the apolipoprotein E (APOE) ?2 allele predicts larger hematoma volumes at presentation. We investigated whether the ?2 allele also identifies individuals at increased risk of hematoma expansion.We analyzed 510 patients with primary ICH and genetic data available from an ongoing prospective cohort study. Baseline and follow-up CT scans were assessed for ICH location and volume using computer-assisted volumetric methods.Individuals with lobar ICH who possessed APOE ?2 were at increased risk for hematoma expansion (OR, 2.72; 95% CI, 1.19-6.23; P=0.009). The highest odds of expansion were in patients who qualified for the diagnosis of cerebral amyloid angiopathy-related ICH and carried the APOE ?2 allele (OR, 6.02; 95% CI, 1.60-22.58; P=0.008). There was no effect of ?2 on hematoma expansion in deep ICH and APOE ?4 had no effect on hematoma expansion in lobar or deep ICH.Possession of APOE ?2 predisposes individuals with lobar ICH to hematoma expansion. This effect is even more pronounced in patients with amyloid angiopathy-related ICH, consistent with the ?2 allele's role in vascular amyloid deposition and vessel fragility.

SUBMITTER: Brouwers HB

PROVIDER: S-EPMC3361564 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Apolipoprotein E genotype predicts hematoma expansion in lobar intracerebral hemorrhage.

Brouwers H Bart HB Biffi Alessandro A Ayres Alison M AM Schwab Kristin K Cortellini Lynelle L Romero Javier M JM Rost Natalia S NS Viswanathan Anand A Greenberg Steven M SM Rosand Jonathan J Goldstein Joshua N JN

Stroke 20120424 6

<h4>Background and purpose</h4>Hematoma volume is the most potent predictor of outcome in spontaneous intracerebral hemorrhage (ICH), and hematoma expansion after hospital presentation occurs in up to 40% of individuals. Among patients with lobar ICH, the apolipoprotein E (APOE) ε2 allele predicts larger hematoma volumes at presentation. We investigated whether the ε2 allele also identifies individuals at increased risk of hematoma expansion.<h4>Methods</h4>We analyzed 510 patients with primary ...[more]

PMID: 22535266

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Project description:BACKGROUND:Hematoma expansion (HE) after intracerebral hemorrhage (ICH) is associated with worse outcome. Lobar ICHs are known to have better outcomes compared to deep ICH; however, it is unclear whether there are HE differences between these locations. We sought to investigate the hypothesis that lobar ICH has less HE compared to deep ICH. METHODS:Primary ICH patients admitted between 2009 and 2016 were included in a prospective single-center ICH cohort study. Patients with preceding anticoagulant use, coagulopathy on admission labs, or presenting after 24?h from symptom onset were excluded. Lobar and deep ICH patients with baseline and follow-up computed tomography (CT) (within 24?h of admission CT) were evaluated. HE was defined primarily as relative growth >?33% given expected baseline hematoma volume differences between locations. Other commonly utilized definitions of HE: >?6 mL, and >?33% or >?6 mL, were additionally assessed. Multivariable logistic regression was used to assess the association of ICH location with HE while adjusting for previously identified covariates of HE. RESULTS:There were 59 lobar and 143 deep ICH patients analyzed. Lobar ICH patients had significantly larger baseline hematoma volumes, lower admission systolic blood pressure, and longer times to admission CT compared to deep ICH. Multivariable logistic regression revealed an association of lobar ICH with lower odds of HE (>?33%) [odds ratio (OR) 0.32; 95% confidence interval (CI) 0.11-0.93; p?=?0.04] compared to deep ICH after adjusting for baseline ICH volume, blood pressure, and time to CT. Secondary analysis did not identify an association of lobar ICH with HE defined as >?6 mL (adjusted OR 1.44; 95% CI 0.59-3.50; p?=?0.41) or >?33% or >?6 mL (adjusted OR 0.71; 95% CI 0.29-1.70; p?=?0.44). CONCLUSION:We identified less HE in lobar compared to deep ICH. The use of absolute growth thresholds in defining HE may be limited when assessing groups with largely different baseline hematoma sizes. Further study is required to replicate our findings and investigate mechanisms for HE differences between lobar and deep ICH locations.

Project description:ObjectiveHematoma enlargement (HE) is associated with clinical outcomes after supratentorial intracerebral hemorrhage (ICH). This study evaluates whether HE characteristics and association with functional outcome differ in deep versus lobar ICH.MethodsPooled analysis of individual patient data between January 2006 and December 2015 from a German-wide cohort study (RETRACE, I + II) investigating ICH related to oral anticoagulants (OAC) at 22 participating centers, and from one single-center registry (UKER-ICH) investigating non-OAC-ICH patients. Altogether, 1954 supratentorial ICH patients were eligible for outcome analyses, which were separately conducted or controlled for OAC, that is, vitamin-K-antagonists (VKA, n = 1186) and non-vitamin-K-antagonist-oral-anticoagulants (NOAC, n = 107). Confounding was addressed using propensity score matching, cox regression modeling and multivariate modeling. Main outcomes were occurrence, extent, and timing of HE (>33%/>6 mL) and its association with 3-month functional outcome.ResultsOccurrence of HE was not different after deep versus lobar ICH in patients with non-OAC-ICH (39/356 [11.0%] vs. 36/305 [11.8%], P = 0.73), VKA-ICH (249/681 [36.6%] vs. 183/505 [36.2%], P = 0.91), and NOAC-ICH (21/69 [30.4%] vs. 12/38 [31.6%], P = 0.90). HE extent did not differ after non-OAC-ICH (deep:+59% [40-122] vs. lobar:+74% [37-124], P = 0.65), but both patients with VKA-ICH and NOAC-ICH showed greater HE extent after deep ICH [VKA-ICH, deep: +94% [54-199] vs. lobar: +56% [35-116], P < 0.001; NOAC-ICH, deep: +74% [56-123] vs. lobar: +40% [21-49], P = 0.001). Deep compared to lobar ICH patients had higher HE hazard during first 13.5 h after onset (Hazard ratio [HR]: 1.85 [1.03-3.31], P = 0.04), followed by lower hazard (13.5-26.5 h, HR: 0.46 [0.23-0.89], P = 0.02), and equal hazard thereafter (HR: 0.96 [0.56-1.65], P = 0.89). Odds ratio for unfavorable outcome was higher after HE in deep (4.31 [2.71-6.86], P < 0.001) versus lobar ICH (2.82 [1.71-4.66], P < 0.001), and only significant after small-medium (1st volume-quarter, deep: 3.09 [1.52-6.29], P < 0.01; lobar: 3.86 [1.35-11.04], P = 0.01) as opposed to large-sized ICH (4th volume-quarter, deep: 1.09 [0.13-9.20], P = 0.94; lobar: 2.24 [0.72-7.04], P = 0.17).InterpretationHE occurrence does not differ among deep and lobar ICH. However, compared to lobar ICH, HE after deep ICH is of greater extent in OAC-ICH, occurs earlier and may be of greater clinical relevance. Overall, clinical significance is more apparent after small-medium compared to large-sized bleedings.

Project description:Background: Early hematoma expansion (HE) occurs in patients with intracerebral hemorrhage (ICH) within the first few hours from ICH onset. Hematoma expansion has been considered as an independent predictor of poor clinical outcome and mortality after ICH. Island sign (IS) on the non-contrast computed tomography (NCCT) appears to increase the rate of detection of HE. However, there is insufficient evidence to declare that IS is an independent predictor for ICH patients prognosis and classification. Objectives: To investigate whether IS on NCCT could predict HE and functional outcome following ICH. Methods: Major databases were systematically searched, including PubMed, EMBASE, Cochrane library, and the Chinese database (CNKI, VIP, and Wanfang databases). Studies about the associations between IS and HE or IS and clinical outcome were included. The pooled result used the odds ratio (OR) with a 95% confidence interval (CI) as effect size. Heterogeneity and publication bias were assessed. Subgroup analysis and meta-regression were applied to detect potential factors of heterogeneity. Results: Eleven studies with 4,310 patients were included in the final analysis. The average incidence rate of IS and HE were 21.58 and 33%, respectively. The ideal timing for assessing HE was also not uniform or standardized. We separately performed two meta-analyses. First, 10 studies were included to estimate the association between IS and HE. The pooled OR was statistically significant (OR = 7.61, 95% CI = 3.10-18.67, P < 0.001). Second, four studies were included in the meta-analysis, and the pooled result showed that IS had a significantly positive relationship with poor outcome (OR = 3.83, 95% CI = 2.51-5.85, P < 0.001). Conclusions: This meta-analysis showed that NCCT IS is of great importance and value for evaluation of HE and poor outcome in patients with ICH. Future studies should focus on developing consensus guidelines, and more studies with large sample size and longitudinal design are needed to validate the conclusions.

Dataset Information

Apolipoprotein E genotype predicts hematoma expansion in lobar intracerebral hemorrhage.

Publications

Apolipoprotein E genotype predicts hematoma expansion in lobar intracerebral hemorrhage.

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