Dataset Information

Genetic risk of Spontaneous intracerebral hemorrhage: Systematic review and future directions.

ABSTRACT:

Background

Although highly heritable, few genes have been linked to spontaneous intracerebral hemorrhage (SICH), which does not currently have any evidence-based disease-modifying therapy. Individuals of African ancestry are especially susceptible to SICH, even more so for indigenous Africans. We systematically reviewed the genetic variants associated with SICH and examined opportunities for rapidly advancing SICH genomic research for precision medicine.

Method

We searched the National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) Genome Wide Association Study (GWAS) catalog and PubMed for original research articles on genetic variants associated with SICH as of 15 June 2019 using the PRISMA guideline.

Results

Eight hundred and sixty-four articles were identified using pre-specified search criteria, of which 64 met the study inclusion criteria. Among eligible articles, only 9 utilized GWAS approach while the rest were candidate gene studies. Thirty-eight genetic loci were found to be variously associated with the risk of SICH, hematoma volume, functional outcome and mortality, out of which 8 were from GWAS including APOE, CR1, KCNK17, 1q22, CETP, STYK1, COL4A2 and 17p12. None of the studies included indigenous Africans.

Conclusion

Given this limited information on the genetic contributors to SICH, more genomic studies are needed to provide additional insights into the pathophysiology of SICH, and develop targeted preventive and therapeutic strategies. This call for additional investigation of the pathogenesis of SICH is likely to yield more discoveries in the unexplored indigenous African populations which also have a greater predilection.

SUBMITTER: Wahab KW

PROVIDER: S-EPMC7413646 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

Genetic risk of Spontaneous intracerebral hemorrhage: Systematic review and future directions.

Wahab Kolawole Wasiu KW Tiwari Hemant K HK Ovbiagele Bruce B Sarfo Fred F Akinyemi Rufus R Traylor Matthew M Rotimi Charles C Markus Hugh Stephen HS Owolabi Mayowa M

Journal of the neurological sciences 20191013

<h4>Background</h4>Although highly heritable, few genes have been linked to spontaneous intracerebral hemorrhage (SICH), which does not currently have any evidence-based disease-modifying therapy. Individuals of African ancestry are especially susceptible to SICH, even more so for indigenous Africans. We systematically reviewed the genetic variants associated with SICH and examined opportunities for rapidly advancing SICH genomic research for precision medicine.<h4>Method</h4>We searched the Nat ...[more]

PMID: 31669726

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Project description:ImportanceLimited evidence is available concerning optimal seizure prophylaxis after spontaneous intracerebral hemorrhage (sICH).ObjectiveTo evaluate which of 4 seizure prophylaxis strategies provides the greatest net benefit for patients with sICH.Design, setting, and participantsThis decision analysis used models to simulate the following 4 common scenarios: (1) a 60-year-old man with low risk of early (≤7 days after stroke) (10%) and late (3.6% or 9.8%) seizures and average risk of short- (9%) and long-term (30%) adverse drug reaction (ADR); (2) an 80-year-old woman with low risk of early (10%) and late (3.6% or 9.8%) seizures and high short- (24%) and long-term (80%) ADR risks; (3) a 55-year-old man with high risk of early (19%) and late (34.8% or 46.2%) seizures and low short- (9%) and long-term (30%) ADR risks; and (4) a 45-year-old woman with high risk of early (19%) and late (34.8% or 46.2%) seizures and high short- (18%) and long-term (60%) ADR risks.InterventionsThe following 4 antiseizure drug strategies were included: (1) conservative, consisting of short-term (7-day) secondary early-seizure prophylaxis with long-term therapy after late seizure; (2) moderate, consisting of long-term secondary early-seizure prophylaxis or late-seizure therapy; (3) aggressive, consisting of long-term primary prophylaxis; and (4) risk guided, consisting of short-term secondary early-seizure prophylaxis among low-risk patients (2HELPS2B score, 0), short-term primary prophylaxis among patients at higher risk (2HELPS2B score, ≥1), and long-term secondary therapy for late seizure.Main outcomes and measuresQuality-adjusted life-years (QALYs).ResultsFor scenario 1, the risk-guided strategy (8.13 QALYs) was preferred over the conservative (8.08 QALYs), moderate (8.07 QALYs), and aggressive (7.88 QALYs) strategies. For scenario 2, the conservative strategy (2.18 QALYs) was preferred over the risk-guided (2.17 QALYs), moderate (2.09 QALYs), and aggressive (1.15 QALYs) strategies. For scenario 3, the aggressive strategy (9.21 QALYs) was preferred over the risk-guided (8.98 QALYs), moderate (8.93 QALYs), and conservative (8.77 QALYs) strategies. For scenario 4, the risk-guided strategy (11.53 QALYs) was preferred over the conservative (11.23 QALYs), moderate (10.93 QALYs), and aggressive (8.08 QALYs) strategies. Sensitivity analyses suggested that short-term strategies (conservative and risk guided) are preferred under most scenarios, and the risk-guided strategy performs comparably to or better than alternative strategies in most settings.Conclusions and relevanceThis decision analytical model suggests that short-term (7-day) prophylaxis dominates longer-term therapy after sICH. Use of the 2HELPS2B score to guide clinical decisions for initiation of short-term primary vs secondary early-seizure prophylaxis should be considered for all patients after sICH.

Project description:Background and purposeRecent epidemiological data indicate that the absolute number of hemorrhagic stroke cases increased by 47% between 1990 and 2010 and continued to cause high rates of death and disability. The last systematic review and meta-analysis of incidence and long-term survival of intracerebral hemorrhage (ICH) were published 11 and 7 years ago, respectively, and lacked comparison between different income groups, therefore, a more up to date analysis is needed. We aim to investigate the ICH incidence and long-term survival data in countries of different income groups.Materials methodsWe systematically searched Ovid Medline for population-based longitudinal studies of first-ever spontaneous ICH published from January 2000 to December 2020. We performed meta-analyses on the incidence and survival rate in countries of 4 different income groups with random-effects models (severe inconsistency). The I 2 was used to measure the heterogeneity. Heterogeneity was further investigated by conducting the meta-regression on the study mid-year. Time trends of the survival rate were assessed by weighted linear regression.ResultsWe identified 84 eligible papers, including 68 publications reporting incidence and 24 publications on the survival rate. The pooled incidence of ICH per 100,000 per person-years was 26.47 (95% CI: 21.84-32.07) worldwide, 25.9 (95% CI: 22.63-29.63) in high-income countries (HIC), 28.45 (95% CI: 15.90-50.88) in upper-middle-income countries, and 31.73 (95% CI: 18.41-54.7) in lower-middle-income countries. The 1-year pooled survival rate was from 50% (95% CI: 47-54%; n = 4,380) worldwide to 50% (95% CI: 47-54%) in HIC, and 46% (95% CI: 38-55%) in upper-middle income countries. The 5-year pooled survival rate was 41% (95% CI: 35-48%; n = 864) worldwide, 41% (95% CI: 32-50%) in high-income and upper-middle countries. No publications were found reporting the long-term survival in lower-middle-income and low-income countries. No time trends in incidence or survival were found by meta-regression.ConclusionThe pooled ICH incidence was highest in lower-middle-income countries. About half of ICH patients survived 1 year, and about two-fifths survived 5 years. Reliable population-based studies estimating the ICH incidence and long-term survival in low-income and low-middle-income countries are needed to help prevention of ICH.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=170140, PROSPERO CRD42020170140.

Dataset Information

Genetic risk of Spontaneous intracerebral hemorrhage: Systematic review and future directions.

Background

Method

Results

Conclusion

Publications

Genetic risk of Spontaneous intracerebral hemorrhage: Systematic review and future directions.

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