Evidence map›Paper›PMID 36756894›Full record

ArticleStroke2023

Genetic Risk Score Improves Risk Stratification for Anticoagulation-Related Intracerebral Hemorrhage.

Ernst Mayerhofer, Livia Parodi, Savvina Prapiadou, Rainer Malik, Jonathan Rosand, Marios K Georgakis, Christopher D Anderson

Open access · hybridAbstract read
In one paragraph

Article in Stroke, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.2field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Ernst MayerhoferCenter for Genomic Medicine (E.M., L.P., S.P., J.R., M.K.G., C.D.A.), Massachusetts General Hospital, Boston.ORCID 0000-0001-8902-4209
Livia ParodiCenter for Genomic Medicine (E.M., L.P., S.P., J.R., M.K.G., C.D.A.), Massachusetts General Hospital, Boston.ORCID 0000-0003-0605-2381
Savvina PrapiadouCenter for Genomic Medicine (E.M., L.P., S.P., J.R., M.K.G., C.D.A.), Massachusetts General Hospital, Boston.ORCID 0000-0001-7415-2566
Rainer MalikInstitute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University Munich, Germany (R.M., M.K.G.).ORCID 0000-0001-9212-2520
Jonathan RosandCenter for Genomic Medicine (E.M., L.P., S.P., J.R., M.K.G., C.D.A.), Massachusetts General Hospital, Boston.ORCID 0000-0002-1014-9138
Marios K Georgakis *Center for Genomic Medicine (E.M., L.P., S.P., J.R., M.K.G., C.D.A.), Massachusetts General Hospital, Boston.ORCID 0000-0003-3507-3659
Christopher D Anderson *Center for Genomic Medicine (E.M., L.P., S.P., J.R., M.K.G., C.D.A.), Massachusetts General Hospital, Boston.ORCID 0000-0002-0053-2002
Broad Institute · USLudwig-Maximilians-Universität München · DE

Funding

Ethnic/Racial Variation in Intracerebral Hemorrhage (ERICH)U01NS069763 · NINDS · UNIVERSITY OF CINCINNATI · PI ANDERSON, CHRISTOPHER DAVID, DEMEL, STACIE · 2010 to 2024
$34.2M
Sequencing Annotation and Functional Analysis in Risk of Intracerebral HemorrhageR01NS103924 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI ANDERSON, CHRISTOPHER DAVID · 2018 to 2022
$3.4M
NINDS NIH HHS R01 NS103924NINDS NIH HHS U01 NS069763
6 · The paper itself

Abstract

backgroundIntracerebral hemorrhage (ICH) is the most devastating adverse outcome for patients on anticoagulants. Clinical risk scores that quantify bleeding risk can guide decision-making in situations when indication or duration for anticoagulation is uncertain. We investigated whether integration of a genetic risk score into an existing risk factor-based CRS could improve risk stratification for anticoagulation-related ICH.

methodsWe constructed 153 genetic risk scores from genome-wide association data of 1545 ICH cases and 1481 controls and validated them in 431 ICH cases and 431 matched controls from the population-based UK Biobank. The score that explained the largest variance in ICH risk was selected and tested for prediction of incident ICH in an independent cohort of 5530 anticoagulant users. A CRS for major anticoagulation-related hemorrhage, based on 8/9 components of the HAS-BLED score, was compared with a combined clinical and genetic risk score incorporating an additional point for high genetic risk for ICH.

resultsAmong anticoagulated individuals, 94 ICH occurred over a mean follow-up of 11.9 years. Compared with the lowest genetic risk score tertile, being in the highest tertile was associated with a two-fold increased risk for incident ICH (hazard ratio, 2.08 [95% CI, 1.22-3.56]). Although the CRS predicted incident ICH with a hazard ratio of 1.24 per 1-point increase (95% CI [1.01-1.53]), adding a point for high genetic ICH risk led to a stronger association (hazard ratio of 1.33 per 1-point increase [95% CI, 1.11-1.59]) with improved risk stratification (C index 0.57 versus 0.53) and maintained calibration (integrated calibration index 0.001 for both). The new clinical and genetic risk score showed 19% improvement in high-risk classification among individuals with ICH and a net reclassification improvement of 0.10.

conclusionsAmong anticoagulant users, a prediction score incorporating genomic information is superior to a clinical risk score alone for ICH risk stratification and could serve in clinical decision-making.

Indexed as

Atrial FibrillationGenome-Wide Association StudyAnticoagulantsCerebral HemorrhageHumansRisk AssessmentRisk FactorsAnticoagulantsanticoagulationcalibrationcerebral hemorrhagegeneticsrisk factors

Identifiers

PMID36756894
PMCPMC9992221
OpenAlexW4319657184

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.