Use of a Polygenic Risk Score Improves Prediction of Myocardial Injury After Non-Cardiac Surgery.


Journal

Circulation. Genomic and precision medicine
ISSN: 2574-8300
Titre abrégé: Circ Genom Precis Med
Pays: United States
ID NLM: 101714113

Informations de publication

Date de publication:
08 2020
Historique:
pubmed: 11 6 2020
medline: 27 10 2021
entrez: 11 6 2020
Statut: ppublish

Résumé

While postoperative myocardial injury remains a major driver of morbidity and mortality, the ability to accurately identify patients at risk remains limited despite decades of clinical research. The role of genetic information in predicting myocardial injury after noncardiac surgery (MINS) remains unknown and requires large scale electronic health record and genomic data sets. In this retrospective observational study of adult patients undergoing noncardiac surgery, we defined MINS as new troponin elevation within 30 days following surgery. To determine the incremental value of polygenic risk score (PRS) for coronary artery disease, we added the score to 3 models of MINS risk: revised cardiac risk index, a model comprised entirely of preoperative variables, and a model with combined preoperative plus intraoperative variables. We assessed performance without and with PRSs via area under the receiver operating characteristic curve and net reclassification index. Among 90 053 procedures across 40 498 genotyped individuals, we observed 429 cases with MINS (0.5%). PRS for coronary artery disease was independently associated with MINS for each multivariable model created (odds ratio=1.12 [95% CI, 1.02-1.24], The addition of a PRS does not significantly improve discrimination but remains independently associated with MINS and improves goodness of fit. As genetic analysis becomes more common, clinicians will have an opportunity to use polygenic risk to predict perioperative complications. Further studies are necessary to determine if PRSs can inform MINS surveillance.

Sections du résumé

BACKGROUND
While postoperative myocardial injury remains a major driver of morbidity and mortality, the ability to accurately identify patients at risk remains limited despite decades of clinical research. The role of genetic information in predicting myocardial injury after noncardiac surgery (MINS) remains unknown and requires large scale electronic health record and genomic data sets.
METHODS
In this retrospective observational study of adult patients undergoing noncardiac surgery, we defined MINS as new troponin elevation within 30 days following surgery. To determine the incremental value of polygenic risk score (PRS) for coronary artery disease, we added the score to 3 models of MINS risk: revised cardiac risk index, a model comprised entirely of preoperative variables, and a model with combined preoperative plus intraoperative variables. We assessed performance without and with PRSs via area under the receiver operating characteristic curve and net reclassification index.
RESULTS
Among 90 053 procedures across 40 498 genotyped individuals, we observed 429 cases with MINS (0.5%). PRS for coronary artery disease was independently associated with MINS for each multivariable model created (odds ratio=1.12 [95% CI, 1.02-1.24],
CONCLUSIONS
The addition of a PRS does not significantly improve discrimination but remains independently associated with MINS and improves goodness of fit. As genetic analysis becomes more common, clinicians will have an opportunity to use polygenic risk to predict perioperative complications. Further studies are necessary to determine if PRSs can inform MINS surveillance.

Identifiants

pubmed: 32517536
doi: 10.1161/CIRCGEN.119.002817
pmc: PMC7442662
mid: NIHMS1605323
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e002817

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL109946
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL141701
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135824
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127564
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142023
Pays : United States

Références

Br J Anaesth. 2018 Apr;120(4):725-733
pubmed: 29576113
Circulation. 2018 Mar 20;137(12):1221-1232
pubmed: 29203498
Anesth Analg. 2017 Feb;124(2):603-617
pubmed: 28099325
Circulation. 1999 Sep 7;100(10):1043-9
pubmed: 10477528
Glob Heart. 2012 Dec;7(4):275-95
pubmed: 25689940
Nature. 2018 Oct;562(7726):181-183
pubmed: 30305759
Anesth Analg. 2016 Mar;122(3):818-24
pubmed: 26891393
Anesthesiology. 2009 Jan;110(1):58-66
pubmed: 19104171
Nat Genet. 2018 Sep;50(9):1219-1224
pubmed: 30104762
Catheter Cardiovasc Interv. 2012 Nov 1;80(5):768-76
pubmed: 22419582
JAMA. 2017 Apr 25;317(16):1642-1651
pubmed: 28444280
Am Heart J. 2013 Aug;166(2):325-332.e1
pubmed: 23895816
Genome Biol. 2018 Aug 20;19(1):120
pubmed: 30124172
Curr Opin Cardiol. 2014 Jul;29(4):307-11
pubmed: 25029449
Anesthesiology. 2014 Mar;120(3):564-78
pubmed: 24534856
Anesthesiology. 2018 Feb;128(2):272-282
pubmed: 29337743
J Am Coll Surg. 2013 Nov;217(5):833-42.e1-3
pubmed: 24055383
Br J Surg. 2015 Feb;102(3):148-58
pubmed: 25627261

Auteurs

Nicholas J Douville (NJ)

Department of Anesthesiology, Michigan Medicine, Ann Arbor (N.J.D., A.L., C.M.B., S.K., M.E., M.R.M.).

Ida Surakka (I)

Division of Cardiovascular Medicine, Department of Internal Medicine (I.S.), University of Michigan, Ann Arbor.

Aleda Leis (A)

Department of Anesthesiology, Michigan Medicine, Ann Arbor (N.J.D., A.L., C.M.B., S.K., M.E., M.R.M.).

Christopher B Douville (CB)

Ludwig Center for Cancer Genetics and Therapeutics (C.B.D.), Johns Hopkins University School of Medicine, Baltimore, MD.
Sidney Kimmel Cancer Center (C.B.D.), Johns Hopkins University School of Medicine, Baltimore, MD.
Sol Goldman Pancreatic Cancer Research Center (C.B.D.), Johns Hopkins University School of Medicine, Baltimore, MD.

Whitney E Hornsby (WE)

Department of Internal Medicine (W.E.H., C.J.W.), University of Michigan, Ann Arbor.

Chad M Brummett (CM)

Department of Anesthesiology, Michigan Medicine, Ann Arbor (N.J.D., A.L., C.M.B., S.K., M.E., M.R.M.).

Sachin Kheterpal (S)

Department of Anesthesiology, Michigan Medicine, Ann Arbor (N.J.D., A.L., C.M.B., S.K., M.E., M.R.M.).

Cristen J Willer (CJ)

Department of Internal Medicine (W.E.H., C.J.W.), University of Michigan, Ann Arbor.
Department of Computational Medicine and Bioinformatics (C.J.W.), University of Michigan, Ann Arbor.
Department of Human Genetics (C.J.W.), University of Michigan, Ann Arbor.

Milo Engoren (M)

Department of Anesthesiology, Michigan Medicine, Ann Arbor (N.J.D., A.L., C.M.B., S.K., M.E., M.R.M.).

Michael R Mathis (MR)

Department of Anesthesiology, Michigan Medicine, Ann Arbor (N.J.D., A.L., C.M.B., S.K., M.E., M.R.M.).

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