Polygenic Risk Scores in Myocardial Injury After Noncardiac Surgery: A VISION Substudy

Ann Le¹, Guillaume Paré², P J Devereaux³, Ibrahim Quazi⁴, Shihong Mao⁵, Michael Chong⁶, Diane Heels-Ansdell⁴, Emmanuelle Duceppe⁷, Michael Ke Wang⁸, Ameen Patel⁹, Maria Tiboni⁹, Patrick Magloire⁹, Amit X Garg¹⁰, Sandra N Ofori³, David Conen³, Jessica Spence¹¹, Emilie Belley-Côté⁸, Caleb Beck¹², William F McIntyre⁸, Richard Whitlock⁵, Jeff S Healey⁸, Shirley Pettit⁵, Flavia K Borges¹³; VISION Investigators

Affiliations

¹ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Medical Sciences, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada.
² Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Medical Sciences, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada; Thrombosis and Atherosclerosis Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote School of Medicine, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
³ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁴ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
⁵ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada.
⁶ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Medical Sciences, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada.
⁷ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Centre hospitalier de l'Université de Montréal, Université de Montréal, Montréal, Quebec, Canada.
⁸ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁹ Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
¹⁰ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Division of Nephrology, London Health Sciences Centre, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
¹¹ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Anesthesia and Critical Care, McMaster University, Hamilton, Ontario, Canada.
¹² Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Ecology and Evolution, University of Lausanne, Faculty of Biology and Medicine, Quartier Centre, Lausanne, Switzerland.
¹³ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: flavia.borges@phri.ca.

PMID: 40147046
PMCID: PMC11992376
DOI: 10.1016/j.jacadv.2025.101680

Polygenic Risk Scores in Myocardial Injury After Noncardiac Surgery: A VISION Substudy

Ann Le et al. JACC Adv. 2025 Apr.

. 2025 Apr;4(4):101680.

doi: 10.1016/j.jacadv.2025.101680. Epub 2025 Mar 26.

Authors

Affiliations

¹ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Medical Sciences, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada.
² Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Medical Sciences, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada; Thrombosis and Atherosclerosis Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote School of Medicine, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
³ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁴ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
⁵ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada.
⁶ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Medical Sciences, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada.
⁷ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Centre hospitalier de l'Université de Montréal, Université de Montréal, Montréal, Quebec, Canada.
⁸ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁹ Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
¹⁰ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Division of Nephrology, London Health Sciences Centre, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
¹¹ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Anesthesia and Critical Care, McMaster University, Hamilton, Ontario, Canada.
¹² Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Ecology and Evolution, University of Lausanne, Faculty of Biology and Medicine, Quartier Centre, Lausanne, Switzerland.
¹³ Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: flavia.borges@phri.ca.

PMID: 40147046
PMCID: PMC11992376
DOI: 10.1016/j.jacadv.2025.101680

Abstract

Background: Myocardial injury after noncardiac surgery (MINS) is the most prevalent vascular complication following surgical procedures. Although the revised cardiac risk index (RCRI) is widely used to predict postoperative cardiovascular complications, its predictive accuracy is suboptimal.

Objectives: Considering genetic influences may improve risk prediction. The authors propose integrating polygenic risk scores (PRS) with the RCRI to enhance MINS prediction. Identification of PRS associated with MINS could provide pathophysiological insights.

Methods: This is a case-control study nested within the Vascular Events in Noncardiac Surgery Participants Cohort Evaluation cohort, including patients aged 45 and above who underwent noncardiac surgery. Daily troponin levels were measured preoperatively and on days 1, 2, and 3 postoperatively. PRS was computed for MINS risk factors using publicly available summary statistics. Logistic regression models were used to assess the association between each PRS and MINS. PRS discrimination was assessed independently and in combination with RCRI.

Results: A total of 253 MINS cases were matched with 253 controls, adjusted for age, sex, and limited to individuals of European ancestry (n_total = 506). The type II diabetes (T2D) PRS (OR: 1.26; 95% CI: 1.00-1.58; P = 0.047) and the HbA1c PRS (OR: 1.26; 95% CI: 1.03-1.54; P = 0.026) were associated with MINS. No other PRS, including those for coronary artery disease, stroke, and lipid biomarkers, showed significant associations.

Conclusions: The T2D PRS and the HbA1c PRS were associated with an increased risk of MINS. The findings may reflect the multifactorial pathophysiology of MINS. Larger genetic studies and trials evaluating perioperative glucose management warrant consideration.

Keywords: VISION; cardiovascular genetics; myocardial injury after noncardiac surgery MINS; polygenic risk scores; revised cardiac risk index.

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Conflict of interest statement

Funding support and author disclosures This project received support from the New Investigator Fund, Hamilton Health Sciences. Dr Borges holds a McMaster University Department of HEI Mid-Career Research Award. Dr Duceppe is supported by a clinician-bursary award from Fonds de Recherche du Quebec-Sante. Dr Wang is the recipient of the CIHR Canada Graduate Scholarships-Doctoral Research Award. Dr Borges has received investigator-initiated grants from Roche Diagnostics and SIEMENS not related to the scope of this work. Dr Paré has received consulting fees from Bayer, Sanofi, Amgen, and Illumina. Dr Devereaux is a member of a research group with a policy of not accepting honorariums or other payments from industry for their own personal financial gain (they do accept honorariums/payments from industry to support research endeavors and costs to participate in meetings; has received grants from Abbott Diagnostics, AOP Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CloudDX, Coviden, Octapharma, Philips Healthcare, Roche Diagnostics, Siemens, and Stryker; has participated in advisory board meetings for GlaxoSmithKline, Boehringer Ingelheim, Bayer, and Quidel Canada; has attended an expert panel meeting with AstraZeneca and Boehringer Ingelheim; was a consultant for Roche Pharma, Abbott Diagnostics, AstraZeneca, Renibus, Roche Canada, and Trimedic; and been invited as a speaker with Bayer Inc and Novartis Pharma Canada (these are all unrelated to the scope of this work). Dr Duceppe has received investigator-initiated research grants from Roche Diagnostics and Abbott Laboratories and lecture fees from Roche Diagnostics, not related to the work in this manuscript. Dr Conen has received consulting honorarium from Trimedics; and speaking honorarium from Servier. Dr Spence has received grants as research support from AOP Pharmaceuticals; and received consulting honorarium from VarmX outside of the scope of this work. Dr Belley-Côté has received grants from Bayer, Roche, BMS-Pfizer, and Abbott; and a consulting honorarium from Trimedic Therapeutics Inc outside the submitted work. Dr McIntyre has received research grants from Trimedics; speaking honorarium from iRhythm; and consulting honorarium from Trimedics and Atricure, all unrelated to current work. Dr Healey was funded by an unrestricted grant from Boston Scientific; and has received grants from BMS/Pfizer and Medtronic unrelated to the scope of this work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

**Figure 1**
Overview of Experimental Design for Vascular Events in Noncardiac Surgery Participants Cohort Evaluation Myocardial Injury After Noncardiac Surgery Polygenic Risk Score Study This figure shows the flow of participant selection, along with the analyses that were conducted on the samples to determine the association between PRS and MINS. The VISION Biobank sample originally consisted of 4,428 patients, from which 600 patients were randomly selected for MINS case-control matching. Among the 600 patients, those without matches, misrepresented ancestry, and lack of RCRI availability were filtered out, resulting in a final sample of 253 cases (patients with MINS) and 253 controls (patients without MINS) matched for age and sex. Conditional logistic regression and discrimination capacity analyses were performed on this sample. AUC = area under the curve; MINS = myocardial injury after noncardiac surgery; PRS = polygenic risk score; RCRI = revised cardiac risk index; ROC = receiver operating characteristic; VISION = Vascular Events in Noncardiac Surgery Participants Cohort Evaluation.

**Figure 2**
Myocardial Injury After Noncardiac Surgery OR According to Quintile of Hemoglobin A1c Polygenic Risk Score This figure displays the OR of association per quintile of HbA1c PRS, with the 1st quintile as a reference. The HbA1c PRS can stratify MINS risk without RCRI. CIs for logistic regression estimates are also shown. HbA1C = hemoglobin A1c; other abbreviations as in Figure 1.

**Figure 3**
Association Between Polygenic Risk Score and Myocardial Injury After Noncardiac Surgery The following forest plots display the association of all traits for which PRS were created by order of descending OR per unit of SD with a 95% CI, as determined through conditional logistic regression. (A) Association of each trait’s PRS without adjustment for RCRI. (B) Association of each trait’s PRS with adjustment for RCRI. (A) PRS, no RCRI, (B) PRS with RCRI. Abbreviations as in Figure 1.

**Central Illustration**
Polygenic Risk Scores in Myocardial Injury After Noncardiac Surgery: A VISION Substudy A summary of the risk prediction methods for MINS observed in this study, namely revised cardiac risk index (RCRI) and genetic or polygenic risk score (PRS), along with their combined performance as reflected by our results. RCRI is represented as the six components that are considered during its calculation. PRS for MINS are created from genome-wide association studies (GWAS) relevant to its risk factors, with type II diabetes PRS and hemoglobin A1c PRS being the standout scores. This integrated framework displays the complexity of MINS pathophysiology as reflected in the study and highlights opportunities for improving risk prediction (created with https://BioRender.com). HbA1c = hemoglobin A1c; T2D = type II diabetes; other abbreviations as in Figure 1.

See this image and copyright information in PMC

References

1. Duceppe E., Parlow J., MacDonald P., et al. Canadian cardiovascular society guidelines on perioperative cardiac risk assessment and management for patients who undergo noncardiac surgery. Can J Cardiol. 2017;33(1):17–32. - PubMed
1. Writing Committee for the VISION Study Investigators, Devereaux P.J., Biccard B.M., et al. Association of postoperative high-sensitivity troponin levels with myocardial injury and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2017;317(16):1642. - PubMed
1. Smilowitz N.R., Redel-Traub G., Hausvater A., et al. Myocardial injury after noncardiac surgery: a systematic review and meta-analysis. Cardiol Rev. 2019;27(6):267–273. - PMC - PubMed
1. The Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) Study Investigators, Spence J., LeManach Y., et al. Association between complications and death within 30 days after noncardiac surgery. CMAJ. 2019;191(30):E830–E837. - PMC - PubMed
1. VISION Pilot Study Investigators; Devereaux PJ, Bradley D, et al. An international prospective cohort study evaluating major vascular complications among patients undergoing noncardiac surgery: the VISION Pilot Study. Open Med. 2011;5(4):e193–e200. - PMC - PubMed

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Polygenic Risk Scores in Myocardial Injury After Noncardiac Surgery: A VISION Substudy

Affiliations

Polygenic Risk Scores in Myocardial Injury After Noncardiac Surgery: A VISION Substudy

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

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