Polygenic Risk Scores in Myocardial Injury After Noncardiac Surgery

Figures

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  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.

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  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.

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  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.

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  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.