Olga Mineeva, Chunying Li, Franco Giulianini, Simeon Häfliger, Vadim Bubes, Gunnar Raetsch, Samia Mora, Olga V Demler
{"title":"Development and Validation of Novel Residual Risk Scores for Patients With ASCVD.","authors":"Olga Mineeva, Chunying Li, Franco Giulianini, Simeon Häfliger, Vadim Bubes, Gunnar Raetsch, Samia Mora, Olga V Demler","doi":"10.1016/j.jacadv.2025.102162","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Despite clinical need, personalized risk scores for established atherosclerotic cardiovascular disease (ASCVD) are scarce.</p><p><strong>Objectives: </strong>The objective of the study was to develop and validate 10-year residual risk scores for cardiovascular death in patients with established ASCVD.</p><p><strong>Methods: </strong>Prospective observational cohort study. Models developed and validated in U.K. Biobank (UKB) (baseline 2006-2010; follow-up through 2021) and externally validated in Mass General Brigham cohort (MGB) (baseline 2007; follow-up through 2018). Analyzed on October 2022-February 2024. Eligible participants had established ASCVD. Guideline-based clinical factors plus additional biomarkers and self-reported health ratings.</p><p><strong>Primary outcome: </strong>10-year cardiovascular death. Elastic-net Cox and gradient-boosted tree models. C statistics and goodness-of-fit assessed in holdout set.</p><p><strong>Results: </strong>UKB: 32,994 participants (mean age 61; 11,727 [35.5%] women; 2,660 [8.0%] cardiovascular deaths), with 9,899 (30%) randomly selected as a holdout validation set. MGB: 54,969 patients (mean age 71; 22,738 [41.4%] women; 6,927 [12.6%] cardiovascular deaths). Median follow-up: 10 years (IQR 10-10) in UKB; 9.4 years (5-10) in MGB. We developed 2 residual risk scores, RRS16 and RRS24, incorporating 16 and 24 algorithmically selected factors. RRS16 used routinely available factors; RRS24 also included self-reported health and additional biomarkers. RRS16 achieved C statistics of 0.752 (95% CI: 0.736-0.768) in UKB and 0.750 (0.744-0.756) in MGB, outperforming the 2018 the American Heart Association (AHA) guideline model (0.658 [0.642-0.674] in UKB, 0.580 [0.574-0.586] in MGB). RRS24 achieved 0.784 (0.768-0.800) in UKB. Both models well calibrated (P > 0.1). RRS16 calculator: https://mora.bwh.harvard.edu/rrs16/.</p><p><strong>Conclusions: </strong>RRS16 and RRS24 outperformed AHA guideline model in estimating the residual risk in patients with established ASCVD. Both are clinically applicable but require further validation in diverse populations.</p>","PeriodicalId":73527,"journal":{"name":"JACC advances","volume":"4 11 Pt 1","pages":"102162"},"PeriodicalIF":0.0000,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JACC advances","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.jacadv.2025.102162","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Despite clinical need, personalized risk scores for established atherosclerotic cardiovascular disease (ASCVD) are scarce.
Objectives: The objective of the study was to develop and validate 10-year residual risk scores for cardiovascular death in patients with established ASCVD.
Methods: Prospective observational cohort study. Models developed and validated in U.K. Biobank (UKB) (baseline 2006-2010; follow-up through 2021) and externally validated in Mass General Brigham cohort (MGB) (baseline 2007; follow-up through 2018). Analyzed on October 2022-February 2024. Eligible participants had established ASCVD. Guideline-based clinical factors plus additional biomarkers and self-reported health ratings.
Primary outcome: 10-year cardiovascular death. Elastic-net Cox and gradient-boosted tree models. C statistics and goodness-of-fit assessed in holdout set.
Results: UKB: 32,994 participants (mean age 61; 11,727 [35.5%] women; 2,660 [8.0%] cardiovascular deaths), with 9,899 (30%) randomly selected as a holdout validation set. MGB: 54,969 patients (mean age 71; 22,738 [41.4%] women; 6,927 [12.6%] cardiovascular deaths). Median follow-up: 10 years (IQR 10-10) in UKB; 9.4 years (5-10) in MGB. We developed 2 residual risk scores, RRS16 and RRS24, incorporating 16 and 24 algorithmically selected factors. RRS16 used routinely available factors; RRS24 also included self-reported health and additional biomarkers. RRS16 achieved C statistics of 0.752 (95% CI: 0.736-0.768) in UKB and 0.750 (0.744-0.756) in MGB, outperforming the 2018 the American Heart Association (AHA) guideline model (0.658 [0.642-0.674] in UKB, 0.580 [0.574-0.586] in MGB). RRS24 achieved 0.784 (0.768-0.800) in UKB. Both models well calibrated (P > 0.1). RRS16 calculator: https://mora.bwh.harvard.edu/rrs16/.
Conclusions: RRS16 and RRS24 outperformed AHA guideline model in estimating the residual risk in patients with established ASCVD. Both are clinically applicable but require further validation in diverse populations.
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