Improving 10-year cardiovascular risk prediction in apparently healthy people: flexible addition of risk modifiers on top of SCORE2

Steven Hj Hageman, Carmen Petitjean, Lisa Pennells, Stephen Kaptoge, Romin Pajouheshnia, Taavi Tillmann, Michael J Blaha, Robyn L McClelland, Kunihiro Matsushita, Vijay Nambi, Olaf H Klungel, Patrick C Souverein, Yvonne T van der Schouw, Wm Monique Verschuren, Nils Lehmann, Raimund Erbel, Karl-Heinz Jöckel, Emanuele Di Angelantonio, Frank Lj Visseren, Jannick An Dorresteijn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

AIMS: In clinical practice, factors associated with cardiovascular disease (CVD) like albuminuria, education level, or coronary artery calcium (CAC) are often known, but not incorporated in cardiovascular risk prediction models. The aims of the current study were to evaluate a methodology for the flexible addition of risk modifying characteristics on top of SCORE2 and to quantify the added value of several clinically relevant risk modifying characteristics.

METHODS AND RESULTS: Individuals without previous CVD or DM were included from the UK Biobank; Atherosclerosis Risk in Communities (ARIC); Multi-Ethnic Study of Atherosclerosis (MESA); European Prospective Investigation into Cancer, The Netherlands (EPIC-NL); and Heinz Nixdorf Recall (HNR) studies (n = 409 757) in whom 16 166 CVD events and 19 149 non-cardiovascular deaths were observed over exactly 10.0 years of follow-up. The effect of each possible risk modifying characteristic was derived using competing risk-adjusted Fine and Gray models. The risk modifying characteristics were applied to individual predictions with a flexible method using the population prevalence and the subdistribution hazard ratio (SHR) of the relevant predictor. Risk modifying characteristics that increased discrimination most were CAC percentile with 0.0198 [95% confidence interval (CI) 0.0115; 0.0281] and hs-Troponin-T with 0.0100 (95% CI 0.0063; 0.0137). External validation was performed in the Clinical Practice Research Datalink (CPRD) cohort (UK, n = 518 015, 12 675 CVD events). Adjustment of SCORE2-predicted risks with both single and multiple risk modifiers did not negatively affect calibration and led to a modest increase in discrimination [0.740 (95% CI 0.736-0.745) vs. unimproved SCORE2 risk C-index 0.737 (95% CI 0.732-0.741)].

CONCLUSION: The current paper presents a method on how to integrate possible risk modifying characteristics that are not included in existing CVD risk models for the prediction of CVD event risk in apparently healthy people. This flexible methodology improves the accuracy of predicted risks and increases applicability of prediction models for individuals with additional risk known modifiers.

Original languageEnglish
Pages (from-to)1705-1714
Number of pages10
JournalEuropean Journal of Preventive Cardiology
Volume30
Issue number15
Early online date2 Jun 2023
DOIs
Publication statusPublished - 26 Oct 2023

Keywords

  • Biomarkers
  • Cardiovascular
  • Coronary calcium score
  • Risk prediction
  • Risk stratification
  • SCORE2

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