Multinational validation of the PREVENT and SCORE2 cardiovascular risk equations across 6.4 million individuals

Neuen BL, Major RW, Grams ME, Sang Y, Coresh J, Ballew SH, Surapaneni A, Alencar de Pinho N, Ärnlöv J, Arnott C, Bell S, Berry J, Brenner H, Ciemins E, Chang AR, Cushman M, de Lemos JA, Diaz-Tocados JM, Farjat AE, Fletcher RA, Gansevoort RT, Heerspink HJ, Herrington WG, Hong C, Horwitz EJ, Hwang SJ, Jassal SK, Kalra PA, Katz R, Khan SS, Kovesdy CP, Kronenberg F, Lees JS, Lloyd-Jones DM, Mill JG, Naimark DM, Ndumele C, Polkinghorne KR, Psaty BM, Schloemer P, Shlipak MG, Shrestha P, Song Z, Staplin N, Steubl D, Vart P, Visseren FL, Woodward M, Yamagishi K, Young BA, Sabanayagam C, Valdivielso JM, Giedraitis V, Larsson A, Tangri N, Ascher SB, Vernooij RW, Baricevic-Jones I, Rengarajan S, Sinha S, Chinnadurai R, Landray M, Baigent C, Chong C, Zhang X, Xue C, Cheng CY, Ilori T, Cheung K, Gutierrez O, Sumida K, Rifkin D, Ix J, Bergstrom J, Medcalf JF, Brunskill NJ, Caus M, Martin-Conde ML, Bermudez-Lopez M, Cambray S, Lambourg E, Livingstone SJ, Palmer C, Pearson E, Saritas T, Schneider M, Bechtel-Walz W, Schultheiss UT, Judge P, Haynes R, Giatti L, de Almeida MdCC, Bensenor I, da Fonseca MdJM, Bracco P, Wang H, Niu M, Engelhard M, Pencina MJ, Shah A, Joshi P, Khera A, Ayers C, Rao P, Lash J, Chen J, Weir M, Perkovic V, Jardine M, Mahaffey KW, Metzger M, Stengel B, Massy Z, de Pinho NA, Iso H, Imano H, Muraki I, Neal B, Chadban S, Takada M, Li Y, Yatsuya H, Harris K, Chalmers J (2026)

Publication Type: Journal article

Publication year: 2026

Journal

DOI: 10.1038/s41591-026-04437-z

Abstract

The American Heart Association’s PREVENT equations estimate risk of total cardiovascular disease (CVD), atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF) to guide lipid-lowering and blood pressure-lowering therapy in people ages 30−79 years in the United States. The SCORE2 risk algorithm is used to estimate CVD risk for similar purposes in people ages 40 and older in Europe. Neither set of equations has been comprehensively validated in global observational cohorts and randomized trials. In this study, in 44 observational cohorts and 18 randomized trials, we assessed discrimination and calibration of the two risk algorithms across geographical regions (North America, Europe and Asia/Other or multiregional trials). We also created scaling factors for risk prediction over 1–9 years using the PREVENT equations, enabling shorter-term risk prediction for research purposes or to facilitate clinical trial enrollment. Over 5.1 years of mean follow-up, 293,737 PREVENT total CVD events (fatal and non-fatal ASCVD or HF) and 258,086 SCORE2 CVD events (myocardial infarction, stroke or cardiovascular death) were observed among 6,422,714 and 5,437,384 individuals, respectively. Despite differences in CVD outcome definitions, target populations and predictor variables, overall discrimination and calibration were similar for both equations, with generally good performance across regions, including in multiregional randomized trials. These findings lend support for adoption of PREVENT or SCORE2 for cardiovascular risk stratification across diverse settings.

Authors with CRIS profile

Involved external institutions

New York University (NYU) United States (USA) (US) University of Oxford United Kingdom (GB) Duke University United States (USA) (US) MetroHealth Medical Center United States (USA) (US) Framingham Heart Study United States (USA) (US) University of California, San Diego (UC San Diego, UCSD) United States (USA) (US) Salford Royal Hospital United Kingdom (GB) University of Washington United States (USA) (US) Northwestern University United States (USA) (US) The University of Tennessee Health Science Center United States (USA) (US) Medizinische Universität Innsbruck Austria (AT) University of Glasgow United Kingdom (GB) Boston University United States (USA) (US) Federal University of Espírito Santo / Universidade Federal do Espírito Santo (UFES) Brazil (BR) University of Toronto Canada (CA) Johns Hopkins University (JHU) United States (USA) (US) MonashHeart (formerly: Cardiology, Monash Medical Centre) Australia (AU) Bayer HealthCare AG Germany (DE) University of California San Francisco (UCSF) United States (USA) (US) Nagoya University / 名古屋大学 Japan (JP) Boehringer Ingelheim Pharma GmbH & Co. KG Germany (DE) University of Groningen / Rijksuniversiteit Groningen Netherlands (NL) Universiteit Utrecht (UU) / Utrecht University Netherlands (NL) University of New South Wales (UNSW) Australia (AU) University of Tsukuba / 筑波大学 Japan (JP) National University of Singapore (NUS) Singapore (SG) Institut de Recerca Biomèdica de Lleida (IRBLleida) Spain (ES) Uppsala University Sweden (SE) University of Manitoba Canada (CA) University Medical Centre Utrecht (UMC Utrecht) Netherlands (NL) Northern Care Alliance NHS Trust United Kingdom (GB) University of Leicester United Kingdom (GB) Research Center in Epidemiology and Population Health / Centre de recherche en Epidémiologie et Santé des Populations (CESP) France (FR) Karolinska Institute Sweden (SE) University of Dundee United Kingdom (GB) The University of Texas at Tyler (UTT) United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) American Medical Group Association (AMGA) United States (USA) (US) Geisinger Medical Center United States (USA) (US) University of Vermont United States (USA) (US) University of Texas Southwestern Medical Center (UT Southwestern) United States (USA) (US) Bayer AG Germany (DE) University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen Netherlands (NL) University of Alabama at Birmingham (UAB) United States (USA) (US) West Los Angeles VA Medical Center United States (USA) (US) Kindai University / 近畿大学 Japan (JP) Universitätsklinikum Aachen (UKA) Germany (DE) Universitätsklinikum Freiburg Germany (DE) Universidade Federal de Minas Gerais (UFMG) Brazil (BR) Oswaldo Cruz Foundation / Fundação Oswaldo Cruz (FIOCRUZ) Brazil (BR) University of São Paulo / Universidade de São Paulo (USP) Brazil (BR) Universidade Federal do Rio Grande do Sul (UFRGS) Brazil (BR) University of Michigan United States (USA) (US) University of Illinois at Chicago United States (USA) (US) University of Maryland Medical Center (UMMC) United States (USA) (US) University of Sydney (USYD) Australia (AU) Stanford University United States (USA) (US) Japan Institute for Health Security (JIHS) / 国立健康危機管理研究機構 Japan (JP)

How to cite

APA:

Neuen, B.L., Major, R.W., Grams, M.E., Sang, Y., Coresh, J., Ballew, S.H.,... Chalmers, J. (2026). Multinational validation of the PREVENT and SCORE2 cardiovascular risk equations across 6.4 million individuals. Nature Medicine. https://doi.org/10.1038/s41591-026-04437-z

MLA:

Neuen, Brendon L., et al. "Multinational validation of the PREVENT and SCORE2 cardiovascular risk equations across 6.4 million individuals." Nature Medicine (2026).

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