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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\u20139\u2009years using the PREVENT equations, enabling shorter-term risk prediction for research purposes or to facilitate clinical trial enrollment. Over 5.1\u2009years 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.<\/jats:p>","DOI":"10.1038\/s41591-026-04437-z","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T08:16:09Z","timestamp":1777968969000},"page":"2629-2638","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Multinational validation of the PREVENT and SCORE2 cardiovascular risk equations across 6.4 million individuals"],"prefix":"10.1038","volume":"32","author":[{"given":"Brendon L.","family":"Neuen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupert W.","family":"Major","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4430-6023","authenticated-orcid":false,"given":"Morgan E.","family":"Grams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Sang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4598-0669","authenticated-orcid":false,"given":"Josef","family":"Coresh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7547-3764","authenticated-orcid":false,"given":"Shoshana H.","family":"Ballew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Surapaneni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Alencar de Pinho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"\u00c4rnl\u00f6v","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Arnott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9100-1575","authenticated-orcid":false,"given":"Samira","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarett","family":"Berry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-1572","authenticated-orcid":false,"given":"Hermann","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Ciemins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander R.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7871-6143","authenticated-orcid":false,"given":"Mary","family":"Cushman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"de Lemos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5192-5212","authenticated-orcid":false,"given":"Juan Miguel","family":"Diaz-Tocados","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo E.","family":"Farjat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Fletcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3223-0906","authenticated-orcid":false,"given":"Ron T.","family":"Gansevoort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J. 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It is now available under a Creative Commons Attribution 4.0 International license, CC-BY, \u00a9 The Author(s). The error has been corrected in the online version of the article.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"B.L.N. is supported by grants from the Australian National Health and Medical Research Council, the Medical Research Future Fund, New South Wales Health and the Ramaciotti Foundation. He has received fees for travel and publication support, advisory boards, scientific presentations and steering committee roles from AstraZeneca, Alexion, Bayer, Boehringer Ingelheim, Cornerstone Medical Education, CSL Behring, CSL Seqirus, the Limbic, Medscape, Menarini, MJH Life Sciences, Novo Nordisk, Otsuka, Travere Therapeutics and Vera Therapeutics. R.W.M. is supported by grants from the National Institute for Health and Care Research and, previously, Kidney Research UK. He has received fees for travel, subsistence and scientific presentations from AstraZeneca, Bayer and Boehringer Ingelheim. J.A. has received lecture fees from AstraZeneca, Novartis and Boehringer Ingelheim and served on advisory boards for AstraZeneca and Boehringer Ingelheim, all unrelated to the present work. N.A.d.P has received grants from the French National Research Agency, the French Ministry of Higher Education and Research, with GlaxoSmithKline (GSK), Boehringer Ingelheim France, Novo Nordisk and Fresenius Medical Care. M.C. has research support from the Argosy Foundation. J.A.d.L. reports fees for participation in data monitoring committees from AstraZeneca, Novo Nordisk, Eli Lilly, Merck, Regeneron, Amgen and Verve Therapeutics. C.P.K. received honoraria from Abbott, Akebia, AstraZeneca, Bayer, Boehringer Ingelheim and Renubus, and royalties from UpToDate and Springer, unrelated to the present work. J.M.V. is supported by grants from the Spanish Instituto de Salud Carlos III (PI21\/01099, PI24\/00408, PMP21\/00109 and PMP22\/00033), the RICORS 2040 program (RD24\/0004\/0015), the Diputaci\u00f3 de Lleida and the European Commission EP PerMed (EU-Calprotect). He has received fees for scientific presentations from Vifor Fresenius Medical Care. C.S. has nothing to disclose. B.M.P. serves on the steering committee of the Yale Open Data Access Project, funded by Johnson & Johnson. He received funding from a National Institutes of Health grant (HL105756). P.A.K. is supported by grants from CSL Vifor, and he has received speaker\/lecture fees from AstraZeneca, Novartis, CSL Vifor, Pharmacosmos and Medice. M.W. is a consultant to Perisphere. H.B. has nothing to disclose. J.G.M. has received grants from the National Council for Scientific and Technologic Development (CNPq-Brazil), the Foundation of Support for Research (Esp\u00edrito Santo State (Fapes)\/Brazil) and the Brazilian Ministry of Health (MS\/Decit). K.R.P. has nothing to disclose. F.K. has nothing to disclose. C.A. has received grants\/funding from the Australian National Health and Medical Research Council, the Medical Research Future Fund and New South Wales Health. She has received hononaria or sat on advisory boards\/steering committees for AstraZeneca and Novo Nordisk. J.S.L. has received personal lectureship honoraria from AstraZeneca and consulting fees from Boehringer Ingelheim, outside the present work. A.R.C. is supported by grants from Boeringer Ingelheim, Novartis and the National Kidney Foundation. He has received fees for participating on an advisory board for Amgen. A.E.F. is an employee of Bayer BV. P.S. is an employee of Bayer AG. H.J.L.H. has served as a consultant for AstraZeneca, Alexion, Amgen, Bayer Pharmaceuticals, Boehringer Ingelheim, Dimerix, Eli Lilly, Janssen, Merck, Novartis, Novo Nordisk, Roche and Travere Therapeutics and has received grant support from AstraZeneca, Boehringer Ingelheim, Janssen and Novo Nordisk. W.G.H. has received funding in the form of grants from Boehringer Ingelheim and Eli Lilly and fellowship funding from the UK Medical Research Council and Kidney Research UK. He follows a long-term departmental policy to decline honoraria from the drug and food industry, except for reasonable travel expenses for meetings. N.S. has received funding in the form of grants from Boehringer Ingelheim, Eli Lilly and Novo Nordisk. She follows a long-term departmental policy to decline honoraria from the drug and food industry, except for reasonable travel expenses for meetings. S.B. has received consultancy fees from AstraZeneca, GlaxoSmithKline, Novo Nordisk and Stada UK, and research funding from AstraZeneca. J.C. is on the scientific advisory board for Healthy.io with equity ownership. The remaining authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}