Darryl P LeongRita YusufRomaina IqbalAlvaro AvezumAfzalhussein YusufaliAnnika RosengrenJephat ChifambaFernando LanasMaria Luz DiazJ Jaime MirandaKairat DavletovErkin MirrakhimovKaren YeatesRasha KhatibKhalid F AlhabibSadi GulecMaria José PaucarJose Patricio Lopez-LopezViswanathan MohanRajeev GuptaBiju SomanP V M LakshmiPaul PoirierKoon TeoKatarzyna ZatonskaNafiza Mat-NasirGalina ArtamonovaBo HuZhiguang LiuXiaoyun LiuAntonio DansSumathy RangarajanSalim YusufMaria Luz DiazAgustina GalatteMauricio SalvadorMaria Soledad HerreraSabrina BellottiSilvana Di BenedettiSilvia BérgamoMohammad O RahmanRita YusufSyed AKS AhmedAfreen Z KhanNazratun NayeemMira MitraShahidul IslamFuad PashaAlvaro Avezum JuniorPrecil Diego Miranda NevesRafael Amorim Belo NunesLarissa Oliveira SantosLidiane Fatima Assis SilvaThais Paula PioClaudia MalerbaScott LearMeghan MacLeodErica CorberVeronica de JongIna VukmirovichDanijela GasevicVaven GhagAzlan Nur SaidyRochelle NocosJasmine LimKaren SuarezBrianna NasrallahHassan MirAndreas WielgoszPaul PoirierMarie-Eve PichéTomas CiezaGinette TurbideMyriam PettigrewAnne-Sophie BourlaudSumathy RangarajanKoon TeoSonia AnandClara ChowMartin O'DonnellErica SmithAndrew MenteDarryl LeongAndrew SmythPhilip JosephMyLinh DuongAditya KhetanHarry KlimisRussell D'SouzaVictoria MillerMarjan Walli-AttaeiShofiqul IslamChinthanie RamasundarahettigeShrikant BangdiwalaKumar BalasubramanianGloria WongNishitha JeyachandradhasXiumei YangCissy TangLeslie FaragoMartin ZarateJerad GodreaultMark HaskinsMahesh JethvaDat Nguyen-QuangAndrew PineauGianluca RigitanoAshish VaghelaMahshid DehghanAlannah AlibertiAyah ZakiDawn AgapayKaran ChryslerDavid KrolFathimath ShifalyJacqueline RimacMonica JakymyshynMaha MushtahaNazar KandyRoxanna SolanoSudha GopalShameena RamachamNobu ShimizuTina TonganaFernando T LanasPamela J SerónMaría J OliverosJéssica I HidalgoYasmín G PalaciosBenjamín E RuizCamilo A AcostaLisheng LiuWei LiBo HuLu YinJun ZhuYan LiangYi SunYang WangQing DengXingyu WangXiaoru ChengChuangshi WangSidong LiWeida LiuXinyue LangZhiguang LiuShelly LA TseGuoliang HanFanghong LuYan HouXiaoyang LiaoDi ChenPeng ZhangNing LiRensheng LeiMinfan FuYu LiuXiaojie XingYouzhu YangQuanyong XiangJinhua TangZhengrong LiuDeren QiangAiying HanJinkui YangXinbin WuChunmei LiuGuomin HeQian ZhaoAobulikasimu ResalaitiHui WangYahong ZhiYali WangYuanting MaHaibing MaLihua HuLi ZhangGuoqing LiuJunying WangHui JinKai YouTao PengJing SuYingxin ZhaoPatricio Lopez-JaramilloMaritza Perez-MayorgaJohanna Otero-WandurragaPaul Anthony CamachoCarlos Cure-CureMiguel Urina-TrianaAlfonso CampoEdgar ArcosClaudia NarvaezAristides SotomayorDoris GomezHenry GarciaManuel Urina-TrianaGregorio Sanchez-Vallejo,Gregorio Sanchez-VallejoJose Patricio Lopez-LopezMaria Angelica MuñozOlga Lucia BelloTatiana VasquezMonica NiñoShislem RodriguezMaria Camila CampoFELIX GALLEGOS, CAMILO EDGAR VINICIOCAMILO EDGAR VINICIOFELIX GALLEGOSMavel Lopez-FlecherMichelle VegaKatherine J. GrandaANDRANGO PAUCAR, KATHERINE VALENTINAKATHERINE VALENTINAANDRANGO PAUCARANDRANGO PAUCAR, SELENA ARACELYSELENA ARACELYANDRANGO PAUCARPrem K. MonyMario VazSumathi SwaminathanAnkalmadagu V. BharathiKiruba SankarAnura V. KurpadKrishnaswamy G. JayachitraNitesh KumarRaju AnthonyKaramala MuraliChengi BalajiKrishnappa AmaranadhPonnuswamy VijayalakshmiSirana SandhyaJennifer Jayaprakash DNalini Sharin ToppoNaveen JagadeeshanParvathi NarayanappaPooja H TelagaviViswanathan MohanRanjit Mohan AnjanaMohan DeepaKumar ParthibanLakshmanan DhanasekaranSundaram SureshkumarManivel NandhakumarDoss KalaivaniElumalai KarthickKakade VivekSanthappan VijaybaskarRajeev GuptaLalit Mohan SharmaIndu MohanRooma BhargavaMadhusudan SharmaDevendra SharmaRaman Kutty VelappallilVijayakumar KrishnapillaiSanjeev NairKamala RammohanManu Muraleedharan SarojiniThomas IypeVeena AmbilyArunlal Anitha Rajappan NairDivya SanthakumariJith SreeranganSucharitha KamalamRajesh KumarPinnaka Venkata Maha LakshmiManmeet KaurVivek SagarRitin MohindraRupali MahajanKamaldev SharmaRupinder SinghPinki BhattJyoti MauryaBabita ChauhanKamaldeep SinghRoya KelishadiNoushin MohammadifardAhmad BahonarKairat DavletovBatyrbek AssembekovMuktar KulimbetErkin MirrakhimovSaamay AbilovaErkaiym BektashevaYrysbek Mamat uuluMalik NabievRano ArapovaUmid ZakirovAzamat AsanbaevNursultan AsanalievNafiza Mat-NasirKean Kiet NgTengku Saifuddin Tengku IsmailAnis Safura RamliNorashikin Mohamed Noor KhanMazapuspavina Md YasinFarnaza AriffinMaizatullifah MiskanSuraya Abdul-RazakNik Munirah Nik Mohd-NasirNoorhida BaharudinMohamed Syarif Mohamed-YassinHasidah Abdul-HamidRazif DasimanBoon Peng HohFadhlina Ab MajidNajmin Abu BakarRasyidah SallehMardhiah BaharomSiti Radziah NorlizanNoor Azziana IsmailSarina AliChe Wan Juliana Che Wan JaafarAzmi Mohd TamilZALEHA MD ISAROSNAH ISMAILNoraidah SaianNurul Hafiza Ab Razaksiti norzulaikha rahimKhairul Hazdi YusofFARAH ADILLA FAUZINur Nadia MohamedFATIN AZIERAH FAUZInurul afifah jusohMohd Hasni JaafarNoorhassim ISMAILKhawar KazmiRehman KhawajaShehzad AliMuhammad AsimMohan JummaSana BachalNighat AlmasSafa NoreenUmaiyeh KhammashRasha KhatibRita GiacamanLia Aileen M. Palileo - VillanuevaAntonio L. DansMarc Evans M. AbatChareece Mae T. Zamora - PudolLouie P. PudolSheila Lyn P. PudolDiana Rose B. TubigKristine Joy C. TenorioCharlene C. AbaquinMary Stephanie M. MalayangJorissa A. BordeosKeenah S. SalvadorPaola Kristina S. GenosasClifford D. VillasNikki Fe Dominique C. GuereroAngelica N. DorillaGenoveva B. NethercottDante D. MoralesJose Donato A. MagnoLauren Kay M. EvangelistaLauro L. Abrahan IVDaniel Francisco T. MoralesKatarzyna ZatońskaAndrzej SzubaAlicja Basiak-RasałaKatarzyna Połtyn-ZaradnaTomasz ZatońskiMaria WołyniecDorota RóżańskaBożena Regulska-IlowRafał IlowMarta ManczukPawel MacekOlga L. BarbarashGalina V. ArtamonovaElena V. IndukaevaEvgeny D. BazdyrevDaria P. TsygankovaOlga V. NachratovaAlyena S. AgienkoKhalid F AlhabibMostafa AlshamiriHani AltaradiMonzir AbdulrahmanRehab NouriLanthe KrugerCristian RicciAndries F van OortSarah J MossMarlien PietersHerculina S KrugerElizabeth Catherina (Rina) SwartThandi PuoaneNasheeta PeerAndre KengneEstelle Victoria (Vicky) LambertNaomi (Dinky) LevittNelia SteynLungiswa TsholekileJuley de SmidtLloyd LeachEhimario IgumborBonaventure EgbujieAnnika RosengrenMarie AndreassonAnnica GustavssonJeanette Kembro JohanssonIng-Marie Jonsson LindgrenIda SegerqvistLisel WirdemanAnn-Louise HummelbladBruno F. SunguyaKaren E. YeatesNicola J. WestAytekin OguzSadi GulecAhmet TemizhanKubilay KarsidagYuksel AltuntasNese ImeryuzMirac Vural KeskinlerK. Burcu Tumerdem CalikOzge Telci CakliliA. Arzu AkalinMustafa KilickapAfzalhussein M YusufaliHamda H KhansahebMadiha H S AbdelmotagaliAlawi Alsheikh-AliTom LoneyMarwan ZidanDouaa F YoussefOlfat Z S AhmadEman F El-SayedMai H AwadallaSuad H AhmedJephat ChifambaTatenda L NcubeBrian J NcubeTavengwa G ManenjiNyasha G Chigariro2025-07-282025-07-282025-08https://doi.org/10.1016/S2214-109X(25)00155-XBackground: Current strategies to prevent adverse cardiovascular outcomes focus primary prevention in high-risk groups and secondary prevention in people with known cardiovascular disease. We aimed to determine the proportion of events occurring in lower-risk groups globally. Methods: We included people aged 40 years to younger than 75 years who were enrolled in the Prospective Urban Rural Epidemiology (PURE) study, which is an ongoing, international, prospective, population-based cohort study that started recruiting adults from households selected to be broadly representative of the sociodemographic composition of their communities. We prospectively documented fatal or non-fatal myocardial infarction, stroke, heart failure, or any other fatal cardiovascular event stratified by history of cardiovascular disease and by the 10-year predicted disease risk scores based on WHO 2019 laboratory risk tables (<10% [low], 10% to <20% [intermediate], and ≥20% [high]) in people without previous cardiovascular disease from 26 high-income, middle-income, and low-income countries. Outcome event rates were standardised for the cohort's age and sex distribution. Findings: Between July 11, 2000, and May 6, 2019, 128 973 participants were included from 26 countries (mean age 53·6 years [SD 8·2]; 75 858 [58·8%] were female and 53 115 [41·2%] were male). We observed 11 483 outcome events affecting 8·9% of the cohort during a median follow-up of 12·3 years (IQR 9·8–14·6). Among participants, 89 508 (69·4%) had a low cardiovascular disease risk, 22 363 (17·3%) had an intermediate cardiovascular disease risk, and 5529 (4·3%) had a high cardiovascular disease risk, while 11 573 (9·0%) had known cardiovascular disease. The age-standardised and sex-standardised cardiovascular disease incidence rates per 1000 person-years was 4·1 (95% CI 4·0–4·2) in the low-risk group, 17·7 (15·2–20·2) in the intermediate-risk group, and 40·8 (25·1–56·4) in the high-risk group. Overall, 41% of outcome events occurred in cardiovascular disease-naive participants at low risk. The proportion of adverse cardiovascular outcomes occurring in this low-risk group was inversely related to country income level (32% in high-income, 38% in middle-income, and 54% in low-income countries) and was higher in women (51%) than in men (32%). Interpretation: To achieve a substantial population-level reduction in cardiovascular disease, a fundamental change is needed, so that preventive strategies for cardiovascular disease extend beyond those at high or even intermediate predicted risk to include those at considered to be at low risk. Funding: The funding bodies are listed in the appendix (p 29).journal-article