Prospective Associations of Obesity and Obesity Severity With 9 Cardiovascular Outcomes: The Cross-Cohort Collaboration
Year: 2026
Type: article
Abstract: BACKGROUND: Obesity is an established risk factor for cardiovascular disease (CVD); however, the overall and sex-specific relationships across the full spectrum of body mass index (BMI), particularly severe obesity defined as class 2 (BMI 35 to <40.0 kg/m 2 ) and class 3 (BMI ≥40 kg/m 2 ), and long-term CVD outcomes remain incompletely described. METHODS: We included 289 875 participants (mean age, 60.3 years; 79.2% women) from 21 cohorts of the Cross-Cohort Collaboration enrolled between 1948 and 2015 with harmonized BMI data, a BMI ≥18.5 kg/m 2 , and at least one of nine adjudicated outcomes: time to first fatal and non-fatal myocardial infarction (MI), fatal and nonfatal stroke, heart failure (HF), atrial fibrillation (AF), total coronary heart disease (CHD), total CVD, CHD mortality, CVD mortality, and all-cause mortality. Multivariable Cox proportional hazard models with restricted cubic splines were used to estimate the hazard ratio (HR) of BMI for each outcome, adjusting for demographic and clinical risk factors. RESULTS: Over 19.2 median years (25th, 11.6; 75th, 23.5 percentile) of follow-up, there were a total of 15 542 incident MI events, 15 467 incident stroke events, 14 172 incident HF events, 9066 diagnosed AF, and 113 918 total deaths, of which 14 647 were CHD-related and 28 879 were CVD-related. Overall, compared with individuals with normal weight, those with class 2 and class 3 obesity had the highest risk of HF (HR, 2.1, 95% CI, 2.0–2.3, and HR, 3.0, 95% CI, 2.7–3.2, respectively) and AF (HR, 1.8, 95% CI 1.7–2.0, and HR, 2.8, 95% CI, 2.5–3.1, respectively). Compared with men, women experienced higher relative increases in the risk associated with severe obesity for outcomes stroke, CVD, and all-cause mortality (P for interaction: <0.001, 0.003, and <0.001, respectively). Furthermore, in men, no increase in stroke risk was observed with higher BMI categories (P trend=0.49), whereas in women, the risk of stroke plateaued across obesity subclasses (compared with normal weight) yet remained significantly increased. CONCLUSIONS: Higher BMI was robustly associated with increased risk for most outcomes, particularly HF and AF, even after adjusting for traditional risk factors. Observed sex differences in the relative hazard of higher BMI categories and stroke, total CVD, and all-cause mortality suggest potential differences in underlying biological mechanisms.
Source: Circulation
Authors: Zeina A. Dardari, Zhiqi Yao, Jianjun Zhang, Giorgos Bakoyannis, Hongmei Nan, Lisa K. Staten, Kunal K. Jha, Erfan Tasdighi, Yara Jelwan, Semenawit Burka, Kunihiro Matsushita, Eleanor M. Simonsick, Joao A.C. Lima, Bruce M. Psaty, Debbie L. Cohen, Lawrence J. Appel, Amit Khera, Amil M. Shah, Michael E. Hall, Suzanne E. Judd, Shelley A. Cole, Ramachandran S. Vasan, Emelia J. Benjamin, Peggy M. Cawthon, Eric Orwoll, Michael J. LaMonte, Charles B. Eaton, Samar R. El Khoudary, Rebecca C. Thurston, Carol A. Derby, Paulo A. Lotufo, Isabela M. Bensenor, Márcio Sommer Bittencourt, Michael J. Blaha
Institutions: Johns Hopkins University, Johns Hopkins Medicine, Indiana University Indianapolis, Indiana University – Purdue University Indianapolis, University of Louisville, Rutgers New Jersey Medical School, National Institute on Aging, University of Washington, University of Pennsylvania, The University of Texas Southwestern Medical Center, American Heart Association, University of Mississippi Medical Center, University of Alabama at Birmingham, Texas Biomedical Research Institute, Boston University, Boston Medical Center, University of California, San Francisco, California Pacific Medical Center, Oregon Health & Science University, University at Buffalo, State University of New York, Brown University, University of Pittsburgh, Albert Einstein College of Medicine, Universidade de São Paulo, Hospital Universitário da Universidade de São Paulo, University of Pittsburgh Medical Center
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: American Diabetes Association, Donald W. Reynolds Foundation, American Heart Association, Hartford Foundation for Public Giving, Eli Lilly and Company, AstraZeneca, Kaiser Permanente, University of Pennsylvania, Jackson State University, Johns Hopkins University, Deutsches Krebsforschungszentrum, Georgia Clinical and Translational Science Alliance, Mississippi State Department of Health, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Novo Nordisk, Financiadora de Estudos e Projetos, Ministério da Saúde, Idorsia Pharmaceuticals, National Institutes of Health, Genentech, University of Illinois at Urbana-Champaign, Perelman School of Medicine, University of Pennsylvania, University of California, San Francisco, Michigan Institute for Clinical and Health Research, Clinical and Translational Science Collaborative of Cleveland, School of Medicine, Case Western Reserve University, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Nursing Research, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities
Awards: G100949702, G1022778538, G1060671437, G1083180012, Cardiovascular Disease in Sioux Indians, G1093951984, G1122870748, G1261793039, MESA, Gender differences in Bone Loss and Incident Fractures, G1269631540, CORONARY HEART DISEASE AND STROKE, G1276754516, G1286721212, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G1294553593, G1295889178, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-FIELD CENTER, G1327449000, G1343185973, Study of Osteoporotic Fractures, G1412221515, G1415733790, VCID and Stroke in a Bi-racial National Cohort, Osteoporotic Fractures in Men (MrOS) - Minneapolis, G1508998135, The Strong Heart Study, Phase V, G1539384734, G1540916838, UT Southwestern Center for Translational Medicine (UL1/KL2/TL1), Study of Women's Health Across the Nation (SWAN) V: UCLA Site, Study of Women's Health Across the Nation (SWAN) V: Chicago site, CORONARY HEART DISEASE AND STROKE, Clinical and Translational Science Institute, CVD in American Indians Biomarker lab and Arizona Field Center, G1711244518, G1729544734, G1730507467, G1735617348, American Indian Chronic Renal Insufficiency Cohort Study (AI-CRIC), G1815451664, Wake Forest Clinical and Translational Science Award, Long term fracture risk and change in peripheral bone in the oldest old men: The MrOS study, Study of Women's Health Across the Nation (SWAN): New Jersey, G197956372, G198381471, Study of Osteoporotic Fractures, Osteoporatic Fractures in Men (MrOS), G2059393314, SUBCLINICAL CARDIOVASCULAR DISEASE COORDINATING CENTER, Rare variants and NHLBI traits in deeply phenotyped cohorts, G2221742881, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G2261104027, G2375109747, G2391309017, G2415573643, MESA, SWAN Genomic Analyses and SWAN Legacy, G2545476352, Continuation of the Chronic Renal Insufficiency Cohort (CRIC) Study, G2577056464, G2585438117, G2600980409, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, G265762973, G2726417417, G2733059257, G278200998, G2809357584, G2815873878, G2837638605, Strong Heart Family Study, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--EBCT READING, G3000461242, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, G3057025668, G3106377335, MORTALITY FOLLOW-UP AND ANALYSES OF MEN IN THE MRFIT, Cardiovascular Evaluation for the SHS Phase V, Prospective meta-analyses of drug-gene interactions: CHARGE GWAS consortium, Study of Women's Health Across the Nation (SWAN) V: Coordinating Center, G3340927746, G3395997892, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G3501419682, G350245564, CHS research resources for the cardiovascular health of older adults, G3570589137, Osteoporotic Fractures in Men (Mr. Os) Palo Alto, G3595232572, The Study of Women's Health Across the Nation (SWAN): The Impact of Midlife and the Menopause Transition on Health and Functioning in Early Old Age, G37449730, G3761253218, G3771679604, G3779191537, MESA, G3860090032, G3903846675, G3943721533, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, G4014515226, G40762112, G4086764833, CVD in American Indians Genetics Center, Study of Women's Health Across the Nation (SWAN) V: Central Laboratory, G4222455271, EPIDEMIOLOGY OF NIDDM AND CVD IN THREE ETHNIC GROUPS, Study of Osteoporotic Fractures, G4309390892, CVD in American Indians Study and Data Management Center and OK Field Center, G4521137762, Osteoporotic Fractures in Men (MrOS) - Administrative Center, G4532643769, G4563812999, G4590187187, G4670072506, Study of Osteoporotic Fractures, G4711807797, Study of Osteoporotic Fractures (SOF)-Pittsburgh Clinic, G4846672139, OPTION 3. 4/1/2014 - 3/31/2015. MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA) - READING CENTER, NHLBI, G4897018079, G4976486911, G5108002584, G5140077856, G514410172, G5211184526, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-ULTRASOUND, G5249188777, GENDER DIFFERENCES IN OSTEOPOROSIS, G5342184217, G537455924, G5478822001, CVD in American Indians: Imaging and Cardiovascular Center, G5586061334, G5601305071, G5605591545, G562502316, G5654179670, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G579045871, G5805320778, G581554933, CHARGE consortium: omics discovery for CVD and aging phenotypes, G5931204509, CHS Events Follow-up Study, G6093314662, G6156766399, G6401035755, Institute for Clinical and Translational Research, The Framingham Heart Study, MESA, G642672552, G6571475356, G6593263942, G6624517043, Osteoporotic Fractures in Men (Mr.OS), G670738241, G6717867015, CHS-Transition Phase, G6742279884, Osteoporotic Fractures in Men (MrOS) - San Francisco Coordinating Center, G6761056355, G67735801, Study of Osteoporotic Fractures, Study of Women's Health Across the Nation (SWAN V): Michigan Site, G697098563, Osteoporotic Fractures in Men (MrOS) - Portland, G7066455283, G7091571603, MORTALITY FOLLOW-UP AND ANALYSIS--MRFIT RANDOMIZED MEN, STUDY OF WOMEN'S HEALTH ACROSS THE NATION (SWAN) V: UC DAVIS/KAISER, G7160016285, G7365228695, G7399262704, G742032275, Osteoporotic Fractures in Men_MrOS Renewal_Birmingham, G751309980, G7526106616, Institute for Clinical and Translational Research, Exceptional Survival: Trajectories to Functional Aging (CHS All Stars), CVD in American Indians The Dakota Field Center, G7706274302, CVD Predictors of Cognitive Function Trajectory over 20 Years, G78770644, G7958222963, Clinical and Translational Science Award, G8287218166, G842756795, Clinical and Translational Science Collaborative of Cleveland, Study of Women's Health Across the Nation(SWAN) V: Pittsburgh, G861947890, 4 of 4: Study of Osteoporotic Fractures (SOF), G8660623442, G867112777, G8676708184, G8683204365, G87163782, G89699440, Cardiovascular Disease in Pima Indians, G9000004549, G9000017360, G9000035636, G9000036570, G9000037139, G9000053383, G9000063950, G9000064938, G9000089129, G9000135092, G9000274598, G9000281326, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases, RURAL: Risk Underlying Rural Areas Longitudinal Cohort Study, Prospective renal insufficiency cohort evaluation: PRICE, Oregon Clinical and Translational Research Institute, Infrastructure for mentored access to CHS data and specimens, Continuation of the University of Illinois Chicago CRIC Clinical Center, Limited Competition for the Continuation of the Chronic Renal Insufficiency Cohort (CRIC) Hopkins Clinical Center, Tulane Clinical Center for Chronic Renal Insufficiency Cohort Study, Chronic Renal Insufficiency Cohort (CRIC) Study, Study of Women's Health Across the Nation - V, G992700738
OpenAlex ID: W7128728825