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Metabolically healthy obese and incident cardiovascular disease events among 3.5 million men and women.
Open accessAbstract
Background Previous studies have been unclear about the cardiovascular risks for metabolically healthy obese individuals.Objectives This study examined the associations among metabolically healthy obese individuals and 4 different presentations of incident cardiovascular disease in a contemporary population.Methods We used linked electronic health records (1995 to 2015) in The Health Improvement Network (THIN) to assemble a cohort of 3.5 million individuals, 18 years of age or older and initially free of cardiovascular disease. We created body size phenotypes defined by body mass index categories (underweight, normal weight, overweight, and obesity) and 3 metabolic abnormalities (diabetes, hypertension, and hyperlipidemia). The primary endpoints were the first record of 1 of 4 cardiovascular presentations (coronary heart disease [CHD], cerebrovascular disease, heart failure, and peripheral vascular disease).Results During a mean follow-up of 5.4 years, obese individuals with no metabolic abnormalities had a higher risk of CHD (multivariate-adjusted hazard ratio [HR]: 1.49; 95% confidence interval [CI]: 1.45 to 1.54), cerebrovascular disease (HR: 1.07; 95% CI: 1.04 to 1.11), and heart failure (HR: 1.96; 95% CI: 1.86 to 2.06) compared with normal weight individuals with 0 metabolic abnormalities. Risk of CHD, cerebrovascular disease, and heart failure in normal weight, overweight, and obese individuals increased with increasing number of metabolic abnormalities.Conclusions Metabolically healthy obese individuals had a higher risk of coronary heart disease, cerebrovascular disease, and heart failure than normal weight metabolically healthy individuals. Even individuals who are normal weight can have metabolic abnormalities and similar risks for cardiovascular disease events.
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“This subgroup, while sometimes characterized as metabolically healthy due to the lack of prevalent disease, is at elevated risk of developing diabetes and other cardiometabolic conditions compared with individuals without obesity.4,5,6,7”
From Factors Associated With Semaglutide Initiation Among Adults With Obesity (2025) · cites this paper as [4]
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“Evidence has shown that metabolically healthy obese subjects display higher risk of coronary heart disease, cerebrovascular disease, and heart failure when compared to normal weight metabolically healthy individuals [19].”
Cai, N., Zhang, L., Ding, S., Tian, X., Mo, L., & Yu, B. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1617929 · Cited by 3
Rozenbaum, Z., Klein, E., Cohen, T., Nir, S., Pereg, D., & Shuvy, M. (2019) · European Heart Journal Acute Cardiovascular Care · doi:10.1177/2048872619825569 · Cited by 3
Sørensen, E. W., Gelpi, M., Knudsen, A. D., Benfield, T., Mocroft, A., & Nielsen, S. D. (2021) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0000000000002802 · Cited by 3
Longitudinal Trends in Body Mass Index for Adults with Congenital Heart Disease
Misra, A., Balakrishnan, P. L., Mewada, A., Singla, M., Singh, G. K., & Aggarwal, S. A. (2021) · Pediatric Cardiology · doi:10.1007/s00246-021-02753-4 · Cited by 3
Cabriales, E. C. G., Rodríguez-Ayala, E., Laviada‐Molina, H., Nava‐González, E. J., Salinas-Osornio, R. A., Orozco, L., Leal‐Berumen, I., Castillo-Pineda, J. C., Gonzalez-Lopez, L., Escudero‐Lourdes, C., et al. (2021) · Biology · doi:10.3390/biology10121342 · Cited by 4
“In order to clasify our 124 SF subjects as metabolically healthy, we used well-defined criteria: absence of abdominal obesity based on waist circumference, absence of metabolic syndrome components, normal lipid values, normal fasting glucose concentrations, normal C-reactive protein concentrations and absence of IR as…”
MethodChen, M., Chen, Q., Liu, W., Tong, H., & Wu, Y. (2022) · PubMed Central · Cited by 3
Pan, J. H., Wang, Z., Dong, C., Yang, B., Tang, L., Jia, P., Yang, S., & Zeng, H. (2022) · BMC Public Health · doi:10.1186/s12889-022-14253-y · Cited by 3
Fan, H. X., Zhang, P., Liu, Z., Zhao, R., Suo, C., Chen, X., & Zhang, T. (2023) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2022.00214 · Cited by 3
Zhang, Y., Fan, X., Zhao, C., Yuan, Z., Cheng, Y., Wu, Y., Han, J., Yuan, Z., Zhao, Y., & Lu, K. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1116307 · Cited by 3
“Our analysis demonstrated the cumulative effect of metabolic risk factors numbers on the risk of MM readmission, which was supported by previous studies (39).”
ResultПостоева, А. В., Dvoryashina, I. V., Kudryavtsev, A. V., & Александрович, П. В. (2023) · Obesity and metabolism · doi:10.14341/omet12926 · Cited by 3
The role of protein kinase D (PKD) in obesity: Lessons from the heart and other tissues.
Renton, M. C., McGee, S. L., & Howlett, K. F. (2024) · Biochimica et biophysica acta. Molecular cell research · doi:10.1016/j.bbamcr.2024.119814 · Cited by 1
Xu, R., Wang, C., Cong, H., & Wang, L. (2025) · Endocrine · doi:10.1007/s12020-025-04169-z · Cited by 3
Biomarkers of Cardiovascular Risk in Obese Women and their Relationship with Zinc Status
Severo, J. S., Morais, J. B. S., Beserra, J. B., Cruz, K. J. C., de Oliveira, A. R. S., dos Santos, L. R., Neto, E. M. D. M., de Macedo, G. F. S., Freitas, B. D. J. E. S. D. A., Henriques, G. S., et al. (2019) · Current Nutrition & Food Science · doi:10.2174/1573401315666191125113128 · Cited by 3
Ferreira, F. G., Juvanhol, L. L., Silva‐Costa, A., & Longo, G. Z. (2020) · American Journal of Human Biology · doi:10.1002/ajhb.23425 · Cited by 3
“For example, there is variation in the risk of type 2 diabetes mellitus and cardiovascular disease among these phenotypes, with MUNW and MHO being considered as intermediate risk and MUO as the highest risk phenotype (Aung et al., 2014; Caleyachetty et al., 2017; Lassale et al., 2018).”
BackgroundThe missing link between inflammation and arterial stiffness among different metabolic phenotypes
Canpolat, A. G., Demir, Ö., Şahin, M., Emral, R., & Çorapçıoğlu, D. (2021) · International journal of clinical practice · doi:10.1111/ijcp.14727 · Cited by 1
Haverich, A., & Boyle, E. C. (2019) · Springer eBooks · doi:10.1007/978-3-030-20245-3_2 · Cited by 4
Yan, Y., Wan, Y., Fan, Z.-P., Gao, X., An-li, J., & Xu, R. (2020) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-020-00847-1 · Cited by 3
Can Obesity and Health Coexist?
Metcalf, K. (2019) · Nutrition Today · doi:10.1097/nt.0000000000000328 · Cited by 3
Oh, J. K., Seo, Y., Hwang, W., Lee, S., Yoon, Y., Kim, K., Park, H. W., Roh, J., Lee, J., & Kim, M. (2025) · Journal of Obesity & Metabolic Syndrome · doi:10.7570/jomes24027 · Cited by 2
An Acupoint Catgut-embedding Therapy for Treating Obesity
Tang, S., Zeng, Y., Zhu, C., Tang, C., & Ma, Z. (2025) · Journal of Visualized Experiments · doi:10.3791/68071 · Cited by 2
Zhao, C., Yang, Y., Yang, Y., Yang, W. H., Mu, L., & Jia, Y. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1608603 · Cited by 2
Work-Related Disorders in Public Transportation Drivers and the Length of Exposure
Popescu, F. G., Bolocan, C., Oancea, M., Drăgoi, I. I., Herisanu, N. A., Oancea, C., Kundnani, N. R., Handra, C. M., Oțelea, M. R., & Surducan, D. A. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14145018 · Cited by 2
Mohammed, A. S., Ahmed, H., Singh, S., Munguti, C., Subramanian, L., Srikanth, S., Kodali, L. S. M., Takagi, M. A., Yasmeen, U., Imtiaz, H., et al. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14155495 · Cited by 2
Bakija, F. Z., Tolvaj, M., Szijártó, Á., Tokodi, M., Ferencz, A., Lakatos, B. K., Ladányi, Z., Kiss, L. Z., Szelid, Z., Soós, P., et al. (2025) · International Journal of Obesity · doi:10.1038/s41366-025-01863-w · Cited by 2
Dong, L., Wang, Y., Ji, D., Shen, Z., Xu, J., Sun, G., Qiu, S., Xu, J., & Guo, H. (2025) · Journal of the American Heart Association · doi:10.1161/jaha.124.037010 · Cited by 2
How is obesity defined? Moving beyond the limitations of current measures to redefine obesity
Chang, A., Cyr, A. M., Weintraub, S. F., Rege, R. M., Myerson, M. L., & Hirsh, B. J. (2026) · Journal of clinical lipidology · doi:10.1016/j.jacl.2025.10.057 · Cited by 2
Metadata
- Authors
- Caleyachetty, R., Thomas, G. N., Toulis, K. A., Mohammed, N., Gokhale, K. M., Balachandran, K., & Nirantharakumar, K.
- Affiliations
- University of Birmingham (GB)
- 424 General Military Hospital (GR)
- Corresponding author
- Thomas, G. Neil
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 70
- Issue
- 12
- Pages
- 1429-1437
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2755267305
- Cited by
- 574
- References
- 37
- Citations by year
- 2026: 48 · 2025: 65 · 2024: 73 · 2023: 60 · 2022: 71 · 2021: 68 · 2020: 66 · 2019: 51 · 2018: 64 · 2017: 8
- FWCI
- 40.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (publishedVersion, cc-by-nc-nd)
- Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
- Funders
- Medical Research Council (MC_PC_15079)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- metabolically healthy obesity, cardiovascular risk, coronary artery disease, cerebrovascular disease, heart failure, peripheral vascular disease, body mass index, metabolic abnormalities, diabetes mellitus, hypertension, hyperlipidemia, normal-weight individuals
- MeSH terms
- Adult, Cardiovascular Diseases, Female, Humans, Male, Middle Aged, Obesity, Prospective Studies, Incidence, Risk Assessment
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