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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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Inflammatory protein signatures in individuals with obesity and metabolic syndrome
Mir, F. A., Abdesselem, H., Cyprian, F. S., Iskandarani, A., Doudin, A., Samra, T. A., Alkasem, M., Abdalhakam, I., Taheri, S., & Abou‐Samra, A. (2023) · Scientific Reports · doi:10.1038/s41598-023-49643-8 · Cited by 22
Dong, S.-Y., Yan, S., Wang, M.-L., Li, Z.-B., Fang, L.-Q., & Zeng, Q. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.05.007 · Cited by 22
Manasse, S. M., Crochiere, R. J., Dallal, D. H., Lieber, E. W., Schumacher, L. M., Crosby, R. D., Butryn, M. L., & Forman, E. M. (2018) · Appetite · doi:10.1016/j.appet.2018.04.025 · Cited by 22
Differences between metabolically healthy and unhealthy obesity in PAI-1 level
Basurto, L., Sánchez, L., Díaz, A., Valle, M., Robledo, A., & Murillo, C. M. (2019) · Thrombosis Research · doi:10.1016/j.thromres.2019.06.013 · Cited by 22
Bonikowske, A. R., Barillas-Lara, M. I., Koepp, K. E., Medina‐Inojosa, J. R., Squires, R. W., López-Jiménez, F. A., & Olson, T. P. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8122147 · Cited by 23
Comparing ecological momentary assessment to sensor-based approaches in predicting dietary lapse
Crochiere, R. J., Zhang, F., Juarascio, A. S., Goldstein, S. P., Thomas, J. G., & Forman, E. M. (2021) · Translational Behavioral Medicine · doi:10.1093/tbm/ibab123 · Cited by 21
Wu, S., Hsu, L., Teng, M., Chou, H., & Ko, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084165 · Cited by 22
Trends in Metabolic Phenotypes According to Body Mass Index Among US Adults, 1999-2018
Liu, J., Zhang, Y., Lavie, C. J., & Moran, A. E. (2022) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2022.02.013 · Cited by 25
Corica, B., Romiti, G. F., Proietti, M., Mei, D. A., Boriani, G., Chao, T., Olshansky, B., Huisman, M. V., & Lip, G. Y. H. (2023) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2023.07.013 · Cited by 23
Barkas, F., Elisaf, M., Liberopoulos, E. N., Liamis, G. L., Ntzani, E., & Rizos, E. C. (2019) · Journal of Cardiology · doi:10.1016/j.jjcc.2019.02.009 · Cited by 21
“Likewise, although overweight/obesity has been considered to be related with IR, a considerable proportion of overweight/obese individuals, the so called ‘metabolically healthy obese’ patients who have normal FPG and TG levels, exhibit lower rates of metabolic complications than expected, such as new-onset T2D and car…”
BackgroundBae, Y. S., Choi, S., Lee, K., Son, J. S., Lee, H., Cho, M. H., Koo, H. Y., Cho, I. Y., Chang, J., Kim, K., et al. (2019) · Journal of the American Heart Association · doi:10.1161/jaha.118.011825 · Cited by 21
Othman, Z. A., Zakaria, Z., Suleiman, J. B., Nna, V. U., Romli, A. C., Ghazali, W. S. W., & Mohamed, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084225 · Cited by 21
Triple–Hormone-Receptor Agonist Retatrutide for Obesity
(2023) · New England Journal of Medicine · doi:10.1056/nejmc2310645 · Cited by 21
Rahmanian, K., Shojaei, M., & Sotoodeh-Jahromi, A. (2019) · Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy · doi:10.2147/dmso.s197476 · Cited by 16
“vascular disease and heart failure than normal weight MH individuals.(36) But, these outcomes in the MHO subjects are controversial.”
BackgroundLee, Y., Kim, D. H., Kim, S. M., Kim, N. H., Choi, K. M., Baik, S. H., Park, Y. G., Han, K., & Yoo, H. J. (2020) · Journal of Diabetes Investigation · doi:10.1111/jdi.13304 · Cited by 19
Oh, C., Park, J. H., Chung, H. S., Yu, J. M., Chung, W., Kang, J. G., & Moon, S. (2020) · Medicine · doi:10.1097/md.0000000000022036 · Cited by 20
“5 million people reported that MHO individuals had a higher risk of coronary artery disease, CVD, and HF.([18]) A recent meta-analysis of 19 studies reported that individuals with MHO were at a high risk of CVD.”
BackgroundInfluentialRifai, M. A., Kanaya, A. M., Kandula, N. R., Patel, J., Al-Mallah, M. H., Budoff, M. J., Cainzos‐Achirica, M., Criqui, M. H., & Virani, S. S. (2022) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2022.101105 · Cited by 20
“001 *Lp(a), mg/dL 17 (9-33) 16 (9-31) 19 (11-35) 0.”
Yuan, Y., Sun, W. Y., & Kong, X. (2022) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-022-00917-7 · Cited by 22
Paczkowska, K., Rachoń, D., Berg, A., Rybka, J., Kapczyńska, K., Bolanowski, M., & Daroszewski, J. (2023) · Nutrients · doi:10.3390/nu15194153 · Cited by 20
“Moreover, there are studies describing a lower risk of developing type 2 diabetes mellitus or cardiovascular disease among MHO patients, but, on the other hand, it is still higher than in metabolically healthy, normal-weight people [28].”
BackgroundAllostatic load and disordered white matter microstructure in overweight adults
Ottino‐González, J., Jurado, M. Á., García‐García, I., Segura, B., Marqués‐Iturria, I., Palacios, M. J. S., Tor, E., Prats-Soteras, X., Caldú, X., Junqué, C., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-34219-8 · Cited by 20
LDL-C:HDL-C ratio and common carotid plaque in Xinjiang Uygur obese adults: a cross-sectional study
Zhao, Q., Liu, F., Wang, Y.-H., Lai, H., Zhao, Q., Luo, J., Ma, Y.-T., Li, X., & Yang, Y. (2018) · BMJ Open · doi:10.1136/bmjopen-2018-022757 · Cited by 20
“Recent data demonstrated that obese individuals who were even metabolically healthy had a higher risk of CVD including coronary artery disease (CAD), heart failure and cerebrovascular disease compared with the normal-weight metabolically healthy individuals.(6) Obesity has been identified as an independent risk factor…”
BackgroundJohnson, C., Drummer, C., Shan, H., Shao, Y., Sun, Y., Lu, Y., Saaoud, F., Xu, K., Nanayakkara, G., Fang, P., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.619951 · Cited by 20
“However, MHO has an increased risk compared with a metabolically healthy (MH) lean state, which remains the case no matter the stringency of criteria applied (16).”
BackgroundObesity is a chronic progressive relapsing disease of particular interest for internal medicine
Sbraccia, P., & Dicker, D. (2022) · Internal and Emergency Medicine · doi:10.1007/s11739-022-03129-z · Cited by 22
Long-term metabolic fate and mortality in obesity without metabolic syndrome
Käräjämäki, A. J., Korkiakoski, A., Hukkanen, J., Kesäniemi, Y. A., & Ukkola, O. H. (2022) · Annals of Medicine · doi:10.1080/07853890.2022.2075915 · Cited by 19
“5-fold higher among MHO subjects as compared to normal weight individuals without metabolic abnormalities, but conflicting with the above-mentioned meta-analysis, the risk was associated with the number of metabolic abnormalities at baseline [30].”
ResultLifestyle elements and risk of metabolic syndrome in adults
Suliga, E., Cieśla, E., Lelonek, M., Piechowska, A., & Głuszek, S. (2022) · PLoS ONE · doi:10.1371/journal.pone.0275510 · Cited by 24
Metabolic syndrome is associated with reduced flow mediated dilation independent of obesity status
Sprung, V. S., Davies, K. A. B., Norman, J. A., Thompson, A., Mitchell, K. L., Wilding, J. P. H., Kemp, G. J., & Cuthbertson, D. J. (2020) · European Journal of Endocrinology · doi:10.1530/eje-20-0098 · Cited by 21
Schizophrenia patients with a metabolically abnormal obese phenotype have milder negative symptoms
Wang, J., Zhang, Y., Liu, Z., Yang, Y., Zhong, Y., Ning, X., Zhang, Y., Zhao, T., Xia, L., Geng, F., et al. (2020) · BMC Psychiatry · doi:10.1186/s12888-020-02809-4 · Cited by 19
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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