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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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“The metabolically healthy obese subgroup was defined as overweight or obese participants with no demonstrable obesity-related metabolic abnormality, such as diabetes, hypertension, or dyslipidemia.(9) We defined individuals as having diabetes, hypertension, and dyslipidemia by coded diagnoses recorded in the NHIS clai…”
BackgroundA comprehensive metabolic profiling of the metabolically healthy obesity phenotype
Telle‐Hansen, V. H., Christensen, J. J., Formo, G. A., Holven, K. B., & Ulven, S. M. (2020) · Lipids in Health and Disease · doi:10.1186/s12944-020-01273-z · Cited by 54
“Some studies have reported individuals with MHO to have an intermediate-stage risk of metabolic disorders compared with individuals with healthy, normal weight (NW) and MUO [4, 5], and that the MHO phenotype is associated with a higher risk of coronary heart disease and heart failure than a healthy, NW phenotype [5].”
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Obesity Without Metabolic Abnormality and Incident CKD: A Population-Based British Cohort Study
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“a metabolically healthy normal weight, but the risk was lower than in those with metabolically unhealthy obesity.(28) Furthermore, obesity can be associated with reduced insulin sensitivity and increased oxidative stress and inflammation, all of which can contribute to CKD.”
BackgroundZwartjes, M., Gerdes, V. E. A., & Nieuwdorp, M. (2021) · Metabolites · doi:10.3390/metabo11080531 · Cited by 52
“showed that patients with obesity patients characterized as ‘metabolically healthy’ have a higher risk of cardiovascular disease (coronary heart disease, cerebrovascular disease, and heart failure) as compared to individuals with normal weight and normal metabolic parameters [44].”
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“, 2011) Several studies have shown that people with MHO have a risk of cardiovascular disease and mortality that is intermediate between those with neither obesity nor metabolic disturbances (metabolically healthy normal weight, or MHN) and those with obesity and metabolic disturbances (metabolically unhealthy obesity…”
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Acetyl-CoA and Metabolite Fluxes Regulate White Adipose Tissue Expansion
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“Meanwhile, these risks increased with an increasing number of metabolic abnormalities.(73) A meta-analysis demonstrated that the pooled adjusted relative risk (RR) for the incident of T2DM was 4.”
BackgroundJCS 2023 Guideline on the Primary Prevention of Coronary Artery Disease
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“The concept that metabolic syndrome in Latin America should consider the criterion of abdominal obesity as mandatory is based on observations from recent studies that show the incidence and prevalence of overweight and obesity have increased progressively during the last six decades and alarmingly so in the last 20 ye…”
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“Furthermore, in a previous report [12], the excess risk of HF in overweight individuals without metabolic abnormalities differed significantly by age and sex demonstrating a stronger positive association in individuals aged < 65 years than in those aged ≥ 65 years, and in females than in males.”
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“(16), which examined metabolically health obesity risk for cardiovascular events in 3.”
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“metabolically healthy, they have a higher risk of subclinical and clinical atherosclerosis than normal weight metabolically healthy individuals.(2,3) On the other hand, 5–8% of the healthy weight population is ‘metabolically obese’.”
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Obesity: The Perfect Storm for Heart Failure
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“209 This association has been ascribed to the strong association between obesity and AF.”
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Metabolic surgery: A clinical update
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“In obese individuals, particularly men, there is a notable reduction in circulating MOTS-c levels, which corresponds to an increased risk of developing CVDs [44–46].”
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“…that MHO is a benign permanent phenotype of obesity, has been consistently challenged by data from large epidemiological studies and meta-analyses, clearly demonstrating that individuals with MHO are at a higher risk of cardiometabolic morbid - ity and mortality in comparison to MHNO [29, 35–38].”
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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