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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Individuals with obesity but without diabetes are at elevated risk of developing diabetes and other cardiometabolic conditions compared with individuals without obesity.
“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]
The Results report that initially metabolically healthy obese individuals developed diabetes, hyperlipidemia, and hypertension during follow-up, at higher reported percentages than the nonobese overweight group. The Conclusions also report higher cardiovascular disease risk than in metabolically healthy normal-weight people. The paper does not provide a diabetes or other metabolic-condition risk comparison with normal-weight people, so it does not fully establish that part of the claim for individuals without obesity generally. (LLM, conf=0.84)
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Cites
Guh, D. P., Zhang, W., Bansback, N., Amarsi, Z., Birmingham, C. L., & Anis, A. H. (2009) · BMC Public Health · doi:10.1186/1471-2458-9-88 · Cited by 3,855 · see citing works
Mechanisms linking obesity with cardiovascular disease
Van Gaal, L. F., Mertens, I. L., & De Block, C. E. (2006) · Nature · doi:10.1038/nature05487 · Cited by 2,814 · cited 1× · see citing works
“Our finding that obesity was associated with a lower risk of PVD was surprising, considering that it may influence the atherosclerotic process (25).”
Epidemiology of Peripheral Artery Disease
Criqui, M. H., & Aboyans, V. (2015) · Circulation Research · doi:10.1161/circresaha.116.303849 · Cited by 1,785 · see citing works
Wildman, R. P. (2008) · Archives of Internal Medicine · doi:10.1001/archinte.168.15.1617 · Cited by 1,618 · see citing works
Prentice, A. M., & Jebb, S. A. (2001) · Obesity Reviews · doi:10.1046/j.1467-789x.2001.00031.x · Cited by 1,267 · see citing works
Newman, A. B., Siscovick, D. S., Manolio, T. A., Polak, J. F., Fried, L. P., Borhani, N. O., & Wolfson, S. K. (1993) · Circulation · doi:10.1161/01.cir.88.3.837 · Cited by 1,150 · see citing works
Are Metabolically Healthy Overweight and Obesity Benign Conditions?
Kramer, C. K., Zinman, B., & Retnakaran, R. R. (2013) · Annals of Internal Medicine · doi:10.7326/0003-4819-159-11-201312030-00008 · Cited by 958 · see citing works
Metabolically healthy obesity: Epidemiology, mechanisms, and clinical implications
Stefan, N., Häring, H.-U., Hu, F. B., & Schulze, M. B. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70062-7 · Cited by 857 · see citing works
Update on Some Epidemiologic Features of Intermittent Claudication: The Framingham Study
Kannel, W. B., & McGee, D. L. (1985) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1985.tb02853.x · Cited by 771 · see citing works
Reviewing the definition of “elderly”
Orimo, H., Ito, H., Suzuki, T., Araki, A., Hosoi, T., & Sawabe, M. (2006) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/j.1447-0594.2006.00341.x · Cited by 693 · see citing works
Blak, B., Thompson, M., Dattani, H., & Bourke, A. (2011) · Journal of Innovation in Health Informatics · doi:10.14236/jhi.v19i4.820 · Cited by 630 · see citing works
Lewis, J. D., Schinnar, R., Bilker, W. B., Wang, X., & Strom, B. L. (2007) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1335 · Cited by 602 · see citing works
Prevalence and clinical correlates of peripheral arterial disease in the Framingham Offspring Study
Murabito, J. M., Evans, J. C., Nieto, K., Larson, M. G., Levy, D. A., & Wilson, P. W. F. (2002) · American Heart Journal · doi:10.1067/mhj.2002.122871 · Cited by 546 · see citing works
The genetic contribution to non-syndromic human obesity
Walley, A. J., Asher, J. E., & Froguel, P. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2594 · Cited by 402 · see citing works
Tomiyama, A. J., Hunger, J. M., Nguyen-Cuu, J., & Wells, C. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.17 · Cited by 349 · see citing works
Metabolic Syndrome in Normal-Weight Americans
St‐Onge, M., Janssen, I., & Heymsfield, S. B. (2004) · Diabetes Care · doi:10.2337/diacare.27.9.2222 · Cited by 308 · see citing works
Beks, P. J., Mackaay, A. J. C., de Neeling, J. N. D., de Vries, H., Bouter, L. M., & Heine, R. J. (1995) · Diabetologia · doi:10.1007/bf02369357 · Cited by 296 · see citing works
Fan, J., Song, Y., Chen, Y., Hui, R., & Zhang, W. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2013.07.230 · Cited by 267 · see citing works
Hypertension management in England: a serial cross-sectional study from 1994 to 2011
Falaschetti, E., Mindell, J. S., Knott, C. S., & Poulter, N. R. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60688-7 · Cited by 263 · see citing works
Allison, M. A., Criqui, M. H., McClelland, R. L., Scott, J. M., McDermott, M. M., Liu, K., Folsom, A. R., Bertoni, A. G., Sharrett, A. R., Homma, S., et al. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.05.049 · Cited by 257 · see citing works
Hooi, J. D., Kester, A. D. M., Stoffers, J., Overdijk, M. M., van Ree, J. W., & Knottnerus, J. A. (2001) · American Journal of Epidemiology · doi:10.1093/aje/153.7.666 · Cited by 220 · see citing works
Zheng, R., Zhou, D., & Zhu, Y. (2016) · Journal of Epidemiology & Community Health · doi:10.1136/jech-2015-206948 · Cited by 204 · see citing works
Mongraw‐Chaffin, M., Peters, S. A. E., Huxley, R., & Woodward, M. (2015) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(15)00086-8 · Cited by 203 · see citing works
Epidemiology of Intermittent Claudication in Middle-aged Men
Bowlin, S. J., Medalie, J. H., Flocke, S. A., Zyzanski, S. J., & Goldbourt, U. (1994) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a117264 · Cited by 147 · see citing works
Validation of ischemic cerebrovascular diagnoses in the health improvement network (THIN)
Ruigómez, A., Martín‐Merino, E., & Rodríguez, L. A. G. (2010) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1919 · Cited by 89 · see citing works
Hammad, T. A., McAdams‐DeMarco, M., Feight, A. G., Iyasu, S., & Pan, G. J. D. (2008) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1672 · Cited by 63 · see citing works
Thomas, M. C., Walker, M., Emberson, J., Thomson, A. G., Lawlor, D. A., Ebrahim, S. B. J., & Whincup, P. H. (2005) · Diabetic Medicine · doi:10.1111/j.1464-5491.2005.01516.x · Cited by 51 · see citing works
Gaist, D., Wallander, M.-A. A., González‐Pérez, A., & García‐Rodríguez, L. A. (2012) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.3391 · Cited by 51 · see citing works
Is the Metabolically Healthy Obesity Phenotype an Irrelevant Artifact for Public Health?
Rey-López, J. P., Rezende, L. F. M., de Sá, T. H., & Stamatakis, E. A. (2015) · American Journal of Epidemiology · doi:10.1093/aje/kwv177 · Cited by 39 · see citing works
Invited Commentary: Limitations and Usefulness of the Metabolically Healthy Obesity Phenotype
Bradshaw, P. T., & Stevens, J. (2015) · American Journal of Epidemiology · doi:10.1093/aje/kwv178 · Cited by 19 · see citing works
The downfalls of BMI-focused policies
Dhurandhar, E. J. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.18 · Cited by 16 · see citing works
A Call to Shift the Public Health Focus Away From Weight
Hunger, J. M., & Tomiyama, A. J. (2015) · American Journal of Public Health · doi:10.2105/ajph.2015.302845 · Cited by 13 · see citing works
Misclassification of cardiometabolic health when using body mass index categories
Caleyachetty, R., Meunnig, P., & Kengne, A. P. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.65 · Cited by 9 · see citing works
Screening for Abnormal Blood Glucose and Type 2 Diabetes Mellitus
Siu, A. L. (2016) · Annals of Internal Medicine · doi:10.7326/l16-0102 · Cited by 9 · see citing works
Weight and cardiometabolic health: new perspectives
Tomiyama, A., Hunger, J., Nguyen-Cuu, J., & Wells, C. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.83 · Cited by 7 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Townsend P, Phillimore P, Beattie A. The construction of a measure of deprivation. Health and Deprivation: Inequality and the North. London: Routledge, 1988.
Cited by
Sorted by citations
Eslam, M., Newsome, P. N., Sarin, S. K., Anstee, Q. M., Targher, G., Romero-Gomez, M., Zelber-Sagi, S., Wai-Sun Wong, V., Dufour, J.-F., Schattenberg, J. M., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.03.039 · Cited by 4,472 · see citing works
MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease
Eslam, M., Sanyal, A. J., George, J., Sanyal, A., Neuschwander-Tetri, B., Tiribelli, C., Kleiner, D. E., Brunt, E., Bugianesi, E., Yki-Järvinen, H., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.11.312 · Cited by 3,286 · see citing works
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529 · see citing works
Blüher, M. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa004 · Cited by 1,090 · see citing works
“5 million men and women for which validated electronic health records were available in the context of The Health Improvement Network (THIN) database is most likely overestimated, because the definition of MHO did not consider blood glucose, blood pressure, or lipid parameter cutoffs (43, 44).”
BackgroundMethodResultInfluentialObesity and cardiovascular disease: revisiting an old relationship
Koliaki, C. C., Liatis, S., & Kokkinos, A. D. (2018) · Metabolism · doi:10.1016/j.metabol.2018.10.011 · Cited by 733 · see citing works
An Overview and Update on Obesity and the Obesity Paradox in Cardiovascular Diseases
Elagizi, A., Kachur, S. M., Lavie, C. J., Carbone, S., Pandey, A., Ortega, F. B., & Milani, R. V. (2018) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2018.07.003 · Cited by 700 · see citing works
Metabolically healthy obesity: facts and fantasies
Smith, G. I., Mittendorfer, B., & Klein, S. (2019) · Journal of Clinical Investigation · doi:10.1172/jci129186 · Cited by 655 · see citing works
Causes, consequences, and treatment of metabolically unhealthy fat distribution
Stefan, N. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(20)30110-8 · Cited by 548 · see citing works
Eckel, N., Li, Y., Kuxhaus, O., Stefan, N., Hu, F. B., & Schulze, M. B. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30137-2 · Cited by 457 · see citing works
Metabolically healthy versus metabolically unhealthy obesity
Iacobini, C., Pugliese, G., Blasetti Fantauzzi, C., Federici, M., & Menini, S. (2019) · Metabolism · doi:10.1016/j.metabol.2018.11.009 · Cited by 453 · see citing works
Healthy Weight and Obesity Prevention
Lavie, C. J., Laddu, D., Arena, R. A., Ortega, F. B., Alpert, M., & Kushner, R. F. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.08.1037 · Cited by 464 · see citing works
“(38) and from most of the currently existing evidence (42–46) that there is no benign obesity should be taken cautiously, given support from these studies indicating that CRF, versus obesity per se, explains the higher risk observed in MHO versus MHNW populations (Figure 2) (8,36,41).”
BackgroundInfluentialObesity and the risk of cardiometabolic diseases
Valenzuela, P. L., Carrera-Bastos, P., Castillo-García, A., Lieberman, D. E., Santos-Lozano, A., & Lucia, A. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00847-5 · Cited by 452 · see citing works
Metabolically Healthy Obesity, Transition to Metabolic Syndrome, and Cardiovascular Risk
Mongraw‐Chaffin, M., Foster, M. C., Anderson, C. A. M., Burke, G. L., Haq, N., Kalyani, R. R., Ouyang, P., Sibley, C. T., Tracy, R. P., Woodward, M., et al. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.02.055 · Cited by 435 · see citing works
Profound Perturbation of the Metabolome in Obesity Is Associated with Health Risk
Cirulli, E. T., Guo, L., Swisher, C. L., Shah, N., Huang, L., Napier, L. A., Kirkness, E. F., Spector, T. D., Caskey, C. T., Thorens, B., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.09.022 · Cited by 385 · see citing works
“Thus, while our findings are in line with the known relationships between metabolically healthy obese status and health-related traits likemetabolic syndrome and body fat (Brochu et al., 2001; Caleyachetty et al., 2017; Karelis et al., 2005), we extend this relationship to the broader category of metabolically healthy…”
BackgroundResultInfluentialBrown, H. L., Warner, J. J., Gianos, E., Gulati, M., Hill, A. J., Hollier, L. M., Rosen, S. E., Rosser, M. L., & Wenger, N. K. (2018) · Circulation · doi:10.1161/cir.0000000000000582 · Cited by 378 · see citing works
Blood metabolome predicts gut microbiome α-diversity in humans
Wilmanski, T. M., Rappaport, N., Earls, J. C., Magis, A. T., Manor, O., Lovejoy, J. C., Omenn, G. S., Hood, L., Gibbons, S. M., & Price, N. D. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0233-9 · Cited by 316 · see citing works
A Review of Obesity, Physical Activity, and Cardiovascular Disease
Elagizi, A., Kachur, S. M., Carbone, S., Lavie, C. J., & Blair, S. N. (2020) · Current Obesity Reports · doi:10.1007/s13679-020-00403-z · Cited by 329 · see citing works
Okamura, T., Tsukamoto, K., Arai, H., Fujioka, Y., Ishigaki, Y., Koba, S., Ohmura, H., Shoji, T., Yokote, K., Yoshida, H., et al. (2023) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.gl2022 · Cited by 317 · see citing works
Obesity and cardiovascular disease: An ESC clinical consensus statement
Koskinas, K. C., Van Craenenbroeck, E. M., Antoniades, C., Blüher, M., Gorter, T. M., Hanssen, H., Marx, N., McDonagh, T. A., Mingrone, G., Rosengren, A., et al. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae508 · Cited by 313 · see citing works
Prolonging healthy aging: Longevity vitamins and proteins
Ames, B. N. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1809045115 · Cited by 273 · see citing works
Metabolically Healthy Obesity: Criteria, Epidemiology, Controversies, and Consequences
Tsatsoulis, A. A., & Paschou, S. Α. (2020) · Current Obesity Reports · doi:10.1007/s13679-020-00375-0 · Cited by 263 · see citing works
Obesity and ageing: Two sides of the same coin
Tam, B. T., Morais, J. A., & Santosa, S. (2020) · Obesity Reviews · doi:10.1111/obr.12991 · Cited by 254 · see citing works
“96).(190) Collectively, abdominal obesity may be a strong catalyst in promoting the early onset of CVD.”
BackgroundTryptophan Dietary Impacts Gut Barrier and Metabolic Diseases
Taleb, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02113 · Cited by 236 · see citing works
Silveira, É. A., Kliemann, N., Noll, M. A., Sarrafzadegan, N., & de Oliveira, C. M. (2020) · Obesity Reviews · doi:10.1111/obr.13088 · Cited by 185 · see citing works
Metabolic health in normal-weight and obese individuals
Schulze, M. B. (2018) · Diabetologia · doi:10.1007/s00125-018-4787-8 · Cited by 183 · see citing works
“THIN [12] Absence of diabetes, hypertension and lipid-lowering drugs Coronary heart disease 1.”
InfluentialMetabolically healthy obesity: from epidemiology and mechanisms to clinical implications
Schulze, M. B., & Stefan, N. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-01008-5 · Cited by 184 · see citing works
Blüher, M. (2025) · Diabetes Obesity and Metabolism · doi:10.1111/dom.16263 · Cited by 215 · see citing works
“51 On the other hand, there are individuals with obesity that do not develop premature obesity-related cardiometabolic diseases.”
Coronary Microvascular Dysfunction and Cardiovascular Risk in Obese Patients
Bajaj, N. S., Osborne, M. T., Gupta, A., Tavakkoli, A., Bravo, P. E., Vita, T. S., Bibbo, C. F., Hainer, J. M., Dorbala, S., Blankstein, R., et al. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.05.049 · Cited by 176 · see citing works
“Yet, recent data suggest that even obese individuals without apparent risk factors may still be at higher risk of adverse events and are not truly “metabolically healthy” (32).”
BackgroundRelevance of body composition in phenotyping the obesities
Salmón‐Gómez, L., Catalán, V., Frühbeck, G., & Gómez‐Ambrosi, J. (2023) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-023-09796-3 · Cited by 177 · see citing works
Lin, H., Zhang, L., Zheng, R., & Zheng, Y. (2017) · Medicine · doi:10.1097/md.0000000000008838 · Cited by 153 · see citing works
Schröder, J. D., Falqueto, H., Mânica, A., Zanini, D., de Oliveira, T., Sá, C. A. D., Cardoso, A. M., & Manfredi, L. H. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-020-02687-0 · Cited by 152 · see citing works
Metabolically healthy obesity: what–s in a name?
Magkos, F. (2019) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz133 · Cited by 144 · see citing works
Opio, J., Croker, E. E., Odongo, G. S., Attia, J., Wynne, K., & McEvoy, M. (2020) · Obesity Reviews · doi:10.1111/obr.13127 · Cited by 138 · see citing works
“The pooled effect size for risk of CVD in groups with MHOW/MHO compared with MHNW did not change when the study by Caleyachetty et al. (2017) with the greatest weighting was removed from analysis.”
BackgroundInfluentialOrtega, F. B., Cadenas‐Sánchez, C., Migueles, J. H., Labayen, I., Ruiz, J. R., Sui, X., Blair, S. N., Martínez‐Vizcaíno, V., & Lavie, C. J. (2018) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2018.07.008 · Cited by 137 · see citing works
“8 million participants (40), and the Nurses’ Health Study (NHS) in 90,257 women”
BackgroundKouvari, M., Panagiotakos, D. B., Yannakoulia, M., Georgousopoulou, E. N., Critselis, E., Chrysohoou, C. A., Tousoulis, D. M., & Pitsavos, C. E. (2019) · Metabolism · doi:10.1016/j.metabol.2019.01.003 · Cited by 133 · see citing works
Obesity and cardiovascular disease: an ESC clinical consensus statement
Koskinas, K. C., Craenenbroeck, E. M. V., Antoniades, C. A., Blüher, M., Gorter, T. M., Hanssen, H., Marx, N., McDonagh, T. A., Mingrone, G., Rosengren, A., et al. (2024) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwae279 · Cited by 132 · see citing works
Ampuero, J., Aller, R., Gallego‐Durán, R., Bañales, J. M., Crespo, J., García‐Monzón, C., Pareja, M. J., Gómez, E. V., Caballería, J., Escudero‐García, D., et al. (2018) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15015 · Cited by 110 · see citing works
Obesity phenotypes and cardiovascular risk: From pathophysiology to clinical management
Preda, A., Carbone, F., Tirandi, A., Montecucco, F., & Liberale, L. (2023) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-023-09813-5 · Cited by 108 · see citing works
The Triglyceride/HDL Ratio as a Surrogate Biomarker for Insulin Resistance
Baneu, P., Văcărescu, C., Dragan, S. R., Cirin, L., Lazăr-Höcher, A.-I., Cozgarea, A., Faur-Grigori, A. A., Crișan, S., Gaiță, D. I., Luca, C. T., et al. (2024) · Biomedicines · doi:10.3390/biomedicines12071493 · Cited by 100 · see citing works
Echouffo-Tcheugui, J. B., Short, M. I., Xanthakis, V., Field, P., Sponholtz, T. R., Larson, M. G., & Vasan, R. S. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01321 · Cited by 95 · see citing works
Blomstrand, P., Sjöblom, P., Nilsson, M., Wijkman, M. O., Engvall, M., Länne, T., Nyström, F. H., Östgren, C. J., & Engvall, J. E. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0756-2 · Cited by 93 · see citing works
Singh, P., Subramanian, A., Adderley, N. J., Gokhale, K. M., Singhal, R., Bellary, S., Nirantharakumar, K., & Tahrani, A. A. (2020) · British journal of surgery · doi:10.1002/bjs.11433 · Cited by 91 · see citing works
Anti-obesity effects of capsaicin and the underlying mechanisms: a review
Li, R., Lan, Y., Chen, C., Cao, Y., Huang, Q., Ho, C., & Lu, M. (2020) · Food & Function · doi:10.1039/d0fo01467b · Cited by 93 · see citing works
Obesity and Risk for First Ischemic Stroke Depends on Metabolic Syndrome: The HUNT Study
Horn, J. W., Feng, T., Mørkedal, B., Strand, L. B., Horn, J., Mukamal, K. J., & Janszky, I. (2021) · Stroke · doi:10.1161/strokeaha.120.033016 · Cited by 92 · see citing works
Adipose Tissue Macrophage Polarization in Healthy and Unhealthy Obesity
Ruggiero, A. D., Key, C.-C. C., & Kavanagh, K. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.625331 · Cited by 89 · see citing works
“There is no universally accepted definition of MHO; many MHO individuals progress to MUO over time, and, although MHO individuals do have higher all-cause mortality and an increased risk of cardiovascular events compared with healthy lean individuals (12, 13), they are at a decreased risk of cardiovascular complicatio…”
BackgroundMorgan-Bathke, M., Raynor, H. A., Baxter, S. D., Halliday, T. M., Lynch, A., Malik, N., Garay, J. L., & Rozga, M. (2023) · Journal of the Academy of Nutrition and Dietetics · doi:10.1016/j.jand.2022.11.014 · Cited by 85 · see citing works
Zhao, M., López‐Bermejo, A., Caserta, C. A., Medeiros, C. C. M., Κόλλιας, Α., Bassols, J., Romeo, E. L., Ramos, T. D. A., Stergiou, G. S., Yang, L., et al. (2018) · Diabetes Care · doi:10.2337/dc18-1536 · Cited by 83 · see citing works
“4 years showed that MHO was associated with CVD compared with metabolicallyhealthynormalweight (30).”
BackgroundResultRyder, J. R., Fox, C. K., & Kelly, A. S. (2018) · Obesity · doi:10.1002/oby.22196 · Cited by 83 · see citing works
“, reducing heterogeneity of response), and (3) improving reimbursement from insurance companies to increase access for youth who meet medical eligibility guidelines.”
BackgroundLin, L., Zhang, J., Jiang, L., Du, R., Hu, C., Lu, J., Wang, T., Li, M., Zhao, Z., Xu, Y., et al. (2020) · Diabetologia · doi:10.1007/s00125-020-05116-5 · Cited by 81 · see citing works
Obesity, Cardiorespiratory Fitness, and Cardiovascular Disease
Haidar, A., & Horwich, T. B. (2023) · Current Cardiology Reports · doi:10.1007/s11886-023-01975-7 · Cited by 80 · see citing works
Beyene, H. B., Giles, C., Huynh, K., Wang, T., Cinel, M. A., Mellett, N. A., Olshansky, G., Meikle, T. G., Watts, G. F., Hung, J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41963-7 · Cited by 74 · see citing works
Metabolically healthy obesity and cardiovascular events: A nationwide cohort study
Fauchier, G., Bisson, A., Bodin, A., Herbert, J., Semaan, C., Angoulvant, D., Ducluzeau, P., Lip, G. Y. H., & Fauchier, L. (2021) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14492 · Cited by 72 · see citing works
Obesity: Recent Advances and Future Perspectives
Janić, M., Janež, A., El‐Tanani, M., & Rizzo, M. (2025) · Biomedicines · doi:10.3390/biomedicines13020368 · Cited by 77 · see citing works
Chrysant, S. G., & Chrysant, G. S. (2019) · Postgraduate Medicine · doi:10.1080/00325481.2019.1568019 · Cited by 70 · see citing works
“[38] analyzed the effects of obesity on the incidence of CHD, cerebrovascular disease, and HF in 3.”
BackgroundInfluentialCho, Y. K., Kang, Y. M., Yoo, J. H., Lee, J., Park, J., Lee, W. J., Kim, Y., & Jung, C. H. (2019) · Metabolism · doi:10.1016/j.metabol.2019.05.002 · Cited by 68 · see citing works
Zhao, Y., Gu, Y., & Zhang, B. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02209-y · Cited by 68 · see citing works
“Existing evidence suggests that metabolic factors play a crucial role in the development of various CVDs [31– 33].”
BackgroundGenário, R., Cipolla‐Neto, J., Bueno, A. A., & Santos, H. O. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105254 · Cited by 68 · see citing works
“Even if obese individuals do not have an associated diagnosis of hypertension, type II diabetes mellitus (T2DM) or dyslipidaemia, yet there is an approximate 49% increased risk for coronary heart disease; 7% increased risk for cerebrovascular diseases and 96% increased risk for heart failure [10].”
BackgroundGill, D., Zuber, V., Dawson, J., Pearson‐Stuttard, J., Carter, A. R., Sanderson, E. C. M., Karhunen, V., Levin, M. G., Wootton, R. E., Program, V. M. V., et al. (2021) · International Journal of Obesity · doi:10.1038/s41366-021-00807-4 · Cited by 67 · see citing works
Kumarendran, B., Šumilo, D., O’Reilly, M., Toulis, K. A., Gokhale, K. M., Wijeyaratne, C. N., Coomarasamy, A., Arlt, W., Tahrani, A. A., & Nirantharakumar, K. (2019) · European Journal of Endocrinology · doi:10.1530/eje-18-0693 · Cited by 68 · see citing works
Genes that make you fat, but keep you healthy
Loos, R. J. F., & Kilpeläinen, T. O. (2018) · Journal of Internal Medicine · doi:10.1111/joim.12827 · Cited by 60 · see citing works
Ndumele, C. E., Rodríguez, F., Dixon, D. L., Khan, S. S., Mukherjee, D., Bajaj, M. S., Bangalore, S., Bozkurt, B., Breathett, K. K., Clarke, S. L., et al. (2026) · Circulation · doi:10.1161/cir.0000000000001453 · Cited by 87 · see citing works
Agbim, U., Carr, R., Pickett-Blakely, O., & Dagogo-Jack, S. (2019) · Current Obesity Reports · doi:10.1007/s13679-019-00349-x · Cited by 56 · see citing works
Metabolically Healthy Obesity Redefined
April-Sanders, A., & Rodríguez, C. J. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2021.8860 · Cited by 62 · see citing works
Obesity, Adipose Tissue, and Inflammation Answered in Questions
Guerreiro, V. A., Carvalho, D. M., & Freitas, P. (2022) · Journal of Obesity · doi:10.1155/2022/2252516 · Cited by 67 · see citing works
Metabolically healthy obesity: Misleading phrase or healthy phenotype?
Tanrıöver, C., Çöpür, S., Gaipov, A., Özlüşen, B., Akcan, R. E., Kuwabara, M., Hornum, M., van Raalte, D. H., & Kanbay, M. (2023) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2023.02.025 · Cited by 62 · see citing works
Agius, R., Pace, N. P., & Fava, S. (2023) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3725 · Cited by 62 · see citing works
“…presence of unhealthy metabolic status is associated with a dose ‐ dependent increase in cardiometabolic and mortality risk compared with MHNW. 216,217,229 One meta ‐ analysis showed that metabolically unhealthy subjects carried a significantly higher risk of incident T2M compared with…”
BackgroundResultReprint of: Healthy Weight and Obesity Prevention
Lavie, C. J., Laddu, D., Arena, R. A., Ortega, F. B., Alpert, M., & Kushner, R. F. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.10.024 · Cited by 58 · see citing works
Body mass index and peripheral artery disease
Heffron, S. P., Dwivedi, A., Rockman, C. R., Xia, Y., Guo, Y., Zhong, J., & Berger, J. S. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.10.017 · Cited by 58 · see citing works
“The observation of elevated risk of PAD (in addition to cerebrovascular disease) in underweight individuals has notably been reported previously and found to persist even after correcting for smoking and other cardiovascular risk factors (34, 35).”
BackgroundSilveira, É. A., Filho, R. R. D. S., Spexoto, M. C. B., Haghighatdoost, F., Sarrafzadegan, N., & de Oliveira, C. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094339 · Cited by 56 · see citing works
Obesity-Associated Organ Damage and Sympathetic Nervous Activity
Lambert, É., Esler, M., Schlaich, M. P., Dixon, J. B., Eikelis, N., & Lambert, G. W. (2019) · Hypertension · doi:10.1161/hypertensionaha.118.11676 · Cited by 60 · see citing works
Ndumele, C. E., Rodriguez, F., Dixon, D. L., Khan, S. S., Mukherjee, D., Bajaj, M., Bangalore, S., Bozkurt, B., Breathett, K., Clarke, S. L., et al. (2026) · JACC · doi:10.1016/j.jacc.2026.03.056 · Cited by 90 · see citing works
Visceral Adipose Tissue Accumulation and Residual Cardiovascular Risk
Jemtel, T. H. L., Samson, R., Milligan, G. P., Jaiswal, A., & Oparil, S. (2018) · Current Hypertension Reports · doi:10.1007/s11906-018-0880-0 · Cited by 56 · see citing works
Zhernakova, Y. V., Zheleznova, E. A., Chazova, I. E., Ощепкова, Е. В., Dolgusheva, Y. A., Yarovaya, E. B., Blinova, N. V., Orlovsky, А. A., Димитриевна, К. И., Shalnova, S. A., et al. (2018) · Terapevticheskii arkhiv · doi:10.26442/terarkh2018901014-22 · Cited by 54 · see citing works
Lavie, C. J., DEEDWANIA, P. C., & Ortega, F. B. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30143-8 · Cited by 53 · see citing works
Park, J., Kim, D. H., Lee, H., Hwang, I., Yoon, Y. E., Park, H. E., Choi, S., Kim, Y.-J., Cho, G., Han, K., et al. (2019) · European Journal of Preventive Cardiology · doi:10.1177/2047487319889714 · Cited by 53 · see citing works
“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 52 · see citing works
“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].”
Lin, C., Chang, Y., Cheng, T., Lo, K., Liu, S., & Yeh, T. (2020) · Obesity Reviews · doi:10.1111/obr.13049 · Cited by 51 · see citing works
Increased cardiometabolic and mortality risk following childhood maltreatment in the United Kingdom
Chandan, J. S., Okoth, K., Gokhale, K. M., Bandyopadhyay, S., Taylor, J., & Nirantharakumar, K. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.119.015855 · Cited by 48 · see citing works
Obesity Without Metabolic Abnormality and Incident CKD: A Population-Based British Cohort Study
Wang, J., Niratharakumar, K., Gokhale, K. M., Tahrani, A. A., Taverner, T., Thomas, G. N., & Dasgupta, I. (2021) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2021.05.008 · Cited by 50 · see citing works
“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. S. Z., Gerdes, V. E. A., & Nieuwdorp, M. (2021) · Metabolites · doi:10.3390/metabo11080531 · Cited by 50 · see citing works
“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].”
BackgroundHeath, L., Jebb, S. A., Aveyard, P. N., & Piernas, C. (2022) · BMC Medicine · doi:10.1186/s12916-022-02236-0 · Cited by 52 · see citing works
Moazzami, K., Lima, B. B., Sullivan, S. M., Shah, A. J., Bremner, J. D., & Vaccarino, V. (2019) · Health Psychology · doi:10.1037/hea0000764 · Cited by 50 · see citing works
“, 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…”
BackgroundBlüher, M., & Laufs, U. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz411 · Cited by 40 · see citing works
Muse, E. D., & Topol, E. J. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.02.002 · Cited by 50 · see citing works
Acetyl-CoA and Metabolite Fluxes Regulate White Adipose Tissue Expansion
Felix, J. B., Cox, A. R., & Hartig, S. M. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.02.008 · Cited by 49 · see citing works
Cheng, D., Zhao, X. Y., Yang, S., Cui, H., & Wang, G. (2021) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s294894 · Cited by 51 · see citing works
“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
Fujiyoshi, A., Kohsaka, S., Hata, J., Hara, M., Kai, H., Masuda, D., Miyamatsu, N., Nishio, Y., Ogura, M., Sata, M., et al. (2024) · Circulation Journal · doi:10.1253/circj.cj-23-0285 · Cited by 47 · see citing works
López-Jaramillo, P. A., Barbosa, E. C. D., Molina, D. I., Sanchez, R. A., Diaz, M., Camacho, P. A., Lanas, F. T., Pasquel, M., Accini, J., Ponte-Negretti, C. I., et al. (2019) · Journal of Hypertension · doi:10.1097/hjh.0000000000002072 · Cited by 46 · see citing works
“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…”
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) · Cardiovascular Diabetology · doi:10.1186/s12933-020-01051-2 · Cited by 44 · see citing works
“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.”
BackgroundKuk, J., Rotondi, M., Sui, X.-M., Blair, S., & Ardern, C. (2018) · Clinical Obesity · doi:10.1111/cob.12263 · Cited by 40 · see citing works
“(16), which examined metabolically health obesity risk for cardiovascular events in 3.”
BackgroundSchrover, I. M., van der Graaf, Y., Spiering, W., & Visseren, F. L. J. (2018) · European Journal of Preventive Cardiology · doi:10.1177/2047487318790722 · Cited by 44 · see citing works
“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’.”
Li, H., He, D., Zheng, D., Amsalu, E., Wang, A., Tao, L., Guo, J. C., Li, X., Wang, W., & Guo, X. (2019) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2019.01.004 · Cited by 44 · see citing works
Svendsen, K., Olsén, T., Rusvik, T. C. N., Ulven, S. M., Holven, K. B., Retterstøl, K., & Telle‐Hansen, V. H. (2020) · Lipids in Health and Disease · doi:10.1186/s12944-020-01282-y · Cited by 44 · see citing works
Obesity: The Perfect Storm for Heart Failure
Lembo, M., Strisciuglio, T., Fonderico, C., Mancusi, C., Izzo, R., Trimarco, V., Bellis, A., Barbato, E., Esposito, G., Morisco, C., et al. (2024) · ESC Heart Failure · doi:10.1002/ehf2.14641 · Cited by 46 · see citing works
“209 This association has been ascribed to the strong association between obesity and AF.”
BackgroundCarbone, F., Després, J., Ioannidis, J. P. A., Neeland, I. J., Garruti, G., Busetto, L., Liberale, L., Ministrini, S., Vilahur, G., Schindler, T. H., et al. (2025) · European Journal of Clinical Investigation · doi:10.1111/eci.70059 · Cited by 45 · see citing works
Nollet, E. E., Westenbrink, B. D., de Boer, R. A., Kuster, D. W. D., & van der Velden, J. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.120.018641 · Cited by 43 · see citing works
Commodore-Mensah, Y. Y., Lazo, M., Tang, O., Echouffo-Tcheugui, J. B., Ndumele, C. E., Nambi, V., Wang, D., Ballantyne, C. M., & Selvin, E. (2021) · Diabetes Care · doi:10.2337/dc20-2227 · Cited by 43 · see citing works
Metabolic surgery: A clinical update
Wilson, R. L., Aminian, A., & Tahrani, A. A. (2021) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14235 · Cited by 42 · see citing works
Li, Y., Li, Z., Ren, Y., Lei, Y., Yang, S., Shi, Y., Peng, H., Yang, W., Guo, T., Yu, Y., et al. (2023) · Journal of Advanced Research · doi:10.1016/j.jare.2023.11.018 · Cited by 43 · see citing works
“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].”
BackgroundKoliaki, C. C., Dalamaga, Μ., Kakounis, K., & Liatis, S. (2025) · Current Obesity Reports · doi:10.1007/s13679-025-00637-9 · Cited by 42 · see citing works
“…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].”
- 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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