Cardiovascular and Metabolic Heterogeneity of Obesity: Clinical Challenges and Implications for Management
Open accessAbstract
The prevalence of obesity has increased globally over the last 2 decades. Although the body mass index has been a convenient and simple index of obesity at the population level, studies have shown that obesity defined by body mass index alone is a remarkably heterogeneous condition with varying cardiovascular and metabolic manifestations across individuals. Adipose tissue is an exquisitely active metabolic organ engaged in cross-talk between various systems; perturbation of adipose tissue results in a pathological response to positive caloric balance in susceptible individuals that directly and indirectly contributes to cardiovascular and metabolic disease. Inadequate subcutaneous adipose tissue expansion in the face of dietary triglycerides leads to visceral and ectopic fat deposition, inflammatory/adipokine dysregulation, and insulin resistance. Conversely, preferential fat storage in the lower body depot may act as a metabolic buffer and protect other tissues from lipotoxicity caused by lipid overflow and ectopic fat. Translational, epidemiological, and clinical studies over the past 30 years have clearly demonstrated a strong link between visceral and ectopic fat and the development of a clinical syndrome characterized by atherogenic dyslipidemia, hyperinsulinemia/glucose intolerance, hypertension, atherosclerosis, and adverse cardiac remodeling/heart failure. This relationship is even more nuanced when clinical entities such as metabolically healthy obesity phenotype and the obesity paradox are considered. Although it is clear that the accumulation of visceral/ectopic fat is a major contributor to cardiovascular and metabolic risk above and beyond the body mass index, implementation of fat distribution assessment into clinical practice remains a challenge. Anthropometric indexes of obesity are easily implemented, but newer imaging-based methods offer improved sensitivity and specificity for measuring specific depots. Lifestyle, pharmacological, and surgical interventions allow a multidisciplinary approach to overweight/obesity that may improve outcomes and align with a public health message to combat the growing epidemic of obesity worldwide and to build healthier lives free of cardiovascular diseases.
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Obesity is associated with increased risks of cardiovascular diseases, diabetes, and musculoskeletal and metabolic disorders.
“Obesity is a serious worldwide health problem associated with increased risks of cardiovascular diseases, diabetes, and musculoskeletal and metabolic disorders (Welsh et al., 2024; Piche et al., 2018; Neeland, Poirier & Despres, 2018).”
From Effect of water-based aerobic training on anthropometric, biochemical, cardiovascular, and explosive strength parameters in young overweight and obese women: a randomized controlled trial (2025) · cites this paper as Neeland, Poirier & Despres, 2018
The sections on obesity classification and adipose effects link obesity with cardiovascular disease, type 2 diabetes, and metabolic disease. The cardiovascular-risk section also lists osteoarthritis as an obesity-related comorbidity, but does not establish an increased risk of musculoskeletal disorders more broadly. The paper emphasizes that risks vary among people with obesity. (LLM, conf=0.82)
Experimental — accuracy not yet measuredObesity increases cardiometabolic risk and premature mortality.
“As a chronic disease, obesity increases cardiometabolic risk [1] and ultimately confers an increased risk of premature mortality [2,3].”
Excess visceral adipose tissue conveys a higher risk of cardiometabolic disorders, including hypertension and type 2 diabetes mellitus, than excess subcutaneous adipose tissue.
“Substantial evidence indicates that excess visceral adipose tissue (VAT) conveys a higher risk of cardiometabolic disorders, including hypertension and T2DM, than does excess subcutaneous adipose tissue (SAT)”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [13]
Among obese individuals with similar BMI or total body adiposity, those with greater visceral and ectopic fat generally have higher cardiometabolic risk than those with less visceral adipose tissue.
“among obese individuals with similar BMI or total body adiposity, those with greater visceral and ectopic fat generally have higher cardiometabolic risk than those with less VAT13.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [13]
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Self-citationHigher Natriuretic Peptide Levels Associate With a Favorable Adipose Tissue Distribution Profile
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Effects of visceral adiposity on glycerol pathways in gluconeogenesis
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Self-citationLow Cardiorespiratory Fitness Levels and Elevated Blood Pressure
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Self-citationWhat is "metabolically healthy obesity"?: from epidemiology to pathophysiological insights.
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Defending the Con Side: Obesity Paradox Does Not Exist
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Weight Loss, Saline Loading, and the Natriuretic Peptide System
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Self-citationThe "Fit but Fat" paradigm addressed using accelerometer-determined physical activity data
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Mechanisms of Adverse Cardiometabolic Consequences of Obesity
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Once-Weekly Semaglutide in Adults with Overweight or Obesity
Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2032183 · Cited by 5,205 · see citing works
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Self-citationVisceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement
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Epicardial adipose tissue in contemporary cardiology
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Obesity, kidney dysfunction and hypertension: mechanistic links
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Self-citationMetabolically healthy versus metabolically unhealthy obesity
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Impact of different ectopic fat depots on cardiovascular and metabolic diseases
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Management of Obesity in Cardiovascular Practice
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Fecal microbiota transplantation in obesity metabolism: A meta analysis and systematic review
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“As a chronic disease, obesity increases cardiometabolic risk [1] and ultimately confers an increased risk of premature mortality [2,3].”
BackgroundLoss of transcriptional repression by BCL6 confers insulin sensitivity in the setting of obesity
Senagolage, M. D., Sommars, M. A., Ramachandran, K., Futtner, C. R., Omura, Y., Allred, A. L., Wang, J., Yang, C., Procissi, D., Evans, R. M., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.074 · Cited by 44 · see citing works
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“Obesity is a serious worldwide health problem associated with increased risks of cardiovascular diseases, diabetes, and musculoskeletal and metabolic disorders ( Welsh et al., 2024 ; Piche et al., 2018 ; Neeland, Poirier & Despres, 2018 ).”
Consenso intersocietario sobre estratificación del riesgo cardiovascular en obesidad
Silveyra, J., Harwicz, P., Busnelli, M. V., Aguirre Ackermann, M., Cappelletti, A. M., Alcalá, G., Salmeri, E., Arrupe, M., Giménez, S., Elbert, A., et al. (2026) · Revista de la Federación Argentina de Cardiología · doi:10.63600/4qke7898
- Authors
- Neeland, I. J., Poirier, P., & Després, J.-P.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Institut universitaire de cardiologie et de pneumologie de Québec (CA)
- Venue
- Circulation
- Published
- 2018-03-27
- Volume
- 137
- Issue
- 13
- Pages
- 1391-1406
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC5875734
- OpenAlex
- W2789727743
- Cited by
- 881
- References
- 114
- Citations by year
- 2026: 116 · 2025: 141 · 2024: 115 · 2023: 114 · 2022: 108 · 2021: 126 · 2020: 84 · 2019: 44 · 2018: 32 · 2015: 1
- FWCI
- 13.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Canadian Institutes of Health Research
- National Institute of Diabetes and Digestive and Kidney Diseases (K23DK106520)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- obesity heterogeneity, body mass index, visceral adipose tissue, ectopic fat, subcutaneous adipose tissue, adipose tissue metabolism, insulin resistance, adipokines, atherogenic dyslipidemia, hypertension, atherosclerosis, heart failure, cardiac remodeling, metabolically healthy obesity, obesity paradox, anthropometric index, obesity treatment
- MeSH terms
- Adipose Tissue, Appetite Depressants, Cardiovascular Diseases, Humans, Metabolic Diseases, Obesity, Risk Factors, Body Mass Index, Adiposity
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