BMI is calculated by dividing body weight in kilograms by height in meters squared. Although simple and inexpensive, the measure cannot show where fat is stored or distinguish fat from muscle. That limitation is important because abdominal fat, particularly visceral adipose tissue surrounding internal organs, is metabolically active and has been linked to insulin resistance, inflammation, high blood pressure and abnormal blood lipid levels. Subcutaneous fat beneath the skin appears to have weaker associations with cardiovascular disease, meaning that two people with identical BMIs may have very different biological risk profiles.

Researchers from the Cross Cohort Collaboration examined whether adding measurements of abdominal fat distribution to BMI could improve predictions of major cardiovascular outcomes. Participants had available WC or WHR data and were assessed for one or more of nine outcomes: fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, heart failure, atrial fibrillation, total coronary heart disease, total cardiovascular disease, coronary heart disease mortality, cardiovascular disease mortality and all-cause mortality. The long follow-up allowed the investigators to evaluate whether body-fat distribution was associated with events that developed years after the initial measurements.

The study showed that central adiposity was present in a meaningful proportion of people whose BMI would traditionally place them in a lower-risk category. Among participants classified as normal weight by BMI, 5 percent had a high waist circumference and 18 percent had a high waist-to-hip ratio. In the overweight group, 39 percent had a high waist circumference and 40 percent had a high waist-to-hip ratio. These results suggest that a substantial number of people may carry elevated abdominal fat without being identified as at risk by BMI alone.

The implications were especially striking among people with normal weight or overweight. Those with a clinically high WC or WHR had a 15 to 50 percent greater risk for most of the nine outcomes compared with participants whose BMI and central-adiposity measures were in lower-risk ranges. The association persisted across several forms of cardiovascular disease, indicating that abdominal fat distribution may provide information beyond the broad weight categories used in routine medical practice.

The findings also complicated the assumption that obesity automatically identifies the people at greatest cardiovascular risk. Among participants with obesity, 9 percent had a low waist circumference and 45 percent had a low waist-to-hip ratio. Individuals with obesity but low WC were not significantly different in risk from normal-weight participants with low WC for most outcomes. The exception was all-cause mortality, for which the obesity group with low WC showed a significantly lower risk. Because the study was observational, however, these results do not establish that a smaller waist protects against disease or explain why different patterns appeared across BMI categories.

“Where fat is distributed matters,” said Michael J. Blaha, MD, MPH, senior author and director of clinical research at the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease. He noted that waist circumference and waist-to-hip ratio appeared to reclassify risk defined by traditional BMI thresholds, including among people considered to have normal weight. Lead author Zeina A. Dardari, PhD, MS, said clinicians should consider central adiposity across the entire BMI spectrum when assessing cardiovascular risk in primary prevention.

Waist circumference is a direct measurement around the abdomen, while WHR compares waist size with hip size. Both are indirect markers of body-fat distribution and can be influenced by sex, age, ethnicity, body shape and measurement technique. Neither test can determine precisely how much visceral fat a person has; imaging methods such as computed tomography or magnetic resonance imaging are more specific but are expensive and impractical for routine screening. Nevertheless, the researchers argue that these simple anthropometric measurements can add clinically relevant information at low cost.

The study has important limitations. Researchers lacked detailed data on physical activity, diet and genetic susceptibility to obesity, all of which can influence cardiovascular disease. WC and WHR were measured only once, so the analysis could not determine how changes in abdominal fat over time affected risk. The findings also describe associations rather than direct cause-and-effect relationships. Even so, the scale and duration of the study support the view that BMI should be treated as one component of cardiovascular assessment rather than a complete measure of health risk. Adding waist-based measurements could help identify people whose apparent weight category conceals a more concerning pattern of fat accumulation.

Subject of Research: The relationship between body mass index, waist circumference, waist-to-hip ratio and long-term cardiovascular disease risk.

Article Title: Risk Reclassification Beyond BMI by Waist Circumference and Waist-to-Hip Ratio Across Nine Cardiovascular Outcomes: Results from the Cross-Cohort Collaboration

News Publication Date: 11-Aug-2026

Web References: Journal of the American College of Cardiology, DOI: 10.1016/j.jacc.2026.05.050

References: Dardari ZA et al., “Risk Reclassification Beyond BMI by Waist Circumference and Waist-to-Hip Ratio Across Nine Cardiovascular Outcomes: Results from the Cross-Cohort Collaboration,” Journal of the American College of Cardiology.

Keywords: cardiovascular disease, heart disease, body mass index, BMI, waist circumference, waist-to-hip ratio, central adiposity, visceral fat, obesity, cardiovascular risk, myocardial infarction, stroke, heart failure, atrial fibrillation

Visceral fat is located deep within the abdominal cavity, surrounding vital organs such as the liver, pancreas, and intestines. This prime anatomical positioning allows VAT to communicate with systemic physiology through the secretion of bioactive molecules, including cytokines, adipokines, exosomes, and lipotoxic metabolites. These secretions mediate inter-organ crosstalk and significantly shape metabolic homeostasis. While subcutaneous adipose tissue has traditionally been considered a relatively benign lipid storage depot, VAT’s secretory profile is more likely to promote insulin resistance, chronic inflammation, and metabolic dysfunction when dysregulated. Yet, this relationship is not absolute and appears to depend heavily on the biological context and tissue microenvironment.

Lipid spillover is a critical pathogenic mechanism implicated in the adverse effects of VAT expansion. When the capacity of VAT to safely store lipids is overwhelmed—due in part to impaired preadipocyte differentiation—the excess lipids overflow into ectopic sites such as liver and muscle. This ectopic lipid deposition contributes directly to lipotoxicity, mitochondrial dysfunction, and systemic insulin resistance. The inability of preadipocytes to mature into healthy adipocytes capable of lipid sequestration exacerbates this harmful state. Thus, adipocyte turnover and regeneration within visceral fat depots emerge as key determinants of metabolic resilience or vulnerability.

Chronic inflammation acts as both a driver and a consequence of VAT dysfunction, perpetuating a vicious cycle detrimental to metabolic health. The infiltration of proinflammatory immune cells, including macrophages and T cells, within visceral adipose tissue exacerbates the secretion of inflammatory cytokines such as TNF-α, IL-6, and MCP-1. This persistent inflammatory milieu impairs insulin signaling pathways and further promotes adipocyte dysfunction. Notably, the inflammatory response in VAT is highly heterogeneous and modulated by genetic predispositions and hormonal changes, including the decline in sex steroids observed during aging.

Aging itself fundamentally alters the biology of visceral adipose tissue. Senescent cells accumulate within VAT, releasing a slew of proinflammatory factors collectively termed the senescence-associated secretory phenotype (SASP). This systemic low-grade inflammation or “inflammaging” contributes to metabolic decline and heightened cardiovascular risk in elderly populations. Moreover, aging diminishes the regenerative capacity of adipose progenitors, amplifying lipid spillover and inflammatory cascades. Consequently, VAT’s pathogenicity intensifies with age, linking visceral adiposity mechanistically to the biological processes underlying chronological and metabolic aging.

Genetic factors add another layer of complexity to VAT-associated metabolic dysfunction. Polymorphisms in genes regulating adipocyte differentiation, inflammatory responses, and lipid metabolism modulate individual susceptibility to harmful VAT expansion. Such genetic variability partially explains why some individuals harbor significant visceral fat reserves yet maintain a metabolically healthy phenotype, while others develop severe insulin resistance and cardiovascular complications at comparatively lower VAT levels. Decoding these genetic influences remains critical for personalized approaches in managing visceral adiposity.

VAT-derived extracellular vesicles, particularly exosomes, have recently garnered attention as key mediators of intercellular communication linking visceral fat to systemic metabolic health. These nanosized vesicles carry lipids, proteins, and nucleic acids, including microRNAs, which can reprogram recipient tissues such as liver, muscle, and endothelium. Exosomes secreted by dysfunctional VAT exhibit altered cargo that promotes insulin resistance, endothelial dysfunction, and impaired lipid metabolism. Elucidating the molecular contents and targets of these vesicles offers promising avenues for diagnostic biomarker development and therapeutic intervention.

Adipokines—hormones secreted by fat cells—also play a pivotal role in modulating the systemic consequences of visceral fat. Leptin, adiponectin, resistin, and visfatin represent just a few of the adipokines intricately involved in energy balance, insulin sensitivity, and inflammation. While leptin resistance is common in VAT accumulation, decreased adiponectin levels exacerbate insulin resistance and vascular dysfunction. Understanding the context-dependent changes in adipokine secretion profiles is essential for refining therapeutic strategies aimed at restoring metabolic equilibrium.

Emerging technological advancements have begun to unravel the metabolic heterogeneity within visceral fat depots. Single-cell transcriptomics and spatial omics approaches have identified distinct adipocyte subpopulations with diverse functions, including thermogenic capability, immune cell crosstalk, and extracellular matrix remodeling. These findings suggest that not all visceral adipocytes contribute equally to metabolic dysfunction. Targeting specific subpopulations may provide more precise and effective ways to curb pathological VAT expansion without compromising essential fat functions.

From a translational perspective, numerous strategies are under investigation to mitigate the deleterious impact of VAT. Lifestyle interventions such as caloric restriction and exercise remain foundational, effectively reducing VAT volume and improving metabolic markers. Pharmacological agents targeting adipogenesis, inflammation, and lipid metabolism are also being developed. Promising experimental approaches include senolytic drugs to eliminate senescent cells within VAT, modulators of adipokine signaling, and exosome-based therapies aimed at reprogramming dysfunctional fat communication networks.

The modulation of hormonal pathways presents another promising therapeutic axis. For example, selective estrogen receptor modulators and androgen replacement therapies may ameliorate sex steroid deficiencies that exacerbate VAT accumulation, particularly in postmenopausal women and aging men. Moreover, glucocorticoid receptor antagonists and novel peptide hormones designed to enhance adipocyte differentiation and function represent expanding frontiers in combating visceral fat-linked metabolic disease.

Notably, the concept of “healthy visceral fat” is gaining traction. Under specific physiological or therapeutic conditions, VAT can engage in beneficial roles such as lipid buffering, endocrine regulation, and immune modulation. This paradigm shift reframes VAT not as an inherently pathological tissue but as one whose health relevance is shaped by its functional state and systemic context. Such perspectives emphasize the importance of maintaining or restoring adipose tissue plasticity and homeostasis for metabolic health and longevity.

Collectively, these insights redefine visceral adipose tissue as a modifiable and context-sensitive contributor to health and disease. Rather than a unidimensional villain in metabolic syndrome and aging, VAT assumes a complex role whose outcomes depend on intricate molecular and cellular interactions. This revised understanding opens novel pathways for interventions tailored not only to reduce VAT mass but also to neutralize its pathological secretions and enhance its beneficial functions.

As research progresses, the integration of multi-omics, advanced imaging, and longitudinal clinical data will be critical to fully disentangle the causal pathways linking VAT, metabolic health, and aging. Such comprehensive knowledge will empower precision medicine strategies tailored to individuals’ genetic backgrounds, environmental exposures, and aging trajectories. Ultimately, targeting VAT holds remarkable promise as a lever for improving metabolic resilience and extending healthy lifespan in the increasingly aging global population.

The recognition that visceral fat biology is plastic and influenced by systemic factors compels us to rethink interventions from purely weight-centric approaches toward nuanced therapies addressing tissue functionality, immune environment, and regenerative capacity. This conceptual evolution heralds a new era in metabolic research, one that embraces the dynamism of adipose tissue in the context of organismal health, aging, and longevity.

In conclusion, visceral adipose tissue represents both a sentinel and an active participant in the complex networks governing metabolic health and aging. The pathogenic potential of VAT is not inherent but emerges from a confluence of impaired adipocyte differentiation, lipid spillover, chronic inflammation, genetic predisposition, hormonal changes, and age-related senescence. By harnessing a deeper mechanistic understanding of these interdependencies, future therapeutic strategies may transform VAT from a menace into a target for promoting metabolic vitality and lifelong health.

Subject of Research:
Visceral adipose tissue’s role in systemic metabolic health, dysfunction, and aging mechanisms.

Article Title:
Visceral adiposity, metabolic health and aging.

Article References:
Maeyens, L.T., Nelson, J.F. & Zhao, S. Visceral adiposity, metabolic health and aging. Nat Aging (2026). https://doi.org/10.1038/s43587-026-01076-4

Image Credits:
AI Generated

DOI:
https://doi.org/10.1038/s43587-026-01076-4