Highlight
- Traditional BMI categories can misclassify cardiovascular risk due to lack of body composition detail.
- Measures of central adiposity — waist circumference (WC) and waist-to-hip ratio (WHR) — reclassify CVD risk across normal weight, overweight, and obesity categories.
- Individuals with normal BMI but elevated WC or WHR experience 15% to 50% higher risk of various cardiovascular outcomes.
- Elevated WC or WHR in obesity identifies a substantial proportion of attributable cardiovascular risk, particularly for heart failure and atrial fibrillation.
Study Background
Body mass index (BMI) is a widely used, simple anthropometric metric to classify individuals as underweight, normal weight, overweight, or obese. Although BMI correlates with total adiposity, it does not differentiate between fat mass and lean mass nor does it provide information on fat distribution. This limitation is clinically important since central adiposity — fat accumulation around the abdomen — has been linked with greater cardiometabolic risk than overall adiposity. Measures such as waist circumference (WC) and waist-to-hip ratio (WHR) serve as proxies for central adiposity and may better capture the heterogeneity in cardiovascular disease (CVD) risk that is overlooked when relying solely on BMI. Given the global burden of CVD and the importance of accurate risk stratification, understanding whether WC and WHR provide incremental prognostic information beyond BMI can inform clinical assessment and public health strategies.
Study Design
This investigation leveraged harmonized pooled data from the Cross-Cohort Collaboration (CCC), encompassing 259,388 adult participants drawn from 15 prospective cohorts with baseline WC or WHR data available alongside long-term follow-up for cardiovascular outcomes. The analysis considered nine primary endpoints involving fatal and nonfatal myocardial infarction, stroke, heart failure, atrial fibrillation, total coronary heart disease, total cardiovascular disease, coronary heart disease mortality, cardiovascular mortality, and all-cause mortality. Median follow-up was 20 years, enabling robust hazard estimation.
Multivariable Cox proportional hazards modeling estimated hazard ratios for elevated versus normal WC and WHR, stratified across conventional BMI categories (normal weight, overweight, obesity). Elevated WC and WHR were defined using clinically established cutoffs. The study also examined the extent of risk reclassification and misclassification inherent to using BMI alone versus incorporating measures of central adiposity.
Key Findings
The study’s findings highlighted pronounced discrepancies between BMI-based classifications and central adiposity measures. Within the normal BMI range, 5% had elevated WC while notably 18% had elevated WHR, translating to hidden risk. Among overweight individuals, roughly 40% exhibited elevated WC or WHR. Surprisingly, in the obese category, 9% had WC and 45% had WHR below clinical risk thresholds, suggesting overestimation of risk based on BMI alone.
Critically, individuals with normal weight or overweight but with elevated WC or WHR had a 15% to 50% increased risk for most cardiovascular outcomes compared to those with normal central adiposity. This underscores the prognostic importance of central fat accumulation even in non-obese individuals.
For the obese subgroup, having low WC was generally not linked with significantly different cardiovascular risk compared with normal weight individuals with low WC, apart from a notably lower risk for all-cause mortality. However, sex-based differences emerged: women with obesity but low WHR still carried elevated risk for all cardiovascular endpoints relative to normal weight women with low WHR, albeit at lower magnitudes than women with obesity and high WHR.
Population attributable risk associated with elevated central adiposity in obesity ranged from 13% to 49%, with the highest estimates observed for heart failure and atrial fibrillation. This implies that a significant fraction of these cardiovascular events in obese individuals could be linked to central adiposity rather than total adiposity alone.
Expert Commentary
This study strengthens the argument for incorporating WC and WHR into routine cardiovascular risk assessment protocols, moving beyond BMI as a solitary obesity metric. Clinicians should be aware of the potential for BMI to obscure elevated risk in patients, particularly those with normal or overweight BMI but central obesity. The sex differences identified highlight the need for sex-specific risk stratification models.
Limitations include reliance on anthropometric surrogates rather than direct imaging of visceral fat and possible cohort heterogeneity despite harmonization. Generalizability to diverse ethnic populations, especially those underrepresented in CCC cohorts, requires further study. Moreover, mechanistic studies could illuminate the pathophysiological basis linking central fat depots with specific cardiovascular outcomes.
Conclusion
The evidence from this large, multi-cohort analysis demonstrates that waist circumference and waist-to-hip ratio provide critical diagnostic and prognostic information beyond BMI across a spectrum of cardiovascular outcomes. Incorporating these simple measurements in clinical practice could improve cardiovascular risk stratification, facilitating targeted preventive strategies. Given the substantial proportion of individuals misclassified if relying solely on BMI, clinicians and public health practitioners should consider central adiposity metrics to better identify those at elevated cardiovascular risk.
Funding and ClinicalTrials.gov
The study was supported by multiple institutions involved in the Cross-Cohort Collaboration. Specific funding sources are not detailed in the primary publication. This observational study utilized harmonized cohort data and was not registered as a clinical trial.
References
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