Risk Reclassification Beyond BMI by Waist Circumference and Waist-to-Hip Ratio Across 9 Cardiovascular Outcomes

Background: Body mass index (BMI) is commonly used to assess total adiposity, yet does not provide insight into overall body composition, potentially obscuring meaningful heterogeneity in cardiovascular disease (CVD) risk. Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are commonly discordant with BMI and may provide additional prognostic information. Objectives: The purpose of this study was to quantify the reclassification and misclassification of traditional normal weight/overweight/obesity categories using central adiposity and to evaluate the prognostic implications for CVD risk using the CCC (Cross-Cohort Collaboration). Methods: We included 259,388 participants from 15 cohorts of the CCC with harmonized data on either WC or WHR data and at least 1 of 9 outcomes: time to first fatal and nonfatal myocardial infarction, fatal and nonfatal stroke, heart failure, atrial fibrillation, total coronary heart disease, total CVD, coronary heart disease mortality, CVD mortality, and all-cause mortality. Multivariable Cox proportional hazards models were used to estimate the HR of higher WC and WHR for each outcome across BMI categories. Results: Our sample included 259,351 individuals with WC data and 218,984 with WHR data, with a median follow-up of 20.0 years (95% CI: 12.7-23.5 years). Among individuals with normal weight, 5% had high WC and 18% had high WHR; among those with overweight, 39% had high WC and 40% had high WHR. Among those with obesity, 9% had low WC and 45% had low WHR. Among individuals with normal weight or overweight, clinically defined high WC or WHR was associated with 15% to 50% greater risk for most outcomes. Among those with obesity, low WC was not associated with a significantly different risk compared with normal weight and low WC, except for all-cause mortality, for which risk was significantly lower. In contrast to men, women with obesity but low WHR retained significantly higher risk for all outcomes compared with normal weight and low WHR; however, the HRs were smaller compared with those with obesity and high WHR. Among individuals with obesity, the population attributable risk associated with elevated WC or WHR ranged from 13% to 49%, with the highest estimates observed for elevated WC in heart failure and atrial fibrillation. Conclusions: WC and WHR identifies misclassification of conventional BMI categories and reclassifies CVD risk across normal weight, overweight, and obesity, adding diagnostic and prognostic value.