Development and Validation of Body Mass Index–Specific Waist Circumference Thresholds in Postmenopausal Women A Prospective Cohort Study

Background: A 2020 consensus statement proposed body mass index (BMI)–specific waist circumference (WC) thresholds to improve patient care. Objective: To determine whether stratifying BMI categories by BMI-specific WC thresholds improves mortality risk prediction. Design: Prospective cohort study. Setting: Women’s Health Initiative multicenter, population-based U.S. study, with enrollment from 1993 to 1998 and follow-up through 2021. Participants: 139 213 postmenopausal women aged 50 to 79 years were included in a development cohort (n ¼ 67 774) and 2 external validation cohorts. Validation Cohort 1 had high prevalence of overweight or obesity (n ¼ 48 335), and Validation Cohort 2 included diverse, geographically separate centers (n ¼ 23 104). Measurements: Height, weight, and WC measured at enrollment. BMI categories were normal weight (18.5 to <25 kg/m²), overweight (25 to <30 kg/m²), obesity-1 (30 to <35 kg/m²), obesity-2 (35 to <40 kg/m²), and obesity-3 (≥40 kg/m²), with further stratification by prespecified WC thresholds (≥80, ≥90, ≥105, ≥115, and ≥115 cm, respectively). Mortality was ascertained annually and was supplemented with serial National Death Index queries. Ten- and 20-year mortality prediction models that included BMI categories were compared to models with BMI categories stratified by WC thresholds using c-statistics and continuous net reclassification improvement (NRI). Results: Over a median of 24 years of follow-up, 69 297 participants died. Multivariable-adjusted mortality risk was consistently greater for BMI categories with large WC than those with normal WC. Compared with women with normal weight and normal WC, women with normal or overweight BMI but large WC (hazard ratios [HRs], 1.17 [95% CI, 1.12 to 1.21] and 1.19 [CI, 1.15 to 1.24], respectively) had risk similar to those with obesity-1 but normal WC (HR, 1.12 [CI, 1.08 to 1.16]). Mortality associated with obesity-1 and large WC (HR, 1.45 [CI, 1.35 to 1.55]) was similar to that with obesity-3 and normal WC (HR, 1.40 [CI, 1.28 to 1.54]). Models with BMI-specific WC thresholds improved discrimination and risk stratification at 10 years for Validation Cohort 1; c-statistics improved by 0.7% (CI, 0.3% to 1.0%) to 61.3% (CI, 60.2% to 62.5%), and continuous NRI was 20.4% (CI, 17.3% to 23.6%). Results were mixed for Validation Cohort 2; risk stratification improved (continuous NRI, 12.3% [CI, 8.5% to 16.0%]), but not discrimination. Results were similar at 20 years. Limitation: The study did not include men or younger women. Conclusion: Further stratifying BMI categories by WC thresholds modestly improved mortality risk stratification, with larger WC predicting greater mortality, although the degree of improvement varied by cohort. Discrimination did not improve consistently.