Intentional Weight Loss, Waist Circumference Reduction, and Mortality Risk Among Postmenopausal Women.

Importance: Research investigating weight loss and mortality risk often fails to differentiate between intentional and unintentional weight loss and typically uses body mass index (BMI) as the measure of excess body weight. Objective: To evaluate associations between weight loss and waist circumference (WC) reduction and mortality, considering weight loss intentionality. Design, Setting, and Participants: This cohort study used data from the Women's Health Initiative Observational Study, which had a prospective cohort with mean follow-up of 18.6 years ending in February 2023. The study included women aged 50 to 79 years at 40 clinical centers in the US. Women with missing data, cancer at baseline, or considered underweight at baseline were excluded. Data were collected from September 1993 to February 2023 and were analyzed from June to December 2024. Exposures: Measured weight loss and WC reduction between baseline and year 3, stratified by women who reported intentional weight loss or not. Main Outcomes and Measures: Outcomes included adjudicated all-cause, cancer, cardiovascular, and other mortality through the end of follow-up. Cox proportional hazards regression models were used to evaluate the associations (hazard ratios [HRs] and 95% CIs) between weight loss, WC reduction, and mortality over 18.6 years of follow-up. Results: This study included 58 961 women at baseline (mean [SD] age, 63.3 [7.2] years; mean [SD] BMI, 27.0 [5.6]; mean [SD] WC, 84.1 [13.0] cm). As of February 28, 2023, 29 183 women (49.5%) died from all causes. Intentional weight loss measured by questionnaire was associated with lower subsequent mortality rates for all-cause mortality (HR, 0.88; 95% CI, 0.86-0.90), cancer mortality (HR, 0.87; 95% CI, 0.82-0.92), cardiovascular mortality (HR, 0.87; 95% CI, 0.83-0.91), and other mortality (HR, 0.89; 95% CI, 0.86-0.92), comparing loss of 5 pounds or more to stable weight. Reported intentional weight loss coupled with actual weight reduction of 5% or more was associated only with lower cardiovascular mortality (HR, 0.90; 95% CI, 0.81-0.99). Reported intentional weight loss coupled with measured WC loss was associated with lower rates of all-cause mortality (HR, 0.91; 95% CI, 0.86-0.95), cancer mortality (HR, 0.85; 95% CI, 0.76-0.95), and cardiovascular mortality (HR, 0.79; 95% CI, 0.72-0.87). Unintentional weight loss or unintentional WC loss were each associated with increased mortality risk for all groups, as were weight gain and WC gain. Conclusions and Relevance: In this cohort study, reported intentional weight loss efforts that were coupled with measured WC reductions were associated with lower risk of all-cause, cancer, and cardiovascular mortality. Attention to diet and exercise that promote reductions in central adiposity should be encouraged.