Effects of repeated weight changes on mortality are not well established. In this prospective cohort study, we followed 34,346 individuals from 1997 to 2018 for all-cause mortality, and 2016 for cause-specific mortality. At baseline, participants self-reported amount and frequency of prior weight loss. During 20.6 (median) years of follow-up, we identified 5627 deaths; 1783 due to cancer and 1596 due to cardiovascular disease (CVD). We used Cox Proportional Hazards models to estimate multivariable-adjusted Hazard Ratios (HRs) and 95% confidence intervals (CI). Participants with a weight loss > 10 kg had higher rates of all-cause (HR 1.22; 95%CI 1.09-1.36) and CVD mortality (HR 1.27; 95%CI 1.01-1.59) compared to individuals with no weight loss. Men who had lost > 10 kg had higher all-cause (HR 1.55; 95%CI 1.31-1.84) and CVD mortality (HR 1.55; 95%CI 1.11-2.15) compared to men with no weight loss. Participants who had lost ≥ 5 kg three times or more prior to baseline had increased rates of all-cause (HR 1.16; 95%CI 1.03-1.30) and CVD mortality (HR 1.49; 95%CI 1.20-1.85) compared to participants with no weight loss. We found no association between weight loss and cancer mortality. We conclude that previous and repeated weight loss may increase all-cause and CVD mortality, especially in men.
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