BackgroundPrevious studies hardly evaluated the association of variability of body mass index (BMI) or waist circumference with clinical adverse events and investigated whether weight cycling had an effect on the prognosis of patients with heart failure with preserved ejection fraction (HFpEF).MethodsThis study was apost-hocanalysis of TOPCAT. Three outcomes were evaluated: the primary endpoint, cardiovascular disease (CVD) death, and heart failure hospitalization. Among them, CVD death and hospitalization were outcomes of heart failure. Kaplan–Meier curves were used to describe the cumulative risk of outcome and were tested using the log-rank test. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95%CIs for outcomes. We also performed a subgroup analysis, and several subgroups were compared.ResultsA total of 3,146 patients were included. In the Kaplan–Meier curves, the coefficients of variation of both BMI and waist circumference were grouped according to quartiles, with the Q4 group having the highest cumulative risk (log-rankP< 0.001). In the coefficient of BMI variation and the outcomes, the HRs for group Q4 of coefficient of variation of BMI were 2.35 (95%CI: 1.82, 3.03) for the primary endpoint, 2.40 (95%CI: 1.69, 3.40) for death, and 2.33 (95%CI: 1.68, 3.22) for HF hospitalization in model 3 (fully adjusted model) compared with group Q1. In the coefficient of waist circumference variation and the outcomes, group Q4 had increased hazard of the primary endpoint [HR: 2.39 (95%CI: 1.84, 3.12)], CVD death [HR: 3.29 (95%CI: 2.28, 4.77)], and HF hospitalization [HR: 1.98 (95%CI 1.43, 2.75)] in model 3 (fully adjusted model) compared with group Q1. In the subgroup analysis, there was a significant interaction in the diabetes mellitus subgroup (Pfor interaction = 0.0234).ConclusionWeight cycling had a negative effect on the prognosis of patients with HFpEF. The presence of comorbid diabetes weakened the relationship between waist circumference variability and clinical adverse events.