Body Mass Index (BMI) and BMI Variability are Risk Factors for Heart Failure with Preserved and Reduced Ejection Fraction in a Longitudinal Cohort Study Using Real-World Electronic Health Records

ObjectiveThe aim of this study is to evaluate the differential impact of BMI and long-term intra-individual BMI variability on the risk of developing heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF)in overweight or obese patients. MethodThe primary outcome was the time to incident HFrEF or HFpEF determined by International Classification of Disease codes (ICD-9 and ICD-10). BMI variability was assessed based on five-year BMI measurements using four metrics: the intra-individual standard deviation (SD), the coefficient of variation (CV), the variability independent of the mean (VIM), and the average successive variability (ASV). The subclassification of HF was based on the LVEF recorded within 90 days of the initial diagnosis. The hazard ratios (HRs) were estimated by multivariable-adjusted Cox proportional hazards regression models. ResultsAmong the 51,444 eligible patients, 1,871 developed HFpEF, and 1,018 developed HFrEF over a follow-up period of the mean of 4.62 years. Per each 1-SD increment, the HRs of SD, CV, VIM and ASV of BMI were 1.10 (95%CI, 1.04-1.16), 1.04 (95%CI, 1.02-1.06), 1.16 (95%CI, 1.06-1.27) and 1.13 (95%CI, 1.04-1.22) for HFpEF, and 1.09 (95%CI, 1.00-1.18), 1.03 (95%CI, 1.00-1.06), 1.15 (95% CI, 1.02-1.31), and 1.08 (95%CI, 0.96-1.21), for HFrEF, respectively. Five statistical models were performed adjusting for different sets of covariates. Moreover, baseline BMI from patients in obesity II and III all exhibited progressively higher HRs for HFpEF with HRs of 1.45 (95%CI, 1.15-1.83), and 2.52 (95%CI, 1.99-3.19), while only patients in obesity class III demonstrated an increased risk for HFrEF with HR of 1.50 (95%CI, 1.11-2.04). Conclusions and RelevanceIn this large cohort of overweight and obese patients, increasing BMI variability was associated with a higher risk of developing HFpEF and HFrEF after adjusting for relevant risk factors. Study ImportanceWhat is already known: O_LIThe variability of body mass index (BMI) is a risk factor for negative cardiovascular outcomes in various cohorts. C_LIO_LIA previous study showed that variability in adiposity indices is related to an increased risk of overall heart failure (HF) in patients with type two diabetes. C_LI What are the new findings in your manuscript: O_LIur analysis examined the differential association between intra-individual BMI variability derived and the increased incidence of two subtypes of (HF), heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF), using real-world clinical patient data. C_LIO_LIassociations were statistically significant across three different metrics, including standard deviation, coefficient of variation, and the variability independent of the mean. C_LIO_LImight your results change the direction of research or the focus of clinical practice? C_LIO_LIis important for clinicians to minimize body weight fluctuation in patients with overweight and obesity to meet weight loss goals due to its potential to reduce the risk of HF, especially given the increasing global prevalence of HFpEF and limited therapeutical options for it. C_LIO_LIstudy also provides evidence of the feasibility and reliability of using electronic medical data collected from various clinical settings to define indicators for clinical decision-making C_LI