Study Background and Disease Burden
Obesity has become a prevalent risk factor in individuals suffering from heart failure, particularly those with heart failure with preserved ejection fraction (HFpEF). HFpEF accounts for a significant proportion of heart failure cases, contributing to morbidity and mortality worldwide. The rising incidence of obesity further complicates the clinical management of patients with HFpEF, necessitating a deeper understanding of how different measures of adiposity affect not just cardiovascular outcomes but renal health as well.
Existing literature indicates a bidirectional relationship between kidney disease and heart failure, often exacerbated in the context of obesity. Chronic kidney disease (CKD) can worsen heart failure symptoms and outcomes, while heart failure can lead to the deterioration of renal function. Given these interconnections, this study evaluates whether specific anthropometric measures related to body fat distribution, such as body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR), influence kidney-related outcomes in patients with HFpEF.
Study Design
This article presents a participant-level pooled analysis drawn from four contemporary clinical trials: DELIVER, PARAGON-HF, TOPCAT Americas, and I-PRESERVE. The objective was to assess the risk of adverse kidney outcomes—including sustained reductions in estimated glomerular filtration rate (eGFR) of ≥50%, the development of end-stage kidney disease (ESKD), and kidney-related mortality—based on various anthropometric measurements of obesity at baseline.
The analysis was conducted using multivariable Cox proportional hazards models, stratified by trial and treatment, to enhance the reliability of the results. Data on BMI was available for all participants in each trial; WC was specifically measured in patients from PARAGON-HF and TOPCAT Americas.
The inclusion criteria encompassed a diverse patient population with established HFpEF, thereby facilitating a comprehensive exploration of the role of obesity in kidney health within this patient subset.
Key Findings
The analysis included a total of 16,919 participants (mean age 71.9 years; 50.7% were women). The distribution of BMI categories was as follows: 18% of participants were classified as normal/underweight, 35% as overweight, and 47% as obese. Furthermore, data from 6,177 participants indicated a mean WC of 105 cm, with 95% classified as having elevated WHtR (≥0.5).
During a median follow-up period of 2.3 years, with interquartile ranges between 0.6 to 2.9 years, 339 kidney-related events were documented. Notably, higher BMI had no statistically significant relationship with the incidence of kidney events (hazard ratio [HR]: 0.99; 95% confidence interval [CI]: 0.96-1.02; p = 0.45). In contrast, greater WC and WHtR were associated with significantly increased risks of adverse kidney outcomes:
– For WC, every 10 cm increment was linked to a risk increase (HR: 1.15; 95% CI: 1.01-1.31; p = 0.03).
– For WHtR, every 0.1 unit increase was correlated with an elevated risk (HR: 1.32; 95% CI: 1.07-1.62; p = 0.01).
These results emphasize that while BMI as a singular measure did not present a relationship with kidney outcomes, central obesity (as indicated by WC and WHtR) provided a more relevant risk assessment in patients with HFpEF.
Expert Commentary
The findings of this pooled analysis align with emerging perspectives in obesity and kidney health, emphasizing the importance of body fat distribution over generalized obesity measures such as BMI. Experts suggest these results could lead to revised recommendations for clinicians, who currently utilize BMI predominantly in assessing patient risk and health status.
Understanding that WC and WHtR may serve as more predictive markers could direct clinicians to better manage patients at risk for renal complications stemming from their heart failure. However, this study is not without limitations. As a secondary analysis of primary trial data, potential confounding variables could exist that were not fully accounted for in the multivariable models.
Additionally, while the study population indeed reflects a sample predominantly composed of older individuals with a substantial incidence of obesity, extrapolating these findings to younger or more diverse populations will require caution. Further research will be necessary to evaluate the mechanistic links between abdominal adiposity and renal dysfunction within this cohort.
Conclusions
This pooled analysis from four large-scale HFpEF trials highlights the prevalence of obesity and excess abdominal adiposity and establishes significant associations between WC and WHtR with increased kidney outcome risks. In contrast, BMI was not significantly associated with these adverse events. As these findings emerge, the focus on how we measure and interpret obesity in clinical practice may need to shift toward more nuanced approaches that consider individual body fat distribution dynamics. Future studies investigating targeted interventions to improve abdominal obesity in HFpEF patients may pave the way for enhanced kidney and overall health outcomes.
References
Lassen MCH, Ostrominski JW, Claggett BL, Neuen BL, Beldhuis IE, Butt JH, Biering-Sørensen T, Desai AS, Lewis EF, Jhund PS, Mc Causland F, Anand IS, Pfeffer MA, Pitt B, Zannad F, Zile MR, McMurray JJV, Solomon SD, Vaduganathan M. Obesity and Risk of Kidney Outcomes in Heart Failure With Preserved Ejection Fraction: A Participant-Level Pooled Analysis of 4 Contemporary Trials. JACC Heart Fail. 2025 Aug;13(8):102498. doi:10.1016/j.jchf.2025.03.042. Epub 2025 Jun 9. PMID: 40494011.