Obesity and Risk of Kidney Outcomes in Heart Failure With Preserved Ejection Fraction: A Participant-Level Pooled Analysis of 4 Contemporary Trials

Mats C H Lassen; John W Ostrominski; Brian L Claggett; Brendon L Neuen; Iris E Beldhuis; Jawad Butt; Tor Biering-Sørensen; Akshay S Desai; Eldrin F Lewis; Pardeep S Jhund; Finnian Mc Causland; Inder S Anand; Marc A Pfeffer; Bertram Pitt; Faiez Zannad; Michael R Zile; John J V McMurray; Scott D Solomon; Muthiah Vaduganathan

doi:10.1016/j.jchf.2025.03.042

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 Jun 9;13(8):102498. doi: 10.1016/j.jchf.2025.03.042. Online ahead of print.

Authors

Mats C H Lassen¹, John W Ostrominski², Brian L Claggett³, Brendon L Neuen⁴, Iris E Beldhuis⁵, Jawad Butt⁶, Tor Biering-Sørensen⁷, Akshay S Desai³, Eldrin F Lewis⁸, Pardeep S Jhund⁹, Finnian Mc Causland¹⁰, Inder S Anand¹¹, Marc A Pfeffer³, Bertram Pitt¹², Faiez Zannad¹³, Michael R Zile¹⁴, John J V McMurray⁹, Scott D Solomon³, Muthiah Vaduganathan¹⁵

Affiliations

¹ Brigham and Women's Hospital, Cardiovascular Division, Harvard Medical School, Boston, Massachusetts, USA; Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
² Brigham and Women's Hospital, Cardiovascular Division, Harvard Medical School, Boston, Massachusetts, USA; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³ Brigham and Women's Hospital, Cardiovascular Division, Harvard Medical School, Boston, Massachusetts, USA.
⁴ The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
⁵ University of Groningen, Department of Cardiology, University Medical Center Groningen, the Netherlands.
⁶ Department of Cardiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark; BHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
⁷ Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cardiovascular Division, Department of Medicine, Stanford University School of Medicine, Palo Alto, California, USA.
⁸ Cardiovascular Division, Department of Medicine, Stanford University School of Medicine, Palo Alto, California, USA.
⁹ BHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
¹⁰ Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
¹¹ Veterans Affairs Medical Center and University of Minnesota, Minneapolis, Minnesota, USA.
¹² Department of Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
¹³ Université de Lorraine, Inserm Clinical Investigation Centre, CHU, Nancy, France.
¹⁴ Ralph H. Johnson Veterans Affairs Medical Center and Medical University of South Carolina, Charleston, South Carolina, USA.
¹⁵ Brigham and Women's Hospital, Cardiovascular Division, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: mvaduganathan@bwh.harvard.edu.

PMID: 40494011
DOI: 10.1016/j.jchf.2025.03.042

Abstract

Background: Obesity is prevalent among patients with heart failure with preserved ejection fraction (HFpEF).

Objectives: This study aims to evaluate whether anthropometrics including body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) are associated with kidney outcomes in patients with HFpEF.

Methods: In this participant-level pooled analysis of DELIVER, PARAGON-HF, TOPCAT Americas, and I-PRESERVE, we evaluated the impact of adiposity-related anthropometrics on risk of kidney outcomes (sustained eGFR reduction of ≥50%, end-stage kidney disease, or kidney-related death). BMI was collected in all trials and WC was collected in PARAGON-HF and TOPCAT. Multivariable Cox models stratified by trial and treatment were used.

Results: Overall, 16,919 participants were included in the analysis (71.9 ± 8.7 years of age; 50.7% women). Of these, 18% were normal/underweight, 35% had overweight, and 47% had obesity as assessed by BMI. WC data was available in 6,177 (105 cm; Q1-Q3: 95-116 cm), and 95% had an elevated WHtR (≥0.5). During follow-up (2.3 years; Q1-Q3: 0.6-2.9 years), 339 kidney outcome events accrued. In multivariable models, higher BMI was not associated with incident kidney events (HR: 0.99; 95% CI: 0.96-1.02; P = 0.45, per 1 kg/m²). However, higher WHtR and WC were positively and linearly associated with the risk of kidney outcomes (WC per 10 cm: HR: 1.15 [95% CI: 1.01-1.31]; P = 0.03; WHtR per 0.1 unit: HR: 1.32 [95% CI: 1.07-1.62]; P = 0.01).

Conclusions: In this participant-level pooled analysis of 4 large-scale HFpEF outcome trials, obesity and excess abdominal adiposity were highly prevalent. WC and WHtR were associated with an increased risk of kidney outcomes, while BMI was not. (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213) (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711) (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302) (Irbesartan in Heart Failure With Preserved Systolic Function [I-PRESERVE]; NCT00095238).

Keywords: heart failure with preserved ejection fraction; kidney outcomes; obesity.

Associated data

ClinicalTrials.gov/NCT00095238