Antecedent Kidney Function and Cardiovascular Mortality in Over 300 000 Patients With Incident Heart Failure With Preserved Ejection Fraction

BACKGROUND: Chronic kidney disease is a frequent comorbidity in heart failure with preserved ejection fraction (HFpEF) and has been proposed as a contributor to its development. However, the spectrum of antecedent kidney function before incident HFpEF and its association with subsequent cardiovascular outcomes remains unclear. METHODS: We conducted a multicenter cohort study across 170 US Veterans Affairs hospitals, including patients with incident HFpEF diagnosed between January 1, 2000, and June 30, 2025. HFpEF was ascertained using natural language processing-derived left ventricular ejection fraction ≥50% closest to the incident HF date and a validated HFpEF algorithm incorporating loop diuretic use, elevated natriuretic peptide levels, and an HFpEF–age, body mass index, and atrial fibrillation score >0.5. Antecedent kidney function was classified using 2 estimated glomerular filtration rate (eGFR) measurements obtained ≥90 days apart before incident HFpEF and urine albumin-to-creatinine ratio. We characterized antecedent kidney function, including albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g), and examined its associations with 5-year cardiovascular death and heart failure hospitalization. Competing-risk analysis was performed accounting for noncardiovascular death as a competing event for cardiovascular death. RESULTS: Of 304 712 patients meeting HFpEF ascertainment criteria, 236 910 comprised the final cohort; 51% had antecedent eGFR ≥60 mL/min per 1.73m 2 . Overall, 15% had an eGFR ≥90 mL/min per 1.73m 2 . Patients with eGFR <60 mL/min per 1.73m 2 were older and had more diabetes and hypertension. 51% of the patients with eGFR <60 mL/min per 1.73m 2 had body mass index <30 kg/m 2 , including 20% with body mass index <25 kg/m 2 . Progressively lower antecedent kidney function was associated with graded increases in cardiovascular death and heart failure hospitalization. Among decedents, the proportion of deaths attributed to cardiovascular causes increased from 25% in the preserved eGFR (≥90 mL/min per 1.73m 2 ) without documented albuminuria to 32% with albuminuria and 38% with advanced kidney dysfunction ( P <0.001). CONCLUSIONS: In this nationwide study of patients with incident HFpEF, antecedent kidney dysfunction was common but not uniformly present before HFpEF onset. Furthermore, among patients who developed HFpEF, antecedent kidney dysfunction identified a higher-risk phenotype, with progressively greater cardiovascular mortality and heart failure hospitalization with declining kidney function.