Antecedent Kidney Function and Cardiovascular Mortality in Over 300 000 Patients With Incident Heart Failure With Preserved Ejection Fraction
Mohamad Karnib, Padmini Selvaganesan, Irfan Helmy, Rosita Zakeri, Yusef Babar Saeed, Mohammed Najeeb Osman, Jayakumar Sahadevan, Amanda Ruth Vest, Yogesh N.V. Reddy, Varun SundaramBACKGROUND:
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 (
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.