Cancer and the risk of death, heart-failure hospitalization, and major adverse cardiovascular events in HFpEF: a propensity-matched cohort study

Background Cancer and heart failure with preserved ejection fraction (HFpEF) frequently coexist in older adults and may share pathobiology, yet the independent effect of cancer on clinical outcomes in HFpEF remains uncertain. Methods We performed a single-center, retrospective cohort study using electronic health records from January 2020 through December 2024. Adults with HFpEF were stratified by a history of biopsy-proven or imaging-confirmed cancer. Primary outcomes were all-cause mortality, heart-failure hospitalization (HFH), and a composite of major adverse cardiovascular events (MACE: nonfatal myocardial infarction, HF rehospitalization, or arrhythmia requiring intervention). Secondary outcomes included change in New York Heart Association (NYHA) class, health status by Kansas City Cardiomyopathy Questionnaire (KCCQ), cause-specific mortality, and HFpEF-related health-care utilization. Propensity-score matching (PSM; 1:1 nearest-neighbor, caliper 0.2) balanced key covariates (age, sex, comorbidities, renal function, biomarkers, NYHA class, and LVEF). Time-to-event analyses used Kaplan–Meier methods and Cox proportional-hazards models with Greenwood 95% confidence bands and Schoenfeld diagnostics; prespecified subgroup analyses evaluated age, diabetes, chronic kidney disease (CKD), and NT-proBNP strata. Results Of 403 eligible patients (cancer, 174; non-cancer, 229; median follow-up, 36 months), PSM yielded 306 patients (153 per group) with excellent covariate balance. In the matched cohort, cumulative incidences at 48 months were higher with cancer than without for all-cause mortality (31.4% vs . 15.0%; log-rank P = 0.012), HFH (36.7% vs . 22.9%; P = 0.031), and MACE (43.1% vs . 32.7%; P = 0.050). In multivariable Cox models for HFH, cancer remained independently associated with risk across progressive adjustments: age-adjusted hazard ratio (HR) 1.42 (95% CI, 1.08–1.87), age-and-sex adjusted HR 1.40 (1.06–1.85), and fully adjusted HR 1.38 (1.02–1.87) after additional control for diabetes, CKD, and NT-proBNP. Subgroup analyses showed directionally consistent cancer effects without significant interactions (all P for interaction ≥0.05); the association was most prominent in patients aged ≥65 years, with diabetes or CKD, and with NT-proBNP above the cohort median. Secondary outcomes supported a greater clinical burden in the cancer group: fewer patients improved and more worsened in NYHA class (P = 0.041), cancer-related mortality was higher (16.3% vs . 3.3%; P<0.001), and HFpEF-related utilization increased (emergency department visits 2.1 ± 1.5 vs . 1.4 ± 1.2 and outpatient encounters 4.8 ± 2.3 vs . 3.9 ± 2.0 per patient-year; P ≤ 0.003). Findings in the unmatched cohort were concordant (48-month incidences: mortality 37.4% vs . 19.7%, HFH 41.4% vs . 30.1%, and MACE 54.0% vs . 39.3%). Subgroup analyses revealed significant associations observed in older patients (≥65 years; HR 1.35, 95% CI 1.02-1.79, P = 0.036), those with diabetes (HR 1.50, 95% CI 1.05-2.14, P = 0.026), CKD (HR 1.55, 95% CI 1.10-2.18, P = 0.013), and higher NT-proBNP levels (> median; HR 1.58, 95% CI 1.12-2.23, P = 0.010). Conclusions In middle-aged and older adults with HFpEF, concomitant cancer confers a sustained and clinically meaningful increase in mortality, HF hospitalization, and major cardiovascular events independent of traditional risk factors and biomarkers. These data support systematic cardio-oncology collaboration, biomarker-guided surveillance, and proactive HFpEF management in patients with cancer.