Increasing CKM Multimorbidity Linked to Higher Mortality and Readmission Risk in Heart Failure: JAMA
A nationwide US cohort study found that heart failure (HF) without other cardiovascular-kidney-metabolic (CKM) conditions was uncommon. Most hospitalized HF patients had multiple overlapping CKM conditions. Increasing CKM multimorbidity was independently associated with stepwise increases in mortality and hospital readmission, with the strongest prognostic impact seen in heart failure with reduced ejection fraction (HFrEF) and the weakest in HF with preserved ejection fraction (HFpEF). The study was published in JAMA Cardiology by Veraprapas K. and colleagues.
Epidemiological prevalence and clinical impact of CKM multimorbidity was assessed through the analysis of national database from the Get With The Guidelines–Heart Failure (GWTG-HF) registry. Study participants included 725,205 individuals with a median age of 72.0 years (IQR 61.0-82.0) and 53.3% male sex hospitalized for heart failure from 2019 to 2025. Besides, post-discharge outcomes in 123,271 Medicare participants (with median age of 80 years [IQR 73-87] and 52.2% female) admitted between 2019 and 2023 were assessed.
Exposure was defined through the number of coexisting CKM diseases (atherosclerotic cardiovascular disease, chronic kidney disease, diabetes, obesity [BMI ≥30 kg/m²]) ranging from one to four. The primary clinical endpoints assessed were in-hospital death, 1-year post-discharge all-cause mortality, and 1-year post-discharge heart failure hospitalization stratified by ejection fraction subgroups.
Key findings:
- Quantitative relationships were seen across 725,205 registry participants and 123,271 Medicare beneficiaries.
- In 725,205 patients who were hospitalized, 71.9% (521,739 individuals) had at least 2 overlapping CKM diagnoses, while only 6.7% (48,732 individuals) had only heart failure.
- Heart failure with preserved ejection fraction was found to have the largest percentage of CKM overlap.
- Compared to those with heart failure alone, those with 4 CKM had significantly increased in-hospital mortality on a stepwise fashion that was greatest in HFrEF (HFrEF aOR, 5.08 [95% CI, 4.43–5.83]; HFmrEF aOR, 2.37 [95% CI, 1.68–3.34]; HFpEF aOR, 2.05 [95% CI, 1.77–2.38]; P for interaction < 0.001).
- Among 4 CKM patients from Medicare beneficiaries, 1-year post-discharge mortality risk was highest in HFrEF (aHR, 2.10 [95% CI, 1.93–2.29]) compared to HFmrEF aHR, 1.38 [95% CI, 1.17–1.63], and HFpEF aHR, 1.09 [95% CI, 1.03–1.17].
- Also, 1-year heart failure readmission risk increased significantly among groups (HFrEF aHR, 2.33 [95% CI, 2.12–2.56]; HFmrEF aHR, 2.20 [95% CI, 1.82–2.66]; HFpEF aHR, 1.91 [95% CI, 1.77–2.06]; P for interaction < 0.001).
Concluding, real-life evidence based on national-level data shows that multimorbidity of cardiovascular, renal, and metabolic diseases is common in patients with heart failure, leading to a rapid and gradual rise in adverse outcomes. The findings made from the study show that even though CKM multimorbidity leads to adverse outcomes in the overall ejection fraction range, this effect is more evident in HFrEF patients.
Reference:
Kittipibul V, Ayodele I, Fonarow GC, et al. Cardiovascular-Kidney-Metabolic Overlap in Patients Hospitalized for Heart Failure. JAMA Cardiol. Published online September 30, 2026. doi:10.1001/jamacardio.2026.4215
