Predictors of mortality in heart failure with reduced ejection fraction: interaction between diabetes mellitus and impaired renal function

Background The harmful effect of diabetes mellitus (DM) on mortality in patients with heart failure with reduced ejection fraction (HFrEF) remains controversial. Furthermore, it seems that no consistent conclusion on whether chronic kidney disease (CKD) modifies the relationship of DM and poor prognosis in patients with HFrEF. Methods We analyzed the individuals with HFrEF from the Cardiorenal ImprovemeNt (CIN) cohort between January 2007 and December 2018. The primary endpoint was all-cause mortality. The patients were divided into four groups (control vs. DM alone vs. CKD alone vs. DM and CKD). Multivariate Cox proportional hazards analysis was conducted to examine the association among DM, CKD and all-cause mortality. Results There were 3,273 patients included in this study (mean age: 62.7 ± 10.9 years, 20.4% were female). During a median follow-up of 5.0 years (interquartile range: 3.0–7.6 years), 740 (22.6%) patients died. Patients with DM have a higher risk of all-cause mortality (HR [95% confidence interval (CI)]:1.28[1.07–1.53]) than those without DM. In patients with CKD, DM had a 61% (HR [95% CI]:1.61[1.26–2.06]) increased adjusted risk of death relative to non-DM, while in patients with non-CKD, there was no significantly difference in risk of all-cause mortality (HR [95% CI]:1.01[0.77–1.32]) between DM and non-DM (p for interaction = 0.013). Conclusions Diabetes is a potent risk factor for mortality in patients with HFrEF. Furthermore, DM had a substantially different effect on all-cause mortality depending on CKD. The association between DM and all-cause mortality was only observed in patients with CKD.