The underestimated risk of prediabetes on cardiovascular and renal outcomes in patients with heart failure

Abstract Introduction The global prevalence of prediabetes and diabetes is increasing, highlighting an urgent public health challenge. While the cardiovascular (CV) risks of diabetes are well established, data on the impact of prediabetes in HF patients remain limited. This study aimed to compare the effects of prediabetes and T2DM on hospitalization for HF (HHF), CV death, renal outcomes, and all-cause mortality in an unselected HF cohort. Methods Patients with HF admitted to a tertiary academic center between January 2005 and July 2019 were included in this analysis and stratified by glycemic status. Prediabetes was defined as an HbA1c level between 5.7% and 6.4% in the absence of diabetes mellitus. Patients were further categorized based on left ventricular ejection fraction (LVEF) into HFrEF (40% LVEF) or HFpEF (≥40% LVEF) groups. The primary outcome was a composite of CV death/HHF. Secondary outcomes included the individual components of the primary outcome, all-cause mortality, and renal outcomes, defined as renal death or the need for kidney replacement therapy. Adjusted cox regression models were used to assess associations. Results A total of 4,426 unselected HF patients (median age: 69 years, 28.2% female) were included in this analysis and followed for a median of 2.8 years. Among them, 39.9% (n=1,767) were classified as diabetic, 30.5% (n=1,349) as prediabetic, and 29.6% (n=1,310) as normoglycemic, with median HbA1c levels of 5.4%, 5.9%, and 6.6%, respectively. Both prediabetes and diabetes were associated with a significantly increased risk of CV death or HHF compared to normoglycemia. In patients with HFrEF, the adjusted hazard ratios (HR) were 1.26 (95%CI: 1.07–1.48) for prediabetes and 1.49 (95%CI:1.28–1.74) for diabetes. Similarly, in those with HFpEF, the HRs were 1.19 (95%CI:1.04–1.36) for prediabetes and 1.63 (95% CI: 1.43–1.85) for diabetes. Notably, while diabetes was associated with an increased risk for both components of the primary outcome, this pattern was not observed in prediabetic patients, as illustrated in Figures 1 and 2. The risk of all-cause mortality was significantly elevated in both prediabetic and diabetic patients, regardless of LVEF. However, for renal outcomes, only diabetes demonstrated a significant association, whereas no such trend was observed for prediabetes (HFrEF: HR 1.73, 95%CI:1.08–2.76; HFpEF: HR 1.67, 95%CI:1.14–2.44). Conclusion Both prediabetes and T2DM were independently associated with an increased risk of CV death or HHF, regardless of LVEF. Notably, while prediabetes was not significantly linked to isolated HHF, it was associated with adverse outcomes, including CV death and all-cause mortality, mirroring its progression to T2DM. In contrast, only T2DM showed a significant association with renal outcomes, with no similar trend observed for prediabetes. These findings underscore the impact of prediabetes on poor prognosis in HF patients and highlight the need for early intervention.Study outcomes in HFrEF patients Study outcomes in HFpEF patients