Nonlinear association of HbA1c/HDL-C ratio with heart failure in adults: a large cross-sectional study

Background Heart failure (HF) remains a leading cause of morbidity and mortality worldwide. The HbA1c/HDL-C ratio, a novel composite biomarker reflecting glycemic control and lipid metabolism, may be associated with HF risk, but its specific relationship remains underexplored. This study aimed to investigate the association between the HbA1c/HDL-C ratio and HF. Methods We utilized samples from two sources: 1,360 inpatients from a cardiology department in 2020 and 101,316 participants from the National Health and Nutrition Examination Survey ( N HANES) 1999–2018. Multivariate logistic regression, subgroup analyses, restricted cubic spline (RCS) regression, and receiver-operating characteristic (ROC) curve analysis were employed to examine the relationship. Results In an analysis of the NHANES sample including 48,922 participants, 1,598 individuals were identified as having HF, corresponding to a prevalence of 3.27%. In a separate clinical sample of 584 participants, 132 had HF, yielding an overall prevalence of 22.60%. After full adjustment, the HbA1c/HDL-C ratio demonstrated a consistent positive association with HF risk in both the NHANES sample (OR =1.07, 95% CI: 1.01–1.14; P = 0.033) and the clinical sample (OR = 1.15, 95% CI: 1.01–1.30; P = 0.029). Furthermore, a nonlinear relationship between the HbA1c/HDL-C ratio and HF risk was observed in both populations, with an inflection point identified at 6.21. Below this threshold (HbA1c/HDL-C < 6.21), the adjusted OR was 1.22 (95% CI: 1.09–1.37; P = 0.001) in the NHANES sample and 1.65 (95% CI: 1.20–2.28; P = 0.002) in the clinical sample. Above the inflection point (HbA1c/HDL-C ≥ 6.21), the association attenuated and became statistically nonsignificant. The ROC curve analysis also confirmed that the HbA1c/HDL-C ratio combination had more robust predictive power for heart failure than HbA1c and HDL-C alone ( P < 0.05). Conclusion This study found a nonlinear positive association between the HbA1c/HDL-C ratio and the risk of HF, identifying key threshold values.