Independent and Joint Associations of Glucose Modified by High-Density Lipoprotein Cholesterol with Mortality in Heart Failure Patients: Evidence from the Jiangxi, China Cohort

Guoan Jian¹Shiming He¹Kun Jiang¹Zhenyu Wang¹Juan Wang¹Houhui Lan¹Guobo Xie²Guotai Sheng²Yan Fang^2*Wei Wang^2*Yang Zou^2*

• ¹Nanchang University, Nanchang, China
• ²Jiangxi Provincial People's Hospital, Nanchang, China

Objective: Metabolic disorders characterized by dysregulation of glucose and lipid homeostasis are significant drivers of heart failure progression. This study proposes using high-density lipoprotein cholesterol (HDL-C) to modify fasting plasma glucose (FPG), and thereby constructing the FPG/HDL-C ratio (FHR) as a novel comprehensive metabolic indicator, and further investigates the synergistic effects of the FHR and its components on mortality in patients with acute decompensated heart failure (ADHF). Methods: This cohort study included 2,328 ADHF patients recruited from the Jiangxi-ADHF II cohort. Multivariable Cox regression and restricted cubic spline models were used to analyze the association between the FHR and 30-day mortality in ADHF patients. To visualize the joint effects of FPG and HDL-C on 30-day mortality risk, we generated two-dimensional heatmaps and three-dimensional surface plots. Finally, mediation models were employed to perform exploratory analysis of the potential mediating roles of inflammatory factor white blood cells, oxidative stress marker gamma-glutamyl transferase, and nutritional factor albumin in the association between FHR and mortality risk. Results: During the 30-day follow-up, 150 deaths (6.44%) occurred in the Jiangxi-ADHF II cohort. Multivariable Cox regression analysis revealed a positive association between FHR and 30-day mortality. Restricted cubic spline analysis showed a U-shaped association instead of a linear pattern, with the lowest mortality risk at FHR values ranging from 4 to 6. Notably, the joint association analysis based on two-dimensional heatmaps and three-dimensional surface plots, demonstrated a concave-shaped association of FPG and HDL-C with 30-day mortality: when both FPG (3–7 mmol/L) and HDL-C (1.05–1.65 mmol/L) were maintained within specific ranges, short-term mortality risk was minimized. Finally, mediation analysis suggested that inflammatory factor white blood cells and the nutritional factor albumin play significant mediating roles in the short-term mortality risk of ADHF patients associated with FHR. Conclusion: This cohort study of the Jiangxi population in China is the first to reveal a U-shaped association between FHR and 30-day mortality in ADHF patients, establishing a synergistic effect of FPG and HDL-C on mortality risk. Based on these findings, we propose implementing a “metabolic synergistic management” strategy for ADHF patients in clinical practice.