Endocrine Abstracts

JOINT2058

Background: Coronary heart disease (CHD) is a common ischemic heart disease, with over 11.39 million patients in China and a mortality rate of 126.91 per 100, 000. Liver injury is a significant risk factor for CHD, but the mechanisms by which it affects CHD risk remain unclear. Fibrosis-4 index (FIB-4) is a common biomarker for liver fibrosis and injury, with established links to cardiovascular diseases. This study investigates whether FIB-4 is an independent risk factor for CHD and explores the metabolomic mechanisms through which FIB-4 influences CHD risk.

Methods: This study recruited 1, 668 healthy participants from central China, with 304 participants undergoing targeted metabolomics analysis. T-tests and rank sum tests compared baseline differences between participants with and without CHD by the end of the follow-up. Proportional Cox regression evaluated the relationship between FIB-4 and CHD, with adjustments for confounders in three models: Model 1 (gender); Model 2 (further adjusted for body mass index (BMI), estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL-C), alkaline phosphatase (ALP), triglycerides (TG), glucose, hemoglobin A1C (HbA1c)); Model 3 (further adjusted for hypertension, hyperlipidemia, diabetes). Spearman correlation identified metabolites associated with liver injury, and FDR correction was applied. A logistic regression model was fitted to identify metabolites independently associated with CHD.

Results: At follow-up, 858 participants had developed CHD, while 810 did not. CHD patients had notably higher levels of SBP, DBP, TG and glucose (p < 0.05), as well as higher FIB-4 values (p < 0.001). After controlling for multiple confounders, proportional Cox regression (Model 3) demonstrated that increased FIB-4 was significantly associated with higher CHD risk, remaining robust after adjusting for covariates (HR 1.250; 95% CI, 1.136-1.375). We identified 108 metabolites associated with liver injury, and through a logistic regression model adjusted for multiple confounders, 15 metabolites were independently associated with CHD. Among these, Guanosine Monophosphate (GMP, OR 0.213; 95% CI, 0.061-0.716), Tryptophanamide (OR 0.885; 95% CI, 0.795-0.986), Lithocholic Acid Acetate (LAA, OR 0.788; 95% CI, 0.646-0.966), Methylmalonic Acid (MMA, OR 0.349; 95% CI, 0.126-0.932), and Glycohyodeoxycholic Acid (GHDCA OR 1.741; 95% CI, 1.039-3.044) were concurrently correlated with liver injury.

Conclusion: Elevated FIB-4 is strongly linked to increased CHD risk. Metabolomics analysis reveals that GMP, Tryptophanamide, LAA, MMA, and GHDCA are associated with both FIB-4 and CHD, potentially implicating these metabolites in the process through which liver injury contributes to CHD development.