Diagnostic Value of Homocysteine Metabolic Pathway in Coronary Atherosclerosis: A Study on Reference Intervals and Risk Prediction

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Abstract
Purpose: To determine the reference intervals of homocysteine (Hcy) metabolic pathway in healthy adults using direct continuous sampling, and to explore their correlations with coronary atherosclerosis (CA) for improving the risk assessment and diagnostic accuracy of CA. Patients and Methods: A total of 426 reference individuals were selected via direct continuous sampling of the two centers from healthy adults based on questionnaires and laboratory indicators. Additionally, 75 patients were diagnosed with CA by cardiologists. Standardized analysis of Hcy, cysteine (Cys) and methionine (Met) levels in serum were conducted using commercial assay kits compatible with LC-MS/MS. Results: Although Met and Hcy showed significant differences between the sexes, they could not meet the criteria for setting reference intervals. After outlier removal and normality conversion, 95% reference intervals of Hcy, Cys and Met were calculated as 7– 25 μmol/L, 227– 410 μmol/L, and 21– 39 μmol/L, respectively. In addition, the correlations among Hcy, Cys, and Met were influenced by CA, and each served as an independent risk factor. The area under the curve (AUC) for the combined three indicators increased to 0.86 (95% CI: 0.81– 0.91). The specificity increased to 83%, while the sensitivity reached 78%. Conclusion: The Hcy metabolic pathway significantly enhances risk assessment capability and may be helpful in providing reference values for the diagnosis and risk prediction of CA.

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