Serum Homocysteine as a Biomarker for Peripheral Arterial Disease Severity: A Cross-sectional Study

Introduction: Hyperhomocysteinaemia is linked to accelerated atherothrombosis, which is an independent risk factor for cardiovascular and cerebrovascular events, and a strong predictor of mortality. Understanding its role in Peripheral Arterial Disease (PAD) could uncover a modifiable target for preventing Chronic Limb-Threatening Ischaemia (CLTI). Aim: To assess the role of serum homocysteine in peripheral arterial disease. Materials and Methods: A cross-sectional study was conducted at the Department of General Surgery and Vascular Surgery, JSS Hospital, Mysuru, Karnataka, India, from June 2023 to December 2024, among 60 participants with a confirmed diagnosis of PAD, included through convenience sampling. Data was collected for the demographics, clinical history, and examination, and was recorded using a standardised questionnaire. Group comparisons were performed using Independent sample t-tests, Analysis of Variance (ANOVA) with Tukey post-hoc tests. Correlations between total Homocysteine levels (tHcy) and clinical variables were assessed using Pearson’s or Spearman’s correlation. A p-value ≤0.05 was considered statistically significant. Results: The average age of participants was approximately 55 years with a wide age range (25–85 years). Homocysteine correlated inversely with age (r-value=-0.33, p-value=0.01) but not with smoking pack-years or blood pressure. Multivariate regression confirmed diabetes as an independent positive predictor of tHcy (β=0.29, p-value=0.015). The Receiver Operating Characteristic (ROC) curve for tHcy discriminating severe PAD showed an Area Under the Curve (AUC) of 0.35. A 10 µmol L-1 cut-off maximised sensitivity (100%) but delivered 6% specificity, yielding limited clinical utility. Conclusion: While not universally predictive, elevated homocysteine levels showed strong associations with acute and severe vascular conditions, particularly in CLTI. Hence, it could serve as a supplementary indicator in conjunction with other clinical variables for stratifying vascular disease severity and tailoring patient-specific management strategies.