Association of Homocysteine with Arterial Stiffness and Kidney Injury Biomarkers in Patients with Suspected Coronary Artery Disease

Background: Hyperhomocysteinemia (homocysteine [Hcy] ≥15 μmol/L) is frequently observed in patients with impaired kidney function and has been associated with vascular remodeling and increased cardiovascular risk. We aimed to evaluate the relationship between Hcy, arterial stiffness, coronary artery disease (CAD), peripheral arterial disease, and biomarkers of kidney injury in patients undergoing elective coronary angiography. Methods: In this prospective observational study, 133 patients undergoing elective coronary angiography were stratified according to serum Hcy levels (Hcy <15 vs. Hcy ≥15 μmol/L). CAD severity was assessed angiographically. Arterial stiffness was evaluated using carotid–femoral pulse wave velocity (cfPWV), while peripheral arterial disease was assessed using ankle–brachial index (ABI). Kidney function was evaluated using serum creatinine, estimated glomerular filtration rate (eGFR), cystatin C, and urinary albumin-to-creatinine ratio (UACR). Correlation, multivariable regression, logistic regression, and receiver operating characteristic (ROC) analyses were performed. Results: Patients with hyperhomocysteinemia demonstrated significantly worse kidney function, including higher serum creatinine, cystatin C, and UACR levels, and lower eGFR (all p < 0.01). Patients with elevated Hcy levels also exhibited significantly higher cfPWV values (11.4 ± 3.3 vs. 9.7 ± 2.1 m/s, p < 0.001). Hcy correlated positively with cystatin C, creatinine, UACR, and cfPWV, and inversely with eGFR. In multivariable linear regression analysis, Hcy remained independently associated with increased cfPWV after adjustment for age, sex, and eGFR (β = 0.137, 95% CI 0.047–0.226, and p = 0.003). This association remained significant in sensitivity analyses incorporating hypertension, diabetes mellitus, LDL cholesterol, and statin therapy (β = 0.124, 95% CI 0.032–0.216, and p = 0.008). No independent associations were observed between Hcy and angiographic CAD severity or ABI values. ROC analysis demonstrated modest discrimination for elevated arterial stiffness (AUC = 0.66, 95% CI 0.56–0.76) and good discrimination for impaired kidney function (AUC = 0.82, 95% CI 0.69–0.92). Conclusions: Elevated Hcy levels were independently associated with impaired kidney function and increased central arterial stiffness, but not with angiographic CAD severity or peripheral arterial disease. These findings suggest that hyperhomocysteinemia may reflect cardiorenal vascular dysfunction and diffuse vascular remodeling rather than focal obstructive atherosclerotic disease. Further studies are needed to determine its clinical utility and prognostic value.