Background: Acute coronary syndrome (ACS) represents a significant global health challenge with substantial morbidity and mortality. Elevated homocysteine level defined as hyperhomocysteinemia has emerged as a potential cardiovascular risk factor, with vitamin B12 and folate serving as crucial cofactors in homocysteine metabolism.

Objective: To evaluate serum homocysteine, vitamin B12, and folate levels across different ACS subtypes and assess their clinical significance as potential biomarkers.

Methods: This cross-sectional observational study was conducted at a tertiary care hospital in Karnataka, India, from January to June 2025. Seventy-three newly diagnosed ACS patients (aged 18-75 years) were categorized into ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina (UA) groups. Serum homocysteine, vitamin B12, and folate levels were measured using chemiluminescence immunoassay.

Results: The study population comprised 51 males (69.9%) and 22 females (30.1%) with a mean age of 55.14±10.65 years. Hyperhomocysteinemia (>13.9 µmol/L) was prevalent across all ACS subtypes: STEMI (78.4%), NSTEMI (83.3%), and UA (100%). Vitamin B12 deficiency (<211 pg/mL) was significantly more frequent in UA (66.7%) and STEMI (35.1%) compared to NSTEMI (13.3%; p=0.015). A strong inverse correlation was observed between homocysteine and vitamin B12 levels (r=-0.648, p<0.001).

Conclusion: Hyperhomocysteinemia is highly prevalent among ACS patients, with vitamin B12 deficiency significantly contributing to elevated homocysteine levels. These findings support the potential utility of routine screening for these biomarkers in ACS management.