Serum iron predicts long-term cardiovascular outcomes in diabetic patients with coronary artery disease, independent of iron status

Background Iron status is crucial in the pathophysiology of coronary artery disease (CAD) and diabetes, with both iron deficiency and overload linked to adverse outcomes. However, the role of serum iron in diabetic patients with CAD remains unclear. Objective To evaluate the prognostic value of iron markers in predicting major adverse cardiac and cerebrovascular events (MACCEs) in diabetic CAD patients. Methods Serum iron, ferritin, transferrin, transferrin saturation, and soluble transferrin receptor were measured in 416 prospectively enrolled diabetic CAD patients. The primary endpoint was 1-year MACCEs, including cardiovascular death, myocardial infarction, stroke, revascularization, and heart failure. Results During a median follow-up of 1.13 years, 38 MACCEs were observed (9.1%). Serum iron was an independent predictor of 1-year MACCEs (hazard ratio [HR]: 0.92; 95% CI: 0.88–0.97; P = 0.003), remaining significant after adjusting for baseline variables, hemoglobin, inflammation, lipid profiles, and iron markers (HR: 0.88; 95% CI: 0.81–0.96; P = 0.001). A decreasing exponential relationship was observed, identifying a clinically relevant threshold of 19 μmol/L. Patients with serum iron ≥19 μmol/L had significantly lower MACCEs compared to those with <19 μmol/L (P < 0.05). Mediation analysis suggested that the protective effect of serum iron was partially mediated through reduced erythrocyte sedimentation rate (15.5%) and increased bilirubin (19.4%). Conclusions Serum iron predicts long-term outcomes in diabetic CAD patients irrespective of iron storage status. A clinically significant threshold of 19 μmol/L was identified for risk stratification, with its protective effects potentially mediated through anti-inflammatory mechanisms.