Identification of Adipsin as a Novel Prognostic Biomarker in Patients With Coronary Artery Disease

BACKGROUND: Circulating proteins are exposed to vascular endothelial layer and influence their functions. Among them, adipsin is a member of the trypsin family of peptidases and is mainly secreted from adipocytes, monocytes, and macrophages, catalyzing the rate‐limiting step of the alternative complement pathway. However, its pathophysiological role in cardiovascular disease remains to be elucidated. Here, we examined whether serum adipsin levels have a prognostic impact in patients with coronary artery disease. METHODS AND RESULTS: In 370 consecutive patients undergoing diagnostic coronary angiography, we performed a cytokine array analysis for screening serum levels of 50 cytokines/chemokines and growth factors. Among them, classification and regression analysis identified adipsin as the best biomarker for prediction of their long‐term prognosis (median 71 months; interquartile range, 55–81 months). Kaplan–Meier curve showed that higher adipsin levels (≥400 ng/mL) were significantly associated with all‐cause death (hazard ratio [HR], 4.2; 95% CI, 1.7–10.6 [P<0.001]) and rehospitalization (HR, 2.4; 95% CI, 1.7–3.5 [P<0.001]). Interestingly, higher high‐sensitivity C‐reactive protein levels (≥1 mg/L) were significantly correlated with all‐cause death (HR, 3.2; 95% CI, 1.7–5.9 [P<0.001]) and rehospitalization (HR, 1.5, 95% CI, 1.1–1.9 [P<0.01]). Importantly, the combination of adipsin (≥400 ng/mL) and high‐sensitivity C‐reactive protein (≥1 mg/L) was more significantly associated with all‐cause death (HR, 21.0; 95% CI, 2.9–154.1 [P<0.001]). Finally, the receiver operating characteristic curve demonstrated that serum adipsin levels predict the death caused by acute myocardial infarction in patients with coronary artery disease (C‐statistic, 0.847). CONCLUSIONS: These results indicate that adipsin is a novel biomarker that predicts all‐cause death and rehospitalization in patients with coronary artery disease, demonstrating the novel aspects of the alternative complementary system in the pathogenesis of coronary artery disease.