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

Abstract

BackgroundCirculating 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 ResultsIn 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).ConclusionsThese 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.

Association between serum adipsin and plaque vulnerability determined by optical coherence tomography in patients with coronary artery disease

“…Interestingly, previous investigations have identified that adipsin can maintain pancreatic beta-cell function in diabetes and that adipsin-deficient animals are prone to glucose intolerance (43,44). This finding seems to be inconsistent with the current knowledge that patients with a high adipsin level are at increased risk for developing atherosclerotic cardiovascular disease (14,26,28). Further studies are therefore needed to elucidate the specific effect of adipsin in CAD and how adipsin is involved in the development of vulnerable plaques.…”

“…Recently, adipsin has been demonstrated not only as a protein signature of CAD and type 2 diabetes mellitus (28,29), but also as a prognostic biomarker for CAD patients (14). However, the specific role of adipsin in the pathogenesis of vulnerable plaques remains to be elucidated.…”

“…Moreover, adipsin is associated with various pathophysiological characteristics underlying atherosclerosis, including low-grade inflammation, endothelial dysfunction, ischemia-reperfusion, and lipid metabolism (11)(12)(13). Recently, it has been demonstrated that higher serum adipsin can predict not only rehospitalization and all-cause death in patients with CAD, but also their future incidence of acute coronary events (14). More importantly, an increased level of adipsin in unstable plaques was detected by immunostaining among AMI patients (14).…”

“…Recently, it has been demonstrated that higher serum adipsin can predict not only rehospitalization and all-cause death in patients with CAD, but also their future incidence of acute coronary events (14). More importantly, an increased level of adipsin in unstable plaques was detected by immunostaining among AMI patients (14). It seems that adipsin may be related to the destabilization of atherosclerotic plaques.…”

Blood Adipokins in Young People with Early Ischemic Heart Disease on the Background of Abdominal Obesity

“…T. Ohtsuki и соавт. [15] после обследования 370 пациентов с коронарным атеросклерозом заключили, что уровень адипсина в сыворотке крови прямо ассоциирован с неблагоприятным прогнозом (смертность и повторная госпитализация) у пациентов с ИБС. G. G. Tafere и соавт.…”