Circulating miRNA-29b and Sclerostin Levels Correlate with Coronary Artery Calcification and Cardiovascular Events in Maintenance Hemodialysis Patients

Abstract

Objective. Coronary artery calcification (CAC) is a common complication in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (MHD), and the extent of CAC is a predominant predictor of cardiovascular outcomes in MHD patients. In this study, we sought to uncover the relationship between circulating miRNA-29b, sclerostin levels, CAC, and cardiovascular events (CVEs) in MHD patients. Methods. This study recruited patients receiving MHD for at least three months in the Hainan General Hospital between January 2016 and June 2019, and all patients were followed up 24 months for CVEs. The serum level of sclerostin was determined by enzyme-linked immunosorbent assay (ELISA) and miRNA-29b expression by real-time qPCR (RT-qPCR). All patients received cardiac CT scans to evaluate CAC, and CAC scores were expressed in Agatston units. The MHD patients with CACs <100 were arranged into the CAC (<100) group, those with 100–400 CACs into the CAC (100–400) group, and those with CACs >400 into the CAC (>400) group. Net reclassification index (NRI) and integrated discrimination index (IDI) were calculated to assess the predictive performance of serum sclerostin level for the occurrence of CVEs. Results. Compared with the CAC (<100) group, the CAC (>400) group had higher proportions of older patients, hypertension and diabetes mellitus patients, longer dialysis duration, higher mean arterial pressure (MAP), higher levels of high-sensitivity C-reactive protein (hs-CRP), alkaline phosphatase (ALP), and phosphate ( $P<0.05$ ). It was found that the CAC (100–400) and CAC (>400) groups exhibited higher serum levels of sclerostin but lower levels of miRNA-29b than the CAC (<100) group ( $P<0.05$ ) and the CAC (>400) group had a higher level of sclerostin and a lower level of miRNA-29b than the CAC (100–400) group ( $P<0.05$ ). The circulating level of miRNA-29b was negatively correlated with the serum level of sclerostin in MHD patients (r = −0.329, $P<0.01$ ). The multivariate logistic regression analysis showed that hs-CRP, phosphate, sclerostin, and miRNA-29b were independent risk factors for CAC in MHD patients ( $P<0.05$ , Table 2). ROC for prediction of CAC by sclerostin yielded 0.773 AUC with 95% CI 0.683–0.864 ( $P<0.01$ ). As depicted by Kaplan–Meier curves of CVE incidence in MHD patients according to median sclerostin (491.88 pg/mL) and median miRNA-29b (Ct = 25.15), we found that serum levels of sclerostin and miRNA-29b were correlated with the incidence of CVEs in MHD patients. When a new model was used to predict the incidence of CVEs, NRI 95% CI was 0.60 (0.16–1.03) ( $P<0.05$ ) and IDI 95% CI was 0.002 (−0.014 to 0.025) ( $P<0.05$ ), suggesting that sclerostin added into the old model could improve the prediction of the incidence of CVEs. Conclusions. These data suggest that circulating miRNA-29b and sclerostin levels are correlated with CAC and incidence of CVEs in MHD patients. Higher sclerostin and lower miRNA-29b may serve as independent risk factors for the incidence of CVEs in MHD patients.