Association Of Admission Monocyte Subsets And Early MACEs In Patients With STEMI Undergoing PCI

Objectives:Monocytes are an essential component of innate immunity and are implicated in many inflammatory diseases. The existence of3distinct monocyte subsets is acknowledged by recent consensus, namely, classical CD14++CD16—(Monl), intermediate CD14++CD16+(Mon2), and nonclassical CD14+CD16++monocytes (Mon3). Experimental researches have domenstrated that improvement of atherosclerosis progression and left ventricular (LV) remoding after myocardial infarction (MI) to proinflammatory monocytes as target. Recent studies have shown that higher human Mon2level is involved in the exacerbation of LV remodeling after ST-elevation myocardial infarction (STEMI). So far, the relationship between admission monocyte and its subsets level and the early prognosis in patients with STEMI, have not been investigated. We use two methods both Flow cytometry (FCM) and blood routine test (RT) for detection of admission peripheral blood monocyte in patients with STEMI undergoing primary percutaneous coronary interventions (PCI). The objectives of this study were therefore1) to determine the association of admission monocyte and its subsets with the early Major Adverse Cardiovascular Events (MACEs) after MI, and2) to validate the correlation and consistency of both FCM and RT in detection of peripheral blood monocyte.Methods:We consecutive recruited acute STEMI patients and stable coronary heart disease (CHD) patients and blood samples were taken immediately at admission for FCM and RT analysis in two groups. Monocyte counts were analyzed by flow cytometry for the three monocyte subsets in all patients. Total White blood cell (WBC), neutrophil, monocyte and lymphocyte counts, and other plasma markers were obtained in each patient. Coronary angiography (CAG) were used to determine the severity of myocardial infarction and target vessel. The MI patients received CAG on admission and then underwent a PCI with coronary stents. In the stable CHD group, patients were selected from among those who underwent CAG and PCI of the culprit artery within48h after admission Risk stratification of MI, such as the GRACE score and SYNTAX score were noted. Transthoracic doppler echocardiography was used to evaluate LV function on24hours after admission The MACEs was defined as cardiovascular death, recurrent myocardial infarction, ischemic revascularization, or nonhemorrhagic stroke in the30days after MI. The prognostic impact of distinct monocyte subsets, peripheral blood cell counts, neutrophil to lymphocyte ratio (NTLR) and monocyte to lymphocyte ratio (MTLR) were examined in MI patients.Results:1We enrolled100STEMI patients and35Stable CHD patients. Comparison of patients with stable CHD:The acute STEMI group contained more smokers than the stable CHD group (P<0.05). The acute STEMI group displayed significantly elevated countes of peripheral blood WBC, neutrophil, RT-measured monocyte, FCM-measured monocyte and Monl, as well as percentages of Monl, compared with the stable CHD group (P<0.05). Conversely, lymphocyte counts, Mon2and Mon3percentages have a trajectory inverse to the above indexes (P<0.05). In addition, MTLR and Monl-MTLR (M1TLR) were higher in patients with STEMI (P<0.05).2Compared with no MACEs patients with acute STEMI:During a follow-up period of30days,7STEMI patients experienced the MACEs. STEMI patients with MACEs had higher peripheral blood FCM-measured monocyte counts, Monl counts and lower LV ejection fraction (LVEF)(P<0.05). The receiver operating characteristics curve analysis revealed that FCM-measured monocyte counts [area under curve (AUC):0.754,95%confidence interval (CI):0.608～0.900], Monl counts (AUC:0.724,95%CI:0.570～0.877), MTLR (AUC:0.834,95%CI:0.732～0.936), M1TLR(AUC:0.811,95%CI:0.696～0.927), Mon2-MTLR (M2TLR)(AUC:0.777,95%CI:0.615～0.938) and RT-measured MTLR (AUC:0.759,95%CI:0.653～0.965) is reasonably accurate in predicting early MACEs in acute STEMI patients (P<0.05). After stratifying the study cohort by the median of index into quartiles, higher FCM-measured MTLR and M1TLR (Log Rank test, P<0.05), but not of FCM-measured monocyte counts, Monl counts, M2TLR and RT-measured MTLR, were univariately associated with the total MACEs in Kaplan-Meier survival analysis.3In a univariate Cox regression analysis, age, blood urea nitrogen, creatinine (Cr), sodium, total bilirubin, aspartate aminotransferase (AST), LVEF, FCM-measured monocyte, Monl counts, Mon2counts, NTLR, RT-measured MTLR, FCM-measured MTLR, M1TLR and M2TLR were significantly associated with the early prognosis in STEMI patients. In a multivariate Cox regression analysis, patients with higher Cr, AST, RT-measured MTLR, FCM-measured MTLR and MITLR predicted higher risk for early adverse outcomes after STEMI (P<0.05). After adjustment of the model for risk factors, including age, gender, Cr, AST and LVEF, FCM-measured MTLR [hazard ratio (HR):1.437;95%CI:1.015to2.036] and M1TLR(HR:1.528;95%CI:1.016to2.299) remained the only independent predictive factors of early MACEs in patients with acute STEMI (P<0.05).4Using the Pearson correlation and Bland-Altman analysis, measurements of peripheral blood monocyte showed good correlation (r=0.861; P<0.0001) and consistency [bias:120.0cell/μL,1.96standard deviation (SD):(-0.767～239.2) cell/μL] between RT and FCM in stable CHD patients. However, moncyte measurements with different methods produced significantly different results in acute STEMI patients, the poor correlation (r=0.578) and consistency [bias:-74.2cell/μL,1.96SD:(-521.3～372.9) cell/μL] were observed.Conclusions:In summary, our work shows the levels of admission peripheral blood Monl subset are increased in STEMI patients with early MACEs. In combination with monocyte and lymphocyte of two inflammatory indexes, FCM-measured admission MTLR and MITLR independently predict30-day MACEs in STEM patients treated with primary PCI. STEMI-induced monocyte mobilization yields poor agreement between RT-and FCM-measured admission monocyte counts.