Analysis Of Biomarkers In Patients With Coronary Arterial Disease And Their Relation With Platelet Reactivity

Background: Cardiovascular disease is becoming one of the leading causes of high disability and mortality in the world. Two types of coronary disease, ST-Elevation Myocardial Infarction(STEMI) and stable coronary arterial heart disease(SCAD) are most common in China. The treatment procedures in Acute coronary syndrome(ACS) of PCI surgery plus anti-platelet therapy does not always result in satisfactory effects due to high on treatment platelet reactivity. Recent progress of research has suggested that leukocytes play an important role in pathogenesis of cardiovascular disease. Some biomarkers in these leukocytes, such as their counting numbers, aggregation between leukocytes and platelet, the surface expression of integrin, have been linked with coronary heart disease, and utilized for cardiovascular(CV) risk assessment. But their expression patterns in STEMI and SCAD remain unclear. In addition, the complement C5 a and cytokine SDF-1 had been demonstrated to a vital role in animal model of myocardial ischemia-reperfusion injury but the dynamic changes in human coronary artery disease and the role in high reactivity of platelet still unclear.Objective: We purpose to examine and compare leukocyte subset counts, leukocyte-platelet aggregates, CD11 c expression, complement C5 a and SDF-1 among patients with ST-Elevation myocardial infarction(STEMI) and stable coronary arterial disease(SCAD) undergoing percutaneous coronary intervention(PCI). Try to discovery the relevant factors to high on-treatment platelet reactivity.Methods:199 patients undergoing PCI were consecutively recruited from Fuwai Hospital. Among them 50 patients were used for a comparative study of stable coronary artery disease and ST segment elevation myocardial infarction, Their blood samples were collected at the fixed time such as STEMI patients at admission, 6am of day 1 and day 4 of immediate PCI, and SCAD patients at 6am, on the day of elective PCI and 1 day after. Samples were further analyzed by hematology analyzer, flow cytometry and Elisa assay; 129 STEMI patients used for relation analysis with platelet reactivity study, blood sample were collected only at 6am of 4 day post PCI, and platelet functional analysis by verifynow detection.Results:1. Leukocyte subset counts in STEMI and SCAD patients treated with PCICompared with SCAD patients, a significant increase was observed in STEMI at T0 and T1 in total leukocytes, neutrophils, monocytes, and ratio of neutrophil/platelet to lymphocyte(NLR/PLR) while PLR only increase at T1. If compared between prior-PCI and post-PCI NLR increased by 33% following PCI in SCAD patients, while a dramatic decrease of about 50% was observed in day 4 of PCI in STEMI patients. STEMI had lower percentage of NPA than SCAD at T0, with an increase at T4. While contrary to the percentage of NPA, STEMI demonstrated higher counts of NPA than SCAD at T0, followed by a gradual decrease. While MPA percentage and adjusted counts was also lower in STEMI than SCAD at T1. Neutrophil expression(MFI) of CD11 c was downregulated at T1 in STEMI compared to that of T0, and regained expression at T4. This change is in sharp contrast to SCAD, whereby neutrophil expression of CD11 c significantly increased following PCI. Monocyte expression of CD11 c exhibited a similar divergence after PCI, between STEMI and SCAD.2. Changes of plasma complement C5 a and SDF-1 in patients with coronary heart disease before and after interventional therapy.Analysis of C5 a and SDF-1α in patients plasma showed the increasing level of C5 a in STEMI patient from the date of administration to day4 post-PCI, while SDF-1α level became significant only in day 4 post-PCI.3. Correlation analysis of C5 a and SDF-1 in patients with ST segment elevation myocardial infarction and platelet reactivity.Plasma C5 a concentration was positively correlated with MPA T4 points and NPA T4 point but negatively correlated with ARU(p<0.05). As for SDF-1, its level was positivily correlated with CRP and c Tn I(p<0.05).Conclusions:We demonstrate different expression patterns of leukocytes’ biomarkers and the concentration of C5 a and SDF-1a in patients with STEMI and SCAD as well as prior-PCI and post-PCI. Our results suggested the need of more precise approach as for selecting risk indicators in the timing of sample collection and the timing of therapeutic intervention. We also proved the negatively correlation of the concentration of C5 a with the aspirin reaction, suggesting the potential of providing a novel therapeutic intervention to aspirin resistence.