| BackgroundCoronary heart disease threatens human health and life seriously,and the pathegenesis of which is ahterosclerosis(AS).Many studied have established the fundamental role for inflammation in mediating all stages of AS.Extracellular S100A8/A9,primarily released from activated neutrophils and monocytes/macrophages,is involved in the pathogenesis of various inflammatory diseases.Animal studies showed that S100A8/A9 regulates vascular inflammation and contributes to the biological response to vascular injury by promoting leukocyte recruitment.Clinical studies demonstrated a positive relationship between plasma S100A8/A9 and the severity of coronary AS in diabetic patients.Until now,the assosiation between circulating S100A8/A9 levels and severity of coronary AS in patients with acute coronary syndromes(ACS)remains unclear.Plasma S1008A/A9 has been shown to correlate with the vulnerability of human carotid plaques.High concentrations of S100A8/A9 in plasma and in the carotid plaques were associated with the incidence of acute cardiovascular events during follow-up.In addition,the plasma S100A8/A9 levels were significantly higher in patients of acute myocardial infarction(AMI)than in those of unstable angina pectoris(UAP),and higher in patients of UAP than in those of stable angina pectoris(SAP).However,the assosiation beween circulating S100A8/A9 levels and coronary vulnerable features is still unkown.Objectives1.To identify the relationship between plasma S100A8/A9 concentration and severity of coronary AS in patients with ACS.2.To evaluate the relationship between plasma S100A8/A9 levels and coronary plaque vulnerability identified by intravascular optical coherence tomography(OCT).Methods1.134 patients of ACS who underwent elective coronary angiography at Xijing Hospital from June 2016 to September 2016 were enrolled consecutively in this study according to the inclusion and exclusion criteria.Plasma levels of S100A8/A9 were measured by enzyme-linked immunosorbent assay(ELISA).Patients were categorized according to Gensini scores as mild(Gensini score 1–20)and severe(Gensini score >20)coronary AS groups.The relationship between plasma S100A8/A9 levels and severity of coronary AS was evaluated using Spearman’s rank correlation coefficient.Significant factors indicating the presence of severe AS were determined using multivariate logistic regression analysis.Receiver operating characteristic(ROC)curves were used to determine the sensitivity and specificity of plasma S100A8/A9 for predicting severe AS.2.We evaluated 44 patients(ACS,n =15;SAP,n =29)with de novo culprit lesions who were examined by OCT between June 2015 and October 2016 in our hospital.Thin-cap fibroatheroma(TCFA)was defined as the arc of necrotic core is greater than 90° with the thinnest fibrous cap thickness <65 μm.Plasma levels of S100A8/A9 were measured by ELISA.The relationship between plasma S100A8/A9 levels and coronary plaque vulnerability of the culprit lesions was analyzed then.Results1.The plasma S100A8/A9 levels were significantly higher in patients of AMI than in those of UAP [273.7(168.0-335.7)ng/ml vs.188.7(143.3-244.2)ng/ml,P <0.001],and higher in patients of severe coronary AS than in those of mild AS [208.5(162.4-273.7)ng/ml vs.150.9(127.1-231.1)ng/ml,P=0.006].2.Spearman correlation analysis showed that the levels of S100A8/A9 were correlated positively with coronary Gensini score(r=0.20,P=0.024),levels of fasting blood glucose(r=0.25,P=0.006)and hs-CRP(r=0.22,P=0.01),circulating leukocyte numbers(r=0.18,P=0.05)and neutrophil numbers(r=0.21,P=0.019)respectively in patients with ACS.3.In multivariate logistic regression analysis,diabetes mellitus [odds ratio: 3.902,95% confidence interval: 1.076 to 14.152),P=0.038] and high plasma S100A8/A9 levels [odds ratio: 1.008,95% confidence interval: 1.002 to 1.014),P=0.013] were independent risk factors of the presence of severe AS.The area under the ROC for plasma S100A8/A9 for prediction of severe AS were 0.665(95% confidence interval: 0.553 to 0.776,P=0.006).A cutoff value of 160.8 ng/ml for S100A8/A9 had an 77% sensitivity,58% specificity for prediction of the presence of severe coronary AS in patients with ACS.4.The levels of plasma S100A8/A9 were significantly higher in patients with TCFA than in those without TCFA [320.9(278.9-350.0)ng/ml vs.239.2(177.5-274.3)ng/ml,P=0.002],higher in patients with plaque rupture than in those without plaque rupture [350.0(309.3-386.0)ng/ml vs.239.2(177.5-276.6)ng/ml,P <0.001],and higher in patients with coronary thrombus versus those without coronary thrombus [335.5(312.2-396.8)ng/ml vs.242.4(180.1-318.6)ng/ml,P=0.003].5.Patients were categorized into the lowest,intermediate,and highest tertiles groups according to plasma S100A8/A9 concentration.The frequency of TCFA was higher in patients with the highest tertiles than in the lowest tertiles of S100A8/A9(P <0.05).In addition,circulating S100A8/A9 levels were correlated inversely with fibrous cap thickness(r=-0.52,P <0.001).6.Multivariate logistic regression analysis showed that ACS [odds ratio: 8.488,95% confidence interval: 1.678 to 42.94,P=0.01] and a higher S100A8/A9 level [odds ratio: 1.015,95% confidence interval: 1.003 to 1.027,P=0.011] were the independent risk factors of TCFA.ROC for S100A8/A9,hs-CRP,and these two combined biomarkers for prediction of TCFA showed the areas under the curves were 0.79(95% confidence interval: 0.64 to 0.94,P=0.002),0.75(95% confidence interval: 0.59 to 0.90,P=0.008)and 0.84(95% confidence interval: 0.70 to 0.98,P <0.001),respectively.The sensitivity and specificity for prediction of TCFA were 93% and 83% when using S100A8/A9 and hs-CRP as a combined predictor.Conclusions1.As a novel inflammatory biomarker,systemic S100A8/A9 levels are associated positively with the severity of coronary AS in patients of ACS.Higher plasma S100A8/A9 concentration is an independent risk factor of severe coronary AS.2.Circulating S100A8/A9 is correlated with coronary plaque vulnerability.Higher S100A8/A9 levels are a powerful indicator of TCFA,and the predictive value for TCFA is significantlly higher when using S100A8/A9 and hs-CRP as a combined predictor. |
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