Relationship Between Pentraxin 3 And Pathological Characteristics And Prognosis Of STEMI Culprit Plaqu

Background:Optical coherence tomography(OCT)is used to evaluate the pathological type and microstructure of coronary plaque,which can help to reveal the pathophysiological mechanism of acute myocardial infarction.Thin-cap fibroatheroma(TCFA)identified by OCT shows typical features of large necrotic cores and thin fibrous caps,which are considered to be precursors of plaque rupture and are associated with plaque progression and cardiovascular risk.Inflammation is one of the research hotspots in the pathogenesis of cardiovascular diseases.Pentraxin-3(PTX3)belongs to the pentraxin superfamily,which is involved in infection and innate immunity and regulates inflammatory response,and has been confirmed to be involved in the pathogenesis of atherosclerosis.Previous small-sample studies have shown that elevated PTX3 concentrations can predict the occurrence of TCFA in patients with stable angina.However,the relationship between PTX3 levels and TCFA in patients with ST-segment elevation myocardial infarction(STEMI)has not been established.In the present study,we aimed to assess the relationship between PTX3 and TCFA at culprit plaques,and to investigate the potential value of PTX3 serves as a biomarker to predict TCFA in STEMI patients.Methods:From March 2017 to March 2019,a total of 236 consecutive patients diagnosed with STEMI in Fuwai Hospital,Beijing,who underwent OCT examination of culprit lesions were enrolled and divided into TCFA group(n=59)and non-TCFA group(n=177).According to the cutoff value of PTX3 level(7.8 ng/mL)determined by Youden index,patients also were divided into high PTX3 group(n=72)and low PTX3 group(n=164).TCFAs were defined as lipid-rich plaques with fibrous cap thickness ≤65 μm.Plasma PTX3 concentrations were determined by enzyme-linked immunosorbent assay.In order to assess the relationship between plasma PTX3 levels and TCFA,a multivariate logistic regression model was used and odds ratios(OR)and 95%confidence intervals(CI)were calculated.Receiver operator characteristic(ROC)curves were drawn to show the predictive power of traditional risk factors alone and in combination with PTX3 concentrations for TCFA.Furthermore,we established a nomogram model using the independent predictors of TCFA screened by multivariate Logistic regression model to quantitatively evaluate the risk of TCFA in the culprit plaques of STEMI patients.Results:The mean age of enrolled patients was 57.5 ± 11.8 years,and 80.9%were male.A total of 59(25.0%)patients had TCFA at the culprit plaque.Patients in the TCFA group had higher levels of PTX3 compared to the non-TCFA group[7.5(3.9-11.0)vs.6.1(4.07.8),P=0.034]and displayed more unstable plaque features,including higher proportion of plaques ruptured(84.7%vs.46.3%,P<0.001),more often associated with macrophage infiltration,thinner fibrous cap thickness and larger lipid arcs.Multivariable logistic regression showed higher PTX3 was an independent predictor of TCFA[per unit,OR:1.47,95%CI:1.09-1.99,P=0.011;high-PTX3 vs.low-PTX3,OR:2.79,95%CI:1.45-5.39,P=0.011).ROC curve analysis showed that when added to models of established risk factors,PTX3 significantly improved the predictive accuracy of TCFA(the area under the curve:0.733 vs 0.677,P difference=0.038)and also resulted in a significant increase in the net reclassification improvement(0.192,95%CI:0.005-0.379,P=0.044)and the integrated discrimination improvement(0.039,95%CI:0.011-0.068,P=0.007).PTX3 levels,LDLC levels and diabetes were screened to be independent predictors of TCFA and served as parameters included in the the nomogram.Conclusions:Plasma PTX3 levels were elevated in STEMI patients with culprit plaque TCFA,and PTX3 level was an independent predictor of culprit plaque TCFA.PTX3 as an inflammatory marker can improve the predictive ability of traditional risk factors for TCFA,help identify vulnerable plaques,and improve risk stratification in STEMI patients.Background:Inflammation plays an important role in the development and progression of cardiovascular disease.High sensitivity C-reactive protein(hsCRP)and pentraxin-3(PTX3)have been confirmed to serve as biomarkers reflex the systemic inflammation and the local vascular inflammation,and to be associated with increased risk of cardiovascular events.In addition,the Global Registry of Acute Coronary Events(GRACE)score is a classic risk assessment system commonly used in clinical practice.The purpose of this study was to explore:(1)the effect of PTX3 levels on the risk of recurrent cardiovascular events in ST-segment elevation myocardial infarction(STEMI)patients;(2)the predictive ability of PTX3 combined with GRACE score on major adverse cardiovascular events(MACE);(3)the combined effect of hsCRP and PTX3 in predicting the risk of MACE in STEMI patients.Methods:A total of 1416 patients who were diagnosed with STEMI and received emergency percutaneous coronary intervention in Beijing Fuwai Hospital from March 2017 to January 2020 were enrolled prospectively and divided into low PTX3 group(n=472,PTX3:1.75-5.78 ng/mL),medium PTX3 group(n=471,PTX3:5.79-8.42 ng/mL)and high PTX3 group(n=473,PTX3:8.43-83.55 ng/mL)mL)based on the tertile of PTX3 levels.The primary endpoint was MACE,including all-cause death,recurrent myocardial infarction,and ischemic stroke.Secondary endpoints were all-cause death,cardiac death,recurrent myocardial infarction,and ischemic stroke.Cumulative survival rates of patients were expressed by Kaplan-Meier curves and compared using the Log-rank test.Multivariate COX proportional hazards regression model was used to evaluate the effect of PTX3 level on cardiovascular events,and hazard ratio(HR)and 95%confidence interval(CI)were calculated.The time-dependent receiver operator characteristic(ROC)curve was used to evaluate the prognostic value of the GRACE score and the combination of PTX3 levels and GRACE score.To analyze the prognostic effect of the combination of plasma PTX3 and hsCRP patients were divided into 4 groups according to the median PTX3 level and the cut-off level(10 mg/L)of hsCRP.Multivariate COX proportional hazards regression model was used to evaluate the combined effect of PTX3 and hsCRP levels on cardiovascular events.Results:The mean age of enrolled patients was 60.4±12.4 years,and 1142(80.6%)men were enrolled.The follow-up time of the study was 718(356.1082)days.During the follow-up period,195 cases(13.8%)of MACE occurred;89 cases(6.3%)of all-cause deaths and 51 cases(3.6%)of central cause deaths;recurrent myocardial infarction 67 cases(4.7%);49 cases(3.5%)of ischemic stroke.The patients in the high PTX3 group were older,had higher levels of hsCRP,fasting blood glucose,glycosylated hemoglobin,admission troponin Ⅰ,peak troponin Ⅰ,TIMI and GRACE scores and presented higher incidence of hyperlipemia,diabetes mellitus and old myocardial infarction but lower proportion of postoperative aspirin and ticagrelor.Multivariate COX regression model analysis showed that PTX3 level was an independent predictor of cardiovascular events(HR:1.08,95%CI:1.01-1.16,P<0.001),and compared with patients in low PTX3 group,patients in high PTX3 group had MACE increased risk by 49%(HR:1.49,95%CI:1.012.20,P=0.043).ROC curve analysis showed that the area under the curves of GRACE score alone and combined with plasma PTX3 levels for predicting the 1-year risk of MACE were 71.0%and 73.3%,respectively,and the area under the curves for predicting the risk of all-cause mortality were 79.8%and 82.6%,respectively.The combination of plasma PTX3 levels and GRACE score significantly increased the 1-year risk of MACE predicted by GRACE score alone in STEMI patients(net reclassification improvement:0.192,95%CI:0.005-0.379,P=0.044;integrated discrimination improvement:0.039,95%CI:0.0110.068,P=0.007)and all-cause mortality(net reclassification improvement:0.266,95%CI:0.067-0.389,P=0.010;integrated discrimination improvement:0.035,95%CI:0.0070.076,P=0.010).Patients with high plasma PTX3 and hsCRP levels were older,had a higher proportion of hyperlipidemia and diabetes,decreased left ventricular ejection fraction and increased TIMI score and GRACE score,and the proportion of patients taking ticagrelor after discharge was lower.After fully adjustment for confounders,patients with PTX3 levels≥median and hsCRP≥10 mg/L had a 59%increased risk of MACE compared with patients with both low PTX3 and hsCRP levels(HR:1.59,95%CI:1.04-2.43,P=0.032).Conclusions:As an inflammatory marker,PTX3 is an independent predictor of increased risk of MACE in STEMI patients.Combining PTX3 concentration with GRACE score can improve the prognostic ability of GRACE score for MACE and all-cause mortality,which could improve risk stratification.In addition,patients with elevated levels of both PTX3 and hsCRP had higher risk clinical features and increased risk of cardiovascular events.Background:Culprit-plaque morphology[plaque rupture(PR)and plaque erosion(PE)identified by optical coherence tomography(OCT)]are the main causes of life-threatening acute coronary events.Previous studies have confirmed that PR and PE reveal different pathological mechanisms of myocardial infarction,and influence clinical outcomes in coronary diseases.High-risk plaque(HRP)is prone to thrombosis and highly likely to progress rapidly.The CLIMA(Relationship Between OCT Coronary Plaque Morphology and Clinical Outcome,NCT02883088)study has demonstrated the prognostic value of OCT-defined HRP to predict cardiovascular events.In addition,inflammation plays a key role in the occurrence and development of coronary atherosclerosis.Pentraxin-3(PTX3),a member of the pentraxin family,has been reported to be serve as an inflammatory marker to reflect coronary plaque vulnerability and clinical outcomes.However,to date,there is a lack of research on the association between OCT defined HRP and cardiovascular events in patients with ST-segment elevation myocardial infarction(STEMI)and the prognostic value of combination of the levels of plasma PTX3 with plaque pathological features.We aimed to explore the predictive value of culprit HRP defined by CLIMA study and culprit plaque morphology for predicting major adverse cardiovascular events(MACE)in patients with STEMI and investigate the prognostic implication of combination of the levels of plasma PTX3 with plaque pathological features.Methods:From March 2017 and March 2019,a total of 426 consecutive patients were diagnosed with STEMI in Fuwai Hospital,Beijing and underwent pre-intervention OCT examination,and 274 patients were included to analyze the relationship between the culprit plaque morphology and cardiovascular risk.After a further exclusion of patients with missing PTX3 levels(n=38),a total of 236 patients were enrolled to analyze the joint action of PR/HRP and PTX3 levels.The patients were divided into 4 groups according to the presence or absence of PR in the culprit plaque and the level of plasma PTX3:PE/lowPTX3 group(n=57),PE/high-PTX3 group(n=47),PR/low-PTX3 group(n=78)and the PR/high-PTX3 group(n=54).The patients were divided into 4 groups according to the presence of OCT defined HRP and the levels of plasma PTX3:non-HRP/low-PTX3 group(n=105),non-HRP/high-PTX3 group(n=73).HRP/low-PTX3 group(n=30)and the HRP/high-PTX3 group(n=28).HRP was defined as a plaque with the simultaneous presence of the following four characteristics:minimal luminal area<3.5 mm2,fibrous cap thickness<75 μm,lipid arc>180°,and presence of macrophage infiltration.MACE was defined as a combination of all-cause death,recurrent myocardial infarction,ischemic stroke,and any coronary-related revascularization.Cumulative survival rates of patients were expressed using Kaplan-Meier curves and compared using the Log-rank test.Univariate and multivariate COX proportional hazards regression models were used to evaluate the relationship of different groups with clinical outcomes,and hazard ratio(HR)and 95%confidence interval(CI)were calculated.Time-dependent receiver operator characteristic(ROC)curves were used to evaluate the prognostic value of different models.Model 1 was traditional cardiovascular risk factors;model 2 was model 1 plus OCT defined HRP;model 3 was model 1 plus OCT defined HRP and the levels of plasma PTX3.The area under the curve(AUC),C statistic,net reclassification improvement(NRI)and integrated discrimination improvement(IDI)were calculated.Results:The mean age of enrolled patients was 57.6 ± 11.8 years,and 80.7%were male.Patients presented with OCT defined HRP in culprit plaque had a higher prevalence of diabetes compared with the non-HRP group(42.6 vs 25.5%,P=0.010)and a higher proportion of three-vessel disease(61.8 vs 35.4%,P=0.005).After adjustment for PR and clinical risk factors,the risk of MACE was 2.05 times higher in the HRP group than in the non-HRP group(HR:2.05,95%CI:1.04-4.02,P=0.038).The effect of HRP on the risk of cardiovascular events was mainly from unplanned revascularization of any coronary artery(HR:2.20,95%CI:1.00-4.782,P=0.049).MACE risk was comparable between PR and PE.In addition,compared with the PE/low-PTX3 group,the PR/high-PTX3 group had a 5.63-fold higher risk of MACE,and the PE/high-PTX3 group had a 5.44-fold higher risk of MACE.Compared with the non-HRP/low-PTX3 group patients,non-HRP/highPTX3 group had 2.58 times higher risk of MACE,and the HRP/high-PTX3 group had 5.01 times higher risk of MACE.The time-related ROC curve showed that adding HRP and PTX3 levels to the traditional risk factor model significantly improved the AUC.Model 2 improved the C statistic compared to Model 1 by 0.033(P=0.042),and Model 3 improved the C statistic compared to Model 1 by 0.052(P=0.021).In addition,both NRI and IDI were improved in Model 2[NRI:0.263.95%CI:0.033-0.523,P=0.030;IDI:0.082.95%CI:0.019-0.222,P<0.001]and Model 3[NRI:0.385.95%CI:0.104-0.573,P<0.001;IDI:0.113,95%CI:0.036-0.248,P<0.001].Conclusion:HRP was present in 24.8%of STEMI patients and associated with higher cardiovascular risk independent of plaque rupture,suggesting that HRP detected by OCT may help identify patients at high risk of future cardiac events.Patients with PR/highPTX3 and PE/high-PTX3 presented a poorer prognosis than those with PE/low-PTX3.Patients with non-HRP/high-PTX3 and HRP/high-PTX3 presented a poorer prognosis than those with non-HRP/low-PTX3.Combining the culprit-plaque characteristics detected by OCT with PTX3 levels enhanced the predictive ability for MACE and contributed to better identification of high-risk patients.