Developing A Prediction Model For Vulnerable Plaques And Investigating The Correlation Between Serum Adipsin And Plaque Characteristics

Part1 Developing a prediction model for vulnerable plaques based on optical coherence tomographyBackgrounds and aims: Acute coronary syndrome(ACS)is usually caused by the rupture of coronary vulnerable plaques,which in turn leads to thrombosis and vascular occlusion.Therefore,early identification of vulnerable plaques is of great importance in clinical setting.Recent histopathological and clinical studies indicated that thin-cap fibroatheroma(TCFA)is the main feature of vulnerable plaques and related to 60%-70% of acute coronary events.However,no prediction model was based on clinical routine examinations to identify vulnerable plaques.Therefore,this study aimed to explore the related factors of coronary vulnerable plaques,develop a prediction model by combining multiple risk factors,and analyze its diagnostic value for vulnerable plaques.Methods: A consecutive series of coronary artery disease(CAD)patients who underwent coronary angiography and simultaneous optical coherence tomography(OCT)examination was enrolled at the Department of Cardiology,Zhongda Hospital of Southeast University from November 2015 to July 2020.Following the inclusion and exclusion criteria,106 coronary vessels from 102 patients(63 males and 39 females)were included(average age: 60.8 ±12.0 years).The vulnerable plaque was defined as a plaque with its fibrous cap thickness<65 μm and lipid arc≥2 quadrants detected by OCT,which is also called TCFA.Patients were divided into TCFA and non-TCFA groups.The predictive factors of vulnerable plaques were screened using the univariate and multivariate logistic regression analyses.The predictive value of model for vulnerable plaques was evaluated by the receiver-operating characteristic(ROC)curve.Results: The two groups had significant differences in left ventricular ejection fraction,white blood cell(WBC),serum creatinine,low-density lipoprotein cholesterol(LDL-C)and lipoprotein(a)(P<0.05 for all).Compared with the non-TCFA group,the TCFA group had a significantly higher proportion of ACS patients(P = 0.008).The two groups had statistically significant differences in the proportions of lipid plaques and fibrous plaques,average lipid arc,maximum lipid arc,lipid length,lipid index,fibrous cap thickness,and the incidence of plaque rupture,plaque erosion,and thrombus(P<0.05 for all).The multivariate logistic regression analysis showed that WBC,serum creatinine,LDL-C and lipoprotein(a)were significantly correlated with vulnerable plaques.The multivariate model based on the 4 variables had an area under the curve(AUC)of 0.814(95% CI 0.726-0.883,P<0.001)with a sensitivity of 87.5%(95% CI 71.93%–95.03%)and a specificity of 64.86%(95% CI 53.50%-74.76%).In addition,the combined model is better than using any indicator alone to predict vulnerable plaques which are statistically significant(P<0.05 for all pairwise comparisons).Conclusions: In CAD patients,WBC,serum creatinine,LDL-C and lipoprotein(a)are independent predictors of vulnerable plaques.The combined model based the 4 variables has a certain diagnostic value for early identification of vulnerable plaques.Part2 Association between serum adipsin and vulnerable plaque characteristics determined by optical coherence tomography in patients with coronary artery diseaseBackground and aim: Vulnerable plaque,a high-risk plaque that tends to rupture and induce acute coronary syndrome(ACS),can be used to predict the risk of cardiovascular events.Early identification of vulnerable plaques can reduce acute coronary events and improve the prognosis of patients with coronary artery disease (CAD).Therefore,discovering new biomarkers of plaque vulnerability is of great importance for reducing residual risk and improving patient management.A recent study showed that adipsin is associated with an increased risk of ACS,which seems to provide clues for the involvement of adipsin in the instability of atherosclerotic plaques.The present study aimed to assess the association between serum adipsin levels in CAD patients and optical coherence tomography(OCT)detected vulnerable plaque characteristics,and to evaluate the possibility of adipsin as a potential biomarker for vulnerable plaques.Methods: CAD patients who underwent coronary angiography and OCT were consecutively enrolled at the Zhongda Hospital of Southeast University from April 2018 to July 2020.According to the inclusion and exclusion criteria,103 coronary lesions from 99 CAD patients were finally included.All patients’ clinical data were recorded at their admission,including age,sex,height,history of hypertension,diabetes,hyperlipidemia,smoking,and relevant preoperative routine examinations.Enzymelinked immunosorbent assay(ELISA)was used to determine the level of serum adipsin.According to the median of serum adipsin,subjects were divided into high(≥2.43 μg/m L)or low adipsin groups(<2.43 μg/m L).Spearman correlation analysis was used to investigate the correlation between serum adipsin and vulnerable plaque characteristics.Multivariate logistic regression analysis was performed to determine whether serum adipsin was as an independent predictor of thin-cap fibroatheroma(TCFA)and receiver-operating characteristic(ROC)curve was used to evaluate the predictive value of serum adipsin for TCFAs.Results: According to the median serum adipsin,49 patients were divided into low adipsin groups and 50 patients were divided into high adipsin groups.Compared with the low adipsin group,the high adipsin group had a higher lipid index(2700.0 vs.1975.9°×mm,P=0.015)and incidence of TCFAs(41.2% vs.21.2%,P=0.028).Serum adipsin was negatively correlated with fibrous cap thickness(ρ=-0.322,P=0.002)while was positively correlated with the average lipid arc(ρ=0.253,P=0.015),maximum lipid arc(ρ=0.211,P=0.044),lipid length(ρ=0.241,P=0.021),lipid index(ρ=0.335,P=0.001)and vulnerability score(ρ=0.254,P=0.014).In addition,the multivariate logistic regression analysis found adipsin was significantly associated with TCFAs(OR: 1.290,95% CI 1.048-1.589,P=0.016)and adipsin can be used as an independent predictor of TCFAs.The level of adipsin in patients with TCFAs was higher than that in patients without TCFAs(3.82 vs.2.20 μg/m L,P<0.001).AUC of adipsin for predicting TCFAs was 0.71(95% CI 0.602-0.817,P<0.001).The serum adipsin level had the best cut-off value of 3.50μg/m L and its sensitivity and specificity were 65.6% and 74.7%,respectively.Conclusions:1.Serum adipsin,as a kind of adipokine,is negatively correlated with the fibrous cap thickness,and positively correlated with the average lipid arc,maximum lipid arc,lipid length,lipid index,and vulnerability score.2.The serum adipsin of CAD patients is associated with the vulnerability of coronary plaques.Serum adipsin is significantly positively correlated with the incidence of TCFAs and is an independent predictor of TCFAs.Serum adipsin has a moderate discrimination for TCFAs.The application of adipsin as a biomarker may improve the diagnosis of vulnerable plaques and bring clinical benefits to CAD patients.