The Relationship Between Serum Clusterin Levels And Long-term Prognosis In Patients With Acute ST-segment Elevation Myocardial Infarction After Percutaneous Coronary Intervention

Objective: The prevalence of cardiovascular disease is on the rise in China,with persistently high mortality rates.Acute ST-segment elevation myocardial infarction(STEMI)is a critical manifestation of cardiovascular disease that has been associated with a growing disease burden.Despite tremendous achievements in the treatment of STEMI patients in recent years,substantial risk of recurrent adverse cardiovascular events remains high.Therefore,exploring novel potential biomarkers could help identify high-risk patients and ultimately guide clinical treatment and improve outcomes.Clusterin is a ubiquitous expressed glycoprotein with cytoprotective,anti-inflammatory,and anti-apoptotic effects,which can prevent myocardial injury.However,there is a lack of studies on the predictive value of clusterin in acute STEMI patients worldwide.This study aimed to assess the prognostic value of serum clusterin in first-time STEMI patients after primary percutaneous coronary intervention(PCI)by measuring serum clusterin levels.Additionally,we conducted a subgroup analysis to evaluate the correlation between serum clusterin levels and markers post-PCI assessed by cardiovascular magnetic resonance(CMR).Methods: This prospective cohort study enrolled consecutive 224 patients who were hospitalized with acute STEMI and underwent reperfusion therapy by primary PCI in department of Cardiology,Shengjing Hospital of China Medical University,from November 2016 to January 2019.Of these patients,90 patients underwent CMR 3-7 days post-PCI.Serum clusterin levels were determined by enzyme linked immunosorbent assay.Patients were divided into high(serum clusterin level ≥254.1ug/mL,n=112)and low clusterin group(serum clusterin level<254.1ug/mL,n=112)based on the median serum clusterin level.The primary endpoint for analyses was a composite of major adverse cardiovascular event(MACE)within 36-month follow-up post-PCI,including nonfatal myocardial reinfarction,congestive heart failure,and all-cause mortality.Cox regression model was used to analyze the prognostic value of serum clusterin levels in acute STEMI patients treated with PCI.The variables with P(27)0.1 in univariate analysis and the traditional risk factors were entered in the multivariable Cox model,including serum clusterin levels,age,sex,smoking,hypertension,diabetes mellitus,Killip class on admission,anterior myocardial infarction,thrombolysis in myocardial infarction flow grade after PCI,troponin-I,brain natriuretic peptide,C-reactive protein,total cholesterol,triglycerides,and low-density lipoprotein cholesterol.The accuracy of serum clusterin,the Global Registry of Acute Coronary Events(GRACE)risk score and the addition of clusterin to GRACE risk score in predicting clinical outcomes of patients 36 months postPCI was compared in the receiver operating characteristic(ROC)curves and areas under the curves(AUC).And incremental predictive ability from adding clusterin to GRACE score was further analyzed using the net reclassification improvement(NRI)and the integrated discrimination improvement(IDI).Results: A total of 71(31.7%)MACEs were recorded during 36-month follow-up period.We observed a higher risk of MACE,congestive heart failure,and all-cause mortality in patients with low clusterin group,comparing patients in high clusterin group(all Log-rank P<0.001).In univariate Cox regression analysis,serum clusterin was an inverse predictor of MACE(P<0.001,HR=0.984,95%CI 0.979-0.989),congestive heart failure(P < 0.001,HR=0.985,95%CI 0.978-0.991),and all-cause mortality(P < 0.001,HR=0.982,95%CI 0.973-0.990)in STEMI patients 36 months post-PCI.After further adjusting the multivariate Cox regression model,serum clusterin remained independently significant as a predictor of MACE(P=0.001,HR=0.989,95%CI 0.983-0.996)and congestive heart failure(P=0.001,HR=0.986,95%CI 0.977-0.995).We compared the AUCs of serum clusterin,GRACE risk score,and the addition of serum clusterin to GRACE risk score to detect the differences between ROC curves.We found that discriminatory performance of serum clusterin was similar to the GRACE risk score in predicting MACEs(AUC,0.785 versus 0.795;P=0.813).The AUC significantly increased after adding clusterin to the GRACE risk score(AUC,0.841 versus 0.795,P=0.038).Adding clusterin to the GRACE risk score could improve discriminatory compared with the GRACE risk score in predicting the risk of MACE during 36-month follow-up period.Further,it had a better prognostic performance than GRACE score alone(NRI=0.633,P(27)0.001;IDI=0.086,P(27)0.001).Subgroup analysis shown that clusterin showed significant positive correlation with left ventricular ejection fraction(r=0.242,P=0.022),and negative correlations with infarction size(r=-0.417,P(27)0.001)and microvascular obstruction(r=-0.338,P=0.001)assessed by CMR.Conclusion: Our study confirmed for the first time that serum clusterin was associated with long-term clinical outcome post-PCI in acute STEMI patients,suggesting clusterin might be a promising novel biomarker with potential added value regarding risk assessment post-PCI.