Study On The Correlation Between Biomarkers And Adverse Prognosis In Patients With Coronary Heart Diseas

PartⅠ Prognostic value of fibrinogen in patients with coronary artery disease and diabetes or prediabetes following percutaneous coronary interventionBackgroundDespite significant advances in revascularization strategies in recent decades,patients with coronary artery disease(CAD)are still at high risk for recurrent cardiovascular events,especially in the setting of glycemic metabolism abnormality.Fibrinogen(FIB)is a key component of the coagulation pathway,and plays a critical role in the pathophysiological processes of thrombosis and atherosclerosis.Previous studies have shown that FIB is an independent risk factor for cardiovascular events in the general population.However,the relationship between FIB and the risk of long-term mortality in CAD patients undergoing percutaneous coronary intervention(PCI)remains unclear,particularly in individuals with coexisting diabetes mellitus(DM)or pre-diabetes(Pre-DM).AimThe aim of this study was to investigate the correlation between FIB and glycemic metabolism,and to evaluate the predictive value of FIB combined with impaired glycemic metabolism for long-term mortality events in patients with CAD undergoing PCI.MethodsThis study was a post-hoc analysis of a large-scale,prospective,observational cohort study.From January 2013 to December 2013,10,724 patients with CAD who underwent PCI at Fuwai Hospital,Chinese Academy of Medical Sciences were consecutively enrolled.In this study,patients were divided into three groups(FIB-L,FIB-M,FIB-H)according to plasma FIB tertile levels,and further divided into normoglycemia(NG),Pre-DM and DM groups according to their glucose metabolic status.Pearson correlation analysis and linear regression analysis were used to investigate the correlation between FIB and glycosylated hemoglobin A1c(HbA1c)and fasting blood glucose(FBG).In the survival analysis,the nonlinear association between FIB and the risk of mortality was first assessed using the restricted cubic spline method.Kaplan-Meier survival curves and multivariable Cox regression analysis were used to explore the predictive value of FIB for long-term mortality events.The primary study endpoint was 5year all-cause mortality,and the secondary study endpoint was 5-year cardiac mortality.ResultsA total of 6,140 patients with available data were included in this study for statistical analysis.FIB was positively correlated with HbA1c and FBG in CAD patients with or without DM(P<0.001).The median follow-up time was 5.1 years(interquartile range:5.0-5.2 years).During the follow-up period,a total of 214(3.5%)all-cause mortality events were observed,127(59.3%)events of which were cardiac mortality.After adjustment for multiple confounders,Cox regression analysis showed that FIB was significantly associated with long-term all-cause mortality(HR:1.86,95%CI:1.28-2.69,P=0.001)and cardiac mortality(HR:1.82,95%CI:1.15-2.89,P=0.011).Compared with the NG group,patients in the DM group had significantly higher risk of long-term all-cause mortality(HR:1.50,95%CI:1.01-2.24,P=0.047)and cardiac mortality(HR:1.73,95%CI:1.01-2.97,P=0.046).When CAD patients were grouped according to the FIB levels and glucose metabolic status,the risk of all-cause mortality was significantly increased in diabetic patients with FIB-M(HR:2.57,95%CI:1.12-5.89,P<0.05),and diabetic patients with FIB-H(HR:3.04,95%CI:1.35-6.82,P<0.05).Notably,the risk of all-cause mortality was also significantly increased in prediabetic patients with FIB-H(HR:2.27,95%CI:1.01-5.12,P<0.05).ConclusionThis study demonstrated that in patients with CAD undergoing PCI,elevated FIB levels were significantly associated with an increased risk of long-term all-cause and cardiac mortality,particularly in individuals with DM or pre-diabetes.Combined assessment of FIB and glucose metabolic status may help identify high-risk individuals who may need close monitoring and aggressive treatment in the CAD population.Part Ⅱ Association of lipoprotein(a)and coronary artery calcification with risk for long-term cardiovascular events in patients with coronary artery diseaseBackgroundPatients with coronary artery disease(CAD)suffer from high recurrence of future ischemic cardiovascular events despite receiving coronary revascularization and optimized drug therapies.Lipoprotein(a)[Lp(a)],a lipoprotein particle structurally similar to low-density cholesterol(LDL-C),has been recognized as an important interventional target to reduce residual cardiovascular risk in recent years.Coronary artery calcification(CAC)is a surrogate biomarker of coronary atherosclerotic plaque burden.The relationship of Lp(a)and CAC with cardiovascular risk has been reported in primary prevention populations.However,there is a relative paucity of studies examining the association of Lp(a)and CAC with adverse cardiovascular events in patients with CAD undergoing percutaneous coronary intervention(PCI).AimThe aim of this study was to investigate the independent and combined association of Lp(a)and CAC with long-term adverse cardiovascular events in patients with CAD undergoing PCI.MethodsThis study was a post-hoc analysis of a large-scale,prospective,observational cohort study.From January 2013 to December 2013,10,724 patients with CAD who underwent PCI at Fuwai Hospital,Chinese Academy of Medical Sciences were consecutively enrolled.The assessment of CAC severity was performed based on preprocedural angiogram analysis by experienced interventional cardiologists independent of this study.And patients were divided into no/mild CAC groups and moderate/severe CAC groups.Serum Lp(a)levels were measured using immunoturbidimetric assay and patients were further grouped according to Lp(a)tertiles and the clinical threshold of 30 mg/dL.Kaplan-Meier survival curves and multivariable Cox regression analysis were used to explore the association of Lp(a)and CAC with cardiovascular events.Moreover,the predictive value of Lp(a)for long-term outcomes in the total population and in different CAC groups was assessed by the restricted cubic spline analysis.The primary endpoint was the major adverse cardiovascular and cerebrovascular events(MACCE),a composite of all-cause death,myocardial infarction,unplanned revascularization and stroke.ResultsA total of 9,773 patients with available Lp(a)levels and CAC estimation were enrolled in the current analysis.During the 5-year follow-up period,there were 1989(20.4%)MACCE events.After multivariable adjustment,elevated Lp(a)and moderate/severe CAC were independently associated with an increased risk of MACCE(all P<0.05).Notably,there was a significant interaction between Lp(a)and CAC.Elevated Lp(a)was associated with MACCE in the setting of moderate/severe CAC,while such association was attenuated in patients with no/mild CAC(P interaction<0.05).Moreover,when combined for risk stratification,patients with moderate/severe CAC and elevated Lp(a)levels had significant higher risk of MACCE(adjusted HR:1.39,95%CI:1.16-1.67,P<0.001)compared with the reference group(no/mild CAC and non-elevated Lp(a)).ConclusionOur study suggested that in patients with CAD undergoing PCI,the association between Lp(a)and cardiovascular risk appeared to be stronger in those with heavy CAC.Combined evaluation of CAC and Lp(a)may help identify high-risk individuals who may require closer monitoring and aggressive clinical management.Part Ⅲ Prognostic value of free fatty acids in patients with coronary artery disease:A multicenter cohort studyBackgroundDespite the implementation of the secondary prevention strategies recommended by the guidelines,patients with coronary artery disease(CAD)still have a high incidence of adverse ischemic events.Free fatty acids(FFA)are an important energy substrate,but abnormal elevation of FFA is a symbol of metabolic alterations.Previous studies have shown that FFA is significantly associated with poor clinical prognosis in the general population.However,there are relatively few studies on the association between FFA and long-term cardiovascular events in secondary prevention populations,especially in patients with CAD.AimThe purpose of this study was to evaluate the predictive value of FFA in long-term death and major adverse cardiovascular events in patients with CAD.MethodsThis study was a post-hoc analysis of a large-scale,prospective,multicenter,observational cohort study.From January 2015 to May 2019,18701 hospitalized CAD patients in cardiology wards at the Chinese Academy of Medical Sciences and 8 other regional tertiary centers were recruited in the PROMISE cohort.Kaplan-Meier survival curves and multivariable Cox regression analysis were used to explore the association of FFA with long-term clinical outcomes.On a continuous scale,the predictive value of FFA for the death and cardiovascular events was evaluated by restricted cubic spline method.Concordance index(C-index),continuous net reclassification improvement(NRI),and integrated discrimination improvement(IDI)were calculated to evaluate whether FFA could improve the prediction value of the basic model.The primary study endpoint was the major adverse cardiovascular events(MACE),a composite of all-cause death,myocardial infarction and unplanned revascularization.The secondary study endpoints were all-cause death and cardiac death.ResultsA total of 15,849 CAD patients were included in this study for statistical analysis.During the 2-year follow-up,468 cases(3%)of all-cause deaths,335 cases(2.1%)of cardiac deaths,and 1279 cases(8.1%)of MACE events were observed.After adjusting for multiple confounding factors,Cox regression analysis showed that FFA was significantly associated with long-term all-cause death(HR:1.71,95%CI:1.28-2.29,P<0.001),cardiac death(HR:1.68,95%CI:1.172.40,P=0.005),and MACE(HR:1.22,95%CI:1.04-1.43,P=0.016).Moreover,after combining FFA with a basic model containing traditional cardiovascular risk factors,the predictive ability of the basic model for all-cause death(C-index:0.835 vs.0.829,P=0.013;NRI:0.245,P<0.001;IDI:0.004,P=0.004),cardiac death(C-index:0.869 vs.0.863,P=0.007;NRI:0.269,P<0.001;IDI:0.003,P=0.006),and MACE(C-index:0.671 vs.0.665,P=0.009;NRI:0.268,P<0.001;IDI:0.004,P<0.001)has been significantly improved.Notably,when patients were stratified by age,the association between FFA and MACE risk seemed to be stronger in elderly CAD patients≥60 years old,while this association was attenuated in individuals<60 years old.ConclusionThis study showed that elevated FFA levels were significantly associated with an increased risk of long-term all-cause death,cardiac death and MACE in patients with CAD.Combined assessment of FFA and other traditional cardiovascular risk factors could help identify individuals at high cardiovascular residual risk for targeted intervention in clinical practice.