Free Triiodothyronine And Global Registry Of Acute Coronary Events Risk Score On Predicting Long-term Major Adverse Cardiac Events In STEMI Patients Undergoing Primary PCI

Part Ⅰ The Association Between Serum free triiodothyronine levels and the severity of coronary artery disease in STEMI patients undergoing primary PCIBackground and Objective:Coronary heart disease(CHD)is a serious disease to human being.Acute coronary syndrome(ACS)is the most severe clinical manifestation of CHD,including ST elevation myocardial infarction(STEMI),non-ST elevation myocardial infarction(NSTEMI),and unstable angina pectoris(UAP).There are higher risk of sudden death and worse prognosis in these patients,especially in STEMI patients.Among all neuroendocrine systems,thyroid hormone plays a major homeostatic role in modulating heart rate and cardiac contractility as well as arterial peripheral resistance.Accumulating evidences revealed that low free triiodothyronine(f T3)is a strong and independent predictor in patients with acute myocardial infarction.In this study,we investigated the relationship between serum free triiodothyronine and other clinical parameters in STEMI patients undergoing PCI,and explored the relationship between fT3 and coronary atherosclerotic stenosis and myocardial infarction injury.Method: Between March 2013 and August 2014,a total of 338 STEMI patients who underwent primary PCI within less than 12 h after the onset of symptoms were enrolled in the present study.The diagnosis was based on the guidelines of the ACC/AHA for the management of STEMI.All patients were divided into two groups according to the median value of f T3 level.The statistical analyses were performed by Software IBM SPSS statistics for windows version 23.Normal distribution of numeric data was assessed by Kolmogorov-Smirnov test.Continuous variables are expressed as mean ± standard deviation(SD).Categorical variables are presented as number and percentage.Comparisons between continuous variables were made using independent samples t-test or Mann–Whitney U test,as appropriate.Comparisons between categorical variables were evaluated using chi-square test.The relationships between f T3 and other clinical variables were assessed by Pearson test.Logistic regression analysis was used to evaluate the independent correlation between f T3 and the severity of coronary artery disease,and multivariate stepwise regression analysis was used to analyze the independent correlation between clinical parameters and Gensini score,CK peak and f T3.Results: 1.The levels of Gensini score,Grace score,CK peak and age,in the higher f T3 patients were significantly higher than patients in lower f T3 group,Compared with the higher f T3 group,the lower f T3 group had a lower proportion of pre-infarction angina pectoris(P=0.042),a higher proportion of TIMI ≤2(P=0.020),anterior myocardial infarction(P = 0.016)and Killip ≥2(P = 0.019).2.Pearson correlation analysis showed that f T3 was negatively correlated with age(r =-0.202,P < 0.001)and Grace score(r =-0.249,P <0.001),Grace score was negatively correlated with age(r =0.860,P <0.001),BNP(r =0.444,P <0.001)and LDL-C(r =0.144,P <0.008),and was negatively correlated with LVEF(r=-0.194,P<0.001).Gensini score was negatively correlated with LVEF(r=-0.200,P<0.001),hs CRP was positively correlated with BNP(r=0.206,P=0.002)and age(r=0.156,P=0.004).3.Logistic regression analysis showed that multiple coronary artery lesions were independently correlated with age,diabetes history and f T3;anterior myocardial infarction was independently correlated with LVEF,CK peak,f T3 and Grace score;anterior descending coronary artery was independently correlated with LVEF,CK peak value,f T3 and Grace score;preoperative TIMI grade ≤2 was independently correlated with preinfarct angina pectoris and f T3 score.Postoperative TIMI grade ≤2 was independently correlated with smoking history,creatinine,hs CRP and f T3;after correction for confounding factors,multiple coronary artery lesions(OR = 0.658,95% CI: 0.486-0.892,P = 0.007),anterior wall myocardial infarction(OR = 0.664,95% CI: 0.486-0.906,P = 0.010),anterior descending artery(OR=0.669,95% CI: 0.494-0.906,P=0.009),and anterior descending artery(OR = 0.010).There were still independent correlations between f T3 and preoperative TIMI ≤2(OR=0.609,95% CI: 0.422-0.879,P=0.008)and postoperative TIMI ≤2(OR=0.642,95% CI: 0.458-0.900,P=0.010).4.Multivariate stepwise regression analysis showed that age,f T3,diabetes mellitus and creatinine entered the Gensini integral regression equation;anterior wall myocardial infarction,Grace score,f T3 and hs CRP entered the CK peak regression equation;and age,hs CRP,pre-infarction angina pectoris and Grace score entered the f T3 regression equation.After correction for confounding factors,f T3 was still independently correlated with Gensini score(regression coefficient =-0.401,P= 0.013),hs CRP(regression coefficient =-0.813,P=0.004)and CK peak value (regression coefficient =-0.572,P=0.011),suggesting that f T3 was independently correlated with inflammation and was an independent risk factor for coronary artery stenosis and myocardial injury.Conclusions: 1.The age,CK peak,Gensini score and Grace score of STEMI patients undergoing direct PCI were higher in the low f T3 group.The proportion of anterior myocardial infarction,Killip ≥2 grade and TIMI ≤2 grade were higher in the low f T3 group,but the incidence of pre-infarction angina was lower.2.FT3 was independently associated with multiple coronary artery lesions,anterior myocardial infarction,preoperative TIMI grade ≤2,Gensini score,CK peak and hs CRP,suggesting that f T3 could be used to assess the severity of coronary stenosis.There was an independent correlation between f T3 and inflammatory markers,which could reflect the low level of inflammation to a certain extent.Part Ⅱ Free Triiodothyronine and Global Registry of Acute Coronary Events risk score on predicting long-term major adverse cardiac events in STEMI patients undergoing primary PCIBackground and Objective: The prognosis of acute coronary heart disease is affected by many factors.Among all neuroendocrine systems,thyroid hormone plays a major homeostatic role in modulating heart rate and cardiac contractility as well as arterial peripheral resistance.Clinical and experimental evidences reveal that low free triiodothyronine is a strong and independent predictor in patients with acute myocardial infarction.Global Registry of Acute Coronary Events(GRACE)score was designed to predict the 6-month follow-up morbidity and mortality in patients with acute coronary syndrome.Later,the ability of GRACE scores in risk stratification was demonstrated to have good predictive value up to five years’ follow-up.Detection of a higher GRACE score was correlated with poorer prognosis.Currently,the AHA and ESC diagnosis and treatment guidelines recommend its use for risk evaluation in patients with acute coronary syndrome.Although clinical data documented that low f T3 levels and high GRACE score is closely related to major adverse cardiac events in acute myocardial infarction patients,no previous research focuses on the combined value of f T3 and GRACE risk score in STEMI patients,nor its correlation to long term follow-up Mace.Thus,the present study,for the first time,investigated whether the risk prediction and prognostic accuracy are improved when the GRACE risk score adding f T3 in STEMI patients who underwent PCI.The primary endpoints involved the occurrence of nonfatal myocardial infarction and all cause of death in 3-years follow-up.Method: Between March 2013 and August 2014,a total of 338 STEMI patients who underwent primary PCI within less than 12 h after the onset of symptoms were enrolled in the present study.The diagnosis was based on the guidelines of the ACC/AHA for the management of STEMI.Mace were defined as nonfatal myocardial infarction and all cause of death.The statistical analyses were performed using Software IBM SPSS statistics for windows version 23.Normal distribution of numeric data was assessed by Kolmogorov-Smirnov test.Continuous variables are expressed as mean ± SD.Categorical variables are presented as number and percentage.Comparisons between continuous variables were made using independent samples t-test or Mann–Whitney U test,as appropriate.Comparisons between categorical variables were evaluated using chi-square test.The relationships between f T3 and other clinical variables were assessed by Pearson test or Spearman test.Cox regression analyses were used to determine the relative risks(hazard ratio [HR])for Mace and all cause of death associated with baseline clinical characteristics and demographic variables.To determine independent predictors of Mace and all cause of death,variables with P value <0.20 in univariate analysis were entered into the multivariate Cox regression analysis.To further assess the prognostic value,Kaplan–Meier survival curve was performed to analyze the difference of Mace in the four groups divided according to the median value of f T3 level and GRACE score.Then,we also generated receiver operating characteristic(ROC)curves to assess the cut-off value of f T3 and GRACE score for predicting Mace during(28.7±11.7)months follow-up period.Results: 1.During the follow-up period(28.7±11.7)months,a total of 113 Mace were recorded.There was no significant difference in clinical demographic variables between Mace group and non-Mace group.However,Mace occurred most frequently in the patients who had a higher Killip classification(P=0.039),higher CK peak(P<0.001),higher GRACE score level(P<0.001),lower angina history(P=0.038),and lower serum concentration of f T3(P=0.033)as compared to non-Mace patients.2.During the follow-up period(28.7±11.7)months,a total of 45 all cause of death were recorded.Death occurred most frequently in the patients who had a higher age(P<0.001),higher Killip classification(P=0.049),higher CK peak(P=0.040),higher GRACE score level(P<0.001),and lower serum concentration of f T3(P<0.001)as compared to survive patients.3.Patients were divided into four groups according to the median of f T3(3.81 pmol/L)and GRACE score(103).Result showed that patients with low f T3 and high GRACE score had the worst outcomes.Correspondingly,Kaplan–Meier survival analysis revealed that the cumulative survival rate free from Mace was the highest in the low f T3 and high GRACE score group(Log-Rank χ2=25.087,P<0.001),and the cumulative survival rate was also the highest in the low f T3 and high GRACE score group(Log-Rank χ2=37.827,P<0.001).4.Univariate analysis of data showed that f T3,GRACE score,hs CRP,Current smoker,Anterior infarction,Killip class,Previous Angina,and LVEF were strongly associated with Mace.A multivariate Cox regression model showed that f T3(HR=0.453,95% CI 0.355-0.578,P<0.001),GRACE score(HR=1.014,95% CI 1.006-1.021,P<0.001),current smoker(HR=1.782,95% CI 1.201-2.643,P=0.004),previous angina(HR=0.563,95% CI 0.365-0.869,P=0.009),Killip class(HR=1.680,95% CI 1.032-2.737,P=0.037)and were associated with Mace.After adjusting for age,current smoker,Killip class and LDL-C,combination of f T3(HR=0.462,95% CI 0.364-0.587,P<0.001)and GRACE(HR=1.011,95% CI 1.004-1.018,P=0.003)score were still significantly associated with Mace.5.Univariate analysis of data showed that f T3,GRACE score,Killip class,LDL-C,Hypertension,and Age were significantly associated with all cause of death.A multivariate Cox regression model showed that f T3(HR=0.435,95% CI 0.297-0.638,P=0.002),GRACE score(HR=1.023,95% CI 1.011-1.035,P<0.001),LDL-C(HR=1.587,95% CI 1.136-2.216,P=0.007),hypertension(HR=2.315,95% CI 1.170-4.581,P=0.016),and Killip class(HR=2.245,95% CI 1.013-4.976,P=0.046)were independent predictors of all cause of death.After adjusting for age,current smoker,anterior infarction,Killip class and LDL-C,combination of f T3(HR=0.495,95% CI 0.355-0.690,P<0.001)and GRACE(HR=1.022,95% CI 1.011-1.034,P<0.001)score were still significantly associated with all cause of death.6.ROC analysis was conducted to determine the cut-off value of f T3 and GRACE score for the prediction of the occurrence of Mace.The cutoff of f T3 was 3.45 pmol/L,with 54.0% sensitivity and 78.2% specificity(AUC=0.714,95% CI 0.657-0.771,P<0.001),And the cutoff of GRACE score was 108.5,with 57.5% sensitivity and 68.9% specificity(AUC=0.651,95% CI 0.589-0.713,P<0.001).Combining f T3 and GRACE risk score yielded a much more valuable predictive value(AUC=0.735,95% CI: 0.680-0.790,P<0.001).NRI=0.071,0.013,respectively.Conclusions: 1.Mace occurred most frequently in the patients who had a higher Killip classification,higher CK peak,higher GRACE score level,lower angina history,and lower serum concentration of f T3 as compared to non-Mace patients.A multivariate Cox regression model showed that f T3 and GRACE score were associated with Mace all cause of death.2.Patients with low f T3 and high GRACE score had the worst outcomes.Correspondingly,the cumulative survival rate and the cumulative survival rate free from Mace were the highest in the low f T3 and high GRACE score group.Combining f T3 and GRACE risk score yielded a much more valuable predictive value.