Study On The Relationship Between Thyroid Function And Prognosis In Hospitalized Patients With Heart Failur

Chapter 1 Clinical features and prognosis of hospitalized heart failure patients with thyroid dysfunctionBackground:Cardiovascular system is one of the target organs of thyroid hormone.Abnormal thyroid hormone may lead to the occurrence and development of cardiovascular diseases,and affect the prognosis of diseases.Our study aimed to investigate the prognostic role of thyroid dysfunction in hospitalized HF patients.Methods:We performed a single-center retrospective cohort study including hospitalized 3733 HF patients between March 2009 to June 2018.Clinical evaluations for all participants were performed,including the collection of demographic characteristics and medical history,vital signs,12-lead electrocardiography,echocardiography,and blood tests.A systematic outpatient review or telephone follow-up was conducted after discharge.The primary endpoint was defined as a combination of all-cause death or heart transplantation or left ventricular assist device implantation.The effects of thyroid hormone on the risk of composite endpoint were evaluated by Cox regression analysis and Kaplan-Meier analysis.Restricted Cubic spline(RCS)regression analysis was used to evaluate the relationship between thyroid hormone as a continuous variable and the composite end point.Results:According to the thyroid function status,they were divided into the normal thyroid function group(n=1865,50.0%),low triiodothyronine(T3)syndrome group(n=610,16.3%),hyperthyroidism group(n=42,1.1%),subclinical hyperthyroidism(n=223,6.0%),hypothyroidism(n=164,4.4%),subclinical hypothyroidism(n=237,6.3%)and others(n=592,15.9%).The median follow-up time was 2.75(1.00,4.94)years,a total of 1659 endpoint events were recorded.Kaplan-Meier survival curve suggested that low free T3(FT3)was associated with worse prognosis(P<0.001),and normal thyroid stimulating hormone(TSH)indicated the best prognosis(P<0.001).In RCS regression analysis,FT3 had a negative relationship with the risk of composite end points,while TSH showed a U-shaped curve distribution.Low FT3(HR=1.33;95%CI 1.15～1.54;P<0.001),elevated TSH(HR=1.37;95%CI 1.15～1.64;P<0.001),LT3S(HR=1.39;95%CI 1.15～1.68;P<0.001),overt hyperthyroidism(HR=1.73;95%Cl 1.00～2.98;P=0.048),subclinical hypothyroidism(HR=1.43;95%CI 1.13～1.82;P=0.003)and overt hypothyroidism(HR=1.76;95%CI 1.33～2.34;P<0.001)independently increased the risk of composite endpoint.Conclusion:LT3S,overt hyperthyroidism,subclinical and overt hypothyroidism were independently associated with poor outcomes in HF.Chapter 2 The prognostic value of free triiodothyronine/free thyroxine ratio in patients hospitalized with heart failureObjective To investigate the effect of free triiodothyronine/free thyroxine(FT3/FT4)ratio on the prognosis of patients with heart failure(HF).Methods A total of 3527 patients hospitalized in Heart Failure Center of Fuwai Hospital from March 2009 to June 2018 were analyzed in our study.Patients were divided into two groups according to median of FT3/FT4 ratio:low FT3/FT4 group(n=1764,FT3/FT4<0.21)and high FT3/FT4 group(n=1763,FT3/FT4≥0.21).The primary endpoint was defined as a composite end point of all-cause death or heart transplantation or implantation of a left ventricular assist device.The baseline characteristics of patients with different FT3/FT4 ratio groups were compared,and the relationship between FT3/FT4 ratio and prognosis of hospitalized patients with HF were analyzed by a multivariate Cox proportional hazard regression model.Results The age of the total population was(56.81±15.97)years,and 2544 cases(72.1%)were males.The median follow-up time was 2.79(1.00,5.03)years and a total of 1542 endpoint events were recorded at the final follow-up.The mean ages of patients in low FT3/FT4 group and high FT3/FT4 group were 58.81 ± 16.46,54.80±15.20(P<0.001),and the cumulative survival rates were 38.4%and 61.9%,respectively(P<0.001).Low FT3/FT4 group had lower left ventricular ejection fraction,higher age,heart rate,N-terminal B-type brain natriuretic peptide(NT-proBNP),higher troponin I,serum creatinine and blood potassium,and lower nutritional indexes including lower body mass index,albumin,hemoglobin,sodium,blood lipid.Multivariate Cox regression model analysis showed that FT3(HR=0.72,95%CI:0.63～0.84,P<0.001),FT3/FT4(HR=0.76,95%CI:0.65～0.87,P<0.001)was associated with all-cause death,heart transplantation,or LVAD implantation in patients with HF.The results of net reclassification index(NRI)and integrated discrimination improvement(IDI)analysis indicated that the predictive value of the log(NT-proBNP)combined with FT3/FT4 ratio was significantly better than that of FT3/FT4 ratio alone(NRI=0.3,P<0.001;IDI=0.094,P<0.001)or Log(NT-proBNP)alone(NRI=0.108,P<0.001;IDI=0.016,P<0.001).Subgroup analysis suggested that the FT3/FT4 ratio was more significant in predicting the risk of composite endpoints in patients with LVEF≥50%(HR=0.65,95%CI:0.50～0.85,P for interaction=0.045).Conclusion Low FT3 and low FT3/FT4 are important risk factors for poor prognosis in hospitalized HF patients,especially in patients with LVEF≥50%.Chapter 3 Correlation between triiodothyronine and inflammatory factors and effect on hospitalized heart failure patientsObjective To investigate the association between triiodothyronine(T3)and inflammatory factors,and its potential effect on long-term outcomes in hospitalized patients with heart failure(HF).Methods A total of 2 475 patients with HF admitted to the Heart Failure Care Unit were consecutively enrolled in this retrospective cohort study from December 2006 to June 2018.Patients were divided into the low T3 syndrome group(n=610,24.6%)andthe normal thyroid function group(n=1 865,75.4%).The median follow-up time was 2.87(1.03,5.00)years.A total of 1 048 all-cause deaths were recorded at the final follow-up.The effects of free T3(FT3)and high-sensitivity C-reactive protein(hsCRP)on the risk of all-cause death were evaluated by Cox regression analysis and Kaplan-Meier analysis.Results The age of the total population was(57±16)years,1 823 cases(73.7%)were male.Compared to those with normal thyroid function,albumin[(36.5±5.4)vs.(40.7±4.7)g/L],hemoglobin[(129.4±25.1)vs.(140.6±20.6)g/L],total cholesterol[3.6(3.0,4.4)vs.4.2(3.5,4.9)mmol/L](all P<0.001)were lower,Whereas age[(60.5±16.0)vs.(55.2±15.4)years],creatinine[105.0(83.6,137.0)vs.87.8(75.6,106.3)mmol/L],log N-terminal B-type natriuretic peptide(NT-proBNP)[(8.2±1.3)vs.(7.2±1.4)ng/L]were higher in LT3S patients(all P<0.001).In Kaplan-Meier survival analysis,patients with lower FT3 and higher hsCRP had significantly lower cumulative survival(P<0.001),and lower FT3 combined with higher hsCRP subgroup had the highest risk of all-cause death(Ptrend<0.001).Restricted cubic spline analysis showed that FT3 had negative relationship with all-cause death,while hsCRP had positive relationship with all-cause death.In multivariate Cox regression analysis,LT3S was an independent predictor of all-cause mortality(HR=1.40,95%CI 1.16-1.69,P<0.001).Subgroup analysis of covariates such as age,sex,body mass index,New York Heart Association grade,coronary heart disease,hypertension,diabetes,creatinine,hsCRP,hemoglobin,left ventricular ejection fraction,and NT-proBNP showed no significant relationship between LT3S and subgroup variables(interaction P value<0.05).Conclusion LT3S is an independent predictor of poor prognosis in patients with heart failure.FT3 combined with hsCRP improve the predictive value of all-cause death in hospitalized patients with heart failure.