European Journal of Heart Failure (2014) 16, 217–226 doi:10.1002/ejhf.42
The effect of thyroid function on clinical outcome in patients with heart failure Shmuel Chen, Ayelet Shauer, Donna R. Zwas, Chaim Lotan, Andre Keren, and Israel Gotsman* Heart Failure Center, Heart Institute, Hadassah University Hospital, Jerusalem, Israel Received 10 July 2013; revised 12 October 2013; accepted 6 November 2013 ; online publish-ahead-of-print 14 December 2013
Aims
Thyroid dysfunction is known to effect cardiac function and is a risk factor for developing heart failure (HF). Data regarding the clinical significance of thyroid-stimulating hormone (TSH) levels alone as a predictor of outcome in patients with HF is sparse. We evaluated the significance of TSH on clinical outcome in a large cohort of patients with chronic HF. ..................................................................................................................................................................... Methods Patients with a diagnosis of HF at a Health Maintenance Organization (n = 5599) were followed for cardiac-related and results hospitalizations and death. Median TSH levels were 2.2 mIU/L (interquartile range 1.4–3.5). We divided patients into quartiles based on TSH levels. Median follow-up time was 434 days and the overall mortality rate was 13.2%. Both a high and a low TSH level was associated with an increased mortality rate. Cox regression analysis after adjustment for other significant predictors demonstrated that the highest TSH quartile was associated with increased mortality compared with those with the lowest mortality [second quartile: TSH 1.4–2.2 mIU/L, hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.08–1.71, P = 0.01]. TSH was also an independent predictor of death and cardiacrelated hospitalization. Analysis of patients not on levothyroxine treatment (78%) demonstrated that TSH was an even stronger predictor of mortality (HR 1.54, 95% CI 1.17–2.03, P = 0.002). Additional analysis based on accepted clinical cut-offs of TSH demonstrated that increasing TSH levels above normal were independently associated with increased mortality and cardiac-related hospitalizations. ..................................................................................................................................................................... Conclusions Increased TSH levels are associated with worse clinical outcome in patients with HF. Thyroid imbalance confers significant risk in HF and warrants attention.
.......................................................................................................... Thyroid-stimulating hormone • Heart failure • Outcome
Introduction Heart failure (HF) has emerged as a major epidemic and is now a significant public health burden. It is associated with considerable morbidity and mortality.1 Thyroid function is known to effect cardiac function, and thyroid dysfunction is a risk factor for developing cardiovascular disease as well as HF.2 – 4 Furthermore, a low triidothyronine (T3) level is a predictor of a more severe outcome in patients with HF.5,6 However, data regarding the clinical significance of thyroid-stimulating hormone (TSH) levels alone as a predictor of outcome are sparse. The significance of a TSH level in the high-normal range, common in patients with HF,7 and the significance of subclinical hypothyroidism in these patients are not well defined. Subclinical hypothyroidism has been shown to
..........................................
Keywords
impact HF progression in one study of patients with HF.8 Recently, a subanalysis of the SCD-HeFT (Sudden Cardiac Death in Heart Failure) trial in patients with reduced left ventricle (LV) function showed that an elevated TSH increased mortality in these patients.9 The purpose of the present study was to evaluate the significance of TSH on clinical outcome including death and hospitalization in a large cohort of patients with chronic HF.
Methods Participants and study design Clalit Health Services is the largest health maintenance organization (HMO) in Israel. It has a central computerized database in which all
*Corresponding author. Tel: +972 2 6776564, Fax: +972 2 6411028, Email: [email protected]
© 2013 The Authors European Journal of Heart Failure © 2013 European Society of Cardiology
218
Statistical analyses The software SPSS version 17.0 for Windows (SPSS Inc., Chicago, IL, USA) and R Statistical Software version 3.0.1 for Windows (R Development Core Team) were used for the analyses. Comparison of the clinical characteristics was performed using the Student’s t-test for continuous variables and the 𝜒 2 test for categorical variables. Log10 was used for logarithmic transformations. Follow-up time was calculated using the Kaplan–Meier estimate of potential follow-up.12 Kaplan–Meier curves, with the log-rank test, were used to compare survival according to TSH levels. Multivariate Cox proportional hazards regression analysis was used to evaluate independent variables that determined survival. Parameters included in the multivariate Cox regression analysis incorporated all significant clinical and laboratory parameters on univariate analysis with the addition of drug therapy in separate models. Proportionality assumptions of the Cox regression models were evaluated by log–log survival curves and with the use of Schoenfeld residuals. An evaluation of the existence of confounding or interactive effects was made between variables and their possible colinearity. TSH was also analysed as a continuous variable using restricted cubic splines with knots at clinical cut-offs of 0.45, 4.5 and 10 mIU/L and at the 50th percentile (2.2 mIU/L). A P-value of
The effect of thyroid function on clinical outcome in patients with heart failure Shmuel Chen, Ayelet Shauer, Donna R. Zwas, Chaim Lotan, Andre Keren, and Israel Gotsman* Heart Failure Center, Heart Institute, Hadassah University Hospital, Jerusalem, Israel Received 10 July 2013; revised 12 October 2013; accepted 6 November 2013 ; online publish-ahead-of-print 14 December 2013
Aims
Thyroid dysfunction is known to effect cardiac function and is a risk factor for developing heart failure (HF). Data regarding the clinical significance of thyroid-stimulating hormone (TSH) levels alone as a predictor of outcome in patients with HF is sparse. We evaluated the significance of TSH on clinical outcome in a large cohort of patients with chronic HF. ..................................................................................................................................................................... Methods Patients with a diagnosis of HF at a Health Maintenance Organization (n = 5599) were followed for cardiac-related and results hospitalizations and death. Median TSH levels were 2.2 mIU/L (interquartile range 1.4–3.5). We divided patients into quartiles based on TSH levels. Median follow-up time was 434 days and the overall mortality rate was 13.2%. Both a high and a low TSH level was associated with an increased mortality rate. Cox regression analysis after adjustment for other significant predictors demonstrated that the highest TSH quartile was associated with increased mortality compared with those with the lowest mortality [second quartile: TSH 1.4–2.2 mIU/L, hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.08–1.71, P = 0.01]. TSH was also an independent predictor of death and cardiacrelated hospitalization. Analysis of patients not on levothyroxine treatment (78%) demonstrated that TSH was an even stronger predictor of mortality (HR 1.54, 95% CI 1.17–2.03, P = 0.002). Additional analysis based on accepted clinical cut-offs of TSH demonstrated that increasing TSH levels above normal were independently associated with increased mortality and cardiac-related hospitalizations. ..................................................................................................................................................................... Conclusions Increased TSH levels are associated with worse clinical outcome in patients with HF. Thyroid imbalance confers significant risk in HF and warrants attention.
.......................................................................................................... Thyroid-stimulating hormone • Heart failure • Outcome
Introduction Heart failure (HF) has emerged as a major epidemic and is now a significant public health burden. It is associated with considerable morbidity and mortality.1 Thyroid function is known to effect cardiac function, and thyroid dysfunction is a risk factor for developing cardiovascular disease as well as HF.2 – 4 Furthermore, a low triidothyronine (T3) level is a predictor of a more severe outcome in patients with HF.5,6 However, data regarding the clinical significance of thyroid-stimulating hormone (TSH) levels alone as a predictor of outcome are sparse. The significance of a TSH level in the high-normal range, common in patients with HF,7 and the significance of subclinical hypothyroidism in these patients are not well defined. Subclinical hypothyroidism has been shown to
..........................................
Keywords
impact HF progression in one study of patients with HF.8 Recently, a subanalysis of the SCD-HeFT (Sudden Cardiac Death in Heart Failure) trial in patients with reduced left ventricle (LV) function showed that an elevated TSH increased mortality in these patients.9 The purpose of the present study was to evaluate the significance of TSH on clinical outcome including death and hospitalization in a large cohort of patients with chronic HF.
Methods Participants and study design Clalit Health Services is the largest health maintenance organization (HMO) in Israel. It has a central computerized database in which all
*Corresponding author. Tel: +972 2 6776564, Fax: +972 2 6411028, Email: [email protected]
© 2013 The Authors European Journal of Heart Failure © 2013 European Society of Cardiology
218
Statistical analyses The software SPSS version 17.0 for Windows (SPSS Inc., Chicago, IL, USA) and R Statistical Software version 3.0.1 for Windows (R Development Core Team) were used for the analyses. Comparison of the clinical characteristics was performed using the Student’s t-test for continuous variables and the 𝜒 2 test for categorical variables. Log10 was used for logarithmic transformations. Follow-up time was calculated using the Kaplan–Meier estimate of potential follow-up.12 Kaplan–Meier curves, with the log-rank test, were used to compare survival according to TSH levels. Multivariate Cox proportional hazards regression analysis was used to evaluate independent variables that determined survival. Parameters included in the multivariate Cox regression analysis incorporated all significant clinical and laboratory parameters on univariate analysis with the addition of drug therapy in separate models. Proportionality assumptions of the Cox regression models were evaluated by log–log survival curves and with the use of Schoenfeld residuals. An evaluation of the existence of confounding or interactive effects was made between variables and their possible colinearity. TSH was also analysed as a continuous variable using restricted cubic splines with knots at clinical cut-offs of 0.45, 4.5 and 10 mIU/L and at the 50th percentile (2.2 mIU/L). A P-value of
