Original Investigation
Dialysis
Thyroid Function, Cardiovascular Events, and Mortality in Diabetic Hemodialysis Patients

https://doi.org/10.1053/j.ajkd.2013.10.009Get rights and content

Background

In dialysis patients, the prevalence of thyroid disorders and their impact on specific cardiovascular (CV) events and mortality are largely unknown. The aim of the present study was to analyze whether subclinical thyroid disorders were associated with CV events and mortality.

Study Design

Prospective multicenter cohort study.

Setting & Participants

Thyroid status and clinical outcomes were explored in 1,000 diabetic hemodialysis patients from 178 centers in Germany.

Predictor

Thyroid status, defined by the following cutoff values: euthyroidism (thyrotropin [TSH], 0.30-4.0 mIU/L; free triiodothyronine [T3], 2.7-7.6 pmol/L; and free thyroxine [T4], 11.0-24.0 pmol/L), subclinical hyperthyroidism (TSH < 0.3 mIU/L and free T3/free T4 within reference ranges), subclinical hypothyroidism (TSH, 4.1-15.0 mIU/L and free T3/free T4 within reference ranges), euthyroid sick syndrome (free T3 < 2.7 pmol/L and TSH/free T4 low or within reference ranges).

Outcomes

During 4 years' follow-up, prespecified adjudicated end points were determined: sudden cardiac death, myocardial infarction, stroke, combined CV events, and overall mortality. Short-term effects within the first 12 months were contrasted to long-term effects (years 2-4).

Measurements

TSH, free T3, and free T4 levels at baseline.

Results

Euthyroidism was present in 78.1% of patients; subclinical hyperthyroidism, in 13.7%; and subclinical hypothyroidism, in 1.6%. Euthyroid sick syndrome was exhibited by 5.4% of patients. The adjusted short-term risk of sudden cardiac death was more than doubled (HR, 2.03; 95% CI, 0.94-4.36) in patients with subclinical hyperthyroidism, and similarly for patients with euthyroid sick syndrome (HR, 2.74; 95% CI, 0.94-7.98) compared with patients with euthyroidism. Short-term mortality was increased almost 3-fold for patients with euthyroid sick syndrome (HR, 2.97; 95% CI, 1.66-5.29), but this effect was not seen in the long term. Subclinical hypothyroidism was not associated with CV events or all-cause mortality. Risks of stroke and myocardial infarction were not affected meaningfully by thyroid disorders.

Limitations

Observational study design.

Conclusions

Sudden cardiac death may be influenced by subclinical hyperthyroidism and euthyroid sick syndrome in the short term. Furthermore, euthyroid sick syndrome is associated strongly with mortality in hemodialysis patients. Regular assessment of thyroid status may help estimate the cardiac risk of dialysis patients.

Section snippets

Study Design and Participants

The study protocol and methodology of 4D (registered at the German medical authority [BfArM], registration no. 401 3206) have been reported previously in detail.27 Briefly, 4D was a prospective randomized controlled trial investigating atorvastatin in 1,255 patients with type 2 diabetes mellitus, aged 18-80 years, and undergoing hemodialysis for less than 2 years. Between March 1998 and October 2002, patients were recruited in 178 dialysis centers in Germany. At each follow-up visit and until

Patient Characteristics and Prevalence of Thyroid Dysfunction

Of 1,255 patients included in 4D, 255 had to be excluded due to incomplete or implausible thyroid test results or the use of amiodarone, thyrostatic agents, or glucocorticoids (equivalent to prednisone  10 mg/d). A flow chart showing the respective numbers of patients with reasons for exclusion is provided in Fig 1. Regarding the concomitant medication for diabetes mellitus in the final study population (n = 1,000), 186 patients did not take diabetes medication, 633 patients received insulin, 124

Discussion

This prospective follow-up study in 1,000 well-characterized diabetic hemodialysis patients analyzes the impact of subclinical thyroid dysfunction on cardiac death. We found a borderline effect in risk of sudden cardiac death in patients with subclinical hyperthyroidism. However, we could not find a significant association between subclinical thyroid dysfunction and MI, stroke, and all-cause mortality. Further, we confirm earlier data of increased mortality in hemodialysis patients with

Acknowledgements

We thank all patients who participated in 4D; all investigators, study nurses, and collaborators involved in patient recruitment and sample and data handling; the laboratory staffs at the Universities of Freiburg, Würzburg, and Graz; and Katja Blouin, Sonja Steinhauer, and Paul Pömpel for support in laboratory work.

Support: Dr Drechsler is grateful to the Medical Faculty of the University of Würzburg for the support with a research fellowship. This work has also been supported by grants from

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