Christiane Drechsler1, Andreas Schneider2, Lena Gutjahr-Lengsfeld2, Matthias Kroiss3, Juan Jesús Carrero4, Vera Krane2, Bruno Allolio3, Christoph Wanner2, Martin Fassnacht5. 1. Department of Medicine 1, Division of Nephrology, University Hospital, University of Würzburg, Würzburg, Germany; Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany. Electronic address: drechsler_c@ukw.de. 2. Department of Medicine 1, Division of Nephrology, University Hospital, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany. 3. Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Endocrine and Diabetes Unit, Department of Medicine 1, University Hospital, University of Würzburg, Würzburg, Germany. 4. Division of Renal Medicine and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. 5. Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Endocrine and Diabetes Unit, Department of Medicine 1, University Hospital, University of Würzburg, Würzburg, Germany; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians Universität München, Munich, Germany.
Abstract
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.
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 hemodialysispatients 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.
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