Connie M Rhee1, Amy S You1, Danh V Nguyen2, Steven M Brunelli3, Matthew J Budoff4, Elani Streja1,5, Tracy Nakata1, Csaba P Kovesdy6,7, Gregory A Brent8,9,10, Kamyar Kalantar-Zadeh1,4,5. 1. Harold Simmons Center for Chronic Disease Research and Epidemiology, University of California Irvine, Orange, California 92868. 2. Division of General Internal Medicine, University of California Irvine, Orange, California 92868. 3. DaVita Clinical Research, Minneapolis, Minnesota 55404. 4. Los Angeles BioMedical Research Institute, Torrance, California 90502. 5. Veterans Affairs Long Beach Healthcare System, Long Beach, California 90822. 6. Division of Nephrology, University of Tennessee Health Science Center, Memphis, Tennessee 38163. 7. Nephrology Section, Memphis Veterans Affairs Medical Center, Memphis, Tennessee 38104. 8. Department of Medicine, VA Greater Los Angeles Healthcare System 90073. 9. Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095. 10. Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095.
Abstract
Context and Objective: Compared with the general population, hemodialysis patients have a substantially higher risk of hypothyroidism, as defined by an elevated serum thyrotropin (TSH) level, and cardiovascular mortality. Whereas an elevated TSH is associated with cardiovascular disease and death in the general population, associations among dialysis patients have been inconsistent. Design, Setting, Participants, and Main Outcome: We examined 541 hemodialysis patients from 17 southern California dialysis centers in the prospective Hypothyroidism, Cardiovascular Health, and Survival study who underwent protocolized measurement of repeated serum TSH levels every 6 months from 2013 to 2015. Associations between TSH tertiles (<1.28, 1.28 to <2.14, and 2.14 to 86.7 mIU/L) and mortality were estimated using time-dependent Cox models with four adjustment levels. In sensitivity analyses, we excluded patients receiving thyroid hormone supplementation. Results: Compared with the lowest TSH tertile, the highest TSH tertile was associated with a 2.2- to 2.5-fold higher mortality risk in unadjusted, case-mix, expanded case-mix+laboratory, and expanded case-mix+laboratory+medication models [hazard ratios (95% confidence interval), 2.54 (1.32 to 4.89), 2.53 (1.30 to 4.93), 2.19 (1.11 to 4.32), and 2.28 (1.45 to 3.58), respectively]. We observed a consistent trend between higher TSH tertiles and numerically higher mortality risk across all models. Similar findings were observed in analyses excluding patients receiving thyroid hormone supplementation. Conclusion: In time-dependent analyses, TSH levels in the high-normal to high range were independently associated with higher death risk in hemodialysis patients. Further studies are indicated to determine whether normalization of TSH levels with thyroid hormone supplementation improves survival in this population.
Context and Objective: Compared with the general population, hemodialysis patients have a substantially higher risk of hypothyroidism, as defined by an elevated serum thyrotropin (TSH) level, and cardiovascular mortality. Whereas an elevated TSH is associated with cardiovascular disease and death in the general population, associations among dialysis patients have been inconsistent. Design, Setting, Participants, and Main Outcome: We examined 541 hemodialysis patients from 17 southern California dialysis centers in the prospective Hypothyroidism, Cardiovascular Health, and Survival study who underwent protocolized measurement of repeated serum TSH levels every 6 months from 2013 to 2015. Associations between TSH tertiles (<1.28, 1.28 to <2.14, and 2.14 to 86.7 mIU/L) and mortality were estimated using time-dependent Cox models with four adjustment levels. In sensitivity analyses, we excluded patients receiving thyroid hormone supplementation. Results: Compared with the lowest TSH tertile, the highest TSH tertile was associated with a 2.2- to 2.5-fold higher mortality risk in unadjusted, case-mix, expanded case-mix+laboratory, and expanded case-mix+laboratory+medication models [hazard ratios (95% confidence interval), 2.54 (1.32 to 4.89), 2.53 (1.30 to 4.93), 2.19 (1.11 to 4.32), and 2.28 (1.45 to 3.58), respectively]. We observed a consistent trend between higher TSH tertiles and numerically higher mortality risk across all models. Similar findings were observed in analyses excluding patients receiving thyroid hormone supplementation. Conclusion: In time-dependent analyses, TSH levels in the high-normal to high range were independently associated with higher death risk in hemodialysis patients. Further studies are indicated to determine whether normalization of TSH levels with thyroid hormone supplementation improves survival in this population.
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