Thyroid function within the reference range and the risk of stroke: An individual participant data analysis

L. Chaker; C. Baumgartner; W.P.J. Den Elzen; T.H. Collet; M.A. Ikram; M.R. Blum; A. Dehghan; C. Drechsler; R.N. Luben; M.L.P. Portegies; G. Iervasi; M. Medici; D.J. Stott; R.P. Dullaart; I. Ford; Alex Bremner; A.B. Newman; C. Wanner; J.A. Sgarbi; M. Dörr; W.T. Longstreth; B.M. Psaty; L. Ferrucci; R.M.B. Maciel; R.G. Westendorp; J.W. Jukema; G. Ceresini; M. Imaizumi; A. Hofman; S.J.L. Bakker; J.A. Franklyn; K.T. Khaw; D.C. Bauer; J.P. Walsh; S. Razvi; J. Gussekloo; H. Völzke; O.H. Franco; A.R. Cappola; N. Rodondi; R.P. Peeters

doi:10.1210/jc.2016-2255

Thyroid function within the reference range and the risk of stroke: An individual participant data analysis

L. Chaker, C. Baumgartner, W.P.J. Den Elzen, T.H. Collet, M.A. Ikram, M.R. Blum, A. Dehghan, C. Drechsler, R.N. Luben, M.L.P. Portegies, G. Iervasi, M. Medici, D.J. Stott, R.P. Dullaart, I. Ford, Alex Bremner, A.B. Newman, C. Wanner, J.A. Sgarbi, M. DörrW.T. Longstreth, B.M. Psaty, L. Ferrucci, R.M.B. Maciel, R.G. Westendorp, J.W. Jukema, G. Ceresini, M. Imaizumi, A. Hofman, S.J.L. Bakker, J.A. Franklyn, K.T. Khaw, D.C. Bauer, J.P. Walsh, S. Razvi, J. Gussekloo, H. Völzke, O.H. Franco, A.R. Cappola, N. Rodondi, R.P. Peeters

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Abstract

Copyright © 2016 by the Endocrine Society.Context: The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several cardiovascular disorders, its association with the risk of stroke has not been evaluated previously. Design and Setting: We identified studies through a systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline TSH, free T4, and stroke outcomes were included, andwecollected individual participant data from each study, including thyroid function measurements and incident all stroke (combined fatal and nonfatal) and fatal stroke. The applied reference range for TSH levels was between 0.45 and 4.49 mIU/L. Results: We collected individual participant data on 43 598 adults with TSH within the reference range from 17 cohorts, with a median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449 908 person-years. Age-and sex-adjusted pooled hazard ratio for TSH was 0.78 (95%confidence interval [CI] 0.65-0.95 across the reference range of TSH) for all stroke and 0.83 (95%CI 0.62-1.09) for fatal stroke. For the free T4 analyses, the hazard ratio was 1.08 (95%CI 0.99-1.15 per SD increase) for all stroke and 1.10 (95%CI 1.04-1.19) for fatal stroke. This was independent of cardiovascular risk factors including systolic blood pressure, total cholesterol, smoking, and prevalent diabetes. Conclusion: Higher levels of TSH within the reference range may decrease the risk of stroke, highlighting the need for further research focusing on the clinical consequences associated with differences within the reference range of thyroid function.

Original language	English
Pages (from-to)	4270-4282
Number of pages	13
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	101
Issue number	11
DOIs	https://doi.org/10.1210/jc.2016-2255
Publication status	Published - Nov 2016

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10.1210/jc.2016-2255

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095234/

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Chaker, L., Baumgartner, C., Den Elzen, W. P. J., Collet, T. H., Ikram, M. A., Blum, M. R., Dehghan, A., Drechsler, C., Luben, R. N., Portegies, M. L. P., Iervasi, G., Medici, M., Stott, D. J., Dullaart, R. P., Ford, I., Bremner, A., Newman, A. B., Wanner, C., Sgarbi, J. A., ... Peeters, R. P. (2016). Thyroid function within the reference range and the risk of stroke: An individual participant data analysis. Journal of Clinical Endocrinology and Metabolism, 101(11), 4270-4282. https://doi.org/10.1210/jc.2016-2255

@article{7d63e0a3ff3e48148d04c690094a2aaf,

title = "Thyroid function within the reference range and the risk of stroke: An individual participant data analysis",

abstract = "Copyright {\textcopyright} 2016 by the Endocrine Society.Context: The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several cardiovascular disorders, its association with the risk of stroke has not been evaluated previously. Design and Setting: We identified studies through a systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline TSH, free T4, and stroke outcomes were included, andwecollected individual participant data from each study, including thyroid function measurements and incident all stroke (combined fatal and nonfatal) and fatal stroke. The applied reference range for TSH levels was between 0.45 and 4.49 mIU/L. Results: We collected individual participant data on 43 598 adults with TSH within the reference range from 17 cohorts, with a median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449 908 person-years. Age-and sex-adjusted pooled hazard ratio for TSH was 0.78 (95%confidence interval [CI] 0.65-0.95 across the reference range of TSH) for all stroke and 0.83 (95%CI 0.62-1.09) for fatal stroke. For the free T4 analyses, the hazard ratio was 1.08 (95%CI 0.99-1.15 per SD increase) for all stroke and 1.10 (95%CI 1.04-1.19) for fatal stroke. This was independent of cardiovascular risk factors including systolic blood pressure, total cholesterol, smoking, and prevalent diabetes. Conclusion: Higher levels of TSH within the reference range may decrease the risk of stroke, highlighting the need for further research focusing on the clinical consequences associated with differences within the reference range of thyroid function.",

author = "L. Chaker and C. Baumgartner and {Den Elzen}, W.P.J. and T.H. Collet and M.A. Ikram and M.R. Blum and A. Dehghan and C. Drechsler and R.N. Luben and M.L.P. Portegies and G. Iervasi and M. Medici and D.J. Stott and R.P. Dullaart and I. Ford and Alex Bremner and A.B. Newman and C. Wanner and J.A. Sgarbi and M. D{\"o}rr and W.T. Longstreth and B.M. Psaty and L. Ferrucci and R.M.B. Maciel and R.G. Westendorp and J.W. Jukema and G. Ceresini and M. Imaizumi and A. Hofman and S.J.L. Bakker and J.A. Franklyn and K.T. Khaw and D.C. Bauer and J.P. Walsh and S. Razvi and J. Gussekloo and H. V{\"o}lzke and O.H. Franco and A.R. Cappola and N. Rodondi and R.P. Peeters",

year = "2016",

month = nov,

doi = "10.1210/jc.2016-2255",

language = "English",

volume = "101",

pages = "4270--4282",

journal = "Journal of Endocrinology & Metabolism",

issn = "0021-972X",

publisher = "ENDOCRINE SOC",

number = "11",

}

Chaker, L, Baumgartner, C, Den Elzen, WPJ, Collet, TH, Ikram, MA, Blum, MR, Dehghan, A, Drechsler, C, Luben, RN, Portegies, MLP, Iervasi, G, Medici, M, Stott, DJ, Dullaart, RP, Ford, I, Bremner, A, Newman, AB, Wanner, C, Sgarbi, JA, Dörr, M, Longstreth, WT, Psaty, BM, Ferrucci, L, Maciel, RMB, Westendorp, RG, Jukema, JW, Ceresini, G, Imaizumi, M, Hofman, A, Bakker, SJL, Franklyn, JA, Khaw, KT, Bauer, DC, Walsh, JP, Razvi, S, Gussekloo, J, Völzke, H, Franco, OH, Cappola, AR, Rodondi, N & Peeters, RP 2016, 'Thyroid function within the reference range and the risk of stroke: An individual participant data analysis', Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 11, pp. 4270-4282. https://doi.org/10.1210/jc.2016-2255

TY - JOUR

T1 - Thyroid function within the reference range and the risk of stroke: An individual participant data analysis

AU - Chaker, L.

AU - Baumgartner, C.

AU - Den Elzen, W.P.J.

AU - Collet, T.H.

AU - Ikram, M.A.

AU - Blum, M.R.

AU - Dehghan, A.

AU - Drechsler, C.

AU - Luben, R.N.

AU - Portegies, M.L.P.

AU - Iervasi, G.

AU - Medici, M.

AU - Stott, D.J.

AU - Dullaart, R.P.

AU - Ford, I.

AU - Bremner, Alex

AU - Newman, A.B.

AU - Wanner, C.

AU - Sgarbi, J.A.

AU - Dörr, M.

AU - Longstreth, W.T.

AU - Psaty, B.M.

AU - Ferrucci, L.

AU - Maciel, R.M.B.

AU - Westendorp, R.G.

AU - Jukema, J.W.

AU - Ceresini, G.

AU - Imaizumi, M.

AU - Hofman, A.

AU - Bakker, S.J.L.

AU - Franklyn, J.A.

AU - Khaw, K.T.

AU - Bauer, D.C.

AU - Walsh, J.P.

AU - Razvi, S.

AU - Gussekloo, J.

AU - Völzke, H.

AU - Franco, O.H.

AU - Cappola, A.R.

AU - Rodondi, N.

AU - Peeters, R.P.

PY - 2016/11

Y1 - 2016/11

N2 - Copyright © 2016 by the Endocrine Society.Context: The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several cardiovascular disorders, its association with the risk of stroke has not been evaluated previously. Design and Setting: We identified studies through a systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline TSH, free T4, and stroke outcomes were included, andwecollected individual participant data from each study, including thyroid function measurements and incident all stroke (combined fatal and nonfatal) and fatal stroke. The applied reference range for TSH levels was between 0.45 and 4.49 mIU/L. Results: We collected individual participant data on 43 598 adults with TSH within the reference range from 17 cohorts, with a median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449 908 person-years. Age-and sex-adjusted pooled hazard ratio for TSH was 0.78 (95%confidence interval [CI] 0.65-0.95 across the reference range of TSH) for all stroke and 0.83 (95%CI 0.62-1.09) for fatal stroke. For the free T4 analyses, the hazard ratio was 1.08 (95%CI 0.99-1.15 per SD increase) for all stroke and 1.10 (95%CI 1.04-1.19) for fatal stroke. This was independent of cardiovascular risk factors including systolic blood pressure, total cholesterol, smoking, and prevalent diabetes. Conclusion: Higher levels of TSH within the reference range may decrease the risk of stroke, highlighting the need for further research focusing on the clinical consequences associated with differences within the reference range of thyroid function.

AB - Copyright © 2016 by the Endocrine Society.Context: The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several cardiovascular disorders, its association with the risk of stroke has not been evaluated previously. Design and Setting: We identified studies through a systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline TSH, free T4, and stroke outcomes were included, andwecollected individual participant data from each study, including thyroid function measurements and incident all stroke (combined fatal and nonfatal) and fatal stroke. The applied reference range for TSH levels was between 0.45 and 4.49 mIU/L. Results: We collected individual participant data on 43 598 adults with TSH within the reference range from 17 cohorts, with a median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449 908 person-years. Age-and sex-adjusted pooled hazard ratio for TSH was 0.78 (95%confidence interval [CI] 0.65-0.95 across the reference range of TSH) for all stroke and 0.83 (95%CI 0.62-1.09) for fatal stroke. For the free T4 analyses, the hazard ratio was 1.08 (95%CI 0.99-1.15 per SD increase) for all stroke and 1.10 (95%CI 1.04-1.19) for fatal stroke. This was independent of cardiovascular risk factors including systolic blood pressure, total cholesterol, smoking, and prevalent diabetes. Conclusion: Higher levels of TSH within the reference range may decrease the risk of stroke, highlighting the need for further research focusing on the clinical consequences associated with differences within the reference range of thyroid function.

U2 - 10.1210/jc.2016-2255

DO - 10.1210/jc.2016-2255

M3 - Article

C2 - 27603906

VL - 101

SP - 4270

EP - 4282

JO - Journal of Endocrinology & Metabolism

JF - Journal of Endocrinology & Metabolism

SN - 0021-972X

IS - 11

ER -

Thyroid function within the reference range and the risk of stroke: An individual participant data analysis

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