Thyroid Function within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis

Layal Chaker; Christine Baumgartner; Wendy P J den Elzen; Tinh-Hai Collet; M Arfan Ikram; Manuel R Blum; Abbas Dehghan; Christiane Drechsler; Robert N Luben; Marileen L P Portegies; Giorgio Iervasi; Marco Medici; David J Stott; Robin P Dullaart; Ian Ford; Alexandra Bremner; Anne B Newman; Christoph Wanner; José A Sgarbi; Marcus Dörr; W T Longstreth; Bruce M Psaty; Luigi Ferrucci; Rui M B Maciel; Rudi G Westendorp; J Wouter Jukema; Graziano Ceresini; Misa Imaizumi; Albert Hofman; Stephan J L Bakker; Jayne A Franklyn; Kay-Tee Khaw; Douglas C Bauer; John P Walsh; Salman Razvi; Jacobijn Gussekloo; Henry Völzke; Oscar H Franco; Anne R Cappola; Nicolas Rodondi; Robin P Peeters; Thyroid Studies Collaboration

doi:10.1210/jc.2016-2255

Thyroid Function within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis

Layal Chaker, Christine Baumgartner, Wendy P J den Elzen, Tinh-Hai Collet, M Arfan Ikram, Manuel R Blum, Abbas Dehghan, Christiane Drechsler, Robert N Luben, Marileen L P Portegies, Giorgio Iervasi, Marco Medici, David J Stott, Robin P Dullaart, Ian Ford, Alexandra Bremner, Anne B Newman, Christoph Wanner, José A Sgarbi, Marcus DörrW T Longstreth, Bruce M Psaty, Luigi Ferrucci, Rui M B Maciel, Rudi G Westendorp, J Wouter Jukema, Graziano Ceresini, Misa Imaizumi, Albert Hofman, Stephan J L Bakker, Jayne A Franklyn, Kay-Tee Khaw, Douglas C Bauer, John P Walsh, Salman Razvi, Jacobijn Gussekloo, Henry Völzke, Oscar H Franco, Anne R Cappola, Nicolas Rodondi, Robin P Peeters, Thyroid Studies Collaboration

Research output: Contribution to journal › Journal article › Research › peer-review

66 Citations (Scopus)

Abstract

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 systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline thyroid-stimulating hormone (TSH), free thyroxine (FT4) and stroke outcomes were included and we collected Individual Participant Data (IPD) from each study, including thyroid function measurements and incident all stroke (combined fatal and non-fatal) and fatal stroke. The applied reference range for TSH levels was between 0.45-4.49 mIU/L.

RESULTS: We collected IPD on 43,598 adults with TSH within the reference range from 17 cohorts, with median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449,908 person-years. Age- and sex-adjusted pooled HR 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 FT4 analyses, the HR 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 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
Article number	jc20162255
Journal	The Journal of Clinical Endocrinology & Metabolism
Volume	101
Issue number	11
Pages (from-to)	4270 – 4282
Number of pages	13
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2016-2255
Publication status	Published - Nov 2016

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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., ... Thyroid Studies Collaboration (2016). Thyroid Function within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis. The Journal of Clinical Endocrinology & Metabolism, 101(11), 4270 – 4282. Article jc20162255. https://doi.org/10.1210/jc.2016-2255

Thyroid Function within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis. / Chaker, Layal; Baumgartner, Christine; den Elzen, Wendy P J et al.
In: The Journal of Clinical Endocrinology & Metabolism, Vol. 101, No. 11, jc20162255, 11.2016, p. 4270 – 4282.

Research output: Contribution to journal › Journal article › Research › peer-review

Chaker, L, Baumgartner, C, den Elzen, WPJ, Collet, T-H, 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, K-T, Bauer, DC, Walsh, JP, Razvi, S, Gussekloo, J, Völzke, H, Franco, OH, Cappola, AR, Rodondi, N, Peeters, RP & Thyroid Studies Collaboration 2016, 'Thyroid Function within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis', The Journal of Clinical Endocrinology & Metabolism, vol. 101, no. 11, jc20162255, pp. 4270 – 4282. https://doi.org/10.1210/jc.2016-2255

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title = "Thyroid Function within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis",

abstract = "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 systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline thyroid-stimulating hormone (TSH), free thyroxine (FT4) and stroke outcomes were included and we collected Individual Participant Data (IPD) from each study, including thyroid function measurements and incident all stroke (combined fatal and non-fatal) and fatal stroke. The applied reference range for TSH levels was between 0.45-4.49 mIU/L.RESULTS: We collected IPD on 43,598 adults with TSH within the reference range from 17 cohorts, with median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449,908 person-years. Age- and sex-adjusted pooled HR 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 FT4 analyses, the HR 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 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 = "Layal Chaker and Christine Baumgartner and {den Elzen}, {Wendy P J} and Tinh-Hai Collet and Ikram, {M Arfan} and Blum, {Manuel R} and Abbas Dehghan and Christiane Drechsler and Luben, {Robert N} and Portegies, {Marileen L P} and Giorgio Iervasi and Marco Medici and Stott, {David J} and Dullaart, {Robin P} and Ian Ford and Alexandra Bremner and Newman, {Anne B} and Christoph Wanner and Sgarbi, {Jos{\'e} A} and Marcus D{\"o}rr and Longstreth, {W T} and Psaty, {Bruce M} and Luigi Ferrucci and Maciel, {Rui M B} and Westendorp, {Rudi G} and Jukema, {J Wouter} and Graziano Ceresini and Misa Imaizumi and Albert Hofman and Bakker, {Stephan J L} and Franklyn, {Jayne A} and Kay-Tee Khaw and Bauer, {Douglas C} and Walsh, {John P} and Salman Razvi and Jacobijn Gussekloo and Henry V{\"o}lzke and Franco, {Oscar H} and Cappola, {Anne R} and Nicolas Rodondi and Peeters, {Robin P} and {Thyroid Studies Collaboration}",

year = "2016",

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

language = "English",

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T1 - Thyroid Function within the Reference Range and the Risk of Stroke

T2 - An Individual Participant Data Analysis

AU - Chaker, Layal

AU - Baumgartner, Christine

AU - den Elzen, Wendy P J

AU - Collet, Tinh-Hai

AU - Ikram, M Arfan

AU - Blum, Manuel R

AU - Dehghan, Abbas

AU - Drechsler, Christiane

AU - Luben, Robert N

AU - Portegies, Marileen L P

AU - Iervasi, Giorgio

AU - Medici, Marco

AU - Stott, David J

AU - Dullaart, Robin P

AU - Ford, Ian

AU - Bremner, Alexandra

AU - Newman, Anne B

AU - Wanner, Christoph

AU - Sgarbi, José A

AU - Dörr, Marcus

AU - Longstreth, W T

AU - Psaty, Bruce M

AU - Ferrucci, Luigi

AU - Maciel, Rui M B

AU - Westendorp, Rudi G

AU - Jukema, J Wouter

AU - Ceresini, Graziano

AU - Imaizumi, Misa

AU - Hofman, Albert

AU - Bakker, Stephan J L

AU - Franklyn, Jayne A

AU - Khaw, Kay-Tee

AU - Bauer, Douglas C

AU - Walsh, John P

AU - Razvi, Salman

AU - Gussekloo, Jacobijn

AU - Völzke, Henry

AU - Franco, Oscar H

AU - Cappola, Anne R

AU - Rodondi, Nicolas

AU - Peeters, Robin P

AU - Thyroid Studies Collaboration

PY - 2016/11

Y1 - 2016/11

N2 - 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 systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline thyroid-stimulating hormone (TSH), free thyroxine (FT4) and stroke outcomes were included and we collected Individual Participant Data (IPD) from each study, including thyroid function measurements and incident all stroke (combined fatal and non-fatal) and fatal stroke. The applied reference range for TSH levels was between 0.45-4.49 mIU/L.RESULTS: We collected IPD on 43,598 adults with TSH within the reference range from 17 cohorts, with median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449,908 person-years. Age- and sex-adjusted pooled HR 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 FT4 analyses, the HR 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 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 - 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 systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline thyroid-stimulating hormone (TSH), free thyroxine (FT4) and stroke outcomes were included and we collected Individual Participant Data (IPD) from each study, including thyroid function measurements and incident all stroke (combined fatal and non-fatal) and fatal stroke. The applied reference range for TSH levels was between 0.45-4.49 mIU/L.RESULTS: We collected IPD on 43,598 adults with TSH within the reference range from 17 cohorts, with median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449,908 person-years. Age- and sex-adjusted pooled HR 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 FT4 analyses, the HR 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 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 - Journal article

C2 - 27603906

SN - 0021-972X

VL - 101

SP - 4270

EP - 4282

JO - The Journal of Clinical Endocrinology & Metabolism

JF - The Journal of Clinical Endocrinology & Metabolism

IS - 11

M1 - jc20162255

ER -