Subclinical hypothyroidism and the risk of stroke events and fatal stroke: An individual participant data analysis

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

doi:10.1210/jc.2015-1438

Subclinical hypothyroidism and the risk of stroke events and fatal stroke: An individual participant data analysis

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

School of Population and Global Health

Research output: Contribution to journal › Article › peer-review

133 Citations (Scopus)

Abstract

Copyright © 2015 by the Endocrine Society. Objective: The objective was to determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Study Selection: Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T4 levels. Data Extraction and Synthesis: We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95% CI, 0.86-1.18) or ≥80 years old (HR, 1.31; 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations. Conclusions: Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.

Original language	English
Pages (from-to)	2181-2191
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	100
Issue number	6
DOIs	https://doi.org/10.1210/jc.2015-1438
Publication status	Published - 2015

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10.1210/jc.2015-1438

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Chaker, L., Baumgartner, C., Den Elzen, W. P. J., Ikram, M. A., Blum, M. R., Collet, T. H., Bakker, S. J. L., Dehghan, A., Drechsler, C., Luben, R. N., Hofman, A., Portegies, M. L. P., Medici, M., Iervasi, G., Stott, D. J., Ford, I., Bremner, A., Wanner, C., Ferrucci, L., ... Peeters, R. P. (2015). Subclinical hypothyroidism and the risk of stroke events and fatal stroke: An individual participant data analysis. Journal of Clinical Endocrinology and Metabolism, 100(6), 2181-2191. https://doi.org/10.1210/jc.2015-1438

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title = "Subclinical hypothyroidism and the risk of stroke events and fatal stroke: An individual participant data analysis",

abstract = "Copyright {\textcopyright} 2015 by the Endocrine Society. Objective: The objective was to determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Study Selection: Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T4 levels. Data Extraction and Synthesis: We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95% CI, 0.86-1.18) or ≥80 years old (HR, 1.31; 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations. Conclusions: Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.",

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

year = "2015",

doi = "10.1210/jc.2015-1438",

language = "English",

volume = "100",

pages = "2181--2191",

journal = "Journal of Endocrinology & Metabolism",

issn = "0021-972X",

publisher = "ENDOCRINE SOC",

number = "6",

}

Chaker, L, Baumgartner, C, Den Elzen, WPJ, Ikram, MA, Blum, MR, Collet, TH, Bakker, SJL, Dehghan, A, Drechsler, C, Luben, RN, Hofman, A, Portegies, MLP, Medici, M, Iervasi, G, Stott, DJ, Ford, I, Bremner, A, Wanner, C, Ferrucci, L, Newman, AB, Dullaart, RP, Sgarbi, JA, Ceresini, G, Maciel, RMB, Westendorp, RG, Jukema, JW, Imaizumi, M, Franklyn, JA, Bauer, DC, Walsh, J, Razvi, S, Khaw, KT, Cappola, AR, Völzke, H, Franco, OH, Gussekloo, J, Rodondi, N & Peeters, RP 2015, 'Subclinical hypothyroidism and the risk of stroke events and fatal stroke: An individual participant data analysis', Journal of Clinical Endocrinology and Metabolism, vol. 100, no. 6, pp. 2181-2191. https://doi.org/10.1210/jc.2015-1438

TY - JOUR

T1 - Subclinical hypothyroidism and the risk of stroke events and fatal stroke: An individual participant data analysis

AU - Chaker, L.

AU - Baumgartner, C.

AU - Den Elzen, W.P.J.

AU - Ikram, M.A.

AU - Blum, M.R.

AU - Collet, T.H.

AU - Bakker, S.J.L.

AU - Dehghan, A.

AU - Drechsler, C.

AU - Luben, R.N.

AU - Hofman, A.

AU - Portegies, M.L.P.

AU - Medici, M.

AU - Iervasi, G.

AU - Stott, D.J.

AU - Ford, I.

AU - Bremner, Alex

AU - Wanner, C.

AU - Ferrucci, L.

AU - Newman, A.B.

AU - Dullaart, R.P.

AU - Sgarbi, J.A.

AU - Ceresini, G.

AU - Maciel, R.M.B.

AU - Westendorp, R.G.

AU - Jukema, J.W.

AU - Imaizumi, M.

AU - Franklyn, J.A.

AU - Bauer, D.C.

AU - Walsh, John

AU - Razvi, S.

AU - Khaw, K.T.

AU - Cappola, A.R.

AU - Völzke, H.

AU - Franco, O.H.

AU - Gussekloo, J.

AU - Rodondi, N.

AU - Peeters, R.P.

PY - 2015

Y1 - 2015

N2 - Copyright © 2015 by the Endocrine Society. Objective: The objective was to determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Study Selection: Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T4 levels. Data Extraction and Synthesis: We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95% CI, 0.86-1.18) or ≥80 years old (HR, 1.31; 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations. Conclusions: Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.

AB - Copyright © 2015 by the Endocrine Society. Objective: The objective was to determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Study Selection: Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T4 levels. Data Extraction and Synthesis: We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95% CI, 0.86-1.18) or ≥80 years old (HR, 1.31; 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations. Conclusions: Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.

U2 - 10.1210/jc.2015-1438

DO - 10.1210/jc.2015-1438

M3 - Article

C2 - 25856213

VL - 100

SP - 2181

EP - 2191

JO - Journal of Endocrinology & Metabolism

JF - Journal of Endocrinology & Metabolism

SN - 0021-972X

IS - 6

ER -

Subclinical hypothyroidism and the risk of stroke events and fatal stroke: An individual participant data analysis

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