Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis

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

doi:10.1210/jc.2015-1438

Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis

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

97 Citations (Scopus)

Abstract

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 Unpublished studies were identified through the Thyroid Studies Collaboration.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
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	100
Issue number	6
Pages (from-to)	2181-2191
Number of pages	11
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2015-1438
Publication status	Published - 1 Jun 2015

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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., ... Thyroid Studies Collaboration (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

Chaker, L, Baumgartner, C, den Elzen, WPJ, Ikram, MA, Blum, MR, Collet, T-H, 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, JP, Razvi, S, Khaw, K-T, Cappola, AR, Völzke, H, Franco, OH, Gussekloo, J, Rodondi, N, Peeters, RP & Thyroid Studies Collaboration 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

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title = "Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis",

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

year = "2015",

month = jun,

day = "1",

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

language = "English",

volume = "100",

pages = "2181--2191",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

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TY - JOUR

T1 - Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke

T2 - An Individual Participant Data Analysis

AU - Chaker, Layal

AU - Baumgartner, Christine

AU - den Elzen, Wendy P J

AU - Ikram, M Arfan

AU - Blum, Manuel R

AU - Collet, Tinh-Hai

AU - Bakker, Stephan J L

AU - Dehghan, Abbas

AU - Drechsler, Christiane

AU - Luben, Robert N

AU - Hofman, Albert

AU - Portegies, Marileen L P

AU - Medici, Marco

AU - Iervasi, Giorgio

AU - Stott, David J

AU - Ford, Ian

AU - Bremner, Alexandra

AU - Wanner, Christoph

AU - Ferrucci, Luigi

AU - Newman, Anne B

AU - Dullaart, Robin P

AU - Sgarbi, José A

AU - Ceresini, Graziano

AU - Maciel, Rui M B

AU - Westendorp, Rudi G

AU - Jukema, J Wouter

AU - Imaizumi, Misa

AU - Franklyn, Jayne A

AU - Bauer, Douglas C

AU - Walsh, John P

AU - Razvi, Salman

AU - Khaw, Kay-Tee

AU - Cappola, Anne R

AU - Völzke, Henry

AU - Franco, Oscar H

AU - Gussekloo, Jacobijn

AU - Rodondi, Nicolas

AU - Peeters, Robin P

AU - Thyroid Studies Collaboration

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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 - 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 - Review

C2 - 25856213

SN - 0021-972X

VL - 100

SP - 2181

EP - 2191

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 6

ER -

Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis

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