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Review
. 2015 Jun;100(6):2181-91.
doi: 10.1210/jc.2015-1438. Epub 2015 Apr 9.

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

Layal Chaker  1 , Christine Baumgartner  1 , Wendy P J den Elzen  1 , M Arfan Ikram  1 , Manuel R Blum  1 , Tinh-Hai Collet  1 , Stephan J L Bakker  1 , Abbas Dehghan  1 , Christiane Drechsler  1 , Robert N Luben  1 , Albert Hofman  1 , Marileen L P Portegies  1 , Marco Medici  1 , Giorgio Iervasi  1 , David J Stott  1 , Ian Ford  1 , Alexandra Bremner  1 , Christoph Wanner  1 , Luigi Ferrucci  1 , Anne B Newman  1 , Robin P Dullaart  1 , José A Sgarbi  1 , Graziano Ceresini  1 , Rui M B Maciel  1 , Rudi G Westendorp  1 , J Wouter Jukema  1 , Misa Imaizumi  1 , Jayne A Franklyn  1 , Douglas C Bauer  1 , John P Walsh  1 , Salman Razvi  1 , Kay-Tee Khaw  1 , Anne R Cappola  1 , Henry Völzke  1 , Oscar H Franco  1 , Jacobijn Gussekloo  1 , Nicolas Rodondi  1 , Robin P Peeters  1 ; Thyroid Studies Collaboration
Affiliations
Review

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

Layal Chaker et al. J Clin Endocrinol Metab. 2015 Jun.

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 Unpublished studies were identified through the Thyroid Studies Collaboration.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.

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Figures

Figure 1.
Figure 1.
The risk of stroke events and fatal stroke in subclinical hypothyroidism vs euthyroidism. HRs and their 95% CIs are represented by squares. Sizes of data markers are proportional to the inverse of the variance of the HRs. A, Data for stroke events were available in 12 studies. A total of 387 participants were excluded from the analysis of stroke events due to missing follow-up data. B, Data for fatal strokes were available in 17 studies. A total of 329 participants were excluded from the analysis of fatal stroke due to missing cause of death.
Figure 2.
Figure 2.
HRs for stroke events and fatal stroke for subclinical hypothyroidism stratified by age vs euthyroidism (A) and according to elevated TSH categories (B). HRs and their 95% CIs are represented by squares. Sizes of data markers are proportional to the inverse of the variance of the HRs. Unfilled squares indicate the reference categories. For the analysis stratified by age, HRs for stroke events and fatal stroke were adjusted for sex and age as a continuous variable to avoid residual confounding within age strata. Data for stroke events were available in 12 studies. A total of 387 participants were excluded from the analysis of stroke events due to missing stroke event data. Data for fatal strokes were available in 17 studies. A total of 329 participants were excluded from the analysis of fatal stroke due to missing cause of death.
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