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Subclinical thyroid dysfunction and the risk of stroke: a systematic review and meta-analysis

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Abstract

Subclinical thyroid dysfunction has been associated with coronary heart disease, but the risk of stroke is unclear. Our aim is to combine the evidence on the association between subclinical thyroid dysfunction and the risk of stroke in prospective cohort studies. We searched Medline (OvidSP), Embase, Web-of-Science, Pubmed Publisher, Cochrane and Google Scholar from inception to November 2013 using a cohort filter, but without language restriction or other limitations. Reference lists of articles were searched. Two independent reviewers screened articles according to pre-specified criteria and selected prospective cohort studies with baseline thyroid function measurements and assessment of stroke outcomes. Data were derived using a standardized data extraction form. Quality was assessed according to previously defined quality indicators by two independent reviewers. We pooled the outcomes using a random-effects model. Of 2,274 articles screened, six cohort studies, including 11,309 participants with 665 stroke events, met the criteria. Four of six studies provided information on subclinical hyperthyroidism including a total of 6,029 participants and five on subclinical hypothyroidism (n = 10,118). The pooled hazard ratio (HR) was 1.08 (95 % CI 0.87–1.34) for subclinical hypothyroidism (I 2 of 0 %) and 1.17 (95 % CI 0.54–2.56) for subclinical hyperthyroidism (I 2 of 67 %) compared to euthyroidism. Subgroup analyses yielded similar results. Our systematic review provides no evidence supporting an increased risk for stroke associated with subclinical thyroid dysfunction. However, the available literature is insufficient and larger datasets are needed to perform extended analyses. Also, there were insufficient events to exclude clinically significant risk from subclinical hyperthyroidism, and more data are required for subgroup analyses.

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Acknowledgments

We would like to express our gratitude to Wichor M. Bramer from the medical library (Medical Library, Erasmus Medical Center, Rotterdam) for the important contribution to the literature search. Dr. R.P. Peeters is supported by a Zon-MW TOP grant (nr 91212044) and an Erasmus MCMRACE grant. Dr. A. Dehghan is supported by NWO grant (veni, 916.12.154) and the EUR Fellowship. Dr. C. Baumgartner is supported by a grant from the Swiss National Science Foundation (SNSF 320030-138267 and 320030-150025 to Prof. Rodondi). Prof. N. Rodondi’s research is supported by a grant from the Swiss National Science Foundation (SNSF 320030-138267) and by a grant from the Swiss Heart Foundation. Prof. O. H. Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.), Metagenics Inc., and AXA. Nestlé Nutrition (Nestec Ltd.), Metagenics Inc., and AXA had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, Thyroid Center, Erasmus University Medical Center, Room Ee502, PO Box 2040, 3000 CA, Rotterdam, The Netherlands

    Layal Chaker, Marco Medici, W. Edward Visser & Robin P. Peeters

  2. Department of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland

    Christine Baumgartner & Nicolas Rodondi

  3. Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands

    M. Arfan Ikram

  4. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands

    Layal Chaker, M. Arfan Ikram, Abbas Dehghan, Albert Hofman & Oscar H. Franco

  5. Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands

    M. Arfan Ikram

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  1. Layal Chaker
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Correspondence to Robin P. Peeters.

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Chaker, L., Baumgartner, C., Ikram, M.A. et al. Subclinical thyroid dysfunction and the risk of stroke: a systematic review and meta-analysis. Eur J Epidemiol 29, 791–800 (2014). https://doi.org/10.1007/s10654-014-9946-8

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