Subclinical thyroid dysfunction and the risk of stroke: a systematic review and meta-analysis
Open accessAbstract
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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A recent systematic review based on six prospective studies did not support an increased risk of stroke in subclinical hyperthyroidism patients.
“A recent systematic review, based on six prospective studies, did not support an increased risk of stroke in SHyper patients [80] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [80]
The overall pooled estimated hazard ratio using a random effects model showed no association of subclinical hyperthyroidism with stroke (HR 1.17; 95% CI 0.54-2.56), although the studies included were highly heterogeneous.
“The overall pooled estimated HR using a random effects model showed no association of SHyper with stroke (HR = 1.17; 95% CI: 0.54-2.56),although the studies included in this meta-analysis were highly heterogeneous [80] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [80]
A meta-analysis of six studies did not find evidence supporting increased stroke risk in participants with subclinical hyperthyroidism.
“A metaanalysis of 6 studies did not find any evidence supporting an increased risk of stroke in participants with SHyper (87).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [87]
A recent meta-analysis of stroke risk in SH found insufficient number of events to draw definitive conclusions.
“A further population-based study found that SH increased the risk for stroke in subjects over age 50 years with a hazard ratio of 3.39 (402), although a recent meta-analysis of stroke risk in SH found insufficient number of events to draw definitive conclusions (403).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [403]
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Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., Rivkees, S. A., Samuels, M., Sosa, J. A., Stan, M. N., et al. (2016) · Thyroid® · doi:10.1089/thy.2016.0229 · Cited by 2,938 · see citing works
“39 (402), although a recent meta-analysis of stroke risk in SH found insufficient number of events to draw definitive conclusions (403).”
BackgroundThyroid Hormones and Cardiovascular Function and Diseases
Razvi, S., Jabbar, A., Pingitore, A., Danzi, S., Biondi, B., Klein, I., Peeters, R., Zaman, A., & Iervasi, G. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.02.045 · Cited by 515 · see citing works
Self-citationBiondi, B., Bartalena, L., Cooper, D. S., Hegedüs, L., Laurberg, P., & Kahaly, G. J. (2015) · European Thyroid Journal · doi:10.1159/000438750 · Cited by 323 · see citing works
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., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2255 · Cited by 92 · see citing works
Self-citationSohn, S. Y., Lee, E., Lee, M. K., & Lee, J. H. (2020) · Endocrinology and Metabolism · doi:10.3803/enm.2020.728 · Cited by 60 · see citing works
Subclinical Hyperthyroidism: A Review of the Clinical Literature
Tsai, K., & Leung, A. M. (2021) · Endocrine Practice · doi:10.1016/j.eprac.2021.02.002 · Cited by 45 · see citing works
- Authors
- Chaker, L., Baumgartner, C., Ikram, M. A., Dehghan, A., Medici, M., Visser, W. E., Hofman, A., Rodondi, N., Peeters, R. P., & Franco, O. H.
- Affiliations
- Erasmus MC (NL)
- University Hospital of Bern (CH)
- Corresponding author
- Peeters, Robin P.
- ORCID
- Venue
- European Journal of Epidemiology
- Published
- 2014-09-02
- Volume
- 29
- Issue
- 11
- Pages
- 791-800
- ISSN
- 0393-2990 (ISSN-L)
- 1573-7284
- OpenAlex
- W2009095347
- Cited by
- 72
- References
- 49
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 8 · 2023: 6 · 2022: 7 · 2021: 5 · 2020: 8 · 2019: 8 · 2018: 4 · 2017: 3 · 2016: 10 · 2015: 8
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- green
- boris.unibe.ch
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- BORIS (University Library Bern) (submittedVersion, other-oa)
- Open Access CRIS of the University of Bern
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- subclinical thyroid dysfunction, stroke risk, subclinical hypothyroidism, subclinical hyperthyroidism, thyroid function, coronary artery disease
- MeSH terms
- Female, Humans, Hyperthyroidism, Hypothyroidism, Male, Thyroid Function Tests, Thyrotropin, Stroke
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