The EPIC-Norfolk Study
Thyroid Function Within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis.
The Journal of clinical endocrinology and metabolism 2016 ; 101: 4270-4282.
Chaker L, Baumgartner C, den Elzen WP, Collet TH, Ikram MA, Blum MR, Dehghan A, Drechsler C, Luben RN, Portegies ML, Iervasi G, Medici M, Stott DJ, Dullaart RP, Ford I, Bremner A, Newman AB, Wanner C, Sgarbi JA, Dörr M, Longstreth WT, Psaty BM, Ferrucci L, Maciel RM, Westendorp RG, Jukema JW, Ceresini G, Imaizumi M, Hofman A, Bakker SJ, Franklyn JA, Khaw KT, Bauer DC, Walsh JP, Razvi S, Gussekloo J, Völzke H, Franco OH, Cappola AR, Rodondi N, Peeters RP, and Thyroid Studies Collaboration Thyroid Studies Collaboration
DOI : 10.1210/jc.2016-2255
PubMed ID : 27603906
PMCID : PMC5095234
URL : https://academic.oup.com/jcem/article/101/11/4270/2765001
Abstract
The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several cardiovascular disorders, its association with the risk of stroke has not been evaluated previously.
We identified studies through a systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline TSH, free T, and stroke outcomes were included, and we collected individual participant data from each study, including thyroid function measurements and incident all stroke (combined fatal and nonfatal) and fatal stroke. The applied reference range for TSH levels was between 0.45 and 4.49 mIU/L.
We collected individual participant data on 43 598 adults with TSH within the reference range from 17 cohorts, with a median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449 908 person-years. Age- and sex-adjusted pooled hazard ratio for TSH was 0.78 (95% confidence interval [CI] 0.65-0.95 across the reference range of TSH) for all stroke and 0.83 (95% CI 0.62-1.09) for fatal stroke. For the free T analyses, the hazard ratio was 1.08 (95% CI 0.99-1.15 per SD increase) for all stroke and 1.10 (95% CI 1.04-1.19) for fatal stroke. This was independent of cardiovascular risk factors including systolic blood pressure, total cholesterol, smoking, and prevalent diabetes.
Higher levels of TSH within the reference range may decrease the risk of stroke, highlighting the need for further research focusing on the clinical consequences associated with differences within the reference range of thyroid function.