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Thyroid Function Within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis.

Layal Chaker1, Christine Baumgartner1, Wendy P J den Elzen1

  • 1Departments of Internal Medicine (R.P.P., L.C., M.M.) and Epidemiology (R.P.P., O.H.F., A.D., A.H., A.I., L.C., M.L.P.P.), Erasmus University Medical Center, 3000 DR Rotterdam, The Netherlands; Rotterdam Thyroid Center (R.P.P., L.C., M.M.) and Department of Radiology and Neurology (M.A.I.), Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; Department of General Internal Medicine (N.R., C.B., M.R.B.), Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; Service of Endocrinology, Diabetes, and Metabolism (T.-H.C.), University Hospital of Lausanne, 1011 Lausanne, Switzerland; Departments of Clinical Chemistry and Laboratory Medicine (W.P.J.d.E.), Public Health and Primary Care (J.G.), and Cardiology (W.J.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands; Departments of Medicine and Epidemiology and Biostatistics (D.C.B.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology, Diabetes, and Metabolism (A.R.C.), Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104; Department of Epidemiology (A.H.), Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115; Department of Endocrinology (S.R.), Gateshead Health Foundation National Health Service Trust, Gateshead, SE18 4QH, United Kingdom; Department of Endocrinology and Diabetes (J.P.W.), Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia; Schools of Medicine and Pharmacology (J.P.W.) and Population Health (A.B.), University of Western Australia, Crawley, Western Australia 6009, Australia; National Council Research Institute of Clinical Physiology (G.I.), 56124 Pisa, Italy; Robertson Centre for Biostatistics (I.F.) and Institute of Cardiovascular and Medical Sciences (D.J.S.), Faculty of Medicine, University of Glasgow, Glasgow G12 8TA, United Kingdom; Department of Epidemiology (A.B.N.), University of Pittsburgh, Pittsburgh, Pennsylvania 15260; Department of Internal Medicine (S.J.L.B., R.P.D.), University Medical Center, University of Groningen, 9700 AB Groningen, The Netherlands; Department of Medicine (C.W., C.D.), Division of Nephrology, University Hospital of Würzburg, and Comprehensive Heart Failure Centre (C.W., C.D.), 97070 Würzburg, Germany; Department of Clinical Studies (M.I.), Radiation Effects Research Foundation, Nagasaki 850-8555, Japan; Department of Clinical and Experimental Medicine (G.C.), University of Parma, 143100 Parma, Italy; National Institute on Aging (L.F.), Baltimore, Maryland 21225; Institute for Community Medicine (H.V.), Clinical-Epidemiological Research/Study of Health in Pomerania, University Medicine, German Centre of Cardiovascular Research, Partner Site, Department of Internal Medicine (M.D.), and University Medicine (M.D.), German Centre of Cardiovascular Research, Partner Site, 17487 Greifswald, Germany; Departments of Neurology and Epidemiology (W.T.L.), and Cardiovascular Health Research Unit (W.T.L.), Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, Washington 98108; Group Health Research Institute (B.M.P.), Group Health Cooperative, Seattle, Washington 98101; Division of Endocrinology (R.M.B.M., J.A.S.), Department of Medicine, Federal University of Sao Paulo, 05508-900 São Paulo, Brazil; Division of Endocrinology (J.A.S.), Faculdade de Medicina de Marília, Marília, Brazil; Department of Public Health and Primary Care (R.N.L., K.-T.K.), University of Cambridge, Cambridge CB2 1TN, United Kingdom; Interuniversity Cardiology Institute of The Netherlands (W.J.), 3508 GA Utrecht, The Netherlands; School of Clinical and Experimental Medicine (J.A.F.), College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom; and Department of Public Health and Center for Healthy Ageing (R.G.W.), Faculty of Health and Medical Sciences, University of Copenhagen, DK-2400 Copenhagen, Denmark.

The Journal of Clinical Endocrinology and Metabolism
|September 8, 2016
PubMed
Summary

Thyroid stimulating hormone (TSH) within normal ranges may reduce stroke risk. Higher free T4 levels within the reference range might increase stroke risk, warranting further investigation into thyroid function

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Area of Science:

  • Endocrinology
  • Neurology
  • Epidemiology

Background:

  • Thyroid function reference ranges are debated.
  • Thyroid function within reference ranges is linked to cardiovascular disorders.
  • The association between thyroid function and stroke risk is not well-established.

Purpose of the Study:

  • To evaluate the association between thyroid function within reference ranges and stroke risk.
  • To analyze the impact of thyroid stimulating hormone (TSH) and free thyroxine (FT4) on stroke incidence.

Main Methods:

  • Systematic literature search and data from the Thyroid Studies Collaboration.
  • Individual participant data from 17 prospective cohort studies were analyzed.
  • Included 43,598 adults with TSH within the 0.45–4.49 mIU/L reference range, with a median follow-up of 11.6 years.

Main Results:

  • Higher TSH levels within the reference range were associated with a reduced risk of all stroke (HR 0.78, 95% CI 0.65–0.95).
  • Higher free T4 levels within the reference range were associated with an increased risk of all stroke (HR 1.08, 95% CI 0.99–1.15 per SD increase).
  • These associations were independent of major cardiovascular risk factors.

Conclusions:

  • Elevated TSH levels within the reference range may be protective against stroke.
  • Increased free T4 levels within the reference range may be associated with a higher stroke risk.
  • Further research is needed to understand the clinical implications of thyroid function variations within reference ranges.