Thyroid Function and Sudden Cardiac Death: A Prospective Population-Based Cohort Study.
The association between thyroid function and cardiovascular disease is well established, but no study to date has assessed whether it is a risk factor for sudden cardiac death (SCD). Therefore, we studied the association of thyroid function with SCD in a prospective population-based cohort.



Participants from the Rotterdam Study ≥45 years with thyroid-stimulating hormone or free thyroxine (FT4) measurements and clinical follow-up were eligible. We assessed the association of thyroid-stimulating hormone and FT4 with the risk of SCD by using an age- and sex-adjusted Cox proportional-hazards model, in all participants and also after restricting the analysis to euthyroid participants (defined by thyroid-stimulating hormone 0.4-4.0 mIU/L). Additional adjustment included cardiovascular risk factors, notably hypertension, serum cholesterol, and smoking. We stratified by age and sex and performed sensitivity analyses by excluding participants with abnormal FT4 values (reference range of 0.85-1.95 ng/dL) and including only witnessed SCDs as outcome. Absolute risks were calculated in a competing risk model by taking death by other causes into account.



We included 10 318 participants with 261 incident SCDs (median follow-up, 9.1 years). Higher levels of FT4 were associated with an increased SCD risk, even in the normal range of thyroid function (hazard ratio, 2.28 per 1 ng/dL FT4; 95% confidence interval, 1.31-3.97). Stratification by age or sex and sensitivity analyses did not change the risk estimates substantially. The absolute 10-year risk of SCD increased in euthyroid participants from 1% to 4% with increasing FT4 levels.



Higher FT4 levels are associated with an increased risk of SCD, even in euthyroid participants.
From Rotterdam Thyroid Center (L.C., R.P.P.), Department of Internal Medicine (L.C., B.H.C.S., R.P.P.), and Department of Epidemiology (L.C., M.E.v.d.B., M.N.N., O.H.F., A.D., A.H., M.E., B.H.C.S., R.P.P.), Erasmus University Medical Center; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Departments of Medical Informatics (P.R.R.) and Cardiology (J.W.D.), Erasmus University Medical Center, Rotterdam, The Netherlands; and Inspectorate of Health Care, Utrecht, The Netherlands (B.H.C.S.).
Layal
L
Chaker
From Rotterdam Thyroid Center (L.C., R.P.P.), Department of Internal Medicine (L.C., B.H.C.S., R.P.P.), and Department of Epidemiology (L.C., M.E.v.d.B., M.N.N., O.H.F., A.D., A.H., M.E., B.H.C.S., R.P.P.), Erasmus University Medical Center; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Departments of Medical Informatics (P.R.R.) and Cardiology (J.W.D.), Erasmus University Medical Center, Rotterdam, The Netherlands; and Inspectorate of Health Care, Utrecht, The Netherlands (B.H.C.S.).
Marten E
ME
van den Berg
From Rotterdam Thyroid Center (L.C., R.P.P.), Department of Internal Medicine (L.C., B.H.C.S., R.P.P.), and Department of Epidemiology (L.C., M.E.v.d.B., M.N.N., O.H.F., A.D., A.H., M.E., B.H.C.S., R.P.P.), Erasmus University Medical Center; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Departments of Medical Informatics (P.R.R.) and Cardiology (J.W.D.), Erasmus University Medical Center, Rotterdam, The Netherlands; and Inspectorate of Health Care, Utrecht, The Netherlands (B.H.C.S.).
Maartje N
MN
Niemeijer
From Rotterdam Thyroid Center (L.C., R.P.P.), Department of Internal Medicine (L.C., B.H.C.S., R.P.P.), and Department of Epidemiology (L.C., M.E.v.d.B., M.N.N., O.H.F., A.D., A.H., M.E., B.H.C.S., R.P.P.), Erasmus University Medical Center; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Departments of Medical Informatics (P.R.R.) and Cardiology (J.W.D.), Erasmus University Medical Center, Rotterdam, The Netherlands; and Inspectorate of Health Care, Utrecht, The Netherlands (B.H.C.S.).
Oscar H
OH
Franco
From Rotterdam Thyroid Center (L.C., R.P.P.), Department of Internal Medicine (L.C., B.H.C.S., R.P.P.), and Department of Epidemiology (L.C., M.E.v.d.B., M.N.N., O.H.F., A.D., A.H., M.E., B.H.C.S., R.P.P.), Erasmus University Medical Center; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Departments of Medical Informatics (P.R.R.) and Cardiology (J.W.D.), Erasmus University Medical Center, Rotterdam, The Netherlands; and Inspectorate of Health Care, Utrecht, The Netherlands (B.H.C.S.).
Abbas
A
Dehghan
From Rotterdam Thyroid Center (L.C., R.P.P.), Department of Internal Medicine (L.C., B.H.C.S., R.P.P.), and Department of Epidemiology (L.C., M.E.v.d.B., M.N.N., O.H.F., A.D., A.H., M.E., B.H.C.S., R.P.P.), Erasmus University Medical Center; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Departments of Medical Informatics (P.R.R.) and Cardiology (J.W.D.), Erasmus University Medical Center, Rotterdam, The Netherlands; and Inspectorate of Health Care, Utrecht, The Netherlands (B.H.C.S.).
Albert
A
Hofman
From Rotterdam Thyroid Center (L.C., R.P.P.), Department of Internal Medicine (L.C., B.H.C.S., R.P.P.), and Department of Epidemiology (L.C., M.E.v.d.B., M.N.N., O.H.F., A.D., A.H., M.E., B.H.C.S., R.P.P.), Erasmus University Medical Center; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Departments of Medical Informatics (P.R.R.) and Cardiology (J.W.D.), Erasmus University Medical Center, Rotterdam, The Netherlands; and Inspectorate of Health Care, Utrecht, The Netherlands (B.H.C.S.).
Peter R
PR
Rijnbeek
From Rotterdam Thyroid Center (L.C., R.P.P.), Department of Internal Medicine (L.C., B.H.C.S., R.P.P.), and Department of Epidemiology (L.C., M.E.v.d.B., M.N.N., O.H.F., A.D., A.H., M.E., B.H.C.S., R.P.P.), Erasmus University Medical Center; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Departments of Medical Informatics (P.R.R.) and Cardiology (J.W.D.), Erasmus University Medical Center, Rotterdam, The Netherlands; and Inspectorate of Health Care, Utrecht, The Netherlands (B.H.C.S.).
Jaap W
JW
Deckers
From Rotterdam Thyroid Center (L.C., R.P.P.), Department of Internal Medicine (L.C., B.H.C.S., R.P.P.), and Department of Epidemiology (L.C., M.E.v.d.B., M.N.N., O.H.F., A.D., A.H., M.E., B.H.C.S., R.P.P.), Erasmus University Medical Center; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Departments of Medical Informatics (P.R.R.) and Cardiology (J.W.D.), Erasmus University Medical Center, Rotterdam, The Netherlands; and Inspectorate of Health Care, Utrecht, The Netherlands (B.H.C.S.).
Mark
M
Eijgelsheim
From Rotterdam Thyroid Center (L.C., R.P.P.), Department of Internal Medicine (L.C., B.H.C.S., R.P.P.), and Department of Epidemiology (L.C., M.E.v.d.B., M.N.N., O.H.F., A.D., A.H., M.E., B.H.C.S., R.P.P.), Erasmus University Medical Center; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Departments of Medical Informatics (P.R.R.) and Cardiology (J.W.D.), Erasmus University Medical Center, Rotterdam, The Netherlands; and Inspectorate of Health Care, Utrecht, The Netherlands (B.H.C.S.). b.stricker@erasmusmc.nl.
Bruno H C
BH
Stricker
From Rotterdam Thyroid Center (L.C., R.P.P.), Department of Internal Medicine (L.C., B.H.C.S., R.P.P.), and Department of Epidemiology (L.C., M.E.v.d.B., M.N.N., O.H.F., A.D., A.H., M.E., B.H.C.S., R.P.P.), Erasmus University Medical Center; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Departments of Medical Informatics (P.R.R.) and Cardiology (J.W.D.), Erasmus University Medical Center, Rotterdam, The Netherlands; and Inspectorate of Health Care, Utrecht, The Netherlands (B.H.C.S.).
Robin P
RP
Peeters
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D016757:Death, Sudden, Cardiac / Q000453:epidemiology* / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011159:Population Surveillance / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors; D013960:Thyroid Function Tests / Q000379:methods; D013961:Thyroid Gland / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood*
D015415:Biomarkers; D013972:Thyrotropin; D013974:Thyroxine
death; death, sudden, cardiac; epidemiology; thyroid gland