Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation
Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid...
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| Published in | Circulation (New York, N.Y.) Vol. 136; no. 22; pp. 2100 - 2116 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
28.11.2017
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0009-7322 1524-4539 1524-4539 |
| DOI | 10.1161/CIRCULATIONAHA.117.028753 |
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| Abstract | Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF.
We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF.
Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4;
for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease.
In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF. |
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| AbstractList | Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF.
We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF.
Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4;
for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease.
In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF. Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF.BACKGROUNDAtrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF.We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF.METHODSWe conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF.Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease.RESULTSOf 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease.In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.CONCLUSIONSIn euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF. |
| Author | Collet, Tinh-Hai Bauer, Douglas C. Westendorp, Rudi G. J. Gussekloo, Jacobijn da Costa, Bruno R. Völzke, Henry Floriani, Carmen Cappola, Anne R. Heeringa, Jan Aujesky, Drahomir Ceresini, Graziano Peeters, Robin P. Khaw, Kay-Tee Walsh, John P. Baumgartner, Christine Rodondi, Nicolas Bremner, Alexandra Dörr, Marcus den Elzen, Wendy P.J. Macfarlane, Peter Magnani, Jared W. Luben, Robert Stott, David J. Heckbert, Susan R. Iacoviello, Massimo Feller, Martin |
| AuthorAffiliation | 20 Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom 19 Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands 16 School of Population Health, University of Western Australia, Crawley, WA, Australia 8 Department of Public Health and Primary Care, and Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands 18 Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom 2 Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland 10 Departments of Internal Medicine and Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands 22 Heart and Vascular Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States 9 Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands 15 Department of Endocrinology & Diabetes, Sir Charles Gairdner Ho |
| AuthorAffiliation_xml | – name: 7 Department of Clinical and Experimental Medicine, Geriatric Endocrine Unit, University Hospital of Parma, Parma, Italy – name: 22 Heart and Vascular Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States – name: 10 Departments of Internal Medicine and Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands – name: 9 Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands – name: 13 Department of Internal Medicine, University Medicine Greifswald, Greifswald, Germany and German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany – name: 14 School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, Australia – name: 18 Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom – name: 21 Department of Public Health and Center for Healthy Ageing, University of Copenhagen, Copenhagen, Denmark – name: 4 Departments of Medicine and Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA, United States – name: 16 School of Population Health, University of Western Australia, Crawley, WA, Australia – name: 3 Service of Endocrinology, Diabetes and Metabolism, University Hospital of Lausanne, Lausanne, Switzerland – name: 12 Institute for Community Medicine, Clinical-Epidemiological Research, University Medicine Greifswald, Greifswald, Germany and German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany – name: 20 Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom – name: 8 Department of Public Health and Primary Care, and Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands – name: 11 Department of Public Health and Primary Care, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom – name: 6 Department of Epidemiology, University of Washington, Seattle, WA, United States – name: 1 Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland – name: 2 Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland – name: 17 Cardiology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy – name: 19 Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands – name: 5 University of Pennsylvania School of Medicine, Philadelphia, PA, United States – name: 15 Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia |
| Author_xml | – sequence: 1 givenname: Christine surname: Baumgartner fullname: Baumgartner, Christine organization: Department of General Internal Medicine, Inselspital, Bern University Hospital, (C.B., M.F., C.F., D.A., N.R.) – sequence: 2 givenname: Bruno R. surname: da Costa fullname: da Costa, Bruno R. organization: Institute of Primary Health Care (BIHAM) (B.R.d.C., M.F., N.R.), University of Bern, Switzerland; Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Institue of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada (B.R.d.C.) – sequence: 3 givenname: Tinh-Hai surname: Collet fullname: Collet, Tinh-Hai organization: Service of Endocrinology, Diabetes and Metabolism, University Hospital of Lausanne, Switzerland (T.-H.C.) – sequence: 4 givenname: Martin surname: Feller fullname: Feller, Martin organization: Department of General Internal Medicine, Inselspital, Bern University Hospital, (C.B., M.F., C.F., D.A., N.R.), Institute of Primary Health Care (BIHAM) (B.R.d.C., M.F., N.R.) – sequence: 5 givenname: Carmen surname: Floriani fullname: Floriani, Carmen organization: Department of General Internal Medicine, Inselspital, Bern University Hospital, (C.B., M.F., C.F., D.A., N.R.) – sequence: 6 givenname: Douglas C. surname: Bauer fullname: Bauer, Douglas C. organization: Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco (D.C.B.) – sequence: 7 givenname: Anne R. surname: Cappola fullname: Cappola, Anne R. organization: University of Pennsylvania School of Medicine, Philadelphia (A.R.C.) – sequence: 8 givenname: Susan R. surname: Heckbert fullname: Heckbert, Susan R. organization: Department of Epidemiology, University of Washington, Seattle (S.R.H.) – sequence: 9 givenname: Graziano surname: Ceresini fullname: Ceresini, Graziano organization: Department of Clinical and Experimental Medicine, Geriatric Endocrine Unit, University Hospital of Parma, Italy (G.C.) – sequence: 10 givenname: Jacobijn surname: Gussekloo fullname: Gussekloo, Jacobijn organization: Department of Public Health and Primary Care, and Department of Gerontology and Geriatrics (J.G.) – sequence: 11 givenname: Wendy P.J. surname: den Elzen fullname: den Elzen, Wendy P.J. organization: Department of Clinical Chemistry and Laboratory Medicine (W.P.J.d.E.) – sequence: 12 givenname: Robin P. surname: Peeters fullname: Peeters, Robin P. organization: Leiden University Medical Center, The Netherlands; Departments of Internal Medicine and Epidemiology (R.P.P.) – sequence: 13 givenname: Robert surname: Luben fullname: Luben, Robert organization: Erasmus Medical Center, Rotterdam, The Netherlands; Department of Public Health and Primary Care, University of Cambridge, Addenbrooke’s Hospital, United Kingdom (R.L., K.-T.K.) – sequence: 14 givenname: Henry surname: Völzke fullname: Völzke, Henry organization: Institute for Community Medicine, Clinical-Epidemiological Research (H.V.) – sequence: 15 givenname: Marcus surname: Dörr fullname: Dörr, Marcus organization: Department of Internal Medicine (M.D.) – sequence: 16 givenname: John P. surname: Walsh fullname: Walsh, John P. organization: University Medicine Greifswald, Germany, and German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Germany; School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia (J.P.W.);, Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia (J.P.W.) – sequence: 17 givenname: Alexandra surname: Bremner fullname: Bremner, Alexandra organization: School of Population Health, University of Western Australia, Crawley, Australia (A.B.) – sequence: 18 givenname: Massimo surname: Iacoviello fullname: Iacoviello, Massimo organization: Cardiology Unit, Department of Emergency and Organ Transplantation, University of Bari, Italy (M.I.) – sequence: 19 givenname: Peter surname: Macfarlane fullname: Macfarlane, Peter organization: Institute of Health and Wellbeing (P.M.) – sequence: 20 givenname: Jan surname: Heeringa fullname: Heeringa, Jan organization: Department of Epidemiology and Biostatistics (J.H.) – sequence: 21 givenname: David J. surname: Stott fullname: Stott, David J. organization: Institute of Cardiovascular and Medical Sciences, (D.J.S.) – sequence: 22 givenname: Rudi G. J. surname: Westendorp fullname: Westendorp, Rudi G. J. organization: University of Glasgow, United Kingdom; Department of Public Health and Center for Healthy Aging, University of Copenhagen, Denmark (R.G.J.W.) – sequence: 23 givenname: Kay-Tee surname: Khaw fullname: Khaw, Kay-Tee organization: Erasmus Medical Center, Rotterdam, The Netherlands; Department of Public Health and Primary Care, University of Cambridge, Addenbrooke’s Hospital, United Kingdom (R.L., K.-T.K.) – sequence: 24 givenname: Jared W. surname: Magnani fullname: Magnani, Jared W. organization: Heart and Vascular Institute, Department of Medicine, University of Pittsburgh, PA (J.W.M.) – sequence: 25 givenname: Drahomir surname: Aujesky fullname: Aujesky, Drahomir organization: Department of General Internal Medicine, Inselspital, Bern University Hospital, (C.B., M.F., C.F., D.A., N.R.) – sequence: 26 givenname: Nicolas surname: Rodondi fullname: Rodondi, Nicolas organization: Department of General Internal Medicine, Inselspital, Bern University Hospital, (C.B., M.F., C.F., D.A., N.R.), Institute of Primary Health Care (BIHAM) (B.R.d.C., M.F., N.R.) |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29061566$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Adult Aged Aged, 80 and over Asymptomatic Diseases Atrial Fibrillation - diagnosis Atrial Fibrillation - epidemiology Biomarkers - blood Chi-Square Distribution Female Humans Hypothyroidism - blood Hypothyroidism - diagnosis Hypothyroidism - epidemiology Hypothyroidism - physiopathology Incidence Male Middle Aged Predictive Value of Tests Prognosis Proportional Hazards Models Risk Assessment Risk Factors Thyroid Function Tests Thyroid Gland - metabolism Thyroid Gland - physiopathology Thyrotropin - blood Thyroxine - blood Time Factors Young Adult |
| Title | Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation |
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