Thyroid Function Within the Normal Range, Subclinical Hypothyroidism and the Risk of Atrial Fibrillation

Christine Baumgartner; Bruno R. da Costa; Tinh-Hai Collet; Martin Feller; Carmen Floriani; Douglas C. Bauer; Anne R. Cappola; Susan R. Heckbert; Graziano Ceresini; Jacobijn Gussekloo; Wendy P. J. den Elzen; Robin P. Peeters; Robert Luben; Henry Völzke; Marcus Dörr; John P. Walsh; Alexandra Bremner; Massimo Iacoviello; Peter Macfarlane; Jan Heeringa; David J. Stott; Rudi G. J. Westendorp; Kay-Tee Khaw; Jared W. Magnani; Drahomir Aujesky; Nicolas Rodondi; Thyroid Studies Collaboration

doi:10.1161/circulationaha.117.028753

Thyroid Function Within the Normal Range, Subclinical Hypothyroidism and the Risk of Atrial Fibrillation

Christine Baumgartner, Bruno R. da Costa, Tinh-Hai Collet, Martin Feller, Carmen Floriani, Douglas C. Bauer, Anne R. Cappola, Susan R. Heckbert, Graziano Ceresini, Jacobijn Gussekloo, Wendy P. J. den Elzen, Robin P. Peeters, Robert Luben, Henry Völzke, Marcus Dörr, John P. Walsh, Alexandra Bremner, Massimo Iacoviello, Peter Macfarlane, Jan HeeringaDavid J. Stott, Rudi G. J. Westendorp, Kay-Tee Khaw, Jared W. Magnani, Drahomir Aujesky, Nicolas Rodondi, Thyroid Studies Collaboration

60 Citations (Scopus)

Abstract

Background -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. Methods -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. Results -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 ageand 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. Conclusions -In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.

Original language	English
Journal	Circulation
Volume	136
Issue number	22
Pages (from-to)	2100-2116
Number of pages	17
ISSN	0009-7322
DOIs	https://doi.org/10.1161/circulationaha.117.028753
Publication status	Published - 28 Nov 2017

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Baumgartner, C., da Costa, B. R., Collet, T-H., Feller, M., Floriani, C., Bauer, D. C., Cappola, A. R., Heckbert, S. R., Ceresini, G., Gussekloo, J., den Elzen, W. P. J., Peeters, R. P., Luben, R., Völzke, H., Dörr, M., Walsh, J. P., Bremner, A., Iacoviello, M., Macfarlane, P., ... Thyroid Studies Collaboration (2017). Thyroid Function Within the Normal Range, Subclinical Hypothyroidism and the Risk of Atrial Fibrillation. Circulation, 136(22), 2100-2116. https://doi.org/10.1161/circulationaha.117.028753

Baumgartner, C, da Costa, BR, Collet, T-H, Feller, M, Floriani, C, Bauer, DC, Cappola, AR, Heckbert, SR, Ceresini, G, Gussekloo, J, den Elzen, WPJ, Peeters, RP, Luben, R, Völzke, H, Dörr, M, Walsh, JP, Bremner, A, Iacoviello, M, Macfarlane, P, Heeringa, J, Stott, DJ, Westendorp, RGJ, Khaw, K-T, Magnani, JW, Aujesky, D, Rodondi, N & Thyroid Studies Collaboration 2017, 'Thyroid Function Within the Normal Range, Subclinical Hypothyroidism and the Risk of Atrial Fibrillation', Circulation, vol. 136, no. 22, pp. 2100-2116. https://doi.org/10.1161/circulationaha.117.028753

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title = "Thyroid Function Within the Normal Range, Subclinical Hypothyroidism and the Risk of Atrial Fibrillation",

abstract = "Background -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. Methods -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. Results -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 ageand 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. Conclusions -In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.",

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author = "Christine Baumgartner and {da Costa}, {Bruno R.} and Tinh-Hai Collet and Martin Feller and Carmen Floriani and Bauer, {Douglas C.} and Cappola, {Anne R.} and Heckbert, {Susan R.} and Graziano Ceresini and Jacobijn Gussekloo and {den Elzen}, {Wendy P. J.} and Peeters, {Robin P.} and Robert Luben and Henry V{\"o}lzke and Marcus D{\"o}rr and Walsh, {John P.} and Alexandra Bremner and Massimo Iacoviello and Peter Macfarlane and Jan Heeringa and Stott, {David J.} and Westendorp, {Rudi G. J.} and Kay-Tee Khaw and Magnani, {Jared W.} and Drahomir Aujesky and Nicolas Rodondi and {Thyroid Studies Collaboration}",

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doi = "10.1161/circulationaha.117.028753",

language = "English",

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pages = "2100--2116",

journal = "Circulation",

issn = "0009-7322",

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T1 - Thyroid Function Within the Normal Range, Subclinical Hypothyroidism and the Risk of Atrial Fibrillation

AU - Baumgartner, Christine

AU - da Costa, Bruno R.

AU - Collet, Tinh-Hai

AU - Feller, Martin

AU - Floriani, Carmen

AU - Bauer, Douglas C.

AU - Cappola, Anne R.

AU - Heckbert, Susan R.

AU - Ceresini, Graziano

AU - Gussekloo, Jacobijn

AU - den Elzen, Wendy P. J.

AU - Peeters, Robin P.

AU - Luben, Robert

AU - Völzke, Henry

AU - Dörr, Marcus

AU - Walsh, John P.

AU - Bremner, Alexandra

AU - Iacoviello, Massimo

AU - Macfarlane, Peter

AU - Heeringa, Jan

AU - Stott, David J.

AU - Westendorp, Rudi G. J.

AU - Khaw, Kay-Tee

AU - Magnani, Jared W.

AU - Aujesky, Drahomir

AU - Rodondi, Nicolas

AU - Thyroid Studies Collaboration

PY - 2017/11/28

Y1 - 2017/11/28

N2 - Background -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. Methods -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. Results -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 ageand 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. Conclusions -In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.

AB - Background -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. Methods -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. Results -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 ageand 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. Conclusions -In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.

KW - Journal Article

U2 - 10.1161/circulationaha.117.028753

DO - 10.1161/circulationaha.117.028753

M3 - Journal article

C2 - 29061566

SN - 0009-7322

VL - 136

SP - 2100

EP - 2116

JO - Circulation

JF - Circulation

IS - 22

ER -

Thyroid Function Within the Normal Range, Subclinical Hypothyroidism and the Risk of Atrial Fibrillation

Abstract

Keywords

UN SDGs

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