The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Thyroid Status, Cardiovascular Risk, and Mortality in Older Adults
Abstract
CONTEXT: Previous studies have suggested that subclinical abnormalities in thyroid-stimulating hormone levels are associated with detrimental effects on the cardiovascular system. OBJECTIVE: To determine the relationship between baseline thyroid status and incident atrial fibrillation, incident cardiovascular disease, and mortality in older men and women not taking thyroid medication. DESIGN, SETTING, AND PARTICIPANTS: A total of 3233 US community-dwelling individuals aged 65 years or older with baseline serum thyroid-stimulating hormone levels were enrolled in 1989-1990 in the Cardiovascular Health Study, a large, prospective cohort study. MAIN OUTCOME MEASURES: Incident atrial fibrillation, coronary heart disease, cerebrovascular disease, cardiovascular death, and all-cause death assessed through June 2002. Analyses are reported for 4 groups defined according to thyroid function test results: subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism. RESULTS: Individuals with overt thyrotoxicosis (n = 4) were excluded because of small numbers. Eighty-two percent of participants (n = 2639) had normal thyroid function, 15% (n = 496) had subclinical hypothyroidism, 1.6% (n = 51) had overt hypothyroidism, and 1.5% (n = 47) had subclinical hyperthyroidism. After exclusion of those with prevalent atrial fibrillation, individuals with subclinical hyperthyroidism had a greater incidence of atrial fibrillation compared with those with normal thyroid function (67 events vs 31 events per 1000 person-years; adjusted hazard ratio, 1.98; 95% confidence interval, 1.29-3.03). No differences were seen between the subclinical hyperthyroidism group and euthyroidism group for incident coronary heart disease, cerebrovascular disease, cardiovascular death, or all-cause death. Likewise, there were no differences between the subclinical hypothyroidism or overt hypothyroidism groups and the euthyroidism group for cardiovascular outcomes or mortality. Specifically, individuals with subclinical hypothyroidism had an adjusted hazard ratio of 1.07 (95% confidence interval, 0.90-1.28) for incident coronary heart disease. CONCLUSION: Our data show an association between subclinical hyperthyroidism and development of atrial fibrillation but do not support the hypothesis that unrecognized subclinical hyperthyroidism or subclinical hypothyroidism is associated with other cardiovascular disorders or mortality.
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In the citing paper
“A high TSH level within the normal range appears to be protective and has been shown to be associated with reduced mortality risk in older euthyroid individuals.149”
From Hypothyroidism (2024) · cites this paper as [149]
In the citing paper
“Cardiac AEs, including tachycardia, palpitations and atrial fibrillation, arise from increased myocardial oxygen consumption and enhanced β‐adrenergic sensitivity.”
From Risk of cardiac, neuropsychiatric and musculoskeletal adverse events with levothyroxine: Systematic review (2026) · cites this paper as [6]
In the citing paper
“Cardiovascular symptoms are the most frequent indicators of mild thyroid hormone excess in the elderly, similar to overt hyperthyroidism [52,53] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [53]
In the citing paper
“A 2-to 3-fold increased risk of atrial fibrillation (AF) was associated with SHyper in elderly subjects in two large prospective studies [52,53] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [53]
In the citing paper
“An increased incidence of AF has also been observed in elderly persons with low serum TSH (0.1-0.5 mIU/l) with an HR of 1.6 (95% CI: 1.0-2.5)[52] and 1.85 (95% CI: 1.14-3.00)[53] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [53]
In the citing paper
“Contradicting this, two other studies included in this meta-analysis reported a non-significant decreased risk for stroke associated with SHyper [53,82] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [53]
In the citing paper
“Older patients with low TSH and higher fT4 have a higher prevalence and incidence of atrial fibrillation compared with euthyroid subjects (94–98)”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [94]
In the citing paper
“Trials of levothyroxine in SCH using surrogate markers have shown improvement in LV function, vascular endothelial function, atherogenic lipid particles, or cardiac mitochondrial function (4,91,105-108).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [105]
In the citing paper
“In addition, several studies of older patients have shown SCH to have either a protective or no impact on CV disease risk (103-105).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [105]
In the citing paper
“these findings have not been reproduced by all studies (13, 17, 25, 26)”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [13]
In the citing paper
“However, there is significant heterogeneity within the literature, with some large and well-conducted studies failing to reproduce these associations (13, 21), as well as unresolved questions about causality.”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [13]
In the citing paper
“in cohort studies, subclinical hyperthyroidism or lower serum TSH have been associated with many involutional disease states including dementia, osteoporosis, AF, muscle weakness, low bone density, and fracture (12–14, 18, 20, 48, 49).”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [13]
In the citing paper
“In contrast with subclinical hypothyroidism, many previous studies have shown that low serum TSH is associated with poor outcomes, either increased all-cause or vascular mortality, or AF (12–14, 17, 29, 36, 37).”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [13]
In the citing paper
“It has widely been assumed that these associations are caused by subclinical hyperthyroidism with detrimental effects of excess thyroid hormone, for instance its proarrhythmic effect on the heart leading to AF, despite the fact that serum thyroid hormones are within reference range (1, 13–15, 29, 41, 42).”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [13]
In the citing paper
“Some studies report increased overall mortality rates in SH subjects (374,379-383), especially older subjects, while others indicate no relation (384)(385)(386)(387).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [384]
In the citing paper
“Some other, smaller studies have reached similar conclusions (374,383), although other smaller studies have failed to find a correlation (380,381,384,386).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [384]
In the citing paper
“Sawin et al. (399) first reported a 2.8-fold increased risk of atrial fibrillation in SH subjects over age 60 years in 1994, and subsequent studies have confirmed that the risk of arrhythmias, particularly atrial fibrillation, is increased in SH (381,384,388,391,400,401).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [384]
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Beukhof, C. M., Massolt, E. T., Visser, T. J., Korevaar, T. I. M., Medici, M., de Herder, W. W., van Lennep, J. E. R., Mulder, M. T., de Rijke, Y. B., Reiners, C., et al. (2018) · Thyroid · doi:10.1089/thy.2017.0330 · Cited by 39
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Müller, P., Leow, M. K., & Dietrich, J. W. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.942971 · Cited by 39
“In another large cohort study with elderly community-dwelling individuals diminished TSH levels were associated with a higher incidence of all-cause death (121).”
BackgroundChoi, S. H., Lee, Y. J., Park, Y. J., Kim, K. W., Lee, E. J., Lim, S. K., Park, D. J., Kim, S. E., Park, K. S., Jang, H. C., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2536 · Cited by 38
T 3 Augmentation in Major Depressive Disorder: Safety Considerations
Rosenthal, L. J., Goldner, W. S., & O’Reardon, J. P. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10030402 · Cited by 38
Autoimmune thyroiditis as a risk factor for stroke
Karch, A., & Thomas, S. L. (2014) · Neurology · doi:10.1212/wnl.0000000000000377 · Cited by 37
“Three of the studies were conceptually different from this study because they used asymptomatic patients identified as hypothyroid by laboratory tests who were mostly untreated with thyroxine.(7,12,25) We found differences between individuals with and without AIT in the prevalence of traditional cardiovascular risk fa…”
ResultEffects of endocrine disorders on lipids and lipoproteins
Newman, C. B. (2022) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2022.101667 · Cited by 37
Takawale, A. R., Aguilar, M., Bouchrit, Y., & Hiram, R. (2022) · Cells · doi:10.3390/cells11244047 · Cited by 36
Metabolic Syndrome, Thyroid Dysfunction, and Cardiovascular Risk: The Triptych of Evil
Pingitore, A., Gaggini, M., Mastorci, F., Sabatino, L., Cordiviola, L., & Vassalle, C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910628 · Cited by 39
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Tayal, B., Graff, C., Selmer, C., Kragholm, K. H., Kihlstrom, M., Nielsen, J. B., Olsen, A. S., Pietersen, A. H., Holst, A. G., Søgaard, P., et al. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-023854 · Cited by 41
“In addition, our findings are also supported by recent studies demonstrating that thyroid dysfunction have no impact on cardiovascular outcomes and mortality in elderly populations.(8) 32 In the present study, we observed a shorter P-wave duration in hyperthyroidism and a longer PR interval in patients with hypothyroi…”
ResultType 2 Myocardial Infarction: A Geriatric Population-based Model of Pathogenesis
Putot, A., Jeanmichel, M., Chague, F., Manckoundia, P., Cottin, Y., & Zeller, M. (2020) · Aging and Disease · doi:10.14336/ad.2019.0405 · Cited by 36
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“Several studies suggest a graded elationship between TSH and cholesterol levels, even in sublinical hypothyroidism [17,6].”
BackgroundResultIncreased carotid arterial stiffness in subclinical hypothyroidism
Tian, L., Gao, C., Liu, J., & Zhang, X. (2010) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2010.08.005 · Cited by 36
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RetractedThyroid hormone replacement: current status and challenges
Okosieme, O. E. (2011) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2011.600307 · Cited by 33
“Thyroid hormone excess increases the risks of atrial fibrillation [13,50-51], osteoporosis [13,52-53] and fractures [54].”
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“Thyroid dysfunction is associated with morbidity and deleterious outcomes such as increased risk of coronary artery disease and cardiovascular mortality [2].”
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Association of Thyroid Function Genetic Predictors With Atrial Fibrillation
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Expert consensus on diagnosis and treatment for elderly with thyroid diseases in China (2021)
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“Hypertension was defined as self-reported of high blood pressure history, mean blood pressure of more than 140/90 mmHg, or the use of antihypertensive medication [14].”
BackgroundKostopoulos, G., & Effraimidis, G. (2024) · European Thyroid Journal · doi:10.1530/etj-23-0254 · Cited by 36
Biondi, B. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0585 · Cited by 32
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Endocrine system dysfunction and chronic heart failure: a clinical perspective
Lisco, G., Giagulli, V. A., Iovino, M., Zupo, R., Guastamacchia, E., Pergola, G. D., Iacoviello, M., & Triggiani, V. (2021) · Endocrine · doi:10.1007/s12020-021-02912-w · Cited by 34
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Metadata
- Authors
- Cappola, A. R., Fried, L. P., Arnold, A. M., Danese, M. D., Kuller, L. H., Burke, G. L., Tracy, R. P., & Ladenson, P. W.
- Affiliations
- University of Pennsylvania Health System (US)
- Johns Hopkins University (US)
- University of Washington (US)
- University of Pittsburgh (US)
- Wake Forest University (US)
- University of Vermont (US)
- Corresponding author
- Cappola, Anne R.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2006-03-01
- Volume
- 295
- Issue
- 9
- Pages
- 1033
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W1965686740
- Cited by
- 862
- References
- 47
- Citations by year
- 2026: 13 · 2025: 26 · 2024: 41 · 2023: 46 · 2022: 39 · 2021: 35 · 2020: 40 · 2019: 32 · 2018: 42 · 2017: 45 · 2016: 44 · 2015: 39 · 2014: 61 · 2013: 62 · 2012: 64
- FWCI
- 32.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health (n01hc085082-026, n01hc085081-021, n01hc085079-024, n01hc015103-009, n01hc085084-005, n01hc085085-011, n01hc085083-027, n01hc085080-026, n01hc085086-022, n01hc035129-010)
- National Institute on Aging (N01HC85079, N01 HC‐15103, N01‐HC‐35129, K23AG19161, N01‐HC‐85086, K23AG019161)
- National Heart, Lung, and Blood Institute (N01-HC-85081, N01HC85085, N01 HC085086, N01HC-85083, N01HC15103, N01 HC085079, N01HC85082, N01 HC85086, N01 HC035129, N01HC85080, N01 HC015103, N01-HC85079, N01-HC85084, N01HC35129)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- subclinical hypothyroidism, overt hypothyroidism, thyroid-stimulating hormone, atrial fibrillation, cardiovascular disease, coronary artery disease, cerebrovascular disease, cardiovascular mortality, all-cause mortality, older adults, thyroid function, Cardiovascular Health Study, sex differences, hormone replacement therapy
- MeSH terms
- Aged, Atrial Fibrillation, Cardiovascular Diseases, Female, Humans, Hyperthyroidism, Hypothyroidism, Male, Risk Factors, Thyroid Gland, Thyrotropin, Proportional Hazards Models
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