Subclinical Thyroid Dysfunction and the Risk of Heart Failure in Older Persons at High Cardiovascular Risk
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CONTEXT: Subclinical thyroid dysfunction is common in older people. However, its clinical importance is uncertain. OBJECTIVE: Our objective was to determine the extent to which subclinical hyperthyroidism and hypothyroidism influence the risk of heart failure and cardiovascular diseases in older people. SETTING AND DESIGN: The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) is an prospective cohort study. PATIENTS: Patients included men and women aged 70-82 yr (n=5316) with known cardiovascular risk factors or previous cardiovascular disease. MAIN OUTCOME MEASURES: Incidence rate of heart failure hospitalization, atrial fibrillation, and cardiovascular events and mortality according to baseline thyroid status were evaluated. Euthyroid participants (TSH=0.45-4.5 mIU/liter) were compared with those with subclinical hyperthyroidism (TSH<0.45 mIU/liter) and those with subclinical hypothyroidism (TSH≥4.5 mIU/liter, both with normal free T4). RESULTS: Subclinical hyperthyroidism was present in 71 participants and subclinical hypothyroidism in 199 participants. Over 3.2 yr follow-up, the rate of heart failure was higher for subclinical hyperthyroidism compared with euthyroidism [age- and sex-adjusted hazard ratio (HR)=2.93, 95% confidence interval (CI)=1.37-6.24, P=0.005; multivariate-adjusted HR=3.27, 95% CI=1.52-7.02, P=0.002). Subclinical hypothyroidism (only at threshold>10 mIU/liter) was associated with heart failure (age- and sex-adjusted HR=3.01, 95% CI=1.12-8.11, P=0.029; multivariate HR=2.28, 95% CI=0.84-6.23). There were no strong evidence of an association between subclinical thyroid dysfunction and cardiovascular events or mortality, except in those with TSH below 0.1 or over 10 mIU/liter and not taking pravastatin. CONCLUSION: Older people at high cardiovascular risk with low or very high TSH along with normal free T4 appear at increased risk of incident heart failure.
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Cardiovascular morbidity and mortality are particularly increased in men, in elderly patients with high-normal FT4 levels and in patients with underlying heart disease.
“Cardiovascular morbidity and mortality are particularly increased in men, in elderly patients with high-normal FT 4 levels and in patients with underlying heart disease [71-73, 76, 77, 87, 91, 92, 94] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [76]
The Abstract (page unavailable) reports increased incident heart failure in older adults at high cardiovascular risk with low or very high TSH and normal FT4. The paper does not establish that cardiovascular morbidity and mortality are particularly increased in men, at high-normal FT4 levels, or specifically in patients with underlying heart disease; its Results report no significant overall association with cardiovascular events or mortality. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe risk of heart failure was increased in the Prospective Study of Pravastatin in elderly patients with a history of cardiovascular disease.
“The risk of HF was increased in the Prospective Study of Pravastatin (PROSPER Study) in elderly patients with a history of cardiovascular disease [76] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [76]
The Incident heart failure hospitalization section reports increased heart-failure hospitalization in PROSPER participants with subclinical hyperthyroidism compared with euthyroid participants, and says this association did not differ by history of CVD. The claim omits that thyroid-status comparison and describes the participants as having a history of cardiovascular disease, whereas the Study population section says they had either prior vascular disease or cardiovascular risk factors. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSome of these studies, including the meta-analyses, have also examined nonfatal cardiovascular events in SH, with similar increased risks.
“Some of these studies, including the meta-analyses, have also examined nonfatal cardiovascular events in SH, with similar increased risks (383,388,390,391).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [383]
Some other, smaller studies have reached similar conclusions, although other smaller studies have failed to find a correlation.
“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 [383]
Some studies report increased overall mortality rates in SH subjects, especially older subjects, while others indicate no relation.
“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 [383]
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Subclinical Hypothyroidism Is Associated With Adverse Prognosis in Heart Failure Patients
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Elevated TSH in adults treated for hypothyroidism is associated with increased mortality
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Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Disease
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- Authors
- Nanchen, D., Gussekloo, J., Westendorp, R. G. J., Stott, D. J., Jukema, J. W., Trompet, S., Ford, I., Welsh, P., Sattar, N., Macfarlane, P. W., Mooijaart, S. P., Rodondi, N., de Craen, A. J. M., & on behalf of the PROSPER Group
- Affiliations
- Leiden University Medical Center (NL)
- Department of Public Health and Primary Care (J.G.), 2333 ZA Leiden, The Netherlands
- University of Glasgow (GB)
- Department of Cardiology (J.W.J.), 2333 ZA Leiden, The Netherlands
- Robertson Centre for Biostatistics (I.F.), Glasgow G12 8QQ, United Kingdom
- University of Bern (CH)
- Leiden University Medical Center, Department of Gerontology and Geriatrics (D.N., R.G.J.W., S.T., S.P.M., A.J.M.d.C.), 2333 ZA Leiden, The Netherlands
- Corresponding author
- Nanchen, David
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-03-01
- Volume
- 97
- Issue
- 3
- Pages
- 852-861
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2110776403
- Cited by
- 211
- References
- 34
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 11 · 2023: 13 · 2022: 15 · 2021: 14 · 2020: 9 · 2019: 15 · 2018: 12 · 2017: 22 · 2016: 11 · 2015: 25 · 2014: 13 · 2013: 25 · 2012: 14
- FWCI
- 19.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Science Foundation
- Bristol-Myers Squibb
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (132943, 138267, 320030)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (050.060.810, 05040202)
- Université de Lausanne
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- subclinical hyperthyroidism, subclinical hypothyroidism, subclinical thyroid dysfunction, heart failure, heart failure hospitalization, older adults, cardiovascular risk, thyroid-stimulating hormone, atrial fibrillation, cardiovascular events, mortality, pravastatin, free thyroxine, TSH suppression therapy, statin therapy
- MeSH terms
- Aged, Aged, 80 and over, Atrial Fibrillation, Cardiovascular Diseases, Female, Follow-Up Studies, Heart Failure, Humans, Male, Prospective Studies, Risk, Risk Factors, Thyroid Diseases, Survival Rate
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