Thyroid Dysfunction in Heart Failure and Cardiovascular Outcomes
Open accessAbstract
Background: The effects of thyroid dysfunction in patients with preexisting heart failure have not been adequately studied. We examined the prevalence of thyroid dysfunction and associations with cardiovascular outcomes in a large, prospective cohort of outpatients with preexisting heart failure. Methods and Results: We examined associations between thyroid dysfunction and New York Heart Association class, atrial fibrillation, and a composite end point of ventricular assist device placement, heart transplantation, or death in 1365 participants with heart failure enrolled in the Penn Heart Failure Study. Mean age was 57 years, 35% were women, and the majority had New York Heart Association class II (45%) or III (32%) symptoms. More severe heart failure was associated with higher thyroid-stimulating hormone (TSH), higher free thyroxine (FT4), and lower total triiodothyronine (TT3) concentrations ( P <0.001 all models). Atrial fibrillation was positively associated with higher levels of FT4 alone ( P ≤0.01 all models). There were 462 composite end points over a median 4.2 years of follow-up. In adjusted models, compared with euthyroidism, subclinical hypothyroidism (TSH 4.51–19.99 mIU/L with normal FT4) was associated with an increased risk of the composite end point overall (hazard ratio, 1.82; 95% CI, 1.27–2.61; P =0.001) and in the subgroup with TSH ≥7.00 mIU/L (hazard ratio, 3.25; 95% CI, 1.96–5.39; P <0.001), but not in the subgroup with TSH 4.51–6.99 mIU/L (hazard ratio, 1.26; 95% CI, 0.78–2.06; P =0.34). Isolated low T3 was also associated with the composite end point (hazard ratio, 2.12; 95% CI, 1.65–2.72; P <0.001). Conclusions: In patients with preexisting heart failure, subclinical hypothyroidism with TSH ≥7 mIU/L and isolated low T3 levels are associated with poor prognosis. Clinical trials are needed to explore therapeutic effects of T4 and T3 administration in heart failure.
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In humans, hypothyroidism is associated with a poor prognosis in established heart failure.
“In humans, hypothyroidism is associated with a poor prognosis in established heart failure (33) and TH can reduce intrahepatic triglyceride content (34,35).”
From Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document (2021) · cites this paper as [33]
The Conclusions and Discussion report poor outcomes in ambulatory patients with established heart failure who had subclinical hypothyroidism with TSH ≥ 7 mIU/L. The claim omits that threshold and thus implies the association applies to hypothyroidism generally; the Discussion says it was not found for TSH < 7 mIU/L. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn humans, hypothyroidism is associated with a poor prognosis in established heart failure.
“In humans, hypothyroidism is associated with a poor prognosis in established heart failure [33]”
From Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document (2021) · cites this paper as [33]
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- Authors
- Kannan, L., Shaw, P. A., Morley, M. P., Brandimarto, J., Fang, J. C., Sweitzer, N. K., Cappola, T. P., & Cappola, A. R.
- Affiliations
- University of Pennsylvania (US)
- University of Utah (US)
- University of Arizona (US)
- ORCID
- Venue
- Circulation: Heart Failure
- Published
- 2018-12
- Volume
- 11
- Issue
- 12
- Pages
- e005266-e005266
- ISSN
- 1941-3289 (ISSN-L)
- 1941-3297
- PMC
- PMC6352308
- OpenAlex
- W2904496087
- Cited by
- 245
- References
- 33
- Citations by year
- 2026: 17 · 2025: 27 · 2024: 40 · 2023: 50 · 2022: 32 · 2021: 37 · 2020: 28 · 2019: 13 · 2018: 1
- FWCI
- 15.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Heart Failure (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- BG Medicine
- National Institute on Aging (K24AG042765)
- National Heart, Lung, and Blood Institute (R01HL088577)
- 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 › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- heart failure, subclinical hypothyroidism, thyroid-stimulating hormone, free thyroxine, triiodothyronine, atrial fibrillation, cardiovascular outcomes, mortality, heart transplantation, ventricular assist devices, prognosis
- MeSH terms
- Adult, Aged, Female, Heart Failure, Humans, Hypothyroidism, Male, Middle Aged, Prognosis, Prospective Studies, Risk Factors, Severity of Illness Index, Thyroid Function Tests, Thyroid Gland, Thyrotropin, Thyroxine, Time Factors, Triiodothyronine, United States, Biomarkers, Comorbidity, Prevalence, Asymptomatic Diseases
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