Levothyroxine Treatment of Subclinical Hypothyroidism, Fatal and Nonfatal Cardiovascular Events, and Mortality

Razvi, Salman; Weaver, Jolanta U.; Butler, Timothy J.; Pearce, Simon H. S.

doi:10.1001/archinternmed.2012.1159

Cited by 266Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryHormonal and reproductive studies

Levothyroxine Treatment of Subclinical Hypothyroidism, Fatal and Nonfatal Cardiovascular Events, and Mortality

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Razvi, Salman, Weaver, Jolanta U., Butler, Timothy J., Pearce, Simon H. S.·2012·Archives of Internal Medicine

DOI 10.1001/archinternmed.2012.1159

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Abstract

BACKGROUND Subclinical hypothyroidism (SCH) has been associated with ischemic heart disease (IHD); however, it is unknown whether treatment of SCH with levothyroxine sodium will reduce the risk of IHD. The aim of this study was to investigate the association between levothyroxine treatment of SCH with IHD morbidity and mortality. METHODS We used the United Kingdom General Practitioner Research Database to identify individuals with new SCH (serum thyrotropin levels of 5.01-10.0 mIU/L and normal free thyroxine levels) recorded during 2001 with outcomes analyzed until March 2009. All analyses were performed separately for younger (40-70 years) and older (>70 years) individuals. Hazard ratios (HRs) for IHD events (fatal and nonfatal) were calculated after adjustment for conventional IHD risk factors, baseline serum thyrotropin levels, and initiation of levothyroxine treatment as a time-dependent covariate. RESULTS Subclinical hypothyroidism was identified in 3093 younger and 1642 older individuals. For a median follow-up period of 7.6 years, 52.8% and 49.9% of younger and older patients with SCH were treated with levothyroxine, respectively. There were 68 incident IHD events in 1634 younger patients treated with levothyroxine (4.2%) vs 97 IHD events in 1459 untreated individuals (6.6%) (multivariate-adjusted HR, 0.61; 95% CI, 0.39-0.95). In contrast, in the older group there were 104 events in 819 treated patients (12.7%) vs 88 events in 823 untreated individuals (10.7%) (HR, 0.99; 95% CI, 0.59-1.33). CONCLUSIONS Treatment of SCH with levothyroxine was associated with fewer IHD events in younger individuals, but this was not evident in older people. An appropriately powered randomized controlled trial of levothyroxine in SCH examining vascular outcomes is now warranted.

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Subclinical hypothyroidism is associated with increased risk of cardiovascular mortality in younger (<65 years) populations but not in older (≥65 years) individuals.
“Subclinical hypothyroidism is associated with increased risk of cardiovascular mortality in younger (<65 years) populations but not in older (≥65 years) individuals.151,152”
From Hypothyroidism (2024) · cites this paper as [152]
Treatment of subclinical hypothyroidism with levothyroxine in younger individuals was linked with fewer adverse cardiovascular outcomes in younger but not older individuals.
“treatment of subclinical hypothyroidism with levothyroxine in younger individuals was linked with fewer adverse cardiovascular outcomes in younger but not older individuals.151,152”
From Hypothyroidism (2024) · cites this paper as [152]
In a retrospective study, fewer ischemic heart disease events were associated with treatment of subclinical hypothyroidism in those under age 70 years.
“In an additional retrospective study, fewer ischemic heart disease events were associated with treatment of SCH in those under age 70 years (53).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [53]
Levothyroxine therapy is associated with a lower number of coronary ischemic events in young subjects with subclinical hypothyroidism (40-70 years) but not in older ones.
“An analysis of the United Kingdom general practitioner registry showed that LT4 therapy is associated with a lower number of coronary ischemic events in young subjects with SC-HT (40–70 years) but not in older ones [33].”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [33]
A retrospective observational study showed that levothyroxine treatment of subclinical hypothyroidism was associated with fewer ischemic heart disease events in younger individuals but not in older people.
“Furthermore, a retrospective observational study showed that treatment of SCH with levothyroxine was associated with fewer ischemic heart disease events in younger individuals, but this was not evident in older people (102).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [102]

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Long-Term Outcome in Levothyroxine Treated Patients With Subclinical Hypothyroidism and Concomitant Heart Disease
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Authors: Razvi, S., Weaver, J. U., Butler, T. J., & Pearce, S. H. S.
Corresponding author: Razvi, Salman
ORCID: Razvi, Salman
Weaver, Jolanta U.
Pearce, Simon H. S.
Venue: Archives of Internal Medicine
Publisher: American Medical Association (AMA)
Published: 2012-05-28
Volume: 172
Issue: 10
Pages: 811-7
ISSN: 0003-9926 (ISSN-L)
DOI: 10.1001/archinternmed.2012.1159
OpenAlex: W2127148210
Cited by: 266
References: 30
Citations by year: 2026: 9 · 2025: 15 · 2024: 13 · 2023: 16 · 2022: 13 · 2021: 20 · 2020: 22 · 2019: 26 · 2018: 16 · 2017: 23 · 2016: 16 · 2015: 20 · 2014: 23 · 2013: 24 · 2012: 10
FWCI: 19.73
Type: journal article
Language: en
Open access: green
doi.org
Locations: Archives of Internal Medicine (publishedVersion)
PubMed (publishedVersion)
Newcastle University ePrints (Newcastle Univesity)
Funders: Medical Research Council (G0500783)
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, levothyroxine, ischemic heart disease, cardiovascular events, mortality, thyroid-stimulating hormone, age differences, thyroid hormone replacement, cardiovascular risk

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Levothyroxine Treatment of Subclinical Hypothyroidism, Fatal and Nonfatal Cardiovascular Events, and Mortality

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