Cardiovascular and bone health outcomes in older people with subclinical hypothyroidism treated with levothyroxine: a systematic review and meta-analysis

Mia Holley; Salman Razvi; Mohammed Saif Farooq; Rosie Dew; Ian Maxwell; Scott Wilkes

doi:10.1186/s13643-024-02548-7

Cardiovascular and bone health outcomes in older people with subclinical hypothyroidism treated with levothyroxine: a systematic review and meta-analysis

Syst Rev. 2024 May 8;13(1):123. doi: 10.1186/s13643-024-02548-7.

Authors

Mia Holley¹, Salman Razvi², Mohammed Saif Farooq³, Rosie Dew³, Ian Maxwell³, Scott Wilkes³

Affiliations

¹ School of Medicine, Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland, UK. mia.holley@sunderland.ac.uk.
² Translational and Clinical Research Institute, Newcastle University, Newcastle-Upon-Tyne, UK.
³ School of Medicine, Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland, UK.

Abstract

Background: Thyroid dysfunction is common in older people, with females at higher risk. Evidence suggests that thyroid-stimulating hormone (TSH) levels naturally increase with age. However, as uniform serum TSH reference ranges are applied across the adult lifespan, subclinical hypothyroidism (SCH) diagnosis is more likely in older people, with some individuals also being commenced treatment with levothyroxine (LT4). It is unclear whether LT4 treatment in older people with SCH is associated with adverse cardiovascular or bone health outcomes.

Methods: A systematic review and meta-analysis were performed to synthesise previous studies evaluating cardiovascular and bone health outcomes in older people with SCH, comparing LT4 treatment with no treatment. PubMed, Embase, Cochrane Library, MEDLINE, and Web of Science databases were searched from inception until March 13, 2023, and studies that evaluated cardiovascular and bone health events in people with SCH over 50 years old were selected.

Results: Six articles that recruited 3853 participants were found, ranging from 185 to 1642 participants, with the proportion of females ranging from 45 to 80%. The paucity of data resulted in analysis for those aged over 65 years only. Additionally, a study with 12,212 participants aged 18 years and older was identified; however, only data relevant to patients aged 65 years and older were considered for inclusion in the systematic review. Of these 7 studies, 4 assessed cardiovascular outcomes, 1 assessed bone health outcomes, and 2 assessed both. A meta-analysis of cardiovascular outcomes revealed a pooled hazard ratio of 0.89 (95% CI 0.71-1.12), indicating no significant difference in cardiovascular risk between older individuals with SCH treated with LT4 compared to those without treatment. Due to overlapping sub-studies, meta-analysis for bone health outcomes was not possible.

Conclusions: This systematic review and meta-analysis found no significant association between LT4 use and cardiovascular and bone health outcomes in SCH participants over 65 years.

Systematic review registration: PROSPERO CRD42022308006.

Keywords: Bone health; Cardiovascular; Levothyroxine; Subclinical hypothyroidism; Thyroid disease.

Publication types

Systematic Review
Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Bone Density / drug effects
Cardiovascular Diseases*
Female
Humans
Hypothyroidism* / drug therapy
Male
Middle Aged
Thyroxine* / therapeutic use

Substances

Thyroxine

Grants and funding

NIHR200173/National Institute for Health and Care Research