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

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.

Fig. 1

PRISMA flow diagram

Fig. 2

Forest plot of all studies for the association of levothyroxine (LT4) with cardiovascular effects in subclinical hypothyroid (SCH) participants, presented by hazard ratios (HR) and 95% confidence intervals (CI)

Fig. 3

Forest plot of mutually exclusive studies for the association of levothyroxine (LT4) with cardiovascular effects in subclinical hypothyroid (SCH) participants, presented by hazard ratios (HR) and 95% confidence intervals (CI)