ArticleThe Journal of clinical endocrinology and metabolism2025
Assessing the Cardiovascular Effects of Levothyroxine Use in an Ageing United Kingdom Population (ACEL-UK): Cohort Study.
Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The trial behind it
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Who cites it
3 citing papers in PubMed.
- Levothyroxine monotherapy has limited effects on body composition in clinical and subclinical hypothyroidism: a systematic review and meta-analysis.Reviews in endocrine & metabolic disorders · 2026Review
- Assessing the Cardiovascular Effects of Levothyroxine Use in an Ageing United Kingdom Population (ACEL-UK): Cohort Study.The Journal of clinical endocrinology and metabolism · 2025Article
- Risk factors and clinical implications of thyroxine replacement therapy on major adverse cardiovascular events in type 2 diabetes: a retrospective cohort study.Frontiers in endocrinology · 2025Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
contextThyrotropin (TSH) levels tend to rise with age, but standard reference intervals do not reflect this, potentially leading to overdiagnosis of subclinical hypothyroidism (SCH) and excessive levothyroxine (LT4) prescriptions in older adults.
objectiveThis work aimed to compare outcomes in adults older than 50 years with SCH who were either prescribed or not prescribed LT4.
methodsA retrospective cohort study was conducted using data from UK Primary Care patients from the Health Improvement Network. The primary outcome was cardiovascular (CV) events (angina, myocardial infarction, peripheral vascular disease, stent procedures, or stroke). Secondary outcomes included bone events (fragility fractures or osteoporosis) and all-cause mortality. Time-varying hazard ratios (HRs) adjusted for relevant factors were estimated.
resultsThis study included 53 899 patients (baseline median age 67 years (interquartile range [IQR]: 59-76 years); 68.5% female; median TSH 4.6 mU/L (IQR: 4.1-5.4 mU/L). Median follow-up duration was 10 years (IQR: 5.5-10.0 years). Of these, 19 952 (37%) received LT4 and 33 947 (63%) did not. LT4 therapy showed a protective effect against CV events (HR: 0.91; 95% CI, 0.87-0.97; P < .001) but increased risk of bone events (HR: 1.21; 95% CI, 1.14-1.28; P < .001) and all-cause mortality (HR: 1.17; 95% CI, 1.13-1.22; P < .001).
conclusionOur data suggest that LT4 therapy in older individuals with SCH is associated with a trade-off between the potentially beneficial effect on CV risk and the deleterious relationship with bone health and mortality risk. These risks need to be considered, mitigated, and discussed when LT4 therapy is being deliberated in older patients with SCH.
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