Subclinical Hyperthyroidism, Cardiovascular Disease and All-Cause Mortality: Insights from a Large Dutch Primary Care...

Subclinical hyperthyroidism (SHT) has been associated with adverse cardiovascular outcomes, but the magnitude and consistency of these risks, particularly across demographic subgroups, remain unclear.

We conducted a retrospective cohort study using general practitioner (GP) data from the PHARMO Data Network in the Netherlands (2012-2021). Patients with biochemically confirmed SHT (suppressed thyrotropin [TSH] with normal fT4; n = 11,163) were compared with a matched euthyroid reference group (n = 46,058) based on age, sex, and GP practice. Incidence of atherosclerotic complications, atrial fibrillation (AF), heart failure (HF), and all-cause mortality were assessed. Multivariable-adjusted Cox regression models estimated hazard ratios (HRs), adjusting for relevant confounders. Due to data limitations, information on smoking and alcohol use was not available, and medical history concerning comorbid conditions could only be assessed for the one-year period prior to cohort entry.

SHT was associated with a significantly increased risk of AF (HR: 1.37, 95% CI: 1.22-1.55), particularly in those with TSH < 0.1 mU/L (HR: 1.60, 1.32-1.94) and in individuals aged 30-49 years (HR 1.88, 1.05-3.36). HF risk was modestly elevated overall (HR: 1.21, 1.04-1.40), with stronger effects in individuals aged 30-49 years (HR: 3.74, 1.52-9.24) and women (HR: 1.31, 1.10-1.56). All-cause mortality was higher in the SHT group (HR: 1.51, 1.38-1.64), especially in men (HR: 1.75, 1.50-2.05) and individuals aged 30-49 years (HR: 2.95, 1.73-5.04). The association with atherosclerotic complications was weak-to-modest (HR: 1.12, 1.00-1.24).

SHT is linked to increased risks of AF, HF, and all-cause mortality, with higher relative risks in younger patients. These findings challenge the traditional focus on older populations and underscore the need for individualized risk assessment in SHT.