BACKGROUND: Cardiovascular disease remains the most prevalent cause of death in hyperthyroidism. However, the impact on cardiovascular events of varying thyroid status and of treatment remains unclarified. The aims of this study were to investigate the association between hyperthyroidism and cardiovascular events in treated and untreated hyperthyroid individuals, as well as exploring the impact of cumulative periods of hyperthyroidism as a proxy for undertreatment on cardiovascular events.

METHOD: This was a case-control study nested within a population-based cohort of individuals attending health services in Funen County, Denmark, in the period from 1995 to 2011. Data on comorbidities and mortality were collected from The Danish National Patient Register and The Danish Register of Causes of Death. Participants were 275,467 individuals with at least one serum thyrotropin (TSH) measurement in the study period. Hyperthyroidism was defined as at least two measurements of decreased serum TSH within six months, separated by at least 14 days. Incident cases of cardiovascular disease (myocardial infarction, atrial fibrillation, heart failure, stroke, and cardiovascular death) were matched with controls. Conditional logistic regression analyses were performed to calculate odds ratios (OR) for exposure to hyperthyroidism, adjusting for preexisting comorbidities.

RESULTS: A total of 20,651 individuals experienced a cardiovascular event (9.5% incidence rate 13.2/1000 person-years [confidence interval (CI) 13.0-13.4]) compared to euthyroid individuals, conditional logistic regression showed increased cardiovascular risk in untreated hyperthyroid patients (OR = 1.25 [CI 1.06-1.48], p = 0.007) but not in treated hyperthyroid patients (OR = 1.04 [CI 0.90-1.22], p = 0.57)]. The OR for cardiovascular events per six months of decreased TSH was 1.09 ([CI 1.05-1.14], p < 0.001) in treated hyperthyroid individuals, and 1.10 ([CI 1.05-1.15], p < 0.001) in untreated hyperthyroid individuals.

CONCLUSIONS: The risk of cardiovascular disease was found to be increased in untreated hyperthyroid patients, and the duration of decreased TSH associated with increasing risk of cardiovascular outcomes in both treated and untreated hyperthyroid individuals. This suggests that increased cardiovascular risk is driven not only by lack of treatment but also by insufficient therapy. The results support timely treatment and careful monitoring of hyperthyroid patients in order to reduce cardiovascular risk.