Duration of Hyperthyroidism and Lack of Sufficient Treatment Are Associated with Increased Cardiovascular Risk

Abstract

Importance: Cardiovascular disease remains the most prevalent cause of death in hyperthyroidism. However, the impact on cardiovascular events of varying thyroid status and that of treatment remain unclarified. Objective: 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. Design: 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. Setting: Population-based. Participants: 217 167 individuals with at least one serum-TSH measurement in the study period of 1995-2011. Hyperthyroidism was defined as at least two measurements of decreased serum TSH within 6 months, separated by at least 14 days. Main outcomes and measures: 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: 20 651 individuals experienced a cardiovascular event [9.5% incidence rate 13.2/1000 person years, 95% confidence interval (CI) 13.0 to 13.4]. Conditional logistic regression showed increased cardiovascular risk in untreated hyperthyroid patients compared to euthyroid individuals (OR 1.25, 95% CI, 1.06 to 1.48; p=.007), but not in the treated hyperthyroid patients [OR 1.04 (95% CI, 0.90 to 1.22; p=.57)]. OR for cardiovascular events per 6 months of decreased TSH was 1.09 (95% CI, 1.05 to 1.14; p<.001) in treated hyperthyroid individuals, and 1.10 (95% CI, 1.05 to 1.15; p<.001) in untreated hyperthyroid individuals. Conclusion: Risk of cardiovascular disease was found increased in untreated hyperthyroid patients, and 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 not only driven by lack of treatment but also by insufficient therapy. Our results support timely treatment and careful monitoring of hyperthyroid patients in order to reduce cardiovascular risk.