Increased Long-Term Cardiovascular Morbidity Among Patients Treated With Radioactive Iodine for Hyperthyroidism

Saara Metso; Anssi Auvinen; Jorma Salmi; Heini Huhtala; Pia Jaatinen


Clin Endocrinol. 2008;68(3):450-457. 

In This Article

Summary and Introduction

Objective: Previous studies suggest that hyperthyroid patients remain at increased risk of cardiovascular morbidity after restoring euthyroidism. The aim of this study was to compare the rate and causes of hospitalization of hyperthyroid patients treated with radioactive iodine (RAI) with those of an age- and gender-matched reference population in a long-term follow-up study.
Patients and Measurements: A population-based cohort study with a median follow-up time of 9 years was conducted among 2611 hyperthyroid patients treated with RAI between 1969 and 2002 in Tampere University Hospital, and among 2611 reference subjects. Information on hospitalizations was obtained from the nationwide Hospital Discharge Registry. New events were analysed as the main outcome, including only the first hospitalization due to a given indication.
Results: The rate of hospitalization due to cardiovascular disease (CVD) was higher among patients with hyperthyroidism than among the control population [637·1 vs. 476·4 per 10 000 person-years, rate ratio (RR) 1·12, 95% confidence interval (CI) 1·03–1·21]. The risk remained elevated up to 35 years after the RAI treatment. Hospitalizations due to atrial fibrillation (RR 1·35), cerebrovascular disease (RR 1·31), diseases of other arteries and veins (RR 1·22), hypertension (RR 1·20) and heart failure (RR 1·48) were more frequent in the patients than controls, while no such difference was found for coronary artery disease. Hospitalizations due to cancer, infectious and gastrointestinal diseases, and fractures were also more common in patients than in controls.
Conclusions: Hyperthyroidism increases hospitalizations due to CVDs. The excess risk is sustained decades after treatment. Patients treated for hyperthyroidism constitute a high-risk group for CVD and may benefit from preventive interventions.

Radioactive iodine (131I, RAI) has been commonly used as a first-line therapy for hyperthyroidism since the 1940s.[1] Hyperthyroidism has been regarded as a reversible disorder without long-term consequences, when treated effectively. However, long-term follow-up studies have revealed an increased cardiovascular mortality in those with a past history of hyperthyroidism treated with RAI compared with the background population.[2–6] In our recent report,[6] cerebrovascular diseases accounted for most of the increased cardiovascular mortality, consistent with a previous long-term follow-up study.[4] Instead of RAI treatment, hyperthyroidism per se probably accounts for the elevated cardiovascular mortality. Hyperthyroidism is known to exert direct effects on the myocardium and the autonomic nervous system, thus predisposing the patient to cardiovascular morbidity.[7,8] Recently, Flynn et al.[9] reported an increased risk of arrhythmia up to 5 years after treatment of hyperthyroidism, suggesting that the cardiotoxic effects of hyperthyroidism are not fully reversed by restoring euthyroidism. Cardiovascular morbidity also increased in RAI-treated hyperthyroid patients compared with controls in a previous long-term follow-up study.[10]

Hypothyroidism has been suggested to increase the risk of death by causing hypercholesterolaemia, diastolic hypertension and left ventricular dysfunction.[11] However, levothyroxine-treated hypothyroidism after RAI treatment has seemed to protect against death instead of predisposing to it.[5,6] This might reflect the impact of an effective cure of hyperthyroidism. An initial hypothyroid state induced by effective treatment has been reported to be a predictor of successful reversion to sinus rhythm in those with atrial fibrillation (AF) during hyperthyroidism.[12]

To date, no long-term studies have been published on the incidence of different cardiovascular diseases (CVDs) or hospitalizations after RAI treatment for hyperthyroidism. The purpose of the present study was to assess the rate and causes of hospitalization after RAI treatment for hyperthyroidism, especially focusing on CVD. We also compared hospitalization due to CVD between subgroups of patients by the aetiology of hyperthyroidism, age, dose of RAI, recurrent hyperthyroidism, and the development of hypothyroidism.


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