Risk of Coronary Events 55 Years after Thymic Irradiation in the Hempelmann Cohort

Studies of cancer survivors treated with older radiotherapy (RT) techniques (pre-1990s) strongly suggest that ionizing radiation to the chest increases the risk of coronary heart disease (CHD). Our goal was to evaluate the impact of more modern cardiac shielding techniques of RT on the magnitude and timing of CHD risk by studying a cohort exposed to similar levels of cardiac irradiation years ago.

Between 2004 and 2008, we re-established a population-based, longitudinal cohort of 2,657 subjects exposed to irradiation for an enlarged thymus during infancy between 1926 and 1957 and 4,388 of their non-irradiated siblings. CHD events were assessed using a mailed survey and from causes of death listed in the National Death Index. We used Poisson regression methods to compare incidence rates by irradiation status and cardiac radiation dose. Results were adjusted for the CHD risk factors of attained-age, sex, diabetes, dyslipidemia hypertension and smoking.

Median age at time of follow-up was 57.5 years (range 41.2 - 88.8 yrs) for irradiated and non-irradiated siblings. The mean estimated cardiac dose amongst the irradiated was 1.45 Gray (range 0.17 - 20.20 Gy), with 91% receiving <3.00 Gy. During a combined 339,924 person-years of follow-up, 213 myocardial infarctions (MI) and 350 CHD events (MI, bypass surgery and angioplasty) occurred. After adjustment for attained age, gender, and other CHD risk factors, the rate ratio for MI incidence in the irradiated group was 0.98 (95%CI, 0.74 - 1.30), and for any CHD event was 1.07 (95%CI, 0.86 - 1.32). Higher radiation doses were not associated with more MIs or CHD events in this dose range, in either the crude or the adjusted analyses.

Radiation to the heart during childhood of <3 Gy, the exposure in most of our cohort, does not increase the lifelong risk of CHD. Reducing cardiac radiation to this amount without increasing other cardiotoxic therapies may eliminate the increased CHD risk associated with radiotherapy for childhood cancer. By extension there is unlikely to be increased CHD risk from relatively higher dose imaging techniques, such as CT, because such techniques use much smaller radiation doses than received by our cohort.