Coronary Artery Disease and Mortality from All Cardiac Causes

The Big Heart Disease Lie

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Numerous studies demonstrate that Hodgkin's disease (HD) survivors treated with mediastinal irradiation have an increased risk of fatal CVD [68-71]. Relative risk estimates for all survivors range from 2.2-7.2, compared with age and gender-matched controls from the general population [68-70]. The absolute excess risk of fatal cardiovascular disease is 11.9-48.9 per 10,000 patient years, depending upon patient characteristics [70]. This increased risk becomes statistically significant 5-10 years after radiotherapy [71, 72], and is largely due to fatal myocardial infarctions [70].

Myocardial infarction (MI) may be the most important cardiac concern for survivors treated with radiotherapy since the 1970s. While risk of death from cardiac causes other than myocardial infarction has decreased with the use of subcarinal blocking, the incidence of fatal MI has not changed significantly. This was demonstrated by a study of 2,232 HD patients treated at Stanford during 1960-1991. The study showed that the relative risk of non-MI cardiac death decreased from 5.3 to 1.4 with subcarinal blocking, while the relative risk for fatal MI did not change significantly [70]. This might be explained by the continued exposure of the proximal coronary arteries to radiation despite the protection to the base of the heart afforded by the subcarinal blocking.

The risk of thoracic irradiation should be considered in the context of other cardiovascular risk fac-tors,but information on the prevalence of risk factors in comparison populations is generally lacking. One report that did assess other risk factors [26] demonstrated that patients experiencing an MI also had a higher frequency of elevated cholesterol, tobacco use and obesity than the US population as a whole. In fact, each survivor with an event had at least one other known cardiac risk factor [26]. Unfortunately, risk factor information for those without events was not gathered, so further analysis was not possible. Glanzmann et al. [73] evaluated patients with HD for the risk of fatal myocardial infarction associated with modern techniques of mantle irradiation in the context of known cardiac risk factors: smoking, hypertension, obesity, hypercholesterolemia and diabetes. The total group of survivors had a significantly high-er-than-expected incidence of fatal myocardial infarctions and/or sudden death at a mean follow up of 11.2 years (the relative risk of myocardial infarctions alone was 4.2, and the relative risk of either outcome was 6.7). The risk of cardiac events in patients without other known cardiovascular risk factors, however, was not significantly different from that of the age-matched population. This underscores the fact that radiotherapy is only one of several risk factors for cardiovascular disease.

Nevertheless, case reports [25,74-77] and studies of acute myocardial infarction in young survivors of chest radiotherapy,presumably without other known risk factors, suggest that mediastinal irradiation alone may be sufficient to increase the likelihood of fatal coronary artery disease. Fatal myocardial infarctions have occurred in children as young as 12 years of age after mediastinal radiotherapy [76]. Survivors of childhood (<21 years of age) HD treated between 1961 and 1991 suffered fatal myocardial infarctions 41.5 times more frequently than the age-matched general population [71]. Deaths occurred 3-22 years after therapy. These deaths were limited to those exposed to > 42 Gy of irradiation but 71 % of this cohort received > 40 Gy. Although it is uncommon to treat children today with >25-30 Gy, it is unclear whether limiting exposure has impacted the rate of fatal MI in HD survivors [70,78]. Whatever the case may be with respect to current treatment protocols, the many HD survivors who were treated successfully with the higher doses remain at risk for cardiovascular sequelae.

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