We found a relation between the cumulative exposure to low-dose ionizing radiation from cardiac imaging and therapeutic procedures after acute myocardial infarction, and the risk of incident cancer. Although most patients were exposed to low or moderate levels of radiation, a substantial group were exposed to high levels and in general tended to be younger male patients with fewer comorbidities.
Previous studies have shown increased rates of use of imaging tests and therapeutic procedures involving low-dose ionizing radiation in North America.7–12
This trend is particularly evident among patients with known or suspected coronary artery disease. There has been a marked increase in the number of imaging tests used to screen for this disease, including computed tomography angiography and radioisotope nuclear scans. In many centres, these types of tests have supplanted earlier tests that do not use radiation, such as exercise treadmill and stress echocardiography.12,17,21,31,32
Magnetic resonance imaging of the coronary arteries does not use radiation, but it is not being used as extensively as computed tomography angiography.
Although there is a paucity of data in the literature, our results are generally consistent with prior estimates of the risk of cancer associated with exposure to low-dose ionizing radiation. Specifically, the US Scoliosis Cohort Study involving young patients exposed to serial radiographic studies showed a relative risk of 1.6 for breast cancer for an average dose of 108 mSV33
(extrapolation from our model generated an HR of 1.353 for all cancers for this same dose). The Japanese Life-Span Study involving atomic bomb survivors showed a relative risk of 1.1–1.2 for solid cancers for an average dose of 200 mSv3
(HR 1.751 in extrapolation from our model). A pooled analysis of data for children exposed to external radiation showed a relative risk of 2.5 for thyroid cancer for an average dose of 50 mSv34
(HR 1.150 among adults in extrapolation from our model). The higher effect among children is thought to be due to higher radiation sensitivity at a lower age.
It has been argued that patients who undergo frequent testing involving low-dose ionizing radiation tend to be older patients who are more likely to experience an adverse outcome related to their primary disease (e.g., coronary artery disease) rather than a radiation-related cancer. In our cohort, the median age was 63.2 years, and younger patients were more likely to be exposed to higher doses of radiation. Although mortality is increased among patients with acute myocardial infarction, disease-specific mortality has been decreasing since the 1960s.35,36
For the average patient surviving an acute myocardial infarction, life expectancy is substantial.36,37
Our results suggest that exposure to low-dose ionizing radiation directly affects the likelihood of cancer. Although these patients most likely will die of cardiac-related causes, the increased exposure to low-dose ionizing radiation increases their risk of cancer and perhaps mortality.
The potential increase in cancer-related death associated with exposure to radiation from cardiac imaging and therapeutic procedures has to be weighed against the potential risk of death from cardiovascular diseases for which these procedures are indicated and the resulting decrease in mortality expected with their use. Although we think that our results are important for identifying and quantifying possible harms, we also think that a valid evaluation to determine where the balance between these competing risks falls is not possible from our study, given its relatively short time horizon and the potential for residual confounding.
A number of limitations of our study should be noted. First, we did not directly measure the doses of low-dose ionizing radiation in our cohort of patients. Instead, we used an administrative database to identify the cardiac imaging and therapeutic procedures that patients underwent and then used estimated doses7
to calculate the cumulative exposure for each patient. There is variability in these estimates.38,39
Technical aspects of these tests vary with the centre and operator, and perfect estimation of dose is not possible. We relied on a well-cited, recently published source to attempt to minimize this source of measurement error.7,29
Second, potential confounders entered into the models were limited to variables collected in the administrative database; therefore, there is a risk of residual confounding by indication. This risk is lowest for the association between exposure to radiation from cardiac procedures and cancer because cardiac imaging and therapeutic procedures are seldom indicated for the work-up of cancer, which makes it an ideal setting to test our hypothesis. The opposite is true for the association between exposure to radiation from noncardiac procedures and cancer (as supported by the HR observed in our model). Confounding by indication remains significant.
Third, we did not ascertain the difference between high, acute exposure to low-dose ionizing radiation after acute myocardial infarction and low, repeated exposure.
Fourth, we examined a cohort of patients who had acute myocardial infarction in Canada between 1996 and 2006. Canadian patients undergo fewer imaging and therapeutic procedures than American patients.40
Furthermore, the explosion of imaging techniques and therapeutic procedures has been rather recent.32,41
Thus, our cohort likely had lower levels of exposure to low-dose ionizing radiation than current patients with acute myocardial infarction in North America. Consequently, the numbers that we present may be underestimates of the level of exposure to radiation that current patients are experiencing.
We found that a substantial proportion of patients were exposed to high levels of low-dose ionizing radiation from cardiac imaging and therapeutic procedures after acute myocardial infarction. We were able to show that exposure to radiation from cardiac imaging was associated with an increased risk of cancer in this patient population. Even moderate levels of exposure were associated with an increased risk of cancer.
These results call into question whether our current enthusiasm for imaging and therapeutic procedures after acute myocardial infarction should be tempered. We should at least consider putting into place a system of prospectively documenting the imaging tests and procedures that each patient undergoes and estimating his or her cumulative exposure to low-dose ionizing radiation.42