Author + information
- aRutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
- bIcahn School of Medicine at Mount Sinai, New York, New York
- ↵∗Reprint requests and correspondence:
Dr. Paolo Boffetta, Icahn School of Medicine at Mount Sinai, 17 East 102 Street, Floor 4 West, Room 110, New York, New York 10029.
Heart failure (HF) is associated with high morbidity and mortality (1). A significant number of deaths in these patients are from cardiac causes (2). In this issue of the Journal, Hasin et al. (3) present the findings from a prospective study of 1,081 patients with myocardial infarction (MI) in Olmsted County, Minnesota. After a mean follow-up period of 4.9 ± 3 years, 228 of these participants with MI developed heart failure. The incidence of nonmelanoma skin cancers in these 228 participants during the period of follow-up was 33.7 per 1,000 person-years, significantly higher than the 15.6 per 1,000 person-years incidence in patients who did not develop HF (p = 0.002). These findings are similar to results reported by the same group in 2013 from a case-control study in which the cancer risk was higher in 961 patients with HF than in community controls (4). These findings suggest that patients who develop HF after MI may have an increased cancer risk. However, the mechanism underlying this possible association is not well understood. The first question to arise from these findings is if HF itself is playing a causative role in carcinogenesis. However, as the average follow-up period for this study was <5 years, and the median time from MI to cancer diagnosis was 2.8 years, it is unlikely that HF is playing a causative role in carcinogenesis, because cancer has a latent period of at least a few years from the time of exposure to the risk factor. However, a role in late stages of the carcinogenic process (e.g., related to the proliferation of a mutated clone) cannot be excluded.
The study by Hasin et al. (3) has a number of strengths. First, it is a prospective study with more than 1,000 participants. Moreover, it was performed in Olmsted County, Minnesota, with access to a comprehensive patient database via the Rochester Epidemiological Project. This is a unique resource to answer clinical epidemiological questions. Also, the study includes an analysis into the role of medications prescribed for MI on the association between HF and cancer. No significant medication-related effect on cancer risk was found.
The association between HF and cancer risk may be due to shared risk factors. Patients in this study who developed HF after a diagnosis of MI were about 10 years older on average, had more comorbidities, and had lower rates of reperfusion/revascularizations performed than the other patients. Adjusting for age, sex, and comorbidities reduced the strength of the association between HF and cancer risk, although further adjustment for smoking, body mass index, aspirin use, and various cardiovascular parameters had little impact on the results. However, some of the potential confounders, such as smoking, were analyzed in broad categories, and data on other shared risk factors for HF and cancer, such as heavy alcohol intake, were missing. Therefore, one cannot rule out completely residual confounding.
Another factor to consider is that patients with MI who get HF may experience a more intense medical surveillance than other patients. This could cause overdiagnosis and lead-time bias, with participants in the HF group getting diagnosed either with clinically irrelevant cancers or at an earlier stage of clinically relevant cancers. Interestingly, mortality rates from cancer were not associated with a diagnosis of HF (and vice versa), which could be explained by overdiagnosis or lead-time bias. A stratified analysis by cancer stage and an analysis of diagnostic procedures and health care utilization in this patient population would help to clarify this issue. Another potential explanation for these findings is that they may be secondary to altered immunity and healing, as suggested by the authors on the basis of the finding that the cancer risk was higher in patients with reduced ejection fraction.
An important clinical question that arises from these results is whether patients with HF warrant more cancer screening testing than the population at large. This can be answered, in part, by looking at the main types of cancers in the 2 groups being studied. It is interesting to note that although the number of cases in each group was small, the most frequent cancers in patients with HF were respiratory and digestive cancers for which we do not have routine screening tests (except for low-dose CT scans in heavy smokers for lung cancer). The predominance of these 2 types of cancers also suggests a role of shared risk factors, because both HF and cancer are associated with risk factors such as smoking and alcohol (5–8). Unfortunately, details on the cancer sites of patients included in the previous study performed by this group (4) are not available for comparison. Further studies of the incidence of cancers by site in other large populations are warranted in order to derive more definitive findings.
In conclusion, the study by Hasin et al. (3) reports novel findings about a potential association between HF and cancer risk. However, it raises some interesting questions about the role of shared risk factors and other sources of bias in patients with HF that may account for the observed association with cancer. More definite evidence is needed before recommendations for cancer prevention in this patient group can be developed.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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