Heart Disease and Cancer

Heart Disease and CancerAre the Two Killers Colluding?Article, see p 678 N oncommunicable diseases kill 40 million people each year, accounting for 70% of all deaths globally.In this context, 17.7 million people die annually as a consequence of cardiovascular diseases, whereas cancer accounts for 8.8 million deaths per year. 1 Evidence linking cardiovascular diseases with a higher incidence of cancer has been suggested previously in community-based observational trials. 2 In 2013, Hasin et al 3 found an interconnection between heart failure and consequent cancer diagnosis.These findings were reproduced in a prospective cohort study of patients with myocardial infarction-induced heart failure.4 Banke et al 5 observed similar results in a large Danish heart failure cohort.It is important to note, however, that these epidemiological studies do not differentiate between heart failure with preserved or reduced ejection fraction, which may be relevant because these conditions appear distinct.Shared risk factors and biological mechanisms possibly explain this relationship.Indeed, cardiovascular risk factors such as unhealthy diet, tobacco smoking, obesity, diabetes mellitus, and hypertension have been found to be associated with an increased cancer risk.6 Moreover, it has been speculated that cardiovascular drugs (ie, angiotensin-converting enzyme inhibitors and β-blockers), radiation during diagnostic assessment, epigenetic mechanisms, and regenerative signaling are all potential links connecting both illnesses.2,6 With regard to common molecular pathways, chronic inflammation and oxidative stress are likely candidates, because they play central roles in the pathophysiology of both cardiovascular diseases and cancer.6 Nonetheless, despite the evidence described in the aforementioned population studies and shared risk factors/biological mechanisms, the possibility that other comorbidities may explain the association between cardiovascular disease and cancer cannot be ruled out.7 Moreover, inasmuch as the clinical assessment of patients with heart failure occurs regularly, an apparent higher risk of cancer may reflect merely earlier diagnosis rather than a higher incidence.7 The study by Meijers et al 8 in this issue of Circulation presents new evidence suggesting that heart failure promotes intestinal precancerous polyp growth.The authors report compelling data using the APC min mouse strain, which harbors a nonsense mutation in APC leading to persistence of β-catenin and a susceptibility to spontaneous intestinal adenoma formation.9-11 Six weeks after the induction of myocardial infarction with subsequent heart failure (left ventricular ejection fraction≈32% one week after myocardial infarction), these mice developed an increased number and size of intestinal polyps in comparison with the sham-operated control.Moreover, the authors found an association between polyp growth and left ventricular ejection fraction and cardiac fibrosis, both of which correlate with the magnitude of heart failure-induced myocardial remodeling.