Physicians' Academy for Cardiovascular Education

Cardiac factors may mediate the association between HF and cancer

Heart failure stimulates tumor growth by circulating factors

Literature - Meijers WC, Maglione M, Bakker SJL et al. - Circulation 2018; 138:678-691

Introduction and methods

HF as a consequence of cancer treatment has been widely studied and is an accepted phenomenon. However, cancer development as a consequence of HF has not been studied. A few recent studies have shown a relationship between HF and incidence of cancer [1-4], but causality has not been demonstrated. Therefore, this study examined the possibly causal relationship between HF and cancer development.

Two mouse models were used with mice highly susceptible to spontaneous intestinal adenoma development. In the first model, myocardial infarction (MI) was induced in mice (n=22) and results were compared to sham-operated control mice (n=10). In the second model, mice received an MI heart (n=17) or a sham donor heart (n=7) while the native heart was left in situ. Myocardial expression levels of five selected candidate proteins with predictive value were measured in controls and HF patients using samples from the PREVEND study (Prevention of Renal and Vascular End-Stage Disease) and the VitD-CHF study (Study to Investigate the Effects of Vitamin D Administration on Plasma Renin Activity in Patients With Stable Chronic Heart Failure). Furthermore, the relationship between cardiac and inflammatory biomarkers and new-onset cancer was studied in 8319 subjects enrolled in the PREVEND study.

Main results


Presence of HF is associated with increased formation and accelerated tumor growth in a mouse model of intestinal cancer. Several myocardial biomarkers were identified that were upregulated in mice with HF and also in patients with chronic HF. In a cohort study, cardiac markers, including NT-proBNP, and inflammatory markers, including C-reactive protein, were associated with the prediction of new-onset cancer. Altogether, these results suggest that HF may be a risk factor for incident cancer.

Editorial comment

In their editorial article, Kitsis, Riquelme and Lavendero [5] raise several questions after summarizing the mouse experiments by Meijers et al.: ‘Can these observations be extrapolated to other precancerous or cancerous lesions? Would heart failure of nonischemic origin elicit the same response? Does heart failure also promote metastasis?’ Although they recognize the novelty of a possible molecular mechanism, they mention that a more comprehensive assessment is needed to definitively link heart disease and cancer. Moreover, they believe an unbiased proteomics approach would be more appropriate to identify the biomarkers connecting HF and tumor growth and experiments with altered levels of these mediators are needed to prove cause and effect. They end by saying that these are ‘potentially groundbreaking results that will stimulate further delineation of the connections between heart disease and cancer’ and ’we may be at the gates of a new scientific research field’.


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