Preventing cardiovascular disease also means preventing cancer!

In Canada, cancer and cardiovascular disease are respectively the leading and second leading causes of death, alone responsible for approximately 50% of all annual deaths. These two major classes of diseases are usually considered as completely separate phenomena, with no connection between the two. On the one hand, the ravages caused by cancer are a consequence of the uncontrolled growth of cells, leading to the development of tumours that invade organs and disrupt their normal functioning; on the other hand, cardiovascular diseases such as myocardial infarction and stroke are rather ischemic diseases, i.e., caused by an abnormal growth of cell clusters (plaques) in the wall of the arteries that block blood flow to the heart and brain.

Commonalities
Despite these very different clinical manifestations, several signs suggest that the development of cancer and cardiovascular diseases could involve similar phenomena. For example, it is striking that most of the main factors that increase the risk of cardiovascular diseases also represent risk factors for several types of cancer (Table 1), which implies the existence of certain commonalities in the progression of these two classes of disease.

Table 1. Common risk factors for cardiovascular disease and cancer.

A fundamental feature of all of these common risk factors for cardiovascular disease and cancer (smoking, sedentary lifestyle, poor diet, obesity, diabetes) is to promote the development of chronic inflammatory conditions. Since it is clearly established that inflammation plays an absolutely essential role in the progression of atherosclerosis responsible for cardiovascular events as well as in the development of several types of cancer, it is therefore very likely that this inflammation represents a “root of evil” common to both diseases. This is particularly well illustrated by the results of the CANTOS study, where it was shown that an antibody neutralizing the inflammatory protein interleukin-1b reduced both the risk of cardiovascular events and cancer, particularly lung cancer.

Increase in cancers
The results of a recent study reinforce this close link between cardiovascular disease and cancer. In this study, researchers used IBM MarketScan 2009-2019 research databases, which contain anonymized data for approximately 161 million patients, including health insurance claims records for inpatient services, outpatient visits, and outpatient prescription drugs. Among this cohort, they identified 27 million individuals aged 18 and over, without a diagnosis of cancer during the first 2 years of registration in the databases, and then classified them into two large groups according to the presence or absence of cardiovascular disease. Patients with cardiovascular disease (CVD) were in turn separated into two further groups according to the nature of their disease, either CVD with atherosclerosis (aCVD) or without atherosclerosis (naCVD) (examples of each of the two types of CVD are shown in Table 2).

Table 2. Examples of cardiovascular diseases attributable or not to atherosclerosis.

The analysis of new cases of cancer affecting these populations in the following years clearly shows that the presence of cardiovascular disease significantly increases the risk of future cancer, this risk being particularly higher in patients with CVD with atherosclerosis (Figure 1). After controlling for various possible confounding factors (age, sex, diabetes, hypertension, kidney disease, hyperlipidemia, statin use, socioeconomic status), the authors calculated that the cancer risk ratio was 19% (HR= 1.19) higher for patients with CVD with atherosclerosis and 8% higher for patients with CVD without atherosclerosis (HR=1.08) compared to those without CVD.

Figure 1. Influence of cardiovascular disease on future cancer incidence. The results represent the cumulative new diagnoses of cancer (all types combined, except non-melanoma skin cancers) in 27 million individuals who were at baseline without cardiovascular disease (black line) or with cardiovascular disease without (blue line) or with (red line) atherosclerosis. Adapted from Bell et al. (2023).

A more detailed analysis revealed that the risk of certain types of cancer is particularly high in patients affected by CVD with atherosclerosis (Figure 2). This is particularly the case for lung cancer, with a nearly 3-time increase in risk, possibly because most of these cancers are linked to smoking, itself an important risk factor for CVD. However, the risk of lung cancer remains higher than in the absence of CVD (HR=1.43), even after taking into account tobacco use by the participants, and it is therefore likely that this increase does indeed reflect an association between the presence of CVD and an increased risk of lung cancer. The results of the CANTOS study mentioned earlier, where an anti-inflammatory drug reduced the risk of both CVD and lung cancer, may suggest that chronic inflammation contributes to this higher risk.

Figure 2. Change in the risk of incidence of different cancers associated with the presence of cardiovascular disease caused by atherosclerosis. Adapted from Bell et al. (2023).

It should also be noted that the presence of CVD with atherosclerosis doubles the risk of brain and liver cancers. This association is particularly interesting in the case of the brain because the factors that increase the risk of this cancer remain very poorly understood, and the prevention of CVD could therefore prove to be a promising approach to reduce the risk of these often incurable cancers. At the other end of the spectrum, we can note that the risk of several cancers influenced by hormones (breast, uterus, ovaries, prostate) is rather reduced in the presence of CVD with atherosclerosis (similar reductions are also observed for CVD without atherosclerosis). This surprising result remains to be confirmed, however, because a retrospective analysis of studies carried out on women with breast cancer indicates that a cardiovascular event was associated with a 60% increase in the risk of breast cancer recurrence and a 60% increase in the mortality risk associated with this cancer. According to this study, it seems that following the infarction, the immune response is reprogrammed to become immunosuppressive, which prevents the elimination of cancer cells by killer T lymphocytes (CD8).

Two-way link
If a CVD increases the risk of several cancers, the opposite is also true. We have known since the work of Armand Trousseau (1801-1867) that patients with cancer are at very high risk of developing coagulation problems such as deep vein thrombosis (phlebitis). In addition to increasing the risk of pulmonary embolism, this hypercoagulability (called Trousseau syndrome) can also affect the arteries that supply the heart and brain and therefore significantly increase the risk of heart attack and stroke. For example, a recent study showed that in the six months following the cancer diagnosis, the risk of myocardial infarction is tripled and that of stroke is doubled compared to the general population. A cardiovascular event can even be a warning sign of the presence of an undiagnosed cancer. For example, a study reported that the risk of arterial thrombosis was increased fivefold in the month preceding the cancer diagnosis. There is therefore clearly a two-way link between CVD and cancer, with each type of disease potentially influencing the development of the other.

Two birds, one stone
In terms of prevention, this close interaction between cancer and cardiovascular disease suggests that it is possible to kill two birds with one stone and simultaneously reduce the risk of being affected by these two diseases by adopting a healthy lifestyle. Quitting smoking, exercising, staying as lean as possible, and replacing the consumption of ultra-processed foods with a plant-rich diet are all concrete ways (and within everyone’s reach) to reverse chronic inflammation and therefore reduce the risk of cardiovascular disease, cancer and chronic diseases in general.