Reducing Cardiovascular and Cancer Risk: How to Address Global Primary Prevention in Clinical Practice

Abstract

Emerging evidence suggesting the possibility that interventions able to prevent cardiovascular disease (CVD) may also be effective in the prevention of cancer have recently stimulated great interest in the medical community. In particular, data from both experimental and observational studies have demonstrated that aspirin may play a role in preventing different types of cancer. Although the use of aspirin in the secondary prevention of CVD is well established, aspirin in primary prevention is not systematically recommended because the absolute cardiovascular event reduction is similar to the absolute excess in major bleedings. By adding to its cardiovascular prevention benefits, the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in primary prevention in favor of the latter and broaden the indication for treatment with aspirin in populations at average risk. Prospective and randomized studies are currently investigating the effect of aspirin in prevention of both cancer and CVD; however, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention already could be made on the basis of a balanced evaluation of the benefit/risk ratio.

Figure 1

Possible mechanisms underlying antitumor effect of aspirin and other drugs used in the treatment of CVD. Low‐dose aspirin and high‐dose aspirin may affect different steps of colon tumorigenesis. By selectively blocking platelet‐COX‐1 activity and the release of mediators such as TxA₂, PDGF, TGF‐β, and PGE2, low‐dose aspirin may inhibit relatively early events in the progression from normal mucosa to adenoma that are involved in platelet‐dependent induction of cell transformation. In particular, low‐dose aspirin might counteract the overexpression of COX‐2 and subsequent increase of PGE2, induced by platelets, in stromal and epithelial intestinal cells, thereby inhibiting cell proliferation and angiogenesis. High‐dose aspirin might directly inhibit COX‐2 activity once it is expressed in intestinal adenomas, reducing the progression of the neoplastic lesion and metastasis. It has also been proposed that statins, ACEIs, ARBs, and β‐blockers, acting through different pathways, may reduce angiogenesis, cell proliferation and migration, and inflammation. Abbreviations: ACEI, angiotensin‐converting enzyme inhibitor; Ag I, angiotensin I; Ag II, angiotensin II; Ang, angiotensinogen; ARB, angiotensin receptor blocker; β2‐R, β2 receptor; AT1‐R, angiotensin II type I receptor; COX‐1, cyclooxygenase‐1; CVD, cardiovascular disease; HMG‐CoA, HMG‐CoA reductase; ICAM‐1, intercellular adhesion molecule‐1; MAPK, mitogen‐activated protein kinase; NFκB, nuclear factor κ B; PDGF, platelet‐derived growth factor; PGE2, prostaglandin E2; RAS, RAS protein superfamily of small GTPases; Rho, rho mainfamily of small GTPases; STAT1, signal transducer and activator of transcription‐1; TGF‐β, transforming growth factor β; TXA2, thromboxane A₂; VCAM‐1, vascular cell adhesion molecule‐1; VEGF, vascular endothelial growth factor.

Figure 2

Model for predicting CRC risk in men. Instructions: Draw a perpendicular line from the patient's age to the “points” axis and record the value. Repeat this process for the remaining variables and tally. The 10‐year risk of CRC is identified where a line drawn straight down from the “total points” axis intersects the “10‐year risk of CRC (%).” From Wells et al.69 Abbreviations: CRC, colorectal cancer.

Figure 3

When to prescribe aspirin in primary prevention: 3 different clinical settings. The setting of low‐risk CVD is not shown because in this case aspirin is not indicated, whatever the risk of cancer. Abbreviations: ASA, acetylsalicylic acid (aspirin); CVD, cardiovascular disease.