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CANCER SURVIVORS AND CARDIOVASCULAR DISEASES

There is an aspect of cancer that requires equal attention- the risk of cardiovascular disease(s) in cancer survivors. I will be using a lot materials from a publication by Okwuosa et al titled “Cardiovascular Disease in Cancer Survivors”, Postgrad Medical Journal 2017;93:82–90.

Heart disease and cancer are leading causes of death in the world overall. There have been dramatic improvements in cancer therapies, and consequent significant improvements in cancer survival. Nextto cancer recurrence or progression and secondmalignancies, the leading cause of death in cancersurvivors is cardiovascular diseases (CVDs) due to the intense oncological treatment which thesepatients have received.

The risk of cardiovascular morbidity is shown to be highert han that of tumour recurrence in these cancer survivors. Many decades after diagnosis, cancer survivors had 15-fold increased rates of congestive heart failure (CHF), 10-fold higher rates of CVD,9-fold higher rates of stroke and higher incidence of cardiovascular risk factors, compared with controls.

Cancer-related cardiovascular morbidity and mortality is attributed to cancer therapy with chemotherapies and radiation therapies, and risks may persist up to45 years after therapy. A number of cancer therapies have long-term cardiovascular after-effects, leading to higher rates of cardiovascular morbidity and mortality in cancersurvivors. 

These include chemotherapies such asdoxorubicin and cisplatin, hormone therapies and radiation therapy. The anticipated long-term cardiovascular issues include cardiomyopathy/heart failure, hypertension, dysrhythmias and autonomic dysfunction, valvular heart disease, coronary artery disease (CAD) and pericardial diseases.

The mostnotable chemotherapeutic class of drugs implicated in this process is anthracyclines (particularly doxorubicin). Anthracyclines are particularly known to increase the risk of cardiomyopathy with systolicdysfunction and heart failure by generation of freeradicals, leading to cardiac cell damage. As such, more than 50% of all patients exposed to anthracycline chemotherapy will show some degree of cardiac dysfunction 10–20 years after chemotherapy and 5% will develop overt heart failure withup to 60% mortality.

The risk of cardiomyopathy associated with anthracyclines varies based on a variety of factors. These include the type of anthracycline (doxorubicin carries higher risk than epirubicin or liposomal doxorubicin), the route and speedof administration, concomitant radiation therapy orother cardiotoxic chemotherapy, concomitantcardiac risk factors, old and young age and femalesex.

Cancer survivors overall have a greater risk of cardiovascular risk factors. The prevalence of cardiovascular risk factors was notably higher in cancer survivors compared with their siblings in the Childhood Cancer Survivor Study of 8599survivors (52% male) and 2936 siblings (46% male). In this study, survivors were more likely to take medications for hyper-tension, dyslipidaemia and diabetes compared with their siblings.

Radiation therapy has been shown to significantly reduce rates of cancer recurrence and mortality due to cancer, but is associated with irradiation of surrounding organs, other than the area of tumour. Chest wall radiation as seen in patients with lung cancer, lymphoma, oesophageal cancer and breast cancer is associated with irradiation to the heart. Radiation-induced heart disease which occurs in up to 50% of patients post-chest wall radiation therapy includes a combination of cardiac abnormalities such as valvular heart disease, pericardial disease, conduction disturbances and arrhythmias which can occur up to20–30 years after radiation therapy. Autonomic dysfunction as a cardiovascular after-effects of radiation therapy has more recently come into recognition.

In light of these cardiovascular effects, cancer survivors require special attention and regular monitoring and reviews. Cardiovascular risk factors, such as hypertension, diabetes mellitus and dyslipidaemia, are also of importancein the survivorship years as they could lead to overt CVD andassociated complications.There is need for goodprimary care, with regular follow-up visits and requisite investigations. Annual ECGs should beobtained, along with annual blood tests to assess renal functionand electrolytes, liver and thyroid functions and glucose/haemoglobin A1c, lipid profile, blood haemoglobin and haematocritlevels as useful initial assessments.

Some patient groups with prior or higher future risk of cardiovascular events require regular follow-up visits with a cardiologist—preferably an onco-cardiologist well versed incardiovascular expectations relating to cancer therapies.

Many of the treatment modalities for various CVDs in cancer survivors are as for that of the general population. Nonetheless, a number of major issues are worthy of note regarding the treatment of CVD among cancer survivors. There is a small window of opportunity that exists in the treatment of anthracycline-related cardiomyopathy, after which the chances of full heart recovery are much reduced. In a related study the possibility of full heart recovery steadily decreased with time and was 0% if heart failure therapy was initiated 6 months after the end of chemotherapy among patients who developed heart failure after anthracycline-basedchemotherapy. As such, close monitoring with prompt recognition and institution of heart failure therapies are necessary to counteract the lifelong risk of heart failure in cancer survivors.

Another treatment matter worth noting is that some specific cancertherapeutic agents (e.g.s bevacizumab) administered over extended periods of time, as well as cisplatin that cause lifelong risk of hypertension. This is due to endothelial dysfunction and consequent vascular stiffness. The endpoint is a decrease in Nitric Oxide (NO) levels leading to systemic vasoconstriction and blood pressure elevation. As such, agents that stimulate NO production(such as nitrates) or those that counteract vascular stiffness(such as dihydropyridine calcium channel blockers) might be more useful in adequately controlling blood pressures in cancer survivors exposed to these agents.

The production of free radicals by anthracycline agents and decrease in nitric oxide as referred to in the case of bevacizumab clearly indicate a useful role for chemo preventive agents such as polyphenol-rich cocoa.

More recently, many of the standard heart failure agents (ACE inhibitors/angiotensin receptor blockers (ARBs) and beta blockers) have shown some promise both in the prevention and in the treatment of chemotherapy-induced cardiotoxicity. There is also a useful function for statins which have recently been shown to reduce cancer-related mortality.

Cancer therapeutics has come a long way towards potentially curing and prolonging the life of patients with cancer. As such, the number of cancer survivors will also increase. These benefits associated with cancer treatments are sometimes countered by CVD and CVD events as the primary on-malignant cause of death in cancer survivors.

Certain chemotherapies, radiation therapy and hormone therapy are associated with CVD in the cancer survivorship years, some lasting more than 20 years after treatment. Knowledge and awareness of these agents and associated cardiovascular risks, as well as diagnosis of CVD and management in these settings, are of utmost importance. The approach should be multidisciplinary- with the affected patient as the focus.

Prevention of CVD in the first place is even more paramount. Again regular/daily consume polyphenol-rich for optimum heart health.

DR. EDWARD O. AMPORFUL

CHIEF PHARMACIST

COCOA CLINIC

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