Intersections of Cancer, Cardiovascular Disease Presents Challenges, Opportunities for Multidisciplinary Care

Several panelists discussed the complexities of cardiovascular care in patients with cancer during a session at the American College of Cardiology Scientific Sessions, including challenges associated with immune checkpoint inhibitors (ICIs), BRAF and MEK inhibitors, and opportunities to improve global disparities in cardio-oncology.

Atrial fibrillation (AF) and atherosclerotic cardiovascular disease (ASCVD) are frequent challenges among patients with cancer, according to presenter Palladinesh Thavendiranathan, MD, SM, a cardiologist at the Toronto General Hospital. Two large epidemiological studies have found that this is a major problem, with an approximately 63% increased risk of AF in patients with cancer at about an 8-year follow-up.

There appear to be 2 peaks in cardiovascular risk among patients with cancer, with the greatest risk within the first year of diagnosis and approximately 5 years later, although there are likely different mechanisms driving these peaks, according to the session. There are several key links, including cancer subtypes, age, shared risk factors, and potential biological links.

For instance, hematological malignancies do have associations with cardiovascular disease, with multiple myeloma and lung cancer most commonly associated with AF; stroke risk associated with multiple cancer types; and lung and hematologic malignancies associated with increased risks of coronary disease and myocardial infarction. Age also presents risks for both cancer and cardiovascular disease, Thavendiranathan noted.

“Cancer survivors, who are largely an older cohort, are more likely to have existing ASCVD and AF, and that potentially explains the clustering of diseases,” he said.

Of course, the links between cardiovascular disease and cancer are a bi-directional relationship. According to a 2016 study, patients with AF had a 48% higher risk of cancer.

Cancer treatments can drive cardiovascular disease, as well. Surgery has a 12.6% AF rate, whereas anti-cancer drugs have both direct and indirect impacts on cardiovascular health, Thavendiranathan said. Some of the most commonly used therapies have these effects, such as immune checkpoint inhibitors (ICIs), endocrine therapies in breast cancer, and chemotherapies. There are also disproportionately high cardiovascular signals from kinase inhibitors, particularly ibrutinib with its higher risk of AF.

Thavendiranathan did acknowledge that the associations between CVD and cancer may not always be causal. Patients with AF, ASCVD, or cancer have higher contact with the health care system, making it more likely that other conditions will be identified. Similarly, antiplatelet or anticoagulation treatment can lead to bleeding events, which unmask hematologic malignancies.

“There’s a lot of work ongoing in this space, and I think we will understand in the next few years…the specific causes that link these entities together,” Thavendiranathan concluded.

In another presentation, Eric H. Yang, MD, a cardiologist at University of California Los Angeles, discussed ICIs and some key cardiovascular considerations, particularly given their increasingly widespread use.

“It’s been over a decade since ICIs have made their debut on the cancer stage, and really with this amazing mechanism…harnessing the immune system’s own T cell capacities and kill capacities to effectively recognize and kill cancer cells,” Yang said.

ICIs have been game-changing, particularly for cancers such as melanoma and lung cancer. However, immune-related adverse events are common with these treatments. Lots of attention has been given to myocarditis, which Yang said is a relatively rare complication, but there may be longer effects on atherosclerosis and other cardiovascular complications.

Yang said increased attention is needed regarding AF and ASCVD, as well as other potential cardiovascular complications with using ICIs. Estimates suggest that up to 13% of patients with cancer could benefit from ICI therapy, but some recent clinical research suggests that effects of programmed death cell ligand-1 (PD-L1) blockade may have up-regulatory effects on T cell activity, promoting inflammation and both direct and indirect mechanisms of atherosclerosis.

“As cardiologists, we all know atherosclerosis from a lipid perspective…but this is an interesting opportunity to see how cancer treatments can also play a bigger role in how this affects longer ASCVD health, especially in the cancer population,” Yang said.

Yang emphasized that data on atherosclerosis have always been available, and he urged clinicians to take advantage of this previous work to make treatment decisions.

“We still have a long way to go, but…should we be focusing more on ASCVD more as a forest and not missing the forest for the trees?” Yang asked the audience.

Like ICIs, BRAF and MEK inhibitors are being used more and more, said presenter Hector R. Villarraga, MD, FACC, FESC, FASE. Villarraga focused his presentation on melanoma and said 50% of cases of the disease contain a mutation in the gene encoding the RAF (BRAF), a protein kinase that phosphorylates the MEK protein. Before 2010, survival rates for stage 3 or 4 melanoma were around 1%, which has since improved to 30% with the addition of new treatments.

BRAF inhibition as an adjuvant therapy has shown an approximate 50% improved time to relapse, whereas BRAF-MEK inhibition has shown 80% improvement, Villarraga said.

Some of the main cardiovascular adverse effects associated with these treatments are venous thromboembolism, hypertension, AF, left ventricular systolic dysfunction, peripheral edema, and QTc prolongation.

Villarraga proposed several steps for screening and monitoring when using BRAF and MEK inhibitors. Clinicians should check blood pressure every 4 weeks, with a target of <140/90 mmHg, although <130/80 mmHg would be ideal. Additionally, an EKG should be performed every 4 weeks and an echocardiogram should be administered after 4 weeks of therapy then every 12 weeks moving forward.

He added that lifestyle changes to manage risk factors such as diabetes, high cholesterol, inactivity, and smoking are necessary, although he acknowledged that it can be difficult to ask patients with cancer to make these changes. However, once their anti-cancer therapy is completed and they are feeling stronger, reminding patients to make these changes is important to improve cardiovascular health.

Finally, presenter Diego B. Sadler, MD, a cardiologist with Cleveland Clinic, discussed global disparities in cardio-oncology and some potential ways to improve these issues. Cardiovascular mortality has broadly decreased globally, although Sadler said there are some areas in Asia, Latin America, and Africa where mortality has increased. Modifiable risk factors have been more challenging, with obesity rising and tobacco use just slightly decreasing.

Studies of social determinants of health have also found that patients living in areas with high social vulnerability have increased mortality from both cancer and cardiovascular disease. Although there is existing traditional data examining these issues, Sadler noted that new techniques such as precision medicine and artificial intelligence (AI) are being used to examine these issues.

However, a report from the World Economic Forum addressed AI’s role in health inequity and found that the ability of AI to improve health inequity is largely dependent on the data put into it.

“AI is as good as the data we feed it is, and if the clinical trials in our databases are not representative of the overall populations…then it will not really be effective,” Sadler said.

Moving forward, addressing global cardio-oncology inequities requires collaboration on all levels, Sadler said, including state and local levels, high- and low-income areas, and between health care providers.

REFERENCE

Sadler DB, Villarraga HR, Yang EH, Thavendiranathan P, Chen MH, Bloom MW. Navigating Cardiovascular Care in Patients With Cancer: The Latest Traffic Updates. Presented at: American College of Cardiology 2023 Scientific Session. March 4, 2023.