During the 11th ICTHIC, Hugo Ten Cate talked about the evolving data on cardiovascular complications in cancer. Here, we summarize the highlights of his speech.
Cancer and CVD
An association exists between cancer and cardiovascular disease (CVD), suggesting the involvement of shared risk factors. Childhood cancer survivors possess an increased risk of diverse CVD, including cardiomyopathy/heart failure, coronary artery disease, stroke, pericardial disease, arrhythmias, and valvular and vascular dysfunction. In addition, CVD risk factors elevate the risk of new cancer [1].
A paper summarizes data on single cardiovascular risk factors and their association with cancer development. An overlap exists in the risk factors for CVD and malignancy: tobacco smoking, obesity, diabetes, hypertension, diet and limited physical activity are associated with CVD and malignancy risk. It is suggested that chronic inflammation may be an underlying joint mechanism [2]. Perhaps, it could be possible to reduce the risk of malignancy by controlling cardiovascular risk factors could reduce, but certainly, this possibility needs further exploration.
Another study shows that premature atherosclerotic CVD is associated with increased cancer risk in young adults. In the study, participants between 18 and 55 years prone to developing premature atherosclerotic CVD had an increased risk of cancer, specifically breast cancer, head and neck cancer, gynecological cancer and urinary cancer. These individuals also correlated with lower levels of education, lower income levels, and experience delays in seeking care for financial reasons. They also had poor nutrition and exercise habits [3].
The authors speculated that risk factors, such as smoking, alcohol and poor lifestyle, might be underlying CVD and malignancy drivers. Living habits and environment deeply impact the risk of CVD and cancer and are associated with risk factors that drive both CVD and cancer [3].
A large study based on the Surveillance Epidemiology and End Results-Medicare linked database showed that patients with incident cancer face a substantially increased short-term risk of arterial thromboembolism (ATE). The 6-month cumulative incidence of myocardial infarction (MI) was 2.0% in patients with cancer compared to 0.7% in age-matched controls without cancer [4].
CVD and ATE
A study based on the Danish registries collecting cancer patients between 1997 and 2017 evaluated the risk of ATE in 458,462 cancer patients and 1,375,386 comparator individuals. In the 6-month period following cancer diagnosis, the cumulative incidence for ATE was 1.50% (95% CI: 1.47–1.54%) in cancer patients and 0.76% (95% CI: 0.75–0.77%) in comparator individuals. Cancer patients had about a twofold elevated risk of ATE [5].
The study also identifies age (>75 years), prior ATE, distant metastasis, and chemotherapy as predictors of ATE [5].
CVD and stroke
Cancer is associated with an increased risk of stroke recurrence, severity, early neurological deterioration, and in-hospital death. In addition, 12% of all stroke patients have an occult malignancy, and patients with an already discovered malignant tumor are at increased risk of developing ischemic stroke. Also, cancer survivors have an overall relative risk for stroke of 1.66, twice as high as the general population [1].
The risk of fatal stroke varies with cancer subsite, age, gender, and time after diagnosis, and it further increases with follow-up time after diagnosis. In comparison to other cancer subsites, patients with brain and gastro-intestinal malignancies are at a relatively high risk of dying of stroke [1].
Cancer can lead to stroke via tumor emboli, non-bacterial thrombotic endocarditis, septic thrombi, direct tumor effects on the cerebral vasculature, and cancer treatment adverse effects.
D-dimer levels are elevated in cancer-related ischemic stroke compared to non-cancer-related ischemic stroke, indicating a hypercoagulable state [1].
In addition, circulating extracellular vesicles (EVs) play a role in cancer-associated thrombosis and tumor progression. A study indicates that cancer cell-derived EVs mediate coagulopathy resulting in ischemic stroke via tumor factor-independent mechanisms. The levels of cancer cell-derived EVs were higher in cancer-related stroke than in other groups (p<0.05 in all the cases) and were related to stroke via coagulopathy as measured by D-dimer levels [6].
Therefore, there are various drivers of hypercoagulability in these patients that we further need to identify.
CVD and myocardial infarction
MI is more prevalent in patients with cancer. The 6-month cumulative incidence of MI is 2.0% in patients with cancer, as opposed to 0.7% in age-matched controls without cancer [4].
In addition, cancer and coronary artery disease are connected through shared risk factors and pathological mechanisms.
- Common risk factors predispose to heart disease and cancer, such as age, obesity, tobacco use, diabetes and hyperlipidemia.
- Cancer causes a prothrombic and chronic inflammatory state, further contributing to acute coronary syndrome (ACS) risk.
- Chemotherapeutic agents have increased cardiovascular adverse events, such as hypertension, angina pectoris, acute MI and Takotsubo.
- External factors may play a role, including the regular pausing of anti-thrombotic therapy and additional surveillance in patients with cancer [1].
Management of the patient with ACS and cancer
Due to exclusion from large clinical trials, there is a lack of data regarding how to best treat these complex and high-risk patients.
A recent review summarizes a few treatment suggestions for patients with ACS [7].
Optimal treatment among cancer patients with ACS is unclear and can vary based on comorbid conditions. However, based on currently available retrospective data, many cancer patients with ACS would likely benefit from aspirin (assuming platelets greater than 10,000/ml), clopidogrel (if platelets greater than 30,000/ml), β-blockers, statin and ACE inhibitors or angiotensin II receptor blockers [7].
All cancer patients with ST-elevation MI, non-ST-elevation MI or unstable angina should be considered for invasive management unless an absolute contraindication exists [7].
Finally, cancer patients with ACS should have their cancer treatment temporarily suspended.
Future research is needed to better assess management among all cancer patients but also according to sub-types [7].
Keep reading about “Bleeding risk, cancer, and atrial fibrillation.”
References
- Willems RAL, Winckers K, Biesmans C, de Vos-Geelen J, ten Cate H. Evolving data on cardiovascular complications in cancer. Thromb Res. 2022; 213(1):S87-S94. doi: 10.1016/j.thromres.2022.01.003
- Koene RJ, Prizment AE, Blaes A, Konety SH. Shared risk factors in cardiovascular disease and cancer. Circulation. 2016;133(11):1104-1114. doi:10.1161/CIRCULATIONAHA.115.020406
- Jain V, Rifai MA, Brinzevich D, Taj M, Saleh M, Krittanawong C, Patel J, Patel A, Lee MT, Mahtta D, Virani SS. Association of premature atherosclerotic cardiovascular disease with higher risk of cancer: a behavioral risk factor surveillance system study. Eur J Prev Cardiol. 2022;29(3):493-501. doi: 10.1093/eurjpc/zwab084.
- Navi BB, Reiner AS, Kamel H, Iadecola C, Okin PM, Elkind MSV, Panageas KS, DeAngelis LM. Risk of arterial thromboembolism in patients with cancer. J Am Coll Cardiol. 2017;70(8):926-938. doi: 10.1016/j.jacc.2017.06.047.
- Mulder FI, Horváth-Puhó E, van Es N, Pedersen L, Büller HR, Bøtker HE, Sørensen HT. Arterial Thromboembolism in Cancer Patients: A Danish Population-Based Cohort Study. JACC CardioOncol. 2021;3(2):205-218. doi: 10.1016/j.jaccao.2021.02.007.
- Bang OY, Chung JW, Lee MJ, Kim SJ, Cho YH, Kim GM, Chung CS, Lee KH, Ahn MJ, Moon GJ. Cancer cell-derived extracellular vesicles are associated with coagulopathy causing ischemic stroke via tissue factor-independent way: The OASIS-CANCER study. PLoS One. 2016;11(7):e0159170. doi: 10.1371/journal.pone.0159170.
- Moran TB, Plana JC. Management of patients with acute coronary syndrome and cancer. Curr Cardiol Rep. 2020;22(12):159. doi:10.1007/s11886-020-01409-8.