The purpose of this state-of-the-art review is to address the knowledge gaps in the screening process to quantify coronary artery disease (CAD) risk in cancer survivors, the mechanistic links between cancer and CAD, and the downstream implications of screening. The following are key points to remember:

1. Cancer survivors have a 1.3- to 3.6-fold increase in developing CAD and a 1.7- to 18.5-fold increase in developing atherosclerotic risk factors compared to the general population. This increased risk is caused by a combination of common mechanisms, shared risk factors, and the impact of cancer therapy.
2. The highest incidence of CAD is observed in the first decade of survival (44%), falling to 33% and 23% in patients who survive >10-19 years and >20 years, respectively.
3. The association of cancer with atherogenic pathways can be explained primarily by chronic inflammation, prothrombotic state, and oxidative stress leading to endothelial dysfunction and injury.
4. Common cardiovascular disease risk factors associated with cancer include obesity, smoking, diabetes mellitus, hypertension, hyperlipidemia, and diet. Obesity is a risk factor for 13 types of cancer, whereas smoking reduces the availability of vascular nitric oxide, and increases circulating inflammatory markers and carcinogen intake. Diabetes and hypertension are associated with risks of gastrointestinal, lung, genitourinary and breast cancer, and hyperinsulinemia and insulin-like growth factor-1 may lead to cancer if not regulated.
5. Clonal hematopoiesis, which has been long been associated with hematological malignancies, has now been shown to contribute to CAD by accelerating atherosclerosis through unknown mechanisms.
6. Chemotherapeutic agents contribute to an 8% absolute risk of developing CAD over 20 years post-treatment, and can cause metabolic syndrome, which increases CAD risk.
7. Endothelial dysfunction caused by monoclonal antibodies such as vascular endothelial growth factor, their inhibitors, and fluorouracil agents may lead to coronary vasospasm and thrombus formation. Tyrosine-kinase inhibitors inhibit angiogenesis and mitochondrial function, increasing the risk of atherosclerosis. Gonadotropin-releasing hormone agonists, aromatase inhibitors, and immune checkpoint inhibitors are all associated with an increased risk of CAD due to increased levels of low-density lipoprotein and triglycerides, pro-inflammatory effects, and the release of inflammatory cytokines, respectively. Radiotherapy has been linked to endothelial damage, microvascular and macrovascular changes in coronary arteries, and an increase in heart disease mortality in women receiving left-sided radiation therapy.
8. Coronary artery calcium score is a low-risk, noninvasive, and affordable screening tool for many cancers, and can aid in the decision to treat in patients with intermediate risk. Biomarkers such as high-sensitivity troponin T, glycogen phosphorylase isoenzyme BB, and heart-type fatty acid binding protein may help in the identification and monitoring of CAD in cancer survivors.
9. Aspirin, angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers, beta-blockers, and statins are the primary cardioprotective medications used in cancer survivors. Careful consideration should be taken when combining these drugs with chemotherapeutic agents due to potential for drug-drug interactions.
10. Revascularization strategies, such as percutaneous coronary intervention (PCI) or bypass surgery, may need to be considered for cancer survivors with ongoing angina. Thrombocytopenia should not be an absolute contraindication for PCI, and the decision should be made collaboratively between the patient and their health care team. Surgery should not be declined in cancer survivors, as they generally have similar outcomes compared to those without cancer, with the exception of an increased risk of major bleeding.

Clinical Topics: Cardiac Surgery, Cardio-Oncology, Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Prevention, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and SIHD, Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease, Diet, Hypertension, Smoking

Keywords: Adrenergic beta-Antagonists, Angina Pectoris, Angiotensin-Converting Enzyme Inhibitors, Aspirin, Atherosclerosis, Biomarkers, Cancer Survivors, Cardiotoxicity, Clonal Hematopoiesis, Coronary Artery Bypass, Coronary Artery Disease, Diabetes Mellitus, Diet, Drug Interactions, Hemorrhage, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipidemias, Hypertension, Metabolic Syndrome, Myocardial Revascularization, Neoplasms, Obesity, Percutaneous Coronary Intervention, Plaque, Atherosclerotic, Radiotherapy, Risk Factors, Secondary Prevention, Smoking, Thrombocytopenia, Thrombosis, Troponin T, Vascular Diseases

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