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Atherosclerotic heart disease remains a major cause of morbidity and mortality worldwide. The past few decades have seen the emergence of chronic inflammation as a mediator of atherosclerosis. Although the heart and vascular system remain the organ systems most affected in the atherosclerotic process, chronic inflammation and ischemia trigger a systemic multi-organ response. The liver is a critical organ for systemic hemostasis and recent developments have established an important role of the liver in response to atherosclerosis and myocardial ischemia. In addition, the rapid emergence of systemic liver diseases has unraveled a pathophysiological link with heart disease with therapeutic implications. In this review, we explore the relationship between the liver and the heart in myocardial ischemia, describe epidemiological associations between various liver pathologies and coronary heart disease, and elucidate practical challenges in the clinical management of patients with concomitant coronary heart disease and hepatic abnormalities., Competing Interests: Declaration of Competing Interest The author has no financial or other conflicts of interest to disclose., (Copyright © 2021. Published by Elsevier Inc.)