1104 Abstract—Cardiovascular disease (CVD) and cancer are the 2 leading causes of death worldwide. Although commonly thought of as 2 separate disease entities, CVD and cancer possess various similarities and possible interactions, including a number of similar risk factors (eg, obesity, diabetes mellitus), suggesting a shared biology for which there is emerging evidence. Although chronic inflammation is an indispensable feature of the pathogenesis and progression of both CVD and cancer, additional mechanisms can be found at their intersection. Therapeutic advances, despite improving longevity, have increased the overlap between these diseases, with millions of cancer survivors now at risk of developing CVD. Cardiac risk factors have a major impact on subsequent treatment-related cardiotoxicity. In this review, we explore the risk factors common to both CVD and cancer, highlighting the major epidemiological studies and potential biological mechanisms that account for them. (Circulation. 2016;133:1104–1114. DOI: 10.1161/CIRCULATIONAHA.115.020406.) Key Words: cardiology ◼ cardiovascular diseases ◼ clinical oncology ◼ risk factors © 2016 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.115.020406 From Department of Medicine, Division of Cardiovascular Medicine, University of Minnesota, Minneapolis (R.J.K., S.H.K.); Department of Epidemiology and Community Health, University of Minnesota, Minneapolis (A.E.P.); Department of Medicine, Division of Oncology, University of Minnesota, Minneapolis (A.B.); and Masonic Cancer Center, University of Minnesota, Minneapolis (A.E.P.). Correspondence to Ryan J Koene, MD, University of Minnesota, 420 Delaware St SE, MMC 508, Minneapolis, MN 55455. E-mail koene030@umn.edu Shared Risk Factors in Cardiovascular Disease and Cancer Ryan J. Koene, MD; Anna E. Prizment, PhD; Anne Blaes, MD, MS; Suma H. Konety, MD, MS C ardiovascular disease (CVD) and cancer are the largest contributors to the burden of chronic disease in the United States. 1 With an estimated 15 and 14 million people with CVD (excluding hypertension) and a history of cancer, respectively, these numbers will undoubtedly rise as the population grows older and therapies enhance longevity. 2,3 Emerging evidence suggests a relationship between CVD and cancer. A num- ber of shared risk factors build the case for a shared biology. Although inflammation appears to be a major unifying factor in the etiology and progression of these diseases, additional mechanisms have been described. Recent efforts in cardio- oncology have begun to revise the focus toward disease pre- vention and treatment, in terms of balancing the potential causal effects from 1 disease to the other. Biological Mechanisms Common to CVD and Cancer Inflammation in CVD Inflammation is a unifying theme among a variety of diseases, including both cardiovascular disease (CVD) and cancer. 4,5 Common conditions such as obesity, hyperglycemia, hyper- tension, and hypertriglyceridemia induce inflammation, 6–9 and this may, in part, explain why CVD and cancer share several risk factors. Other sources of inflammation are widespread, including microbial and viral infections, allergen exposure, radiation, toxic chemicals, alcohol consumption, tobacco use, and other chronic and autoimmune diseases. 10 Atherosclerosis was once viewed as a lipid storage dis- ease, although it is now known that inflammation mediates all of its stages, from initiation to progression and, ultimately, thrombosis. Conditions such as hypertension, smoking, dyslipidemia, and insulin resistance all appear to trigger atherosclerosis, in promoting the expression of adhesion molecules by endothelial cells, allowing leukocyte attach- ment to blood vessel walls that normally resist their attach- ment. 5,11 Patients with elevated C-reactive protein (CRP), a biomarker of inflammation, have increased CVD events. 12 Thus, immunotherapy for CVD reduction has become an area of intense interest. Statins, perhaps best known for their cholesterol-lowering effects, have been shown to also have anti-inflammatory benefits independent of cholesterol lowering (the use of CRP as a biomarker has validated this postulate). 5 Additional clinical data with immuno- therapy are anticipated, including the Canakinumab Anti- inflammatory Thrombosis Outcomes Study (CANTOS) study (ClinicalTrials.gov: CACZ885M2301), comparing Canakinumab, an inhibitor of interleukin-1β, a proinflam- matory cytokine involved in atherosclerosis and the regula- tion of CRP, with placebo. Inflammation in Cancer The role of inflammation in promoting carcinogenesis and tumor progression has been established. As early as the 19th century, Rudolf Virchow observed leukocytes within neoplas- tic tissue and speculated that cancer arises from inflammatory sites. 13 In recent decades, extensive factual and circumstan- tial evidence has shown several cancer types to be induced by infection or chronic inflammatory disease (eg, human papillo- mavirus and cervical cancer, Helicobacter pylori and stomach cancer, Epstein-Barr virus and lymphoma). 13 Inflammation within the tumor microenvironment has effects that promote malignant transformation of cells, carcinogenesis, and its Contemporary Reviews in Cardiovascular Medicine Downloaded from http://ahajournals.org by on June 15, 2020