Tobacco, Metabolic and Inflammatory Pathways, and CVD Risk

Cardiovascular diseases account for 25% of all deaths worldwide; 64% of all deaths are due to chronic noncommunicable diseases, and 39% of these are due to cardiovascular diseases [1]. As demonstrated in the INTERHEART, a study of risk factors for first myocardial infarction in 52 countries and over 27,000 subjects [2], and INTERSTROKE, a study of the importance of conventional and emerging risk factors of stroke in different regions and ethnic groups of the world [3], multicountry case–control studies, tobacco use is a potent risk factor for myocardial infarctions and strokes, and these associations are consistent across countries. It is estimated that there are 1 billion tobacco users worldwide, and tobacco is a leading cause of global mortality, responsible for 6 million deaths annually [4]. In addition to the growing body of literature regarding the epidemiology of tobacco use, there have been extensive studies investigating the biochemical pathways that link smoking with cardiovascular disease pathophysiology and the evolution of atherothrombotic plaque. However, this literature is wide-ranging and complex as tobacco products such as cigarettes contain over 4,720 chemical compounds and 10 to 10 free radicals, and this is in addition to the well-known compounds such as carbon monoxide and nicotine [5]. Also, each pathway is neither mutually exclusive nor linear, and there are a vast number of interactions between chemicals, and interconnectivity between the inflammatory and biochemical pathways that they induce. The purpose of this review, therefore, is to distill this literature and provide a comprehensive but concise overview of the pathways that connect tobacco use, and particularly smoking, with the development of cardiovascular disease. We use a framework (Fig. 1) as an overview of the topic to