Tobacco-related cardiovascular diseases in the 21st century.

C igarette smoking activates platelets, induces endothelial inflammation, and promotes vascular dysfunction leading to accelerated atherosclerosis, plaque rupture, acute coronary syndromes, and death. Over several decades, notable advances in public policy in the United States have reduced initiation and increased cessation of cigarette smoking, thus lowering the prevalence of tobacco product consumption and related cardiovascular disease (CVD). Indeed, most people in developed countries understand the harm of cigarette smoking and the health and economic benefits of abstinence and cessation. However, these public health successes have slowed recently, 1 reflecting perhaps a higher degree of addiction in remaining smokers and also a degree of fatigue in further advancing preventive and treatment strategies, as well as scientific knowledge more generally. Several realities underscore the current challenges to further reducing tobacco-related CVD. First, rates of tobacco product use continue to increase in developing nations and, in combination with dietary and additional lifestyle changes, will drive a surge of CVD in the coming decades in these societies. Second, even in developed countries, tobacco use continues to be stubbornly prevalent particularly in minorities, in patients with psychiatric disorders, and in economically disadvantaged populations and represents a major cause of preventable morbidity and mortality. Last, and in some respects of most direct concern to our research community, mechanistic insights into how tobacco consumption causes CVDs and how this affects individual risk have not kept pace with epidemiological or public health advances. Although we have gained some knowledge of the genetic basis for cigarette smoking behavior and nicotine addiction, 2 we have an incomplete knowledge at the molecular level of the processes that promote CVD, have learned little regarding individualized and genetic risk of CVD complications in those exposed, and have surprisingly limited knowledge of the specific constituents of cigarette smoke that lead to CVD. 3 Thus, we are poorly positioned to apply mechanism-based strategies to treat smoking-related CVD or to execute preventive strategies in those at greatest risk. In this miniseries, we focus on mechanistic aspects of tobacco-related CVD as a focus for galvanizing scientific efforts for the 21st century global epidemic challenge. Norman and Curci highlight how cigarette smoking dominates as a risk factor for abdominal aortic aneurysm and emphasize recent experimental insights but acknowledge our incomplete mech-anistic understanding of abdominal aortic aneurysm in smokers. Barau and Ambrose provide an update on the role and potential mechanisms of cigarette smoking in platelet activation , thrombosis, …