Cigarette smoking is the single most alterable risk factor contributing to premature morbidity and mortality in the United States. About one in five deaths from cardiovascular disease is attributable to smoking. Smoking costs Americans over $157 billion annually in health-related economic costs (1, 2). Cigarette smoking predisposes to several different clinical atherosclerotic syndromes, including stable angina, acute coronary syndromes, sudden death, and stroke (1). In addition, smoking is associated with an increased incidence of aortic and peripheral atherosclerosis, which may lead to abdominal aortic aneurysms and intermittent claudication (1). Even passive smoking (environmental tobacco exposure) is reported to increase coronary artery disease (CAD) risk by 30% (1, 3). Endothelial dysfunction is an important pathophysiological mechanism of atherosclerosis (4). Compelling evidence suggests that endothelial cell (EC) dysfunction is associated with (and caused by) each of the risk factors for atherosclerosis, including smoking. However, the precise mechanisms by which cigarette smoking and its components such as nicotine may cause endothelial dysfunction leading to adverse cardiovascular events remain to be fully elucidated. The present chapter summarizes the historical as well as the current perspectives on the evidence and potential mechanism(s) of cigarette smoking-related endothelial dysfunction and cardiovascular disease.

HISTORICAL PERSPECTIVES

About 500 years ago, Columbus and his crew brought tobacco (dried leaves and seeds) from the New World to Europe. By the early part of the 19th century, tobacco was rolled in paper and smoked as cigarettes (5). It was not until the late 1930s that it was initially proposed that cigarette smoking might be associated with increased cardiac mortality (5). In the 1950s, seminal prospective cohort studies on British male physicians demonstrated that cardiovascular disease is more common in smokers than in nonsmokers (5, 6).