Abstract
Cigarette smoking is a well-known cardiovascular risk factor associated with an estimated 311 premature cardiovascular deaths per 100,000 smokers in the United States each year. The mechanism of arterial damage due to tobacco smoke is not fully elucidated. One plausible theory suggests that toxic exposure to one or more chemical constituents found in tobacco smoke causes persistent inflammatory changes at the level of the endothelial cell, which leads to arterial damage and atherosclerosis. The toxic elements found in tobacco smoke currently thought to be most responsible for cardiovascular toxicity include nicotine, carbon monoxide (CO), oxidant gases, polycyclic aromatic hydrocarbons (PAHs), and particulate matter. Cadmium, a pro-inflammatory metal found in cigarette smoke in significant quantities (1mcg/cigarette), is bioavailable by inhalation and has a biological half-life of 14-23 years, as well as a propensity to store in the liver, kidneys, and blood vessels. Cadmium is associated with human and animal cancers of the lungs, kidneys, prostate and breast, and is also associated with kidney toxicity in occupational settings. In animal models, cadmium has been shown to produce adverse cardiovascular outcomes such as hypertension, lipid alterations, arterial inflammation, and atherosclerosis. In humans, epidemiological investigations suggest that cadmium exposure might be associated with adverse cardiovascular outcomes. Smoking and cadmium exposure have similar effects on the cardiovascular system. For example, both induce arterial inflammation and endothelial cell toxicity, and both induce greater risk of disease to the peripheral arteries in the limbs than to cardiac and cerebrovascular arteries. Such similar mechanisms form the basis of this dissertation, in which the goal is to determine if the association between smoking and cardiovascular disease is explained in part by cadmium exposure. The objectives of this dissertation research are to evaluate: 1) the relationship between cadmium biomarkers and cigarette smoke exposure 2) the relationship between cadmium exposure and various cardiovascular outcomes by level of smoking and 3) the role of cadmium as a mediator of cigarette-smoke-induced cardiovascular disease. The results of this dissertation will add to the understanding of the role that cadmium might play regarding in the association between smoking and cardiovascular disease in the U.S. adult population. The findings of this dissertation suggest that cadmium biomarker levels are highly associated with cigarette smoking in a dose dependent fashion and cadmium biomarker levels are associated with adverse cardiovascular outcomes including myocardial infarction and stroke. In addition, cadmium partially mediates the relationship between smoking and coronary artery disease, specifically angina pectoris.