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Antioxidants, cigarette smoking and atherosclerosis

Institution: University of Southern California
Investigator(s): James Dwyer, Ph.D.
Award Cycle: 1998 (Cycle 7) Grant #: 7RT-0034 Award: $730,640
Subject Area: Epidemiology
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
The major adverse health effect of cigarette smoking is an increased risk of cardiovascular diseases. The most prevalent clinical manifestations of these diseases are cardiac chest pain (angina pectoris), heart attack (myocardial infarction) and stroke. The bulk of these events are the result of a progressive disease of the arterial wall known as atherosclerosis and the acute rupture of an atherosclerotic lesion. Atherosclerosis is the accumulation of fats, oxidized cholesterol and other material in the portion of the arterial wall known as the intima. This accumulation occurs over decades. A heart attack or thrombotic stroke occurs when an atherosclerotic lesion ruptures and a blood clot (thrombus) is formed that suddenly restricts the flow of blood to the heart or brain.

Cigarette smoking may increase the risk of atherosclerotic events, such as heart attack, by speeding up the progress of atherosclerosis through all of its stages. However, many autopsy studies of the coronary arteries have failed to find increased coronary atherosclerosis in smokers. This raises the possibility that smoking increases the risk of atherosclerotic events by promoting the rupture of plaques and the formation of occlusive clots. These effects need to be clarified so that progress in treatment and early detection can be made.

In an ongoing study, we are investigating the relation between smoking and an early stage of atherosclerosis. An early manifestation of atherosclerosis is thickening of the arterial wall; this thickening occurs in the inner layer of the artery (the intima). Due to developments at NASA in the processing of digitized videotape, we are now able to measure the thickness of the artery wall with accuracy using a noninvasive and painless probe known as high resolution ultrasound. Our study of 600 middle aged and healthy employees of a large company has yielded the finding that smokers do evidence more atherosclerosis than non-smokers. Our analyses indicate that the atherosclerosis in smokers has progressed an average of six years ahead of non - smokers.

The proposed study aims to extend these findings to the effects of smoking on two other aspects of early atherosclerosis. Our group has developed new technology for the measurement of vascular function and these procedures make it possible to assess vascular function in a large epidemiologic study. These additional measures are hypothesized to reflect different pathologic processes from wall thickening that may occur at even earlier stages of the disease, so that decrements in these arterial functions may be detected at an even earlier age. A second goal of the project is to elucidate the role of dietary and plasma antioxidants (such as vitamin C and vitamin E) in the link between smoking and atherosclerosis. It is hypothesized, for example, that part of the effect of smoking on atherosclerosis is due to a reduction of vitamin C levels in the plasma of smokers.

A better understanding of how smoking impacts atherosclerosis could lead to better approaches to prevention and treatment of cardiovascular disease among smokers. A finding that cigarette smoking does impact early stages of atherosclerosis could also contribute to smoking cessation efforts. The extent of atherosclerosis can be measured by a number of noninvasive techniques that could be used among smokers to encourage their cessation efforts.

Final Report
This study focused on relations between cigarette smoking and two new indicators of arterial pathology that are associated with atherosclerosis. Atherosclerosis is the arterial disease that leads to most heart attacks and strokes.

The new indicators of arterial pathology were (1) flexibility of the common carotid artery (the large artery supplying blood to the head), and (2) dilation of the brachial artery (an artery supplying blood to the arm) after blood flow is restored. Both of these measurements were achieved non-invasively using 2-dimensional ultrasound imaging. Flexibility of the carotid artery was measured by the change in diameter that occurs between diastole (low pressure) and systole (high pressure) over the cardiac cycle. Brachial dilation was measured as the change in arterial diameter from normal to after several minutes of blocked blood flow to the arm (using a pressure cuff).

Previous clinical studies have suggested that both of these measures are related to the extent of atherosclerosis throughout the major arteries. However, these measures have been included in only a few epidemiologic studies with sampling from a relevant population. The current study involves a randomly selected sample of employees from a large company. Thus, this study offers an opportunity to explore relations between these measures of arterial pathology and risk factors for atherosclerosis, heart disease, and stroke.

It was hypothesized that smokers would show reduced flexibility of the carotid artery and reduced dilation of the brachial artery. Current smokers were not found to differ from never smokers in carotid flexibility. However, former smokers did show a decrement in carotid flexibility. For dilation of the brachial artery, the opposite of the expected relation was observed. While high blood pressure and high serum cholesterol were associated with reduced brachial dilation, current smokers actually showed increased brachial dilation.

The reasons for these findings are unclear. These findings need replication in other population based epidemiologic studies.
Publications

Oxygenated carotenoid lutein and progression of early atherosclerosis: The Los Angeles Atherosclerosis Study
Periodical: Circulation Index Medicus:
Authors: Dwyer JH, Navab M, Dwyer JM, et al ART
Yr: 2001 Vol: 1013 Nbr: Abs: Pg: 2922-2927