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Environmental tobacco smoke and early atherosclerosis

Institution: University of Southern California
Investigator(s): Wendy Mack, Ph.D.
Award Cycle: 1997 (Cycle 6) Grant #: 6RT-0137 Award: $383,814
Subject Area: Epidemiology
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Exposure to the tobacco smoke of others, otherwise known as environmental tobacco smoke (ETS), has been clearly related to the development of heart attacks and strokes. Recently, persons exposed to ETS have been shown to have thicker walls of the artery in the neck (the carotid artery which carries blood to the brain). The thickness of the artery wall is a measure of early damage to the arteries which is thought to occur before the development of heart attacks and strokes. Persons exposed to ETS have also been shown to have lower levels of certain antioxidants (such as vitamin C) in their blood. Since it has been shown that persons with higher blood levels of antioxidants and those who take antioxidant supplements (such as vitamins C and E) are less likely to develop heart attacks and strokes, the decrease in blood levels of antioxidants that has been seen in persons exposed to ETS may partially explain why persons exposed to ETS are more likely to develop heart attacks and strokes and have thicker artery walls.

This proposal is directly responsive to TRDRP research priorities by evaluating the impact of ETS on the health of individuals. Specifically, we will obtain ultrasounds of the neck arteries of individuals to obtain two measures of early damage to the artery: (1) we will measure the thickness of the artery wall, and (2) we will measure how "stiff' the artery wall is (that is, how much the artery expands and contracts; arteries which can expand and contract more are thought to be healthier arteries). We will compare these measures in persons exposed and not exposed to ETS in their daily lives. In addition, we will measure blood levels of antioxidants to determine if these are lower in persons exposed to ETS. If we see that persons exposed to ETS have thicker and/or stiffer artery walls, we will determine if taking vitamin E will reduce the thickness or stiffness in comparison to persons who take a vitamin E placebo. Because we are proposing to do this study within an existing clinical trial testing the effects of vitamin E versus placebo, we will be able to answer these questions at considerable savings.

It has been estimated that about 35,000 to 40,000 deaths per year from heart disease are due to individual exposure to ETS. In addition, the majority of American adults are routinely exposed to ETS in the home or workplace. Thus, there is a clear public health burden of ETS related to heart disease and stroke. Our proposed work will quantify the relationship between ETS and measures of early damage to the artery (that is, thickness of the artery wall and stiffness). It will additionally determine to what extent lowering of blood antioxidants levels due to ETS contribute to early damage to the artery. This work will thus be of great importance in that the assessment of the impact of ETS on these direct measures of damage to the artery before a person suffers a heart attack or stroke will vastly increase our knowledge about how ETS increases the chance of an individual suffering such an event.

Final Report
Using non-invasive ultrasounds of the carotid artery, the intima-media thickness (IMT), or thickness of the artery wall, can be measured. Thickening of the artery wall is a measure of early stage atherosclerosis. Several epidemiological studies have demonstrated a positive relationship between greater carotid artery IMT and increased risk of cardiovascular events (including nonfatal and fatal heart attacks and strokes). With the same carotid artery ultrasounds, we can also measure carotid artery wall stiffness (the degree to which the artery expands over the cardiac cycle). Higher serum levels of antioxidants and use of antioxidant supplements (such as vitamin E) have been shown in epidemiological studies to protect against the development of heart attacks and strokes. This grant has the following objectives: (1) Assess the relationship between exposure to environmental tobacco smoke (ETS) and early carotid artery atherosclerosis (measured by carotid artery IMT and stiffness), (2) Assess the relationship between exposure to ETS and serum levels of antioxidants; (3) Assess the relationship between carotid artery atherosclerosis and serum antioxidants; (4) Compare rates of progression of carotid atherosclerosis in persons exposed and not exposed to ETS; (5) Determine whether randomized assignment to vitamin E supplementation (vs. placebo) ameliorates the deleterious effects of ETS on carotid artery atherosclerosis. In a cohort of 993 subjects screened for participation in a clinical trial of vitamin E versus placebo (the Vitamin E Atherosclerosis Prevention Study, VEAPS), we evaluated the association between exposure to ETS, active smoking and the degree of carotid artery wall thickening (IMT) and carotid artery wall stiffness. Subjects had an average age of 56 (SD=11) years and were 52% female. Carotid artery IMT was greater in active smokers than non-smokers, and was positively associated with number of cigarettes smoked per day (p=0.03) and number of years of smoking (p<0.001). Among 615 persons who had never smoked, persons living with smokers had thicker carotid artery walls (p=0.02). ETS exposure outside of the home (including work and other non-residential activities) was not related to carotid artery IMT. In females only, positive age-adjusted correlations were found between Ep and number of smokers living in the home (r = 0.16, p = 0.07) and average daily hours of exposure to ETS in the home (r = 0.21, p = 0.02). Women, but not men, also had stiffer carotid arteries when exposed to ETS outside of home and work. We found little evidence in this sample that these deleterious effects of active and passive smoking on early atherosclerosis were mediated by measures of oxidant stress or reductions in serum antioxidants. Because the VEAPS clinical trial was extended from a 2-year to a 3year treatment period, the results of specific aims 4 and 5 (comparing rates of progression of atherosclerosis, measured by IMT among persons exposed vs. unexposed-to ETS, and determining whether randomized , assignment to vitamin E affects any deleterious effect of ETS exposure), await the completion of the trial. It has been estimated that about 35,000 to 40;000 deaths per year in the U.S. from heart disease are due to individual exposure to ETS, and about one third of non-smoking American adults are routinely exposed to ETS. Thus, there is a clear public health burden of ETS related to atherosclerosis, heart disease and stroke. Our work on this grant shows that both ETS and active smoking are independent and important determinants of early stage atherosclerosis. The impact of ETS is apparent on subclinical atherosclerosis measured both anatomically by thickness of the artery wall, and physiologically by stiffness of the carotid artery.
Publications

Passive and active exposure to tobacco smoke and subclinical carotid artery atherosclerosis
Periodical: Circulation Index Medicus:
Authors: Mack WJ, Ottesen R, Selzer RH, et al ABS
Yr: 1998 Vol: Suppl 1 Nbr: Abs: I-582 Pg:

Environmental tobacco smoke: serum antioxidants and early artherosclerosis
Periodical: Proceedings of the TRDRP Annual Investigator's Meeting Index Medicus:
Authors: Mack WJ, Selzer R, Lee Z, Ottesen R, Islam T, Hodis HN ABS
Yr: 1998 Vol: Nbr: 7A Abs: Pg:

Passive and active exposure to tobacco smoke and subclinical carotid artery atherosclerosis
Periodical: Circulation Index Medicus:
Authors: Mack WJ, Ottesen R, Selzer RH, et al ABS
Yr: 1998 Vol: Suppl 1 Nbr: Abs: I-582 Pg:

Environmental tobacco smoke: serum antioxidants and early artherosclerosis
Periodical: Proceedings of the TRDRP Annual Investigator's Meeting Index Medicus:
Authors: Mack WJ, Selzer R, Lee Z, Ottesen R, Islam T, Hodis HN ABS
Yr: 1998 Vol: Nbr: 7A Abs: Pg: