A new finding from the Cholesterol Lowering Atherosclerosis Study (CLAS), a clinical trial, indicates that common carotid intima- media thickness (IMT) responds more rapidly and more markedly to LDL-C lowering treatment than angiographic coronary stenosis or carotid roughness. New data from a primate model also show ultrasound detection of intimal thickening in response to a hypercholesterolemic diet within 12 months. These findings suggest that carotid IMT is a reliable and rapidly responding marker of extent of atherosclerosis. However, less than a third of the observed therapeutic benefit on carotid IMT found in CLAS was explained by change in LDL-C and HDL-C, suggesting that related (or other) factors are more directly linked to atherogenic mechanisms. In addition, a Finnish epidemiologic study found that LDL-C was predicative of rate of progression in carotid IMT (IMT) only in persons with high serum levels of (pro-oxidant) copper. HYPOTHESES. These and other data support a model of atherosclerosis in which intracellular accumulation of modified LDL is promoted/retarded by serum pro-oxidants/antioxidants. The proposed epidemiologic study is thus designed to test the specific hypotheses that the positive association between rate of increase in carotid IMT and LDL-C (beta deltaIMT/LDL) is greater in persons with [1] higher levels of serum pro-oxidants (relative to persons with lower levels of serum pro-oxidants), [2] lower levels of serum antioxidants, [3] lower levels of dietary antioxidants; and [4] that regression of carotid IMT associated with smoking cessation will be detected in 30 months. FEASIBILITY. The feasibility of the study stems from [1] recent development of automated interface detection for ultrasound carotid IMT that reduces reproducibility error by 70-90%; [2] models to adjust for error in dietary measures; and [3] availability of subjects from a stable, cooperative, well described, and multi-ethnic population of employees from Southern California Edison. DESIGN. Hypothesis will be tested with longitudinal observation of carotid IMT in Hispanic and non-Hispanic white women and men. The inclusion of Hispanics and women is motivated by their prevalence in the study population (18% Hispanic, 40% women), and by the recent report that incidence of hospitalized myocardial infarction is elevated in Hispanics. 73 persons from each of 4 ethnicity-sex groups aged 40-60 years (n-292), and 83 smokers and recent quitters (n-166) will be recruited from employees in an ongoing study. Baseline blood, diet and potential confounder variables will be related to 18 and 36 month (6, 12, 18, 24 and 30 month in smoker(s) changes in carotid IMT.
Showing the most recent 10 out of 18 publications
