Case control studies have disclosed a strong association between wall thickening of the extracranial carotid arteries (carotid wall thickening, CWT) and angiographic evidence of coronary artery disease (CAD). This association cannot be altogether explained by shared risk factors. Interactive effects between coronary status and risk factors have been observed: differences in CWT between young and old samples with CAD exceed differences in young and old samples free of CAD, and there are interactive effects with other risk factors as well. A strong association between extent of CWT and extent of CAD has also been observed that suggests that CAD patients with CWT are at increased risk for incident coronary heart disease, and pilot data confirm that the relation of CWT to adverse cardiovascular outcome may be of approximately the same magnitude as number of diseased coronary vessels. The data also suggest that patients with CAD are on a """"""""fast track"""""""" for progression of CWT. Uncertainty imposed by earlier case-control study designs urges completion of a longitudinal study of morbidity and mortality outcome now underway and accomplishment of a longitudinal study of CWT progression to confirm these impressions. SPECIFIC HYPOTHESES we will test are: 1.) Incidence of cardiovascular events (bypass surgery, angioplasty, fatal and non-fatal myocardial infarction (MI), and stroke and endarterectomy) in men and women with extensive CWT at baseline exceeds that of those with less extensive baseline CWT; the relation of CWT to outcome is independent of CAD and/or CAD risk factors; and, 2.) CWT progresses more rapidly in males and females with CAD and/or CAD risk factors than in CAD/risk factor free controls.
SPECIFIC AIMS are 1.) to follow-up a cohort of 670 individuals with defined coronary anatomy, extent of CWT, and CAD risk factors over 5-10 years for fatal and non-fatal cardiovascular events. CAD, CWT, and CAD risk factor status at accession will be related to outcome; and, 2.) In a separate (new) cohort of 280 volunteers with and without CAD we will evaluate CWT yearly for 3 years, and multivariable analysis will be used to relate accession status to progression rate. Availability of a unique sample of patients largely already characterized for coronary status (at angiography), CAD risk factors, and CWT, and development of B-mode methods for quantifying CWT and biostatistical approaches for quantifying progression of CWT over a short time span (3 years) provide opportunity for this project. Recent pilot data support its feasibility. Results will allow us to evaluate the ability of B-mode to identify patients at risk for clinical events and to quantify progression and factors associated with progression of CWT in patients with and without CAD. The data will also aid interpretation of cohort studies and clinical trials with CWT as outcome.
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