Case control studies have disclosed a strong association between extracranial carotid intimal-medial thickening (ECIMT) and angiographic evidence of coronary artery disease (CAD). A strong association between extent of ECIMT and extent of CAD has also been observed, and patients with severe ECIMT are at increased risk for incident coronary heart disease. Cross sectional data relating ECIMT to age in patients with and without CAD suggest that patients with CAD are on a """"""""fast track"""""""" for progression of ECIMT. One purpose of this longitudinal study is to determine whether the impression of rapid progression in patients with CAD compared to CAD free controls is correct and to quantify the magnitude of the effect overall as well as the segment specific effect in men and women and as it is influenced by baseline risk factors and baseline ECIMT. Whether rapid progression of ECIMT leads to reduction of lumen diameter or not is unknown. Our recent research indicates a complex relationship between the lumen and the intima-media thickness of (extracranial) arteries. This research will also allow us to quantify the temporal change in arterial dimensions in men and women with and without CAD and the influence on them of CAD risk factors, baseline ECIMT, and baseline arterial dimensions. SPECIFIC HYPOTHESES we will test are: 1.) ECIMT progresses more rapidly in males and females with CAD and/or CAD risk factors than in CAD/risk factor free controls; progression is related to baseline risk factors and baseline ECIMT, but CAD patients have more rapid progression even after control for these factors; 2.) more rapid progression of ECIMT in CAD patients is associated with more rapid narrowing of the lumen of the internal carotid but not of the common carotid artery; this effect is only partly explained by baseline risk factors and baseline ECIMT.
SPECIFIC AIMS are 1.) to obtain 3-year progression rates of ECIMT in a previously accessed cohort of 280 volunteers with and without CAD and use multivariable analysis to relate accession status to progression rate; 2.) to quantify baseline lumen diameter in this cohort and relate it to ECIMT, risk factors, and CAD status; to quantify progression of disease as reflected in narrowing of the lumen of the common and internal carotid arteries over 3 years in this cohort. Patients for SPECIFIC AIMs I and II have already been accessed and are being followed: only completion of the final year of follow-up and analysis is requested as part of this proposal. Recent pilot data provide rationale for and support the feasibility of this project. Results will provide the first quantification of progression of ECIMT in patients with and without CAD, the first definition of associations of arterial dimensions with risk factors, ECIMT, and CAD and of change in arterial dimensions with risk factors, ECIMT, and CAD.
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