Non-invasive measures able to identify persons at greatest risk of ischemic heart disease and stroke are needed. Improved vascular measures would offer early identification of individuals needing more extensive evaluations and reduce unnecessary, costly exams among those at low risk. Two inexpensive, non-invasive measures include B-mode ultrasound evaluation of common carotid artery intima medial thickness (IMT) and microvascular abnormalities on retinal photographs. These measures are significantly associated with some cardiovascular outcomes and risk factors but have major limitations as tools to identify persons with, or at risk of, clinical disease. We propose that addressing certain limitations will improve the association of these vascular measures with clinical disease and, so, also their sensitivity and specificity. One limitation of IMT derives from the effect atherosclerosis has on the arterial media and diameter. First, vascular diameter enlargement is associated with medial atrophy, which could result in misclassification if IMT is used to estimate atherosclerosis severity. This would occur if arterial enlargement is present in some arteries and not others or if enlargement occurs differentially at stages of atherosclerosis. Thus, arteries of differing severity of atherosclerosis would have similar thickness of IMT. Controlling for atherosclerosis-associated remodeling (diameter enlargement) is difficult because body size also impacts arterial diameter. Thus, we propose evaluating whether anthropomorphically specific common carotid diameter, as a surrogate measure for atherosclerotic remodeling, modifies associations between common carotid IMT and atherosclerotic outcomes. A second limiting factor is that both large and small artery damage cause myocardial injury and stroke. Limited associations between carotid IMT and retinal microvascular abnormalities suggest neither measure individually adequately identifies the entire spectrum of vascular disease. Therefore, we will examine separate and joint effects of common carotid artery disease measures (IMT & diameter) and retinal microvascular abnormity measures and test if a composite measure has greater sensitivity and specificity than individual measures. Confirming hypothesized relationships would permit improved vascular measures, allowing earlier identification of those who could benefit from more extensive evaluations and/or treatment and provide greater confidence that those at lower risk do not need additional expensive examinations.
