Rationale for a postintervention continuum of care: insights from intravascular ultrasound.

In 1987, Glagov published a provocative hypothesis that the principal initial response to plaque accumulation was enlargement of the vessel as a whole (remodeling), which preserved luminal diameter until the lesion occupied a substantial proportion of the area within the elastic external membrane (EEM). This model has been confirmed and extended by intravascular ultrasound (IVUS) studies. Remodeling renders most atheromas invisible to angiography. In patients with single-vessel disease, the mean percent of EEM area occupied by atheroma at a segment with an angiographically normal appearance is 39%. IVUS studies further show that the disease progresses in a diffuse manner and that stenotic lesions represent only a small proportion of the total disease burden. We further know that disease can begin as early as the teenage years. Data suggest that up to 25% of individuals < 25 years old may be affected. Atherosclerotic lesions can be effectively targeted with lipid-lowering therapy. Preliminary data suggest that as plaques stabilize and become smaller, a reverse modeling occurs: the EEM area decreases but the lumen size remains unchanged. This may explain why significant reductions in cardiovascular events in clinical trials were accompanied by only modest angiographic evidence of regression. This hypothesis will be tested prospectively in the Reversal of Atherosclerosis with Lipitor (REVERSAL) study.