It is well recognized for that anatomic variations play a key role in the localization of atherosclerosis in the coronary arterial system as well as in other susceptible arteries. Several decades of in vitro research as well as in vivo studies in noncoronary arteries such as carotid arteries, first established that the factor responsible for local atherosclerosis formation and progression was low endothelial shear stress (ESS), caused by irregularities in arterial geometry and the resulting variations in local blood flow patterns.
Recent in vivo studies in humans and diabetic, hypercholesterolemic swine have shown unequivocally that low ESS promotes the development of early fibroatheromas, which subsequently follow an individualized natural history of progression. This individual natural history is critically dependent on the magnitude of low ESS, which subsequently regulates the severity of inflammation within the wall and ultimately the vascular remodeling response. High-risk plaques develop in arterial areas with the lowest values of ESS, which enhance plaque inflammation leading to excessive expansive remodeling. Excessive expansive remodeling leads to perpetuation, or even exacerbation, of the local low ESS environment, thereby setting up a self-perpetuating vicious cycle among low local ESS, inflammation, and excessive expansive remodeling, which transforms an early fibroatheroma to a high-risk plaque. In view of this is seems reasonable to talk of vulnerable anatomy, with the understanding that local coronary anatomy is dynamic, ever changing with the growth and regression of individual plaques and that the mediating factor, connecting anatomy to disease, is ESS.