From here to eternity: a unified kinetic model for the pathophysiology of atherosclerotic events

Two operative pathophysiological models underlie the clinical management of ischemic heart disease: a physical model founded on the magnitude of vascular stenosis and a biochemical model founded on the inflammatory processes within the atherosclerotic plaque. Despite their complementary natures, these 2 models are implicitly competitive—the stenotic model supporting the primacy of aggressive interventional procedures and the inflammatory model supporting the primacy of conservative medical management. We unified these alternative perspectives through a kinetic model that characterizes the pathophysiology of cardiovascular events as a network of exponential transitions between the inflammatory and stenotic states. According to this model, the prevalence of the normative (nonstenotic and noninflammatory) state falls exponentially, while the prevalences of the inflammatory and stenotic states rise to a peak and then fall off exponentially. According to this model, event rate increases as a complex function of both myocardial ischemia and vascular inflammation. Although the model has yet to be prospectively validated, it provides a theoretical foundation for predicting the degree to which atherosclerotic events are due to inflammation versus stenosis and the degree to which they can thereby be prevented by treatment strategies directed at plaque stabilization or relief of ischemia.