Wall shear stress and evolution of coronary atherosclerosis: an emerging intravascular imaging modality

Atherosclerosis is a diffuse systemic process associated with traditional cardiovascular risk factors leading to systemic inflammation, oxidative stress and endothelial dysfunction. However, the pathophysiology and prognosis of individual coronary plaques may be markedly different between two patients with identical systemic risk profiles, implying an important role for genetic predisposition, as well as local factors in the natural history of atherosclerosis. Human autopsy studies have demonstrated that the vast majority of thin-cap f ibroatheromas and ruptured plaques occur in the proximal third of the major coronary arteries [1]. Similarly, clinical studies have demonstrated that culprit lesions in patients with ST-elevation myocardial infarction are frequently located in proximal coronary arteries, immediately distal to bifurcations, and in proximity to major curvatures [2]. This focal distribution of clinically important coronary plaques in segments known to have disturbed blood flow infers an important role for regional wall shear stress (WSS) in the pathogenesis of clinically manifest coronary artery disease (CAD). Abnormal WSS in geometrically susceptible coronary segments is thought to promote the development of atherosclerosis. Indeed, low WSS has been implicated in a number of pathologic mechanisms including increased VCAM-1 expression [3], sustained activation of sterol regulatory element-binding proteins, which are key transcription factors that upregulate the expression of genes that encode the low-density lipoprotein receptor and fatty acid synthase [4,5], increased production of reactive oxygen species [6] and a proatherogenic endothelial cell phenotype [7]. Furthermore, experimental studies in ApoE-knockout mice and porcine models of atherosclerosis have demonstrated that vascular segments with low and oscillatory WSS result in proatherogenic flow-mediated inflammatory responses and development of regional atherosclerosis [8–10]. Pilot clinical data have suggested that these experimental observations linking low WSS to plaque progression may hold true in the human coronary vasculature [11]. We have recently demonstrated that in patients with CAD treated with high-dose statins, coronary segments with low WSS indeed develop greater plaque progression and constrictive vascular remodeling compared with segments with physiologic or high WSS [12].