Abstract
Although experimental studies suggest that low and oscillatory wall shear stress (WSS) promotes plaque transformation to a more vulnerable phenotype, this relationship has not been examined in human atherosclerosis progression. Thus, the aim of this investigation was to examine the association between oscillatory WSS, in combination with WSS magnitude, and coronary atherosclerosis progression. We hypothesized that regions of low and oscillatory WSS will demonstrate progression towards more vulnerable lesions, while regions exposed to low and non-oscillatory WSS will exhibit progression towards more stable lesions. Patients (n = 20) with non-flow-limiting coronary artery disease (CAD) underwent baseline and six-month follow-up angiography, Doppler velocity and radiofrequency intravascular ultrasound (VH-IVUS) acquisition. Computational fluid dynamics models were constructed to compute time-averaged WSS magnitude and oscillatory WSS. Changes in VH-IVUS-defined total plaque and constituent areas were quantified in focal regions (i.e. sectors; n = 14 235) and compared across haemodynamic categories. Compared with sectors exposed to low WSS magnitude, high WSS sectors demonstrated regression of total plaque area (p < 0.001) and fibrous tissue (p < 0.001), and similar progression of necrotic core. Sectors subjected to low and oscillatory WSS exhibited total plaque area regression, while low and non-oscillatory WSS sectors demonstrated total plaque progression (p < 0.001). Furthermore, compared with low and non-oscillatory WSS areas, sectors exposed to low and oscillatory WSS demonstrated regression of fibrous (p < 0.001) and fibrofatty (p < 0.001) tissue and similar progression of necrotic core (p = 0.82) and dense calcium (p = 0.40). Herein, we demonstrate that, in patients with non-obstructive CAD, sectors subjected to low and oscillatory WSS demonstrated regression of total plaque, fibrous and fibrofatty tissue, and progression of necrotic core and dense calcium, which suggest a transformation to a more vulnerable phenotype.