Pathogenesis of atherosclerosis is a complex multifactorial process of vascular wall injury. It is widely accepted that the local hemodynamic factors, in particular, disturbed flow and low/ oscillatory shear stress leads to the plaque development. We present a consistent concept of atherosclerosis aetiology, taking into consideration the four main components contributing in the atheroma formation: geometric, hemodynamic, hemorheological, and mechanical risk factors. Exemplary illustrative flow simulation results for formulated concept have been presented. It assumes the pulsatile non-Newtonian fluid flow and uses realistic coronary artery geometry based on medical imaging and segmentation.