Atherosclerosis is an arterial condition characterized by the accumulation mainly of lipid tissue, resulting in the narrowing and stiffening of arteries. It is the leading cause of death among cardiovascular diseases and its development has been associated with wall shear (WSS) and wall mechanical stress (WMS). This study aimed to analyse WSS and WMS with two morphometric measurements, serving as indicators of the initiation and progression of atherosclerosis. 30 coronary arteries from 10 adult familial hypercholesterolaemic pigs fed a high-fat diet were imaged at 3 time points, using intravascular ultrasound and optical coherence tomography. Two-dimensional geometries of the arteries and their lipid components, in combination with their arterial pressure, were used to calculate WMS both at T1 and T2. WSS data was obtained at T1 and T2 by combining the 3D geometry of the arterial lumen and local flow velocity measurements. Arteries were segmented into 3 mm length and 45° sectors for analysis. It was observed that atherosclerosis developed in response to a high-fat diet, evidenced by a gradual increase in wall thickness over time even in the absence of lipidic components. Areas with thicker walls were predominantly found in regions exposed to low WSS and low WMS. Additionally, low WSS was found to promote atherosclerosis initiation and progression whereas high WMS appeared to support atherosclerosis progression. Throughout all time points, it was observed that WSS had a higher contribution to the development of atherosclerosis compared to WMS.