Carotid and/or femoral atherosclerotic plaques (AP) assessment through imaging studies is an interesting strategy for improving individual cardiovascular risk (CVR) stratification and cardiovascular disease (CVD) and/or events prediction. There is no consensus on who would benefit from image screening aimed at determining AP presence, burden, and characteristics. Aims: (1) to identify, in asymptomatic and non-treated subjects, demographic factors, anthropometric characteristics and cardiovascular risk factors (CRFs), individually or grouped (e.g., CVR equations, pro-atherogenic lipid ratios) associated with carotid and femoral AP presence, burden, geometry, and fibro-lipid content; (2) to identify cut-off values to be used when considering the variables as indicators of increased probability of AP presence, elevated atherosclerotic burden, and/or lipid content, in a selection scheme for subsequent image screening. Methods: CRFs exposure and clinical data were obtained (n
= 581; n
= 144 with AP; 47% females). Arterial (e.g., ultrasonography) and hemodynamic (central [cBP] and peripheral blood pressure; oscillometry/applanation tonometry) data were obtained. Carotid and femoral AP presence, burden (e.g., AP number, involved territories), geometric (area, width, height) and fibro-lipid content (semi-automatic, virtual histology analysis, grayscale analysis and color mapping) were assessed. Lipid profile was obtained. Lipid ratios (Total cholesterol/HDL-cholesterol, LDL-cholesterol/HDL-cholesterol, LogTryglicerides(TG)/HDL-cholesterol) and eight 10-years [y.]/CVR scores were quantified (e.g., Framingham Risk Scores [FRS] for CVD). Results: Age, 10-y./CVR and cBP showed the highest levels of association with AP presence and burden. Individually, classical CRFs and lipid ratios showed almost no association with AP presence. 10-y./CVR levels, age and cBP enabled detecting AP with large surfaces (˃p75th). Lipid ratios showed the largest association with AP fibro-lipid content. Ultrasound evaluation could be considered in asymptomatic and non-treated subjects aiming at population screening of AP (e.g., ˃ 45 y.; 10-y./FRS-CVD ˃ 5–8%); identifying subjects with high atherosclerotic burden (e.g., ˃50 y., 10-y./FRS-CVD ˃ 13–15%) and/or with plaques with high lipid content (e.g., LogTG/HDL ˃ 0.135).