EPIVASCAGE (EPIdemiology of VASCular AGEing) is a 4-year PRC project aiming to examine the association of baseline and vascular ageing progression for incident cardiovascular disease (CVD) and mortality in the community. To this end, EPIVASCAGE will conduct a deep and non-invasive phenotyping of the vascular ageing of large (carotid artery) and small-medium sized arteries (radial artery) and will examine radiomics features in these arterial segments. EPIVASCAGE will rely on the Paris Prospective Study III, an ongoing French community-based prospective study following n=10, 157 men and women aged 50-75 years since 2008. A total of 773 CVD events and 473 deaths are expected by the end of EPIVASCAGE in 2025. A budget of 666 k€ is requested to the ANR. EPIVASCAGE will include 6 work packages (WP). WP1 will be dedicated to the coordination of EPIVASCAGE. In WP2, we will examine the predictive value of already existing and usable structural and functional carotid ageing biomarkers measured at baseline for incident CVD events (n=498 as of June 2020) (manuscript 1). This WP will also be dedicated to the validation of new CVD events, and access to the national health data hub as a complementary source of information is expected to be obtained by month 3. In WP3, we will perform a radiomics analysis on the raw and stored baseline carotid echo-tracking data containing images but also spectral data. Main steps will include data segmentation, image (texture, shape and gray scale) and spectral data extraction using pre-defined matrix and then data reduction (clustering methods). Then we will examine radiomics signatures and their association with incident CVD events (manuscript 2) together with the joint association of structural/functional carotid ageing biomarkers and radiomics signatures for incident CVD (manuscript 3). WP4 will be dedicated to the second PPS3 physical examination (Examination 2, January 2022 to December 2024, 7000 participants awaited, 75% participation rate expected) and data quality assessment. Carotid echo-tracking will be performed as per baseline assessment and an ultrasound of the radial artery will be newly added to assess vascular ageing of medium-small sized arteries. WP5 will be dedicated to carotid ageing progression using carotid ultrasound data measured at baseline and at examination 2. We will then identify actionable determinants of carotid ageing progression of the structural/functional biomarkers (manuscript 4) and of the radiomics features (delta radiomics, manuscript 5). WP6 will be dedicated to the vascular ageing of the small-medium sized radial artery using data collected at examination 2. Structural and functional biomarkers together with radiomics features will be extracted. Actionable determinants of structural/functional biomarkers (manuscript 6) and of the radiomics signatures (manuscript 7) will then be determined. EPIVASCAGE will be led by JP Empana and his team, who is INSERM Research Director, Team leader (U970, Team 4 Integrative Epidemiology of cardiovascular diseases) and PI of the Paris Prospective Study III. EPIVASCAGE involves a multidisciplinary team of experts in CVD epidemiology (Partner 1, P1, Empana’s team), arterial wall mechanics (P2, P Boutouyrie, RM Bruno and F Poli, INSERM U970, team 7), high dimensional statistics (P3, N Chopin and Y Youssfi, Centre for Research in Economics and Statistics, CREST) and ultrasound imaging signal processing (P4, E Bianchini and F Faita, Institute of Clinical Physiology from the university of Pisa, Italy). A strong and established collaborative relationships already exists between team members. The findings from EPIVASCAGE may support a new paradigm shift in the primary prevention of CVD by suggesting that large and small-medium sized arteries may be new and complementary targets for the primary prevention of CVD.