Prevalence and predictors of silent atherosclerosis across life: Design of the REACT Phase 1 study

Background Atherosclerosis may start early in life, progressing silently for decades before clinical presentation of atherosclerotic cardiovascular disease (ASCVD) occur. Current preventive strategies rely on only five risk factors (age, sex, cholesterol levels, blood pressure, and smoking), and the available risk scores do not include young adults (< 40 years old). Importantly, the risk scores do not account for the presence of the actual disease, atherosclerosis, resulting in lower precision at the individual level. The aims of Phase 1 of the REACT initiative are to determine the prevalence of silent atherosclerosis across the lifespan and to identify its sex- and age-specific predictors using both contemporary and more advanced methods such as multi-territory vascular imaging and multi-omics profiling. Methods This prospective cohort study is enrolling 16,000 representative adults (18-70 years, women-to-men ratio 1:1) from Denmark and Spain, without a history of ASCVD. The presence and burden of silent atherosclerosis is assessed by 3D vascular ultrasound of the carotid and femoral arteries, and by computed tomography angiography of the coronary, carotid, and femoral arteries. Microvascular status is assessed by retina imaging. Risk factor assessment for silent atherosclerosis includes traditional factors supplemented with detailed questionnaires, physical examinations, blood and urine analyses, as well as multi-omics profiling. Conclusion By providing a detailed understanding of the predictors and age- and sex stratified prevalence of silent atherosclerosis across multiple vascular territories, phase 1 of the REACT project will inform and advance future personalized ASCVD prevention strategies.