Supported by basic science research methods and resourced by $1.72 million (2012-15), the objectives in Theme 1 explore vascular health by discovering and intervening on determinants of the lifetime burden of atherosclerosis and vascular injury. The Cardiovascular Research Laboratory is equipped for basic studies in molecular biology, cellular cholesterol transport, genetics, proteomics and lipidomics, bioinformatics and genome-wide association studies. This basic science platform is fully integrated with the Vascular Health Unit, Hypertension and Cardiology/Prevention clinics studying cardiometabolic and genetic factors in coronary and peripheral vascular disease. We have led clinical studies translating genomic findings into prevention approaches for aortic valve disease positioning us to be leaders in the multicentre international CHARGE consortium and the EAVALL trial. We led the examination of genetic associations with valvular calcification and aortic stenosis. Our ground-breaking discoveries related to the identification of novel pathways of lipid metabolism and of novel therapeutic targets are paving the way for tailored cardioprotective interventions. These initiatives were foundational in increasing scalability of our work to the genetic epidemiology of vascular disease using translational genomics to understand the biological variance expressed in disease risk helping to identify novel therapeutic targets.