Heart attack and stroke are the most common causes of death globally. These diseases are usually due to changes in the blood vessel walls, so-called atherosclerosis or arteriosclerosis. Atherosclerosis can lead to clot formation, which in turn can cause a lack of oxygen in the heart or brain. Higher consumption of dietary factors such as meat and alcohol intake have been reported to be associated with an elevated risk of cardiovascular disease (CVD). However, the underlying biological pathways explaining this association are not yet well understood. The primary objective of this proposed project is to identify metabolomic and proteomic biomarkers associated with these dietary (meat an alcohol intake) components. These biomarkers will be studied in a causal association with risk of CVD using large-scale epidemiological data. To achieve this aim there are two parts of the research plan: Specific aims are, 1. To identify the circulating metabolomic, and proteomic biomarkers that are associated with dietary meat and alcohol intake. 2. To infer whether the meat and alcohol intake associated CVD risk is mediated through these dietary-metabolites and proteome associations. We will analyze the association of dietary meat and alcohol intake with atherosclerosis and future risk of CVD, and quantify whether the disease risk is mediated through these dietary associated metabolome and proteome signatures. By employing Mendelian randomization and mediation analysis, we will identify the causal connections between these dietary-associated metabolomic and proteomic biomarkers with the risk of atherosclerosis and CVD.