Our primary objective is to identify and validate novel strategies to enhance global cardiovascular disease (CVD) risk prediction over two time windows: 1) 10-20 years, representing the full career of the astronaut and 2) 2-5 years, representing the planning and operational phase of a manned mission to Mars. The team of collaborative investigators is pooling data from multiple existing cohort studies to develop two distinct multi-modality risk prediction tools, one based on 10-year global CVD risk and one based on 3-year CVD risk. These models will evaluate novel testing modalities on top of standard risk factors, including coronary calcium, multiple blood based protein biomarkers, as well as imaging-based assessments of cardiac function. Significant progress has been made towards each of the study aims during year 2 of the grant. With regard to Aim 1, the biomarker consortium had several teleconferences to 1) provide expert advice regarding a protocol for treating acute MI in Space and 2) provide recommendations for implementing preliminary findings from this project on current astronaut screening strategies. The primary scientific aims of the grant required pooling of data from large cohort studies. The goals of the first year of funding were to obtain the necessary approvals and data transfer agreements to being the data pooling process. This was accomplished during the first year, when we obtained approval for data transfer from the Dallas Heart Study, MESA, and ARIC, and the Framingham Heart Study. The goal for the second year of funding was to secure data transfer, construct the consolidated database, and perform harmonization of data elements. This goal was successful accomplished by the end of 2015, ahead of schedule. We have already completed preliminary data analyses for Aim 2, and will soon begin analyses for Aim 3. The analyses for Aim 2 have yielded very strong preliminary data, which were presented at the Galveston meeting and are now being prepared for publication. These findings, developed in the DHS and replicated in MESA, demonstrate that 5 screening tests markedly improve global CVD risk prediction compared with standard risk assessment strategies. The results of these analyses will be of direct relevance not only for astronaut screening but also for population screening in routine clinical practice. Overall, we are slightly ahead of schedule with regard to Aim 2 and on track to begin analyses for Aim 3 soon. Aim 4 remains exploratory, designed to explore the feasibility of transforming the Longitudinal Study of Astronaut Health into a prospective state-of-the-art cohort study of the astronaut corps. A meeting was held in Dallas on May 19, 2015, that included Greg Hundley, MD, the director of this Aim, and LSAH leadership.