The most likely cause of a non-traumatic life- or mission-threatening medical events in astronauts are from acute cardiovascular disease (CVD). Current risk prediction models utilize only traditional atherosclerosis risk factors and focus narrowly on coronary heart disease events rather than global cardiovascular risk, ignoring outcomes such as heart failure or atrial fibrillation that could also be potentially mission-threatening. Numerous studies have evaluated novel risk markers in an attempt to improve CVD risk prediction, with several promising imaging and blood-based biomarkers identified. Most of these studies have investigated the incremental predictive value of a single biomarker added to a traditional risk factor model, with a few reporting combinations of biomarkers. Moreover, few studies have evaluated strategies for risk prediction that cross testing modalities. Such a multi-modality approach has the potential to markedly improve CVD risk prediction among potential and existing astronauts, and would have direct relevance to the general population.
The primary objective of this study was to develop a consortium of biomarker and aerospace medicine leaders, with expertise in multiple different testing modalities, and with access to robust existing databases, to identify and validate novel strategies to enhance global 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 Biomarker Consortium aimed to provide “real time” advice to NASA on the design of existing screening programs, the status of new biomarkers, and the interpretation of test results.
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The team of collaborative investigators pooled 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 sequentially evaluated novel testing modalities on top of standard risk factors, including coronary calcium (a measure of the extent of coronary atherosclerosis), multiple blood based protein biomarkers that reflect inflammation, cardiac injury and cardiac stress, as well as imaging-based assessments of cardiac function. Finally, investigators worked directly with NASA researchers in the Human Research Program 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. They utilized the expertise of the Biomarker Consortium to design a novel program for study of the effects of training and space flight on astronaut health.
The investigators derived a multimodality risk prediction tool that led to marked improvement over traditional risk prediction algorithms both for predicting 10 year atherosclerotic risk as well as global and cause-specific CVD risk. Five screening tests - coronary calcium screening by CT, left ventricular hypertrophy by ECG, and elevated levels of N-terminal pro b-type natriuretic peptide (NT-proBNP), high-sensitive cardiac troponin (Ths-cTnT), and high-sensitivity C-reactive protein (hs-CRP) markedly improved global CVD risk prediction compared with standard risk assessment strategies. Investigators created a simple score, consisting of the number of abnormal CVD screening tests. In both MESA and DHS a > 25-fold gradient of risk for CVD was seen across the range of scores. Of particular relevance for NASA, participants with zero abnormal tests results have an extremely low risk for any CVD outcome over 10 years of follow-up. The findings replicate extremely well across the two distinct cohort studies.
de Lemos JA, Ayers CR, Levine B, deFilippi CR, Wang TJ, Hundley WG, Berry JD, Seliger SL, McGuire DK, Ouyang P, Drazner MH, Budoff M, Greenland P, Ballantyne CM, and Khera A. Multimodality strategy for cardiovascular risk assessment: Performance in 2 population-based cohorts. Circulation.
2017. May 30;135(22):2119-32. [DOI]
Crew health and performance is critical to successful human exploration beyond low Earth orbit.
The Human Research Program (HRP) investigates and mitigates the highest risks to human health
and performance, providing essential countermeasures and technologies for human space exploration.
Risks include physiological and performance effects from hazards such as radiation, altered gravity,
and hostile environments, as well as unique challenges in medical support, human factors,
and behavioral health support. The HRP utilizes an Integrated Research Plan (IRP) to identify
the approach and research activities planned to address these risks, which are assigned to specific
Elements within the program. The Human Research Roadmap is the web-based tool for communicating the IRP content.
The Human Research Roadmap is located at: https://humanresearchroadmap.nasa.gov/
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for information of how this experiment is contributing to the HRP's path for risk reduction.