This project from the Cardiovascular Alterations Team was designed to enhance current NASA cardiovascular disease risk reduction strategies by partnering with investigators from the Aerobics Center Longitudinal Study (ACLS) and the Dallas Heart Study (DHS) to determine how to minimize the risk of a catastrophic cardiovascular event in asymptomatic astronauts. During an exploration class space mission, such as a mission to Mars, astronauts will not have access to comprehensive health care services for periods of 2 years, and possibly longer. Since the majority of experienced astronauts are middle aged (average age 46, range 33-58 years), they are at risk for developing serious cardiovascular events which are life-threatening for the astronaut, and mission threatening for NASA. The ability to identify 'at risk' individuals who are currently asymptomatic is a topic of intense research within the cardiovascular community that is relevant both for NASA and public health. The primary objective of this application was to determine the risk of coronary events associated with changes in coronary artery calcium (CAC) scores over time, and to determine whether this risk can be mitigated by increases in physical fitness, or use of lipid lowering therapy.
Hypothesis 1: A change in coronary calcium score over time from <10 to >10, is associated with an increase in risk for coronary events; this risk is most prominent when the CAC score increases above a threshold level of 100.
Hypothesis 2: The increased risk associated with increasing CAC scores is mitigated by increasing levels of physical fitness and/or the use of lipid lowering therapy (statins).
To test these hypotheses, we will accomplish the following specific aims: Specific Aim 1: To identify ALL clinical events in the ACLS data base. We will identify and verify all myocardial infarctions, new onset angina, and revascularization procedures in ACLS patients who fit the astronaut demographics and who have had more than one CAC measurement. Specific Aim 2: To update the ACLS data base to include information about timing and dose of statin medications. This information will be linked with treadmill time and the clinical events from aim 1 to developed robust risk prediction models. The project was completed on time, and within budget. All analyses were completed as planned, and a number of papers have been published (JACC; Imaging) or submitted (JAMA, Mayo Clinic Proceedings). A few are still in preparation and will be completed without additional funding as the analyses are complete and preliminary figures are already finished.
The key take home messages from this project are: 1). The definition of CAC progression -- specifically how to quantify and express it -- critically influences whether patients are classified as "progressors" or "non-progressors." The most common clinical definition of >15% per year, which to date has been used by NASA flight surgeons, is much too sensitive to the baseline CAC value and frequently gives erroneous information (for example and increase of 1 to 2, 10 to 11, or 100 to 101 reflect a 100%, 10%, and 1% change). Different methods can result in divergent classification in up to 30% of individuals. Although we could not define the "best" score, the Hokanson method, based on the square root of the change in CAC seemed to be the most robust, and will be utilized in other publications; 2). Perhaps the most important finding from the complete study, which has just been submitted to JAMA (Journal of the American Medical Association), is that when more than one CAC score is obtained, virtually all the clinically relevant information is obtained from the absolute value of the second CAC scan. Stated from a clinical perspective, these findings imply that if serial CAC scanning is performed, the latest scan should be used for risk assessment and that knowledge of the change in CAC leading to this subsequent score will provide no independent prognostic information. This important finding obviates the need for complex calculations regarding rate of progression, and further emphasizes that risk for future events depends predominantly on the overall atherosclerotic burden, not on how fast the patient gets there. 3). The second major aim involved assessing the mitigating effects of physical fitness on preventing cardiac events associated with CAC. Although this paper is still in preparation, the key figure is presented in detail in the final report section which shows a dose dependent reduction in cardiovascular events with increasing physical fitness and any age and any CAC level. 4). This study stimulated the development of the Astro-CHARM (Cardiovascular Health and Risk Modification) score which is the only scoring system available which quantifies global cardiovascular risk in a relatively young population like the astronaut corps, using routine clinical information plus a CAC score. The primary paper from the overall study confirms that we do NOT have to update this score to include the rate of change -- only the final score. 5). Lastly, a spin off study which derived from our event verification analysis was a study looking at the risk of developing diabetes in patients on statins. This problem has become increasingly recognized, and is of real importance to astronauts since many of them are on statins. We wanted to know whether being physically fit prevented the development of diabetes from statins. The results from the study showed that increased fitness clearly attenuated the risk of diabetes in statin users, but didn't prevent it entirely. This type of project reflects a transition for the Cardiovascular Team & for NASA.
As the future of manned spaceflight transitions to longer durations of exposure, concerns about the intrinsic cardiovascular risks of flying middle aged men and women are superseding concerns about orthostatic tolerance, or even arrhythmias. Thus reassessment of cardiovascular (CV) risks in space is necessary.