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Project Title:  Cardiovascular Imaging and Strategies to Mitigate the Risk for Cardiac Events in Astronauts During Prolonged Spaceflight Reduce
Fiscal Year: FY 2014 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2010  
End Date: 05/31/2014  
Task Last Updated: 10/14/2014 
Download report in PDF pdf
Principal Investigator/Affiliation:   Levine, Benjamin D. M.D. / The University of Texas Southwestern Medical Center at Dallas 
Address:  Institute for Exercise and Environmental Medicine (IEEM) 
7232 Greenville Ave, Suite 435 
Dallas , TX 75231-5129 
Email: benjaminlevine@texashealth.org 
Phone: 214-345-4619  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: The University of Texas Southwestern Medical Center at Dallas 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Radford, Nina  Cooper Clinic 
Khera, Amit  The University of Texas Southwestern Medical Center at Dallas 
Project Information: Grant/Contract No. NCC 9-58-CA02201 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NCC 9-58-CA02201 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Arrhythmia:Risk of Cardiac Rhythm Problems
(2) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) CV08:Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted?
(2) ExMC 1.01:We do not know which emerging technologies are suitable for preflight medical screening for exploration missions (IRP Rev E)
Flight Assignment/Project Notes: NOTE: Risk/Gap changes per IRP Rev E (Ed., 3/19/14)

Task Description: 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.

Research Impact/Earth Benefits: Since this was fundamentally an Earth based investigation with impact/benefits for astronauts, virtually all the findings are relevant for cardiovacular medicine on Earth. The focus of our studies was on the clinical question of how to track and interpret imaging data regarding progression of coronary artery disease. For our studies, we concentrated on coronary artery calcium (CAC) scoring, which gives reliable, clinically relevant information about the overall burden of atherosclerosis in the coronary arteries. Many doctors (including NASA flight surgeons) will get repeat scans to follow the progression of disease. However the clinical implications of such changes, particularly in a relatively young population are unknown.

They key benefits from our studies are:

1). DEFINED HOW TO QUANTIFY PROGRESSION OF CAC: Our publication: Paixao ARM...Levine BD et al. Disagreement Between Different Definitions of Coronary Artery Calcium (CAC) Progression. JACC: Imaging, 2014, in press, demonstrated that different methods of quantifying the "progression" of CAC can result in divergent classification in up to 30% of individuals. The most common clinical definition of >15% per year, which is used currently by NASA flight surgeons, is too sensitive to the baseline CAC value and frequently gives erroneous information, especially in patients with low baseline levels of CAC (for example an increase of 1 to 2, 10 to 11, or 100 to 101 reflect a 100%, 10%, and 1% change, but would still reflect the same absolute change in CAC). It is likely that this paper, along with the subsequent paper described in #2 will substantially change how physicians interpret repeat CAC scans.

2). DETERMINED THAT THE FINAL CAC SCORE, RATHER THAN A MEASURE OF DISEASE PROGRESSION IS THE MOST IMPORTANT PIECE OF INFORMATION FOR PREDICTING CLINICAL EVENTS. So if serial CAC scanning is performed by any physician (including flight surgeons), the latest scan should be used for risk assessment; knowledge of the change in CAC leading to this subsequent score will provide no independent prognostic information. This new finding obviates the need for complex calculations regarding rate of progression, and emphasizes that risk for future events depends mainly on the overall atherosclerotic burden, not on how fast the disease progresses. Radford NB...Levine BD et al. Baseline Value, Follow-Up Value and Progression Rate of Coronary Artery Calcification Score and Risk of Incident Cardiovascular Disease Events. Submitted JAMA 08/2014.

3). HIGHER DEGREES OF FITNESS MITIGATE THE EFFECT OF CAC AT ANY AGE OR LEVEL OF CAC. This study shows that for patients with large amounts of CAC, being high fit reduces the risk of cardiovascular events. It also determines the amount of fitness that is required to afford the most protection at any given age, or amount of CAC. The information will be very important to health care providers to reduce the risk of CV events by prescribing specific levels of fitness. DeFina LF...Levine BD et al. Cardiorespiratory Fitness, Coronary Artery Calcium and Cardiovascular Disease Events. To be presented at American Heart Association meetings 2014.

4). DEVELOPED THE ASTRO-CHARM (Cardiovascular Health and Risk Modification). This score quantifies global cardiovascular risk in a relatively young population like the astronaut corps, using routine clinical information plus a CAC score. After final validation, this scoring system will be placed on-line and made available for all medical practitioners to get a more accurate assessment of cardiovascular risk in their patients.

5). DEMONSTRATED THAT INCREASED FITNESS PROTECTS AGAINST THE DEVELOPMENT OF DIABETES IN PATIENTS ON STATINS. This study provides a strategy (increasing fitness) to prevent diabetes in patients placed on statins. Radford NB...Levine BD et al Impact of Fitness on Incident Diabetes from Statin Use in Primary Prevention. Submitted Mayo Clinic Proceedings 07/2014.

Task Progress & Bibliography Information FY2014 
Task Progress: All aims have been accomplished. Because this section will be made publicly available, a modified selection from "main findings" is reproduced here.

1). DEFINED HOW TO QUANTIFY PROGRESSION OF CAC: The most common clinical definition of >15% per year, which is used by NASA flight surgeons, is too sensitive to the baseline CAC and frequently gives erroneous information, especially in patients with low baseline levels of CAC (for example an increase of 1 to 2, 10 to 11, or 100 to 101 reflect a 100%, 10%, and 1% change, but would still reflect the same absolute change in CAC). 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. This paper has been accepted in the Journal of the American College of Cardiology (JACC): Imaging; Paixao ARM...Levine BD et al. Disagreement Between Different Definitions of Coronary Artery Calcium Progression. JACC: Imaging, 2014, in press.

2). MADE THE NOVEL, CLINICALLY IMPORTANT OBSERVATION THAT THE FINAL CAC SCORE, RATHER THAN A MEASURE OF DISEASE PROGRESSION IS THE MOST IMPORTANT PIECE OF INFORMATION FOR PREDICTING CLINICAL EVENTS. So if serial CAC scanning is performed by flight surgeons, the latest scan should be used for risk assessment; knowledge of the change in CAC leading to this subsequent score will provide no independent prognostic information. This new finding obviates the need for complex calculations regarding rate of progression, and emphasizes that risk for future events depends mainly on the overall atherosclerotic burden, not on how fast the diseases progresses. Radford NB...Levine BD et al. Baseline Value, Follow-Up Value and Progression Rate of Coronary Artery Calcification Score and Risk of Incident Cardiovascular Disease Events. Submitted JAMA 08/2014

3). HIGHER DEGREES OF FITNESS MITIGATE THE EFFECT OF CAC AT ANY AGE OR LEVEL OF CAC. DeFina LF...Levine BD et al. Cardiorespiratory Fitness, Coronary Artery Calcium and Cardiovascular Disease Events. To be presented at American Heart Association meetings 2014; referenced as Circulation 2014; abstract in press.

4). DEVELOPED THE ASTRO-CHARM (Cardiovascular Health and Risk Modification). This score is the only 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 final results from Astro-CHARM, including the functional calculator were delivered to NASA and the Human Research Program (HRP) in February 2014, and is actively being used by flight surgeons now.

5). DEMONSTRATED THAT INCREASED FITNESS PROTECTS AGAINST THE DEVELOPMENT OF DIABETES IN PATIENTS ON STATINS. Radford NB...Levine BD et al. Impact of Fitness on Incident Diabetes from Statin Use in Primary Prevention. Submitted Mayo Clinic Proceedings 07/2014.

Bibliography Type: Description: (Last Updated: 10/16/2019)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings DeFina LF, Leonard D, Willis B, Barlow CE, Radford NB, Khera A, Levine BD. "Cardiorespiratory Fitness, Coronary Artery Calcium and Cardiovascular Disease Events." American Heart Association Scientific Sessions 2014, Chicago, Illinois, November 15-19, 2014.

Circulation. 2014 Nov 25;130(Suppl 2):A20477. http://circ.ahajournals.org/content/130/Suppl_2/A20477.abstract ; accessed 7/23/15. , Nov-2014

Articles in Other Journals or Periodicals Radford NB, DeFina LF, Barlow CE, Kerr A, Chakravorty R, Khera A, Levine BD. "Impact of Fitness on Incident Diabetes from Statin Use in Primary Prevention." Mayo Clinic Proceedings. In press, as of September 2014. , Sep-2014
Articles in Peer-reviewed Journals Radford NB, DeFina LF, Barlow CE, Lakoski SG, Leonard D, Paixao AR, Khera A, Levine BD. "Progression of CAC score and risk of incident CVD." JACC Cardiovasc Imaging. 2016 Dec;9(12):1420-9. Epub 2016 Jun 29. http://dx.doi.org/10.1016/j.jcmg.2016.03.010 ; PubMed PMID: 27372023 (NOTE: previously reported in August 2014 as "submitted" and later in June 2016 as Epub) , Dec-2016
Articles in Peer-reviewed Journals Paixao ARM, Chakravorty R, Khera A, LeonardD, DeFina LF, Barlow CE, Radford NB, Levine BD. "Disagreement between different definitions of coronary artery calcium progression." Journal of the American College of Cardiology: Cardiovascular Imaging. 2015 Jun;8(6):743-4. Epub 2014 Nov 12. http://dx.doi.org/10.1016/j.jcmg.2014.07.019 ; PubMed PMID: 25457766 , Jun-2015
Articles in Peer-reviewed Journals Radford NB, DeFina LF, Barlow CE, Kerr A, Chakravorty R, Khera A, Levine BD. "Effect of fitness on incident diabetes from statin use in primary prevention." Atherosclerosis. 2015 Mar;239(1):43-9. Epub 2014 Dec 23. http://dx.doi.org/10.1016/j.atherosclerosis.2014.12.051 ; PubMed PMID: 25568952 , Mar-2015
Articles in Peer-reviewed Journals Radford NB, DeFina LF, Leonard D, Barlow CE, Willis BL, Gibbons LW, Gilchrist SC, Khera A, Levine BD. "Cardiorespiratory fitness, coronary artery calcium and cardiovascular disease events in a cohort of generally healthy, middle aged men: Results from the Cooper Center Longitudinal Study." Circulation. 2018 May 1;137(18):1888-95. Epub 2018 Jan 17. https://doi.org/10.1161/CIRCULATIONAHA.117.032708 ; PubMed PMID: 29343464 , May-2018
Articles in Peer-reviewed Journals DeFina LF, Radford NB, Barlow CE, Willis BL, Leonard D, Haskell WL, Farrell SW, Pavlovic A, Abel K, Berry JD, Khera A, Levine BD. "Association of all-cause and cardiovascular mortality with high levels of physical activity and concurrent coronary artery calcification." JAMA Cardiol. 2019 Feb;4(2):174-81. https://doi.org/10.1001/jamacardio.2018.4628 ; PubMed PMID: 30698608 , Feb-2019
Awards Levine BD. "Dill Lecture at American College of Sports Medicine Meetings, May 2014." May-2014
Awards Levine B. "Association of American Physicians, April 2014." Apr-2014
Awards Levine B. "Best Doctors, Dallas, January 2014." Jan-2014
Awards Levine B. "Fellow, American Physiological Society, Cardiovascular Section, December 2013." Dec-2013
Awards Levine B. "Hermann Rahn Memorial Lecture, University of Buffalo, June 2013." Jun-2013
Project Title:  Cardiovascular Imaging and Strategies to Mitigate the Risk for Cardiac Events in Astronauts During Prolonged Spaceflight Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2010  
End Date: 05/31/2014  
Task Last Updated: 07/12/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Levine, Benjamin D. M.D. / The University of Texas Southwestern Medical Center at Dallas 
Address:  Institute for Exercise and Environmental Medicine (IEEM) 
7232 Greenville Ave, Suite 435 
Dallas , TX 75231-5129 
Email: benjaminlevine@texashealth.org 
Phone: 214-345-4619  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: The University of Texas Southwestern Medical Center at Dallas 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Radford, Nina  Cooper Institute 
Khera, Amit  The University of Texas Southwestern Medical Center at Dallas 
Project Information: Grant/Contract No. NCC 9-58-CA02201 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NCC 9-58-CA02201 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Arrhythmia:Risk of Cardiac Rhythm Problems
(2) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) CV08:Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted?
(2) ExMC 1.01:We do not know which emerging technologies are suitable for preflight medical screening for exploration missions (IRP Rev E)
Flight Assignment/Project Notes: NOTE: Risk/Gap changes per IRP Rev E (Ed., 3/19/14)

Task Description: This project from the Cardiovascular Alterations Team will enhance current NASA cardiovascular disease risk reduction strategies by partnering with investigators for 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 is 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. After completion of these specific aims we will acquire information that is essential to inform decisions regarding astronaut selection for space exploration and will allow the flight surgeons to minimize the risk for catastrophic cardiovascular events. The project will have wide spread implications for public health and cardiovascular risk reduction in the population at large, especially for the asymptomatic individual.

Research Impact/Earth Benefits: After completion of these specific aims, we will have determined the short term risk of cardiovascular events associated with changes in CAC scores, and its mitigation by fitness and/or medications. This information will inform decisions regarding astronaut selection for exploration class missions and will minimize the risk for catastrophic cardiovascular complications during spaceflight, yet at the same time, ensure that the most experienced and healthy crew are available to fly. The project will also have implications for public health and will clarify the meaning of changes in CAC scores, and produce strategies to reduce the risk for cardiovascular events in the population at large.

Task Progress & Bibliography Information FY2013 
Task Progress: We have completed all event verifications for the entire ACLS data base. THIS ACCOMPLISHMENT REPRESENTS THE KEY PROGRESS REQUIRED TO ACCOMPLISH OUR OBJECTIVES. We have just begun the analysis of the relationship between coronary calcium scores and events, and should have the final data analysis completed by the fall, allowing at least 6 months for paper writing.

Bibliography Type: Description: (Last Updated: 10/16/2019)  Show Cumulative Bibliography Listing
 
 None in FY 2013
Project Title:  Cardiovascular Imaging and Strategies to Mitigate the Risk for Cardiac Events in Astronauts During Prolonged Spaceflight Reduce
Fiscal Year: FY 2012 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2010  
End Date: 05/31/2014  
Task Last Updated: 07/12/2012 
Download report in PDF pdf
Principal Investigator/Affiliation:   Levine, Benjamin D. M.D. / The University of Texas Southwestern Medical Center at Dallas 
Address:  Institute for Exercise and Environmental Medicine (IEEM) 
7232 Greenville Ave, Suite 435 
Dallas , TX 75231-5129 
Email: benjaminlevine@texashealth.org 
Phone: 214-345-4619  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: The University of Texas Southwestern Medical Center at Dallas 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Radford, Nina  Cooper Institute 
Khera, Amit  The University of Texas Southwestern Medical Center at Dallas 
Project Information: Grant/Contract No. NCC 9-58-CA02201 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NCC 9-58-CA02201 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Arrhythmia:Risk of Cardiac Rhythm Problems
(2) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) CV08:Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted?
(2) ExMC 1.01:We do not know which emerging technologies are suitable for preflight medical screening for exploration missions (IRP Rev E)
Task Description: This proposal to the Cardiovascular Alterations Team will enhance current NASA cardiovascular disease risk reduction strategies by partnering with investigators for 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 is 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. After completion of these specific aims we will acquire information that is essential to inform decisions regarding astronaut selection for space exploration and will allow the flight surgeons to minimize the risk for catastrophic cardiovascular events. The project will have wide spread implications for public health and cardiovascular risk reduction in the population at large, especially for the asymptomatic individual.

Research Impact/Earth Benefits: After completion of these specific aims we will acquire information that is essential to inform decisions regarding astronaut selection for space exploration and will allow the flight surgeons to minimize the risk for catastrophic cardiovascular events. The project will have wide spread implications for public health and cardiovascular risk reduction in the population at large, especially for the asymptomatic individual. The novel risk assessment algorithm being developed by NSBRI investigators, NASA flight surgeons, and national CVD prevention experts will have wide ranging influence and may replace the Framingham risk score as the definitive assessment of CV risk.

Task Progress & Bibliography Information FY2012 
Task Progress: We have had great success obtaining complete responses in more than 80% of our multiple scan patients, a response rate that rivals other large prospective trials, using our approach of survey letters, internet mailings, telephone calls, search of electronic medical record, and Medicare data base. We have verified virtually all of 656 events in patients with multiple scans, and >50% of the 1,054 with single scans. This is a very high event rate and will DEFINITELY allow us to accomplish our aims.

Bibliography Type: Description: (Last Updated: 10/16/2019)  Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Hastings JL, Krainski F, Snell PG, Pacini EL, Jain M, Bhella PS, Shibata S, Fu Q, Palmer MD, Levine BD. "Effect of rowing ergometry and oral volume loading on cardiovascular structure and function during bed rest." J Appl Physiol. 2012 May;112(10):1735-43. Epub 2012 Feb 16. PubMed PMID: 22345434 ; http://dx.doi.org/10.1152/japplphysiol.00019.2012 , May-2012
Articles in Peer-reviewed Journals Shibata S, Hastings JL, Prasad A, Fu Q, Bhella PS, Pacini E, Krainski F, Palmer MD, Zhang R, Levine BD. "Congestive heart failure with preserved ejection fraction is associated with severely impaired dynamic Starling mechanism." J Appl Physiol. 2011 Apr;110(4):964-71. Epub 2011 Feb 10. PubMed PMID: 21310890 ; http://dx.doi.org/10.1152/japplphysiol.00826.2010 , Apr-2011
Articles in Peer-reviewed Journals Shibata S, Levine BD. "Biological aortic age derived from the arterial pressure waveform." J Appl Physiol. 2011 Apr;110(4):981-7. Epub 2011 Feb 3. PubMed PMID: 21292839 ; http://dx.doi.org/10.1152/japplphysiol.01261.2010 , Apr-2011
Articles in Peer-reviewed Journals Shibata S, Levine BD. "Effect of exercise training on biologic vascular age in healthy seniors." Am J Physiol Heart Circ Physiol. 2012 Mar 15;302(6):H1340-6. Epub 2012 Jan 20. PubMed PMID: 22268113 ; http://dx.doi.org/10.1152/ajpheart.00511.2011 , Mar-2012
Project Title:  Cardiovascular Imaging and Strategies to Mitigate the Risk for Cardiac Events in Astronauts During Prolonged Spaceflight Reduce
Fiscal Year: FY 2011 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2010  
End Date: 05/31/2014  
Task Last Updated: 06/08/2011 
Download report in PDF pdf
Principal Investigator/Affiliation:   Levine, Benjamin D. M.D. / The University of Texas Southwestern Medical Center at Dallas 
Address:  Institute for Exercise and Environmental Medicine (IEEM) 
7232 Greenville Ave, Suite 435 
Dallas , TX 75231-5129 
Email: benjaminlevine@texashealth.org 
Phone: 214-345-4619  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: The University of Texas Southwestern Medical Center at Dallas 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Radford, Nina  Cooper Institute 
Lakoski, Susan  The University of Texas Southwestern Medical Center at Dallas 
Project Information: Grant/Contract No. NCC 9-58-CA02201 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NCC 9-58-CA02201 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Arrhythmia:Risk of Cardiac Rhythm Problems
(2) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) CV08:Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted?
(2) ExMC 1.01:We do not know which emerging technologies are suitable for preflight medical screening for exploration missions (IRP Rev E)
Task Description: This proposal to the Cardiovascular Alterations Team will enhance current NASA cardiovascular disease risk reduction strategies by partnering with investigators for 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 is 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. After completion of these specific aims we will acquire information that is essential to inform decisions regarding astronaut selection for space exploration and will allow the flight surgeons to minimize the risk for catastrophic cardiovascular events. The project will have wide spread implications for public health and cardiovascular risk reduction in the population at large, especially for the asymptomatic individual.

Research Impact/Earth Benefits: After completion of this project, we will have determined the short term risk of cardiovascular events associated with changes in CAC scores, and its mitigation by fitness and/or medications. This information will inform decisions regarding astronaut selection for exploration class missions and will minimize the risk for catastrophic cardiovascular complications during spaceflight, yet at the same time, ensure that the most experienced and healthy crew are available to fly. The project will also have implications for public health and will clarify the meaning of changes in CAC scores, and produce strategies to reduce the risk for cardiovascular events in the population at large.

Task Progress & Bibliography Information FY2011 
Task Progress: Despite not securing a contract with NSBRI until November of 2010, we have made outstanding progress so far. We have completed the first two and initiated the third of a projected 4 "waves" of patient contact and have refined our process to use e-mail, patient letters, search of the electronic medical record, and most recently, query of the National Medicare Data Base (after identifying deaths from the National Death Index). We have completed event verification on nearly all of the multiple scan patients (almost 7,000) and slightly more than half (16,662 of projected 30,000) of the single scan patients. The third wave was initiated at the beginning of last week. Because of this accelerated pace, we hope to have the first set of recommendations developed by the end of next year.

Bibliography Type: Description: (Last Updated: 10/16/2019)  Show Cumulative Bibliography Listing
 
 None in FY 2011
Project Title:  Cardiovascular Imaging and Strategies to Mitigate the Risk for Cardiac Events in Astronauts During Prolonged Spaceflight Reduce
Fiscal Year: FY 2010 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2010  
End Date: 05/31/2014  
Task Last Updated: 06/21/2010 
Download report in PDF pdf
Principal Investigator/Affiliation:   Levine, Benjamin D. M.D. / The University of Texas Southwestern Medical Center at Dallas 
Address:  Institute for Exercise and Environmental Medicine (IEEM) 
7232 Greenville Ave, Suite 435 
Dallas , TX 75231-5129 
Email: benjaminlevine@texashealth.org 
Phone: 214-345-4619  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: The University of Texas Southwestern Medical Center at Dallas 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Lakoski, Susan  The University of Texas Southwestern Medical Center 
Radford, Nina  Cooper Institute 
Project Information: Grant/Contract No. NCC 9-58-CA02201 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation: 2009 Crew Health NNJ09ZSA002N 
Grant/Contract No.: NCC 9-58-CA02201 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Arrhythmia:Risk of Cardiac Rhythm Problems
(2) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) CV08:Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted?
(2) ExMC 1.01:We do not know which emerging technologies are suitable for preflight medical screening for exploration missions (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date now 5/31/2014 (from 5/31/2011), per NSBRI FY11 report submission (Ed., 6/9/2011)

Task Description: This project will enhance current NASA cardiovascular disease risk-reduction strategies by partnering with investigators with the Aerobics Center Longitudinal Study (ACLS) and the Dallas Heart Study 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 two years, and possibly longer. Since the majority of experienced astronauts are middle-aged (average age is 46, and the range is 33 to 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 project is 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.

Hypotheses

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.

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).

Specific Aims

1) Identify all clinical events in the ACLS database. The researchers 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.

2) Update the ACLS database 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 develop robust, risk-prediction models.

After completion of these specific aims, the researchers will acquire information that is essential to inform decisions regarding astronaut selection for space exploration and that will allow flight surgeons to minimize the risk for catastrophic cardiovascular events. The project will have widespread implications for public health and cardiovascular risk reduction in the population at large, especially for the asymptomatic individual.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2010 
Task Progress: New project for FY2010.

Bibliography Type: Description: (Last Updated: 10/16/2019)  Show Cumulative Bibliography Listing
 
 None in FY 2010