NOTE: End date changed to 08/09/2024 per C. Ribeiro/HHC, HRP (Ed., 1/4/24)

NOTE: End date changed to 12/31/2023 per C. Ribeiro/HHC, HRP (Ed., 8/26/22)

NOTE: End date changed to 8/31/2023 per HRP, HHC Element (Ed., 8/12/21)

Atherosclerosis is the major contributor to cardiovascular disease-related morbidity and mortality. Research indicates that many of the risk factors commonly associated with atherosclerosis contribute to endothelial dysfunction, a process which presents early in life before angiographic evidence of disease and precedes the clinical manifestation of many cardiovascular disease-related disorders. In an effort to compensate for the initial risk factor-related disruptions to homeostasis, there is a compensatory upregulation of atheroprotective mechanisms. However, in the absence of appropriate risk factor management, these defense mechanisms may become overwhelmed and less able to reestablish normal function. Key systems that help maintain vascular homeostasis and are susceptible to differential deleterious alterations include those that help balance levels of oxidative and inflammatory stress. New evidence suggests that long-duration spaceflight may promote oxidative and inflammatory stress through mechanisms such as radiation exposure, diet, physical inactivity, and psychological stress. However, there are no data supporting a causal link between biomarkers of oxidative and inflammatory stress and indices of vascular endothelial dysfunction in spaceflight. As such, we proposed to examine the relation between biomarkers of oxidative and inflammatory stress and well-established measures of vascular endothelial dysfunction (flow mediated dilation (FMD)) and carotid intima-media thickness (cIMT) in astronauts before, during, and after long duration spaceflight.

Most astronauts continue to participate in postflight data collections, scheduled to extend to 5 years after landing, although some have not been consistently available at the planned increments after landing due to retirement from the astronaut corps (n=6) or limited travel opportunities coming from international partner organizations (n=5). To date, 8 astronauts participated in data collection through 5 years after landing, and 2 astronauts have participated in testing only through the 3-year postflight test. Two astronauts discontinued their participation after the 1-year data collection. The Research and Operations Integration Element (ROI) is working to schedule the remaining 3 subjects for the 5-year post-landing data collection, one of whom has been scheduled for December 2022.

Results from this study and previous reports have been used to inform the design of the NASA Standard Measures Study as well Human System Risk Board-defined risk, “Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes” and are included in the corresponding Human Research Program Evidence Report that was drafted in 2022.

NOTE: End date changed to 12/31/2023 per C. Ribeiro/HHC, HRP (Ed., 8/26/22)

NOTE: End date changed to 8/31/2023 per HRP, HHC Element (Ed., 8/12/21)

Atherosclerosis is the major contributor to cardiovascular disease-related morbidity and mortality. Research indicates that many of the risk factors commonly associated with atherosclerosis contribute to endothelial dysfunction, a process which presents early in life before angiographic evidence of disease and precedes the clinical manifestation of many cardiovascular disease-related disorders. In an effort to compensate for the initial risk factor-related disruptions to homeostasis, there is a compensatory upregulation of atheroprotective mechanisms. However, in the absence of appropriate risk factor management, these defense mechanisms may become overwhelmed and less able to reestablish normal function. Key systems that help maintain vascular homeostasis and are susceptible to differential deleterious alterations include those that help balance levels of oxidative and inflammatory stress. New evidence suggests that long-duration spaceflight may promote oxidative and inflammatory stress through mechanisms such as radiation exposure, diet, physical inactivity, and psychological stress. However, there are no data supporting a causal link between biomarkers of oxidative and inflammatory stress and indices of vascular endothelial dysfunction in spaceflight. As such, we proposed to examine the relation between biomarkers of oxidative and inflammatory stress and well-established measures of vascular endothelial dysfunction (flow mediated dilation (FMD)) and carotid intima-media thickness (cIMT) in astronauts before, during, and after long duration spaceflight.

Most astronauts continue to participate in postflight data collections, scheduled to extend to 5 years after landing, although a few are not readily available due to retirement from the astronaut corps or limited travel opportunities coming from international partner organizations, and two have discontinued participation. Thus, we expect that a total of 10 subjects will participate in data collection through 5 years after landing. To date, 8 astronauts have completed data collection through 5 years after landing, and 10 astronauts have completed their 3-year postflight test. Results from this study and previous reports have been used to inform the design of the NASA Standard Measures Study as well the NASA Human System Risk Board-defined risk, “Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes”.

NOTE: End date changed to 8/31/2023 per HRP HHC element (Ed., 8/12/21)

Atherosclerosis is the major contributor to cardiovascular disease-related morbidity and mortality. Research indicates that many of the risk factors commonly associated with atherosclerosis contribute to endothelial dysfunction, a process which presents early in life before angiographic evidence of disease and precedes the clinical manifestation of many cardiovascular disease-related disorders. In an effort to compensate for the initial risk factor-related disruptions to homeostasis, there is a compensatory upregulation of atheroprotective mechanisms. However, in the absence of appropriate risk factor management, these defense mechanisms may become overwhelmed and less able to reestablish normal function. Key systems that help maintain vascular homeostasis and are susceptible to differential deleterious alterations include those that help balance levels of oxidative and inflammatory stress. New evidence suggests that long-duration spaceflight may promote oxidative and inflammatory stress through mechanisms such as radiation exposure, diet, physical inactivity, and psychological stress. However, there are no data supporting a causal link between biomarkers of oxidative and inflammatory stress and indices of vascular endothelial dysfunction in spaceflight. As such, we proposed to examine the relation between biomarkers of oxidative and inflammatory stress and well-established measures of vascular endothelial dysfunction (flow mediated dilation (FMD)) and carotid intima-media thickness (cIMT) in astronauts before, during, and after long duration spaceflight.

Most astronauts continue to participate in postflight data collections, scheduled to extend to 5 years after landing, although a few are not readily available due to retirement from the astronaut corps or limited travel opportunities coming from international partner organizations, and two have discontinued participation. Thus, we expect that a total of 11 subjects will participate in data collection through 5 years after landing. To date, 3 astronauts have completed data collection through 5 years after landing, and 9 astronauts have completed their 3-year postflight test. Results from this study and previous reports have been used to inform the design of the NASA Standard Measures Study as well Human Research Program-defined risks associated with cardiovascular disease.

Atherosclerosis is the major contributor to cardiovascular disease-related morbidity and mortality. Research indicates that many of the risk factors commonly associated with atherosclerosis contribute to endothelial dysfunction, a process which presents early in life before angiographic evidence of disease and precedes the clinical manifestation of many cardiovascular disease-related disorders. In an effort to compensate for the initial risk factor-related disruptions to homeostasis, there is a compensatory upregulation of atheroprotective mechanisms. However, in the absence of appropriate risk factor management, these defense mechanisms may become overwhelmed and less able to reestablish normal function. Key systems that help maintain vascular homeostasis and are susceptible to differential deleterious alterations include those that help balance levels of oxidative and inflammatory stress. New evidence suggests that long-duration spaceflight may promote oxidative and inflammatory stress through mechanisms such as radiation exposure, diet, physical inactivity, and psychological stress. However, there are no data supporting a causal link between biomarkers of oxidative and inflammatory stress and indices of vascular endothelial dysfunction in spaceflight. As such, we proposed to examine the relation between biomarkers of oxidative and inflammatory stress and well-established measures of vascular endothelial dysfunction (flow mediated dilation (FMD)) and carotid intima-media thickness (cIMT) in astronauts before, during, and after long duration spaceflight.

METHODS: To meet the objectives of the study, 13 astronauts have been studied before, during, and up to 5 years after long duration missions aboard ISS. Levels of oxidative and inflammatory stress biomarkers, some of which we have previously shown to be elevated with spaceflight, were measured from blood and urine samples taken before, during, and after spaceflight. Arterial structure have been assessed before, during, and after spaceflight using measures of carotid artery wall thickness, while arterial function will be measured in the brachial artery before flight and after landing. Increased carotid artery wall thickness and decreased brachial artery function, measured using standard clinical ultrasound, are well-established indices of atherosclerosis risk.

RESULTS: While biomarkers of oxidative stress and inflammation are elevated during spaceflight, arterial structure and function were not changed by spaceflight. Biomarkers of oxidative stress and inflammation increased during spaceflight but most returned to preflight levels within 1 week after landing. Common carotid artery intima-media thickness, stiffness, and distensibility were not different than preflight at any time. As a group, neither mean endothelium-dependent nor -independent vasodilation changed from pre- to postflight. It is unclear whether future exploration missions, with an extended duration in altered gravity fields and increased radiation exposure may be problematic.

DISCUSSION: Here we report no significant change in common carotid and brachial arterial structure and function in 13 astronauts participating in long-duration spaceflights aboard the ISS. In general, biomarkers of inflammation and oxidative stress were elevated during the mission, but returned to preflight levels within a week of landing. Further, we examined the relation between the arterial adaptations to spaceflight in individual astronauts and some key biomarkers associated with cardiovascular disease risk and vascular remodeling. In this healthy population of middle-aged astronauts, we found only a weak association between changes in high sensitivity- CRP (Cardiac Rhythm Problems) and carotid artery changes within subjects. Spaceflight-induced changes in endothelium-independent vasodilation, in particular, were related to changes in some of the biomarkers of oxidative stress.

Atherosclerosis is the major contributor to cardiovascular disease-related morbidity and mortality. Research indicates that many of the risk factors commonly associated with atherosclerosis contribute to endothelial dysfunction, a process which presents early in life before angiographic evidence of disease and precedes the clinical manifestation of many cardiovascular disease-related disorders. In an effort to compensate for the initial risk factor-related disruptions to homeostasis, there is a compensatory upregulation of atheroprotective mechanisms. However, in the absence of appropriate risk factor management, these defense mechanisms may become overwhelmed and less able to reestablish normal function. Key systems that help maintain vascular homeostasis and are susceptible to differential deleterious alterations include those that help balance levels of oxidative and inflammatory stress. New evidence suggests that long-duration spaceflight may promote oxidative and inflammatory stress through mechanisms such as radiation exposure, diet, physical inactivity, and psychological stress. However, there are no data supporting a causal link between biomarkers of oxidative and inflammatory stress and indices of vascular endothelial dysfunction in spaceflight. As such, we propose to examine the relation between biomarkers of oxidative and inflammatory stress and well-established measures of vascular endothelial dysfunction (flow mediated dilation (FMD)) and carotid intima-media thickness (cIMT) in astronauts before, during, and after long duration spaceflight.

Atherosclerosis is the major contributor to cardiovascular disease-related morbidity and mortality. Research indicates that many of the risk factors commonly associated with atherosclerosis contribute to endothelial dysfunction, a process which presents early in life before angiographic evidence of disease and precedes the clinical manifestation of many cardiovascular disease-related disorders. In an effort to compensate for the initial risk factor-related disruptions to homeostasis, there is a compensatory upregulation of atheroprotective mechanisms. However, in the absence of appropriate risk factor management, these defense mechanisms may become overwhelmed and less able to reestablish normal function. Key systems that help maintain vascular homeostasis and are susceptible to differential deleterious alterations include those that help balance levels of oxidative and inflammatory stress. New evidence suggests that long-duration spaceflight may promote oxidative and inflammatory stress through mechanisms such as radiation exposure, diet, physical inactivity, and psychological stress. However, there are no data supporting a causal link between biomarkers of oxidative and inflammatory stress and indices of vascular endothelial dysfunction in spaceflight. As such, we propose to examine the relation between biomarkers of oxidative and inflammatory stress and well-established measures of vascular endothelial dysfunction (flow mediated dilation (FMD)) and carotid intima-media thickness (cIMT) in astronauts before, during, and after long duration spaceflight.

Data analysis is in progress. Data shared through required medical testing is being secured.

Atherosclerosis is the major contributor to cardiovascular disease-related morbidity and mortality. Research indicates that many of the risk factors commonly associated with atherosclerosis contribute to endothelial dysfunction, a process which presents early in life before angiographic evidence of disease and precedes the clinical manifestation of many cardiovascular disease-related disorders. In an effort to compensate for the initial risk factor-related disruptions to homeostasis, there is a compensatory upregulation of atheroprotective mechanisms. However, in the absence of appropriate risk factor management, these defense mechanisms may become overwhelmed and less able to reestablish normal function. Key systems that help maintain vascular homeostasis and are susceptible to differential deleterious alterations include those that help balance levels of oxidative and inflammatory stress. New evidence suggests that long-duration spaceflight may promote oxidative and inflammatory stress through mechanisms such as radiation exposure, diet, physical inactivity, and psychological stress. However, there are no data supporting a causal link between biomarkers of oxidative and inflammatory stress and indices of vascular endothelial dysfunction in spaceflight. As such, we propose to examine the relation between biomarkers of oxidative and inflammatory stress and well-established measures of vascular endothelial dysfunction (flow mediated dilation (FMD)) and carotid intima-media thickness (cIMT) in astronauts before, during, and after long duration spaceflight.

Continuation of "Defining the Relation Between Biomarkers of Oxidative and Inflammatory Stress and Atherosclerosis Risk in Astronauts During and After Long-Duration Spaceflight" ; previous Principal Investigator was Dr. Steven Platts until March 2016. See that project for previous reporting.