Imaging and Omics for Cardiovascular Risk During NASA Deep Space Missions

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to develop new approaches for screening astronauts for cardiovascular risk during deep space missions.

Detailed Description
-----------------
The purpose of this study is to develop new approaches for screening astronauts for cardiovascular risk during deep space missions. In this protocol, two different forms of imaging will be used to evaluate coronary plaque development (CT coronary angiography) and microvascular function (myocardial contrast echocardiography) to stratify CV risk. Based on this stratification, omic patterns (targeted metabolomics, lipidomic, and whole genome sequencing) will be assessed to determine whether there are any patterns that can add to existing predictive models. Outcomes measures will involve correlation of omic patterns to incremental risk scaling from lowest (no plaque and normal endothelial function) to highest (+ plaque and endothelial dysfunction).

Conditions
-----------------
Coronary Artery Disease

Intervention / Treatment
-----------------
* Procedure: Myocardial contrast echocardiography


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients referred for clinically indicated CT coronary angiography within 6 months No obstructive coronary plaque and an Agatston score of 0 or At least one obstructive coronary plaque <50% diameter and one other high risk feature on CT-A (positive remodeling, scattered calcification, low Hounsfield units, or napkin ring sign. Exclusion Criteria: Known CAD or other atherosclerotic disease Valvular heart disease (moderate or more) and congenital heart disease Heart failure Pregnancy Allergy to ultrasound contrast agent. Right to left shunt

Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No atherosclerosis cohort<br>This group will have patients who have undergone clinically-indicated CT coronary angiography (CT-A) and who have no plaque and an Agatston score of 0. They will then undergo a myocardial contrast echocardiography study during vasodilator stress to subdivide risk further into No atherosclerosis/endothelial function normal and No atherosclerosis/endothelial function abnormal. Blood will then be collected for metabolomics, lipidomic and whole genome sequencing. | Procedure: Myocardial contrast echocardiography<br>* Myocardial contrast echocardiography will be performed to further stratify risk as described in the cohort section.<br>|
| Atherosclerosis cohort<br>This group will have patients who have undergone clinically-indicated CT coronary angiography (CT-A) and who have non-critical plaque (<50% diameter) and at least 1 high risk feature according to the ROMICAT indices. They will then undergo a myocardial contrast echocardiography study during vasodilator stress to subdivide risk further into atherosclerosis/endothelial function normal and atherosclerosis/endothelial function abnormal. Blood will then be collected for metabolomics, lipidomic and whole genome sequencing. | Procedure: Myocardial contrast echocardiography<br>* Myocardial contrast echocardiography will be performed to further stratify risk as described in the cohort section.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Omic patterns of atherosclerosis | In this study, outcomes are essentially pre-determined by the patient population according to imaging stratification. Omic patterns of will be assessed by advanced informatics modeling (Random Forest analysis) to determine metabolomic, genomic, and lipidomic patterns that vary according to incremental risk scaling from lowest (no plaque and normal endothelial function) to highest (+ plaque and endothelial dysfunction). | 2 weeks |