Inflammation and Cardiovascular Health in Women

Study Overview
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Brief Summary
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Systemic immune activation and inflammation are believed to play a significant role in the development and clinical course of myocardial infarction (MI). Among women with HIV (WHIV), heightened systemic immune activation and inflammation persist, even when HIV infection is well-treated with contemporary antiretroviral therapeutic regimens. Moreover, WHIV in high-resource regions face a three-fold increased risk of myocardial infarction as compared with matched non-HIV-infected women. The goals of this study are to better understand ways in which HIV infection-incited systemic immune activation and inflammation augment MI risk among women.

Detailed Description
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The goals of this study are to better understand ways in which HIV infection-incited systemic immune activation and inflammation augment MI risk among women. To this end, WHIV and non-HIV-infected women will undergo structural and functional cardiovascular imaging studies (Cardiac PET, 99mTc-tilmanocept SPECT/CT, Contrast Enhanced Coronary and Aortic Computed Tomography Angiography) as well as vascular, metabolic/hormonal, and immune phenotyping. Measures of immune activation, arterial inflammation, and cardiovascular pathology will be compared between groups and interrelationships between these parameters will be assessed among WHIV.

Official Title
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Inflammation and Cardiovascular Health in Women

Conditions
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HIV/AIDS, Myocardial Infarction

Intervention / Treatment
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* Radiation: Cardiac PET
* Radiation: 99mTc-tilmanocept SPECT/CT
* Radiation: Contrast Enhanced Coronary and Aortic Computed Tomography Angiography


Participation Criteria
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Eligibility Criteria
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WHIV: Inclusion female nascent sex HIV age 40-79 self-report of stable ART for at least 180 days prior to study entry - any regimen (no more than 30 days missed medication in the last 180 days) Exclusion self-reported history of MI, stroke, coronary revascularization stable or unstable angina symptoms a pre-existing diagnosis of diabetes, being actively treated with oral or injectable antihyperglycemic medication current cocaine use current use of exogenous oral, or transdermal, injected, or depot estrogen or testosterone current treatment with prescription, systemic (oral, IV, or IM) steroids, or anti-inflammatory/immune suppressant medical therapies (excluding topical therapies, UV therapy, ASA-derivative therapies, or NSAIDs) for autoimmune/inflammatory diseases (psoriasis, RA, IBD, lupus), post-transplant care, asthma, or pain syndromes use of oral steroids or prescription oral anti-inflammatory/immune suppressant medication for >7 days within the past 30 days prior to entry pregnant or breastfeeding eGFR < 60 ml/min/1.73 m2 calculated by 2021 CKD-EPI Creatinine known severe allergy to iodinated contrast media (CCTA), dextrans/DTPA/radiometals (99mTc-tilmanocept SPECT/CT), or regadenoson/adenosine (cardiac PET/CT). self-reported significant radiation exposure (>2 CT angiograms) received within the past 12 months concurrent enrollment in conflicting research study. Non-HIV-infected women: As above, save for addition of inclusion criteria for negative HIV test and absent inclusion criteria for HIV and self-report of stable ART.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Women with HIV<br>Individuals with female nascent sex who have been diagnosed with HIV. | Radiation: Cardiac PET<br>* A scan examining blood flow to the heart<br>Radiation: 99mTc-tilmanocept SPECT/CT<br>* A scan to look at inflammation in the arteries<br>Radiation: Contrast Enhanced Coronary and Aortic Computed Tomography Angiography<br>* A scan of the heart and surrounding blood vessels<br>|
| Women without HIV<br>Individuals with female nascent sex who do not have HIV. | Radiation: Cardiac PET<br>* A scan examining blood flow to the heart<br>Radiation: 99mTc-tilmanocept SPECT/CT<br>* A scan to look at inflammation in the arteries<br>Radiation: Contrast Enhanced Coronary and Aortic Computed Tomography Angiography<br>* A scan of the heart and surrounding blood vessels<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coronary flow reserve on Cardiac PET |  | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial inflammation on 99mTc-tilmanocept SPECT/CT |  | Baseline | 
| Atherosclerotic plaque on Contrast Enhanced Coronary and Aortic Computed Tomography Angiography |  | Baseline | 
| Fractional Flow Reserve |  | Baseline | 
| Markers of inflammation/immune activation |  | Baseline | 
| Markers of endothelial dysfunction |  | Baseline | 
| Markers of mitochondrial disease/dysfunction |  | Baseline | 
| Markers of myocardial stretch/injury |  | Baseline | 
| Hormonal/metabolic parameters |  | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Women, Arterial Inflammation, Systemic Immune Activation, Endothelial Dysfunction, Cardiovascular Disease Risk