Inflammation and Cardiovascular Health in Women

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.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; HIV/AIDS
• Intervention / Treatment: Radiation: Cardiac PET; Radiation: 99mTc-tilmanocept SPECT/CT; Radiation: Contrast Enhanced Coronary and Aortic Computed Tomography Angiography

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 62

Contacts and Locations

• Study Contact: Name: Sarah Chu, NP; Phone Number: 617-724-6091; Email: schu4@mgh.harvard.edu
• Study Contact Backup: Name: Sarah Chu, NP

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 77 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

- Women with HIV and women without HIV

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Coronary flow reserve on Cardiac PET	Baseline

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Markella V. Zanni, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2020
• Primary Completion (Actual): November 9, 2023
• Study Completion (Actual): November 9, 2023

Study Registration Dates

• First Submitted: January 8, 2020
• First Submitted That Met QC Criteria: January 8, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 17, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Women; Endothelial Dysfunction; Arterial Inflammation; Systemic Immune Activation; Cardiovascular Disease Risk
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Inflammation
• Other Study ID Numbers: 2019P001220

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No