Observational studies suggest that HIV infection is associated with an increased incidence of cardiovascular disease (CVD) events, including coronary heart disease and sudden cardiac death (SCD), compared to the general population;however, the specific mechanisms leading to this increased risk are not well defined. The Multicenter AIDS Cohort Study (MACS) is an observational cohort study of men who have sex with men (MSM) that includes both HIV-infected (HIV+) and -uninfected (HIV-) participants. We have measured subclinical coronary atherosclerosis by coronary computed tomography angiography (CCTA) in 764 men in the MACS. We found a greater prevalence and extent of non-calcified coronary plaque among HIV+ than HIV- men. Older age was associated with a greater prevalence of non-calcified plaque in HIV+ men, but not HIV- individuals, in cross-sectional analyses of these 40-70-year old men. To clearly define the progression of coronary plaque in HIV+ treated people, a longitudinal CCTA study is needed. We propose a study to determine whether aging HAART-treated HIV+ men experience greater progression of non-calcified plaque volume than HIV- men. We will also identify plaques with specific features that characterize them as potentially vulnerable (i.e., plaques with low attenuation, outward remodeling, and spotty calcification) and put them at high risk for causing acute coronary syndromes. Emerging evidence suggests that HIV+ persons may be at increased risk for sudden cardiac death (SCD) and heart failure (HF) compared to the general population. We will evaluate left ventricular ejection fraction (EF) and myocardial perfusion abnormalities, since these are known to predispose to CVD events, including SCD and HF, and have not been well studied among HIV+ persons. Thus, this proposal will leverage an existing research infrastructure to achieve the following specific aims:
Specific Aim 1 : determine whether aging HIV+ men have a greater progression of non-calcified coronary atherosclerotic plaque than HIV- men over 4-6 years of follow-up. Secondary aims are to determine whether, compared to HIV- men, HIV+ men have a) a greater incidence of new non-calcified plaque and/or slower rates of transition from non-calcified to calcified plaque in individual coronary segments and b) a greater prevalence and incidence of high risk vulnerable plaques Specific Aim 2: determine whether HIV+ men are more likely than HIV- men to have myocardial abnormalities that could predispose them to SCD and HF. We will compare a) left ventricular EF and b) global myocardial perfusion index between HIV+ and HIV- men. Secondary aims include a comparison of the prevalences of left ventricular myocardial scar and resting perfusion abnormalities. The proposed studies will lead to a greater understanding of the pathogenesis and dynamics of CVD among HAART-treated HIV+ persons, knowledge which can then be used to develop effective CVD prevention strategies.

Public Health Relevance

This study will compare changes in atherosclerosis in the heart arteries and the amount of blood flow to the heart muscle using CT scans in men with and without HIV in the Multicenter AIDS Cohort Study (MACS). The baseline scans have already been completed. Men are recruited from Baltimore/Washington, Chicago, Pittsburgh and LA.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL125053-01
Application #
8790664
Study Section
Special Emphasis Panel (ZHL1-CSR-B (M1))
Program Officer
Kirby, Ruth
Project Start
2014-08-07
Project End
2018-04-30
Budget Start
2014-08-07
Budget End
2015-04-30
Support Year
1
Fiscal Year
2014
Total Cost
$781,700
Indirect Cost
$164,646
Name
Johns Hopkins University
Department
None
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218