Journal Article
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Increases in Cardiovascular Diseases in HIV-infected Adults

As discussed in this site’s Case Study on Cardiovascular Diseases, the literature data support the conclusion that there is a 50% increase in myocardial infarction, as well as increases in other cardiovascular diseases in HIV-infected adults. Two recent reports extend these observations to subclinical indicators of cardiovascular disease. The first (Kingsley et al.) uses coronary artery calcium measurements repeated over a 5-year period in men participating in the Multicenter AIDS Cohort Study. HIV-infected men experienced a significant increase in calcium deposits compared to HIV-uninfected adults. In a second study (Hanna et al.), using a subpopulation from the above study but also including women from the Women’s Interagency HIV Study, carotid artery ultrasound was done over seven years. Although intima-media thickness was similar between infected and uninfected individuals, new plaque formation occurred more often in the HIV-infected group. However, in those with baseline CD4 greater than 500, there was no significant difference. Abstracts from these two studies follow:

Incidence and progression of coronary artery calcium in HIV-infected and HIV-uninfected men

Lawrence A. Kingsley, Jennifer Deal, Lisa Jacobson, Matthew Budoff, Mallory Witt, Frank Palella, Bridget Calhoun and Wendy S. Post AIDS 2015, 29:2427–2434

Objective: The aim of this article is to determine whether HIV-infected men have either higher incidence or more rapid progression of coronary artery calcium (CAC) compared with HIV-uninfected controls.

Design: Prospective observational study.

Setting: Multicenter study in four US academic research centers: University of Pittsburgh, Johns Hopkins University, University of California Los Angeles, and Northwestern University.

Participants: Eight hundred and twenty-five men (541 HIV infected and 284 HIV uninfected) enrolled in the cardiovascular substudy of the Multicenter AIDS Cohort Study who underwent serial cardiac computed tomography (CT) imaging during a mean follow-up of 5 years (range, 2–8 years).

Main outcome measures: Incidence and progression of CAC assessed by cardiac CT.

Results: During follow-up, 21% of HIV-infected men developed incident CAC compared with 16% of HIV-uninfected men. This association persisted after adjustment for traditional and HIV associated risk factors: hazard ratio 1.64 (1.13–3.14). However, there was no association between HIV serostatus and CAC progression among men with CAC present at baseline. Current smoking and increased insulin resistance, both modifiable risk factors, were independently associated with increased incidence of CAC. No evidence supporting an elevated risk for either CAC progression or incidence was found for either dyslipidemia or long-term usage of antiretroviral therapy.

Conclusion: In this large study of HIV-infected and HIV-uninfected men who underwent serial cardiac CT scan imaging, HIV-infected men were at significantly higher risk for development of CAC: hazard ratio 1.64 (1.13–3.14). In addition, two important and modifiable risk factors were identified for increased incidence of CAC. Taken together, these findings underscore the potential importance for smoking cessation and interventions to improve insulin resistance among HIV-infected men.

HIV infection is associated with progression of subclinical carotid atherosclerosis

David B. Hanna,, Wendy S. Post,, Jennifer A. Deal, Howard N. Hodis, Lisa P. Jacobson, Wendy J. Mack, Kathryn Anastos,, Stephen J. Gange, Alan L. Landay, Jason M. Lazar, Frank J. Palella, Phyllis C. Tien, Mallory D. Witt,, Xiaonan Xue,1 Mary A. Young, Robert C. Kaplan, and Lawrence A. Kingsley, Clinical Infectious Diseases 2015;61(4):640-50

Background: Individuals infected with human immunodeficiency virus (HIV) live longer as a result of effective treatment, but long-term consequences of infection, treatment, and immunological dysfunction are poorly understood.

Methods: We prospectively examined 1011 women (74% HIV-infected) in the Women’s Interagency HIV Study and 811 men (65% HIV-infected) in the Multicenter AIDS Cohort Study who underwent repeated B-mode carotid artery ultrasound imaging in 2004–2013. Outcomes included changes in right common carotid artery intima-media thickness (CCA-IMT) and new focal carotid artery plaque formation (IMT >1.5 mm) over median 7 years. We assessed the association between HIV serostatus and progression of subclinical atherosclerosis, adjusting for demographic, behavioral, and cardiometabolic risk factors.

Results: Unadjusted mean CCA-IMT increased (725 to 752 μm in women, 757 to 790 µm in men), but CCAIMT progression did not differ by HIV serostatus, either in combined or sex-specific analyses. Focal plaque prevalence increased from 8% to 15% in women and 25% to 34% in men over 7 years. HIV-infected individuals had 1.6-fold greater risk of new plaque formation compared with HIV-uninfected individuals (relative risk [RR] 1.61, 95% CI, 1.12–2.32), adjusting for cardiometabolic factors; the association was similar by sex. Increased plaque occurred even among persistently virologically suppressed HIV-infected individuals compared with uninfected individuals (RR 1.56, 95% CI, 1.07–2.27). HIV-infected individuals with baseline CD4+ ≥500 cells/μL had plaque risk not statistically different from uninfected individuals.

Conclusions: HIV infection is associated with greater increases in focal plaque among women and men, potentially mediated by factors associated with immunodeficiency or HIV replication at levels below current levels of detection.

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