Elsevier

Atherosclerosis

Volume 217, Issue 1, July 2011, Pages 207-213
Atherosclerosis

T cell activation predicts carotid artery stiffness among HIV-infected women

https://doi.org/10.1016/j.atherosclerosis.2011.03.011Get rights and content

Abstract

Objectives

HIV disease is associated with increased arterial stiffness, which may be related to inflammation provoked by HIV-related immune perturbation. We assessed the association of T cell markers of immune activation and immunosenescence with carotid artery stiffness among HIV-infected women.

Methods

Among 114 HIV-infected and 43 HIV-uninfected women, we measured CD4+ and CD8+ T cell populations expressing activation (CD38+HLA-DR+) and senescence (CD28-CD57+) markers. We then related these measures of immune status with parameters of carotid artery stiffness, including decreased distensibility, and increased Young's elastic modulus, as assessed by B-mode ultrasound.

Results

HIV infection was associated with increased CD4+ T cell activation, CD8+ T cell activation and CD8+ T cell senescence. Among HIV-infected women, adjusted for age, HIV medications, and vascular risk factors, higher CD4+CD38+HLA-DR+ T cell frequency was associated with decreased carotid artery distensibility (β = −2.00, 95% confidence interval [CI] = −3.86, −0.14, P = 0.04) and increased Young's modulus (β = 1.00, 95% CI = 0.03, 1.97, P = 0.04). These associations were affected little by further adjustment for CD4+ T cell count and viral load. Among HIV-infected women, higher frequencies of immunosenescent T cells, including CD4+CD28-CD57+ and CD8+CD28-CD57+ T cells, were also associated with decreased arterial distensibility. Among HIV-uninfected women, frequencies of activated or senescent T cells were not significantly associated with measures of carotid stiffness.

Discussion

T cell activation and senescence are associated with arterial stiffness, suggesting that pro-inflammatory populations of T cells may produce functional or structural vascular changes in HIV-infected women.

Section snippets

Study population

The Women's Interagency HIV Study (WIHS) is a prospective multicenter study of 3766 HIV-infected and HIV-uninfected women at six urban US field centers. HIV-infected and HIV-uninfected WIHS participants were initially recruited in 1994–1995, and additional women were added to the cohort in 2001–2002. All WIHS participants are invited to complete study visits every six months for collection of biological specimens, questionnaire data and clinical measurements. In April 2004, all WIHS

Results

Among HIV-infected women, 36% were not currently receiving antiretroviral treatment, 39% were treated and had detectable viremia, and 25% were treated and did not have detectable HIV. As previously described [17], HIV-infected women had higher frequencies of activated CD4+ and CD8+ T cells, and higher frequency of senescent CD8+ T cells, as compared with HIV-uninfected women (Table 1). Other HIV-related and cardiovascular variables appear in Table 1. Pearson correlations between carotid artery

Discussion

Among HIV-infected women, cellular markers of immune activation (defined by presence of CD38 and HLA-DR on circulating CD4+ T cells) were associated with increased carotid artery stiffness. Arterial stiffness was defined as low levels of distensibility and high values of Young's elastic modulus as measured by B-mode carotid artery ultrasound. The associations between activated CD4+ T cell frequency and vascular stiffness persisted after adjustment for HIV RNA and total peripheral CD4+ T cell

Statement of conclusions

Prior evidence suggests that patients infected with HIV may have increased risk of clinical cardiovascular events as well as subclinical structural and functional vascular changes. Among a cohort of HIV-infected women, we studied the association of carotid artery stiffness with expression of markers of T cell activation (CD38+HLA-DR+). Our findings suggest that activation of CD4+ T cells is associated with increased vascular stiffness among HIV-infected women. These findings are important

Funding

This work was supported by the National Institute of Allergy and Infectious Diseases [grant numbers UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590] and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [grant number UO1-HD-32632]. This study was co-funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Additional co-funding

Disclosures

None.

Acknowledgments

Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC, Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen

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