Inflammatory biomarkers and subclinical carotid atherosclerosis in HIV-infected and HIV-uninfected men in the Multicenter AIDS Cohort Study.

Vinita Subramanya,Wendy S Post,Heather S Mckay,Howard N Hodis,Rebeccah M Brusca,Mallory D Witt,Lawrence A Kingsley,Sabina A Haberlen,Russell P Tracy,Frank J Palella,Cristian Apetrei

doi:10.1371/journal.pone.0214735

Vinita Subramanya, Wendy S Post + Show 9 more

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https://doi.org/10.1371/journal.pone.0214735

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Abstract

BackgroundHIV-infected persons have an increased risk of atherosclerosis relative to uninfected individuals. Inflammatory processes may contribute to this risk. We evaluated the associations of 10 biomarkers of systemic inflammation (CRP, IL-6, sTNF-αR1 and 2), monocyte activation (CCL2, sCD163, sCD14), coagulation (fibrinogen, D-dimer), and endothelial dysfunction (ICAM-1) with subclinical carotid atherosclerosis among participants in the Multicenter AIDS Cohort Study (MACS).MethodsCarotid plaque and intima media thickness (IMT) in the common carotid (CCA-IMT) and bifurcation region were assessed by B mode ultrasound among 452 HIV-infected and 276 HIV-uninfected men from 2010–2013. Associations between levels of each biomarker and presence of focal plaque and IMT were assessed by logistic and linear regression models, adjusting for demographics, risk behaviors, traditional cardiovascular disease (CVD) risk factors, and HIV disease characteristics.ResultsCompared to HIV-uninfected men, HIV-infected men had significantly higher levels of 8 of the 10 biomarkers. Overall, men with sCD163, CCL2, IL-6, and CRP levels in the highest quintile had approximately 2 times the odds of carotid plaque relative to those with levels in the lowest quintile, independent of demographic and CVD risk factors. Fibrinogen levels were positively associated with CCA-IMT while ICAM-1, CCL2, and sTNF-αR1 levels were positively associated with bifurcation-IMT. Among HIV-uninfected men, higher levels of sTNF-αR2 were positively associated with CCA-IMT, fibrinogen with bifurcation-IMT and carotid plaque, and ICAM-1 with carotid plaque.ConclusionIn addition to greater levels of systemic inflammation, heightened monocyte activation (sCD163, CCL2) may contribute to the burden of atherosclerosis among HIV-infected persons.

Highlights

HIV-infected individuals have a greater risk of subclinical atherosclerosis and cardiovascular disease (CVD) events, even among those with suppressed HIV RNA levels [1,2,3], compared to HIV-uninfected persons [4, 5]
Systematic reviews demonstrate mixed results regarding the associations between levels of specific biomarkers and surrogate markers of cardiovascular disease among HIVinfected persons [13, 14], studies have reported associations between levels of C reactive protein (CRP), IL-6, TNF alpha receptors 1 and 2, soluble cluster of differentiation 14 (sCD14), soluble cluster of differentiation 163 (sCD163), chemokine ligand 2 (CCL2), and D-dimer with subclinical or incident CVD [5, 11, 14,15,16,17,18]
In previous reports involving HIV-infected and uninfected men in the Multicenter Acquired Immune Deficiency Syndrome (AIDS) Cohort Study (MACS), prevalent subclinical coronary atherosclerosis was positively associated with elevated levels of monocyte activation biomarkers—sCD14, sCD163, CCL2—[18] and other biomarkers of inflammation (IL-6, intercellular cell adhesion molecule-1 (ICAM-1), and sTNF-αR1 and 2) [19], independent of traditional cardiovascular risk factors. Building on this prior work, the aim of the current study was to evaluate the relationship between levels of biomarkers of systemic inflammation (CRP, IL-6, sTNF-αR1 and 2), monocyte activation (CCL2, sCD163, sCD14), coagulation, and endothelial dysfunction (ICAM-1) with three measures of subclinical carotid atherosclerosis—focal carotid plaque, common carotid intima-media thickness (IMT) (CCA-IMT) and bifurcation-IMT—in the same well-characterized study population of HIVinfected and uninfected men

Summary

Introduction

HIV-infected individuals have a greater risk of subclinical atherosclerosis and cardiovascular disease (CVD) events, even among those with suppressed HIV RNA levels [1,2,3], compared to HIV-uninfected persons [4, 5]. Mechanisms underlying this increased HIV-associated risk may include HIV viremia, immune activation, metabolic side effects of antiretroviral therapy, and a higher prevalence of traditional CVD risk factors among HIV-infected persons [6,7,8]. We evaluated the associations of 10 biomarkers of systemic inflammation (CRP, IL-6, sTNF-αR1 and 2), monocyte activation (CCL2, sCD163, sCD14), coagulation (fibrinogen, D-dimer), and endothelial dysfunction (ICAM-1) with subclinical carotid atherosclerosis among participants in the Multicenter AIDS Cohort Study (MACS)

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