Association of Soluble Markers of Inflammation With Peri-coronary Artery Inflammation in People With and Without HIV Infection and Without Cardiovascular Disease

Abstract

Background Inflammation is linked to elevated cardiovascular disease (CVD) risk in people with HIV (PWH) on antiretroviral therapy (ART). Fat attenuation index (FAI) is a measure of peri-coronary inflammation that independently predicts CVD risk in HIV-uninfected persons. Whether FAI is associated with soluble inflammatory markers is unknown. Methods Plasma levels of inflammatory markers were measured in 58 PWH and 16 controls without current symptoms nor prior known CVD who underwent coronary computed tomography angiography and had FAI measurements. A cross-sectional analysis was performed, and associations of markers with FAI values of the right coronary artery (RCA) and left anterior descending artery (LAD) were assessed using multivariable regression models adjusted for potential confounders age, sex, race, low-density lipoprotein cholesterol, body mass index, and use of lipid-lowering medication. Results Several inflammatory markers had significant associations with RCA or LAD FAI in adjusted models, including sCD14, sCD163, TNFR-I, and TNFR-II, CCL5, CX3CL1, IP-10. Conclusions The associations between indices of systemic and peri-coronary inflammation are novel and suggest that these systemic markers and FAI together are promising noninvasive biomarkers that can be applied to assess asymptomatic CVD in people with and without HIV, and also may be useful tools to evaluate effects of anti-inflammatory interventions.

HIV-Associated Cardiovascular Disease Pathogenesis: An Emerging Understanding Through Imaging and Immunology

“…144,145 More recently, several soluble markers of inflammation (sCD14, sCD163, TNFR-I, TNFR-II, CCL [C-C motif chemokine ligand] 5, CX3CL1 [C-X3-C motif chemokine ligand 1], and IL-10) have shown associations with pericoronary inflammation in HIV. 146 Similarly, within HIV-endemic areas in SSA, particularly in Uganda, there was a clear association between inflammation and subclinical CAD in adult women, both with and without HIV. 57 hsCRP (high-sensitivity C-reactive protein) showed a positive correlation with traditional cardiometabolic risk factors in PLWH.…”

Pathophysiology and Clinical Management of Dyslipidemia in People Living with HIV: Sailing through Rough Seas

“…In HIV infection, the subpopulation of CD14+/CD16+ pro-inflammatory monocytes predominates, as indicated by the increased ratio of CD4+/CD8+, expressing activation markers and molecules presenting antigens such as CD38, CD69, CD11b, and CD86, resulting in tissue migration and turnover to cholesterol-overloaded dysfunctional macrophages. These so-called foam cells found in adipose tissue, together with activated CD4 and CD8 T cells and NK and NKT cells, result in the production of inflammatory mediators such chemokines CCL2, CCL5 and CX3CL1, c-reactive protein (CRP), IL-6, IL-8, IL-1β, IL-18, IL-2, IFN-γ, IL-17A, and TNF-α, altering adipose cell function, impairing reverse cholesterol transport, and reducing HDL and apolipoprotein A-I (apoA-I) particle numbers [47][48][49][50][51][52]. Furthermore, these foam cells are highly concentrated in NADPH oxidases, enzymes that, under a hyperlipidemic environment, up-regulate and form oxLDL, inducing endoplasmic reticulum (ER) stress and the production of reactive oxygen species (ROS), exacerbating both inflammation and foam cell formation, which are strong promoters of atherogenesis [53][54][55].…”