The Relationship Between Impaired Coronary Endothelial Function and Systemic Markers of Inflammation in People Living With HIV

Abstract

Background: People with HIV (PWH) are at an increased risk of cardiovascular disease, partially believed to be related to chronically elevated systemic inflammation. Abnormal systemic endothelial function (SEF) and coronary endothelial function (CEF) develop early in atherogenesis and predict adverse events. It is unknown whether abnormal CEF is related to systemic inflammation in PWH. Methods:In this substudy of a prior randomized controlled trial in PWH without prior clinical coronary artery disease suppressed on antiretroviral therapy with CEF as a primary end point (N = 82), we investigated the associations between baseline serum markers of inflammation and adhesion and baseline CEF, assessed by noninvasive MRI measures of percentage changes in coronary blood flow and cross-sectional area during isometric handgrip exercise, and SEF using brachial ultrasound for flow-mediated dilation. We also evaluated whether baseline marker levels were associated with CEF after 8 weeks in the placebo group (N = 40).Results: CEF measures were abnormal at baseline, based on trial entry criteria. A higher value of CEF was directly associated with levels of interleukin 10, whereas CEF at baseline was inversely associated with E-selectin. Worse CEF at 8 weeks was directly associated with baseline tumor necrosis factor alpha, intercellular adhesion molecule 1, C-reactive protein, interferon gamma and sICAM-3. SEF at baseline or 8 weeks was not associated with any baseline markers. Conclusion:Coronary but not systemic endothelial dysfunction was significantly associated with select markers of inflammation and adhesion in PWH. Furthermore, CEF but not SEF at 8 weeks was associated with baseline levels of inflammation. Our findings suggest that abnormal CEF and systemic markers of inflammation are linked in PWH.

Large lessons learned from small vessels: coronary microvascular dysfunction in HIV

“…Cardiac MRI has been used more recently to evaluate CEF by measuring dynamic vasoreactive changes within the coronary artery induced by IHE [56][57][58]. Progressive changes in CEF has been linked to systemic markers of inflammation and adhesion in PWH, including TNFa, ICAM-1,CRP, IFNg, and sICAM-3 [59]. One study utilized a four-group design based on serostatus (PWH or PWOH) and CAD history (with and without CAD).…”