Inflammatory Markers Associated With Subclinical Coronary Artery Disease: The Multicenter AIDS Cohort Study

Abstract

BackgroundDespite evidence for higher risk of coronary artery disease among HIV+ individuals, the underlying mechanisms are not well understood. We investigated associations of inflammatory markers with subclinical coronary artery disease in 923 participants of the Multicenter AIDS Cohort Study (575 HIV+ and 348 HIV− men) who underwent noncontrast computed tomography scans for coronary artery calcification, the majority (n=692) also undergoing coronary computed tomography angiography.Methods and ResultsOutcomes included presence and extent of coronary artery calcification, plus computed tomography angiography analysis of presence, composition, and extent of coronary plaques and severity of coronary stenosis. HIV+ men had significantly higher levels of interleukin‐6 (IL‐6), intercellular adhesion molecule‐1, C‐reactive protein, and soluble‐tumor necrosis factor‐α receptor (sTNFαR) I and II (all P<0.01) and a higher prevalence of noncalcified plaque (63% versus 54%, P=0.02) on computed tomography angiography. Among HIV+ men, for every SD increase in log‐interleukin‐6 and log intercellular adhesion molecule‐1, there was a 30% and 60% increase, respectively, in the prevalence of coronary stenosis ≥50% (all P<0.05). Similarly, sTNFαR I and II in HIV+ participants were associated with an increase in prevalence of coronary stenosis ≥70% (P<0.05). Higher levels of interleukin‐6, sTNFαR I, and sTNFαR II were also associated with greater coronary artery calcification score in HIV+ men (P<0.01).ConclusionsHigher inflammatory marker levels are associated with greater prevalence of coronary stenosis in HIV+ men. Our findings underscore the need for further study to elucidate the relationships of inflammatory pathways with coronary artery disease in HIV+ individuals.

Frailty and subclinical coronary atherosclerosis: The Multicenter AIDS Cohort Study (MACS)

“…29, 36–38 Studies have shown that elevated inflammatory markers are prevalent in older, frail adults and may play an important role, directly or indirectly, in the pathogenesis of frailty. 13, 39 Also, prior work from MACS has demonstrated that higher levels of inflammatory markers and immune activation were associated with increased coronary atherosclerosis 21, 28 and with frailty 29 . However, we found that among HIV-uninfected men that the association of frailty with the presence of CAC and any coronary plaque remained statistically significant even after adjusting for these key inflammatory markers.…”

“…13, 21, 28, 29 Serum/plasma levels of inflammatory markers were measured in samples collected on the day of CT and stored at −70°C until the laboratory work was performed at the University of Vermont Laboratory for Clinical Biochemistry Research (Burlington) with assays described previously. 28 …”

“…Additionally, we performed a sensitivity analysis (Model 3) that further adjusted for inflammatory biomarkers that may mediate any association between frailty and CVD. 13, 21, 28 In the HIV-stratified subgroup, we additionally adjusted for HIV-related factors including CD4 cell count, presence of detectable HIV RNA, nadir CD4 cell count, history of AIDS, duration of HIV-infection, duration of HAART, and use of HAART (Model 4). Of note, body mass index and physical activity were not included as covariates in any models because weight and activity were part of the definition of the frailty phenotype.…”

“…HIV-infected individuals with frailty may be at particularly increased risk for CVD compared to similar HIV-uninfected individuals with frailty due to a greater burden of inflammatory markers associated with HIV-infection. 21 …”

The impact of long-term moderate and heavy alcohol consumption on incident atherosclerosis among persons living with HIV

“…Second, alcohol use is significantly associated with traditional CVD risk factors, including insulin resistance (type II diabetes; Míguez-Burbano et al, 2009), tobacco use (Cook et al, 2013), and illicit drug use (Conen et al, 2009; Cook et al, 2013; Chitsaz et al, 2013). Third, HIV-infection alone increases systemic inflammation (Shrestha et al, 2014; Bahrami et al, 2016) and immune activation (Maniar et al, 2013; Strategies for Management of Antiretroviral Therapy (SMART) Study Group et al, 2006; Hsue et al, 2009; Neuhaus et al, 2010), which are pathophysiologic responses that contribute to the risk for CVD (Bahrami et al, 2016; Hsu et al, 2016; Hansson, 2005). Chronic inflammation and immune activation can lead to the breakdown of the endothelial walls of the gastrointestinal tract, a process that leads to microbial translocation, which triggers further immune and pro-inflammatory responses (Maniar et al, 2013; D’Abramo et al, 2014; Klatt et al, 2013).…”