Plasma IL-6 levels are independently associated with atherosclerosis and mortality in HIV-infected individuals on suppressive antiretroviral therapy

Abstract

Objective To determine the associations of markers of immune activation with atherosclerosis and mortality, in participants with treated and suppressed HIV infection. Design Observational study of 149 HIV-infected participants with virologic suppression on antiretroviral therapy. Methods Cryopreserved mononuclear cells and plasma were used to evaluate markers of T cell and monocyte activation, inflammation and coagulopathy. Carotid artery intima-media thickness (CIMT) was measured by high-resolution ultrasound at the common, bifurcation and internal carotid regions. Associations of immunologic markers with CIMT and all-cause mortality were assessed using multivariable linear regression and Cox proportional hazards regression. Results The majority of participants were male (93%) and white (67%), median age of 48.5 years and median CD4+ T cell count of 522 cells/μL. The median baseline IMT was 1.0 mm. Over a median of 8.3 years of follow-up, 12 deaths occurred. In multivariate analysis, adjusted for traditional cardiovascular risk factors, higher monocyte CCR5 expression (5.4%, 95%CI [2.4–8.4], p=0.001) was associated with greater common carotid IMT. Higher plasma IL-6 was associated with greater bifurcation (8.0%, 95%CI [2.3–13.7], p=0.007) and overall mean IMT (5.2%, 95%CI [0.7–9.7], p=0.026). Finally, higher plasma IL-6 (HR 1.9, 95%CI [1.0–3.7], p=0.030), internal carotid (HR 4.1, 95%CI [1.2–13.7], p=0.022) and mean IMT (HR 5.2, 95%CI [1.2–22.1], p=0.026) were individually associated with all-cause mortality. Conclusions Higher monocyte CCR5 expression and plasma IL-6 were associated with atherosclerosis, independent of traditional cardiovascular risk factors. IL-6 and CIMT were individually associated with all-cause mortality. The impact of therapies targeting immune activation in CVD in treated HIV infection merits additional investigation.

Subclinical atherogenesis in patients with mild psoriasis: A role for IL-6?

“…35 Recently, circulating IL-6 was associated with atherosclerosis in HIV-positive patients independently of traditional risk factors for cardiovascular disease. 36 A link of subclinical atherogenesis with serum IL-6 in patients with mild psoriasis has not been previously reported.…”

Presence, Characteristics, and Prognostic Associations of Carotid Plaque Among People Living With HIV

“…There are also significant data in other diseases that share pathophysiological overlap with HIV. Specifically, the mechanisms of increased vascular risk in HIV are likely related to immune activation and an increase in inflammation 24, 25 and in other diseases where an immune activation and inflammation play a key pathophysiological role, an increase in incidental carotid plaque has been reported 26, 27 . For example, in rheumatoid arthritis and diabetes, data have described an increase in incidental carotid plaque 28, 29 .…”

Epidemiology of ischemic heart disease in HIV

“…Recent data have shown increased mortality with increasing levels of IL-6, soluble CD14 (sCD14), and d-dimer, 69 increased risk of serious non-AIDS conditions or death with increased IL-6 and d-dimer, 70 greater cIMT and higher mortality with higher IL-6, 71 increased risk of non-AIDS events with higher d-dimer, 72 increased microvascular dysfunction with elevated markers of inflammation, coagulation, and T-cell activation, 73 and greater prevalence of severe coronary stenosis and coronary artery calcification score with increased tumor necrosis factor α (TNFα). 74 Inflammation also impacts outcomes following CVD events.…”