Original Article
Pattern of arterial inflammation and inflammatory markers in people living with HIV compared with uninfected people

https://doi.org/10.1007/s12350-020-02522-5Get rights and content

Abstract

Study Design

To compare arterial inflammation (AI) between people living with HIV (PLWH) and uninfected people as assessed by 18F-Fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET).

Methods

We prospectively enrolled 20 PLWH and 20 uninfected people with no known cardiovascular disease and at least 3 traditional cardiovascular risk factors. All patients underwent 18F-FDG-PET/computed tomography (CT) of the thorax and neck. Biomarkers linked to inflammation and atherosclerosis were also determined. The primary outcome was AI in ascending aorta (AA) measured as mean maximum target-to-background ratio (TBRmax). The independent relationships between HIV status and both TBRmax and biomarkers were evaluated by multivariable linear regression adjusted for body mass index, creatinine, statin therapy, and atherosclerotic cardiovascular 10-year estimated risk (ASCVD).

Results

Unadjusted mean TBRmax in AA was slightly higher but not statistically different (P = .18) in PLWH (2.07; IQR 1.97, 2.32]) than uninfected people (2.01; IQR 1.85, 2.16]). On multivariable analysis, PLWH had an independent risk of increased mean log-TBRmax in AA (coef = 0.12; 95%CI 0.01,0.22; P = .032). HIV infection was independently associated with higher values of interleukin-10 (coef = 0.83; 95%CI 0.34, 1.32; P = .001), interferon-γ (coef. = 0.90; 95%CI 0.32, 1.47; P = .003), and vascular cell adhesion molecule-1 (VCAM-1) (coef. = 0.75; 95%CI: 0.42, 1.08, P < .001).

Conclusions

In patients with high cardiovascular risk, HIV status was an independent predictor of increased TBRmax in AA. PLWH also had an increased independent risk of IFN-γ, IL-10, and VCAM-1 levels.

Introduction

The use of antiretroviral therapy (ART) has dramatically reduced the AIDS-related mortality of people living with HIV (PLWH).1 Consequently, PLWH are facing a rising burden of chronic diseases, with cardiovascular disease being a major cause of non-AIDS-related morbidity and mortality.23 Several studies have shown that PLWH have a 1.5- to 2-fold increased risk of myocardial infarction4 (MI) and stroke5 compared with uninfected people. This excess cardiovascular risk is likely due to an interplay of several mechanisms including traditional risk factors, HIV-related factors such as chronic inflammation and immune activation,6 ART-related dyslipidemia,7 co-infections,8 and disparities in care delivery.9,10 Accordingly, cardiovascular risk prediction tools, derived from and used in the general population, may underestimate the risk of atherosclerosis-associated cardiovascular events in PLWH.11,1218F-Fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET) imaging can report on arterial inflammation associated with atherosclerosis, since glucose is the major substrate for macrophages resident in plaque.13,14 It has also been shown that 18F-FDG uptake in the ascending aorta is associated with future cardiovascular events and provides incremental information above traditional risk factors.15 Results from previous studies that have investigated patterns of arterial 18F-FDG-PET in PLWH and control subjects have been inconsistent, some studies suggesting an increased arterial inflammation in HIV patients,16 others refuting this association.17 These studies focused on patients with low cardiovascular risk; however, in clinical practice, many patients with HIV have a high cardiovascular risk based on conventional risk factors.3

Therefore, we performed a prospective study of subjects without known cardiovascular disease but with at least 3 traditional risk factors, with the main aim to compare arterial inflammation, as assessed by 18F-FDG-PET scan of ascending aorta (AA), descending aorta (DA), and carotid arteries (CAs) between PLWH and uninfected people.

Section snippets

Patients

Between November 2017 and July 2019, PLWH and control subjects were prospectively screened during routine outpatient clinic visits of the Department of Infectious Disease and of the Cardiology Unit at St. Orsola University Hospital of Bologna, respectively. They were then enrolled if they met the following inclusion criteria: (1) at least 3 of the following cardiovascular risk factors: (a) age > 55 years for men or > 65 for women, (b) hypertension, (c) hypercholesterolemia, (d) diabetes

Results

Of 65 patients screened, 40 (20 PLWH and 20 uninfected people) were enrolled (Supplemental Figure 1).

PLWH were more likely to be male and to have a history of hypercholesterolemia. They also had higher values of creatinine, total cholesterol, and LDL-cholesterol. Patients with no HIV had a higher body mass index (Table 1). The majority of PLWH showed well-controlled HIV disease (Supplemental Table 2). The minimum ART duration was 3.2 years.

Discussion

The main findings of this prospective study of 40 individuals with high cardiovascular risk and no known cardiovascular disease are as follows: (1) HIV infection was identified as an independent predictor of increased AA wall inflammation as assessed by 18 FDG-PET, and (2) HIV infection was also found to be an independent predictor of increased levels of inflammatory cytokines such as IL-10 and INF-γ, as well as of markers of activated endothelium such as VCAM-1.

Several studies have shown that

Conclusions

In this prospective, cross-sectional study of patients with a moderate–high cardiovascular risk profile, HIV status was identified as an independent predictor of increased AA wall inflammation. PLWH also had an independent risk of increased level of IFN-γ, IL-10, and VCAM-1.

New Knowledge Gained

In patients with moderate-to-high cardiovascular risk, HIV status was an independent predictor of increased ascending aortic wall inflammation as assessed by 18F-Fluorodeoxyglucose-positron emission tomography imaging.

Disclosure

Dr TP has received speaker fee from Abbott. FS has received speaker fees from Abbott Vascular, Eli Lilly, AstraZeneca, Boston Scientific, Medtronic Inc, The Medicines Company, Biotronik, and St. Jude, outside the submitted work. The remaining authors report no financial relationships or conflicts of interest regarding the content herein.

Funding

Open Access funding provided by Alma Mater Studiorum - Università di Bologna.

This work was supported by Department of Experimental, Diagnostic and Speciality Medicine - DIMES, University of Bologna and by Fanti Melloni Foundation. JHFR is part-supported by the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, HEFCE, the EPSRC and the Wellcome Trust. JMT is supported by the Wellcome Trust (211100/Z/18/Z) and the Cambridge British Heart Foundation Centre of Research

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