Original ArticlePattern of arterial inflammation and inflammatory markers in people living with HIV compared with uninfected people
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
References (31)
- et al.
Patterns of cardiovascular mortality for HIV-infected adults in the United States: 1999 to 2013
Am J Cardiol
(2016) - et al.
Imaging atherosclerotic plaque inflammation by fluorodeoxyglucose with positron emission tomography: ready for prime time?
J Am Coll Cardiol.
(2010) - et al.
Measurement of arterial activity on routine FDG PET/CT images improves prediction of risk of future CV events
JACC Cardiovasc Imaging.
(2013) - et al.
HIV infection and arterial inflammation assessed by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET): a prospective cross-sectional study
J Nucl Cardiol
(2015) - et al.
Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a multicenter fluorodeoxyglucose-positron emission tomography/computed tomography feasibility study
J Am Coll Cardiol.
(2013) - et al.
Simvastatin attenuates plaque inflammation—evaluation by fluorodeoxyglucose positron emission tomography
J Am Coll Cardiol
(2006) - et al.
Arterial inflammation in young patients with human immunodeficiency virus infection: a cross-sectional study using F-18 FDG PET/CT
J Nucl Cardiol
(2019) - et al.
Prevalence and risk factors of carotid vessel wall inflammation in coronary artery disease patients: FDG-PET and CT imaging study
JACC Cardiovasc Imaging
(2011) - et al.
Detection of atherosclerotic inflammation by (68)Ga-DOTATATE PET compared to [ (18)F]FDG PET imaging
J Am Coll Cardiol.
(2017) - et al.
18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial
Lancet
(2014)
Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies
The Lancet HIV
HIV infection and incidence of cardiovascular diseases: an analysis of a large healthcare database
J Am Heart Assoc
HIV infection and the risk of acute myocardial infarction
JAMA Intern Med
HIV status and the risk of ischemic stroke among men
Neurology
HIV infection, inflammation, immunosenescence, and aging
Annu Rev Med
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