Arterial Inflammation in Patients With HIV

Study Questions:

What is the degree of arterial wall inflammation and monocyte and macrophage activation in patients with human immunodeficiency virus (HIV) compared with patients not infected with HIV with similar cardiac risk factors?

Methods:

This was a cross-sectional study of 81 participants investigated between November 2009 and July 2011 at the Massachusetts General Hospital. Twenty-seven participants with HIV without known cardiac disease underwent cardiac 18fluorine-2-deoxy-D-glucose-positron emission tomography (18F-FDG-PET) for assessment of arterial wall inflammation, and coronary computed tomography scanning for coronary artery calcium. The HIV group was compared with two separate non-HIV control groups. One control group (n = 27) was matched to the HIV group for age, sex, and Framingham risk score (FRS), and had no known atherosclerotic disease (non-HIV FRS-matched controls). The second control group (n = 27) was matched on sex and selected based on the presence of known atherosclerotic disease (non-HIV atherosclerotic controls). The main outcome measure was the degree of arterial inflammation, which was prospectively determined as the ratio of FDG uptake in the arterial wall of the ascending aorta to venous background as the target-to-background ratio (TBR).

Results:

Participants with HIV demonstrated well-controlled HIV disease (mean [standard deviation] CD4 cell count, 641 [288] cells/μl; median [interquartile range] HIV-RNA level, <48 [<48 to <48] copies/ml). All were receiving antiretroviral therapy (mean [SD] duration, 12.3 [4.3] years). The mean FRS was low in both HIV and non-HIV FRS-matched control participants (6.4; 95% confidence interval [CI], 4.8-8.0 vs. 6.6; 95% CI, 4.9-8.2; p = 0.87). Arterial inflammation in the aorta (aortic TBR) was higher in the HIV group versus the non-HIV FRS-matched control group (2.23; 95% CI, 2.07-2.40 vs. 1.89; 95% CI, 1.80-1.97; p < 0.001), but was similar compared with the non-HIV atherosclerotic control group (2.23; 95% CI, 2.07-2.40 vs. 2.13; 95% CI, 2.03-2.23; p = 0.29). Aortic TBR remained significantly higher in the HIV group versus the non-HIV FRS-matched control group after adjusting for traditional cardiovascular risk factors (p = 0.002) and in stratified analyses among participants with undetectable viral load, zero calcium, FRS of <10, a low-density lipoprotein cholesterol level of <100 mg/dl (<2.59 mmol/L), no statin use, and no smoking (all p ≤ 0.01). Aortic TBR was associated with sCD163 level (p = 0.04), but not with C-reactive protein (p = 0.65) or D-dimer (p = 0.08) among patients with HIV.

Conclusions:

The authors concluded that participants infected with HIV versus noninfected control participants with similar cardiac risk factors had signs of increased arterial inflammation.

Perspective:

This observation that HIV infection is associated with increased arterial inflammation, even among relatively young patients with HIV with low FRS and undetectable viremia, is concordant with the epidemiological observations that patients with HIV have a higher risk of stroke and myocardial infarction than patients without HIV. These findings advance our understanding of the unique pathophysiology and predilection to early increased cardiovascular disease among patients infected with HIV, and suggest that monocyte and macrophage activation could play a critical role in the early expression of subclinical atherosclerosis in patients with HIV. Future studies are indicated to investigate potential agents to reduce the proatherogenic activation of monocytes and macrophages with the goal of reducing risk of atherothrombosis in patients infected with HIV.

Clinical Topics: Noninvasive Imaging, Computed Tomography, Nuclear Imaging

Keywords: Inflammation, CD4 Lymphocyte Count, Fluorodeoxyglucose F18, Monocytes, Biological Markers, Cross-Sectional Studies, HIV Infections, Massachusetts, Macrophage Activation, Positron-Emission Tomography


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