Arterial inflammation in patients with HIV

Abstract

Context: Cardiovascular disease is increased in patients with human immunodeficiency virus (HIV), but the specific mechanisms are unknown.

Objective: To assess arterial wall inflammation in HIV, using 18fluorine-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET), in relationship to traditional and nontraditional risk markers, including soluble CD163 (sCD163), a marker of monocyte and macrophage activation.

Design, setting, and participants: 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 18F-FDG-PET for assessment of arterial wall inflammation and coronary computed tomography scanning for coronary artery calcium. The HIV group was compared with 2 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).

Main outcome measure: Arterial inflammation 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 [SD] 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% CI, 4.8-8.0 vs 6.6; 95% CI, 4.9-8.2; P = .87). Arterial inflammation in the aorta (aortic TBR) was higher in the HIV group vs 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 < .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 = .29). Aortic TBR remained significantly higher in the HIV group vs the non-HIV FRS-matched control group after adjusting for traditional cardiovascular risk factors (P = .002) and in stratified analyses among participants with undetectable viral load, zero calcium, FRS of less than 10, a low-density lipoprotein cholesterol level of less than 100 mg/dL (<2.59 mmol/L), no statin use, and no smoking (all P ≤ .01). Aortic TBR was associated with sCD163 level (P = .04) but not with C-reactive protein (P = .65) or D-dimer (P = .08) among patients with HIV.

Conclusion: Participants infected with HIV vs noninfected control participants with similar cardiac risk factors had signs of increased arterial inflammation, which was associated with a circulating marker of monocyte and macrophage activation.

Figure 1

Figure 1A: The FDG uptake was measured from a point distal to the origin of coronary vessels to avoid myocardial spill over. ¹⁸F-FDG-PET/CT imaging of the ascending thoracic aorta was done according to validated, reproducible methods. To determine the TBR of the aorta, regions of interest are drawn around the aorta in the axial position. This is repeated along the length of the aorta (every 5 mm along the long axis of the vessel). A mean arterial SUV is derived from the serial axial SUV measurements (1.71 in this example). The venous background SUV is derived from 10 measurements obtained in the superior vena cava (SVC). Thereafter, a target-to-background-ratio (TBR) is calculated by dividing the mean arterial SUV by the mean venous SUV. In this example, the TBR is 3.42. Figure 1B: Representative axial and coronal images of the aorta on FDG-PET: There is increased aortic PET-FDG uptake (red coloration) in an HIV-infected subject (age = 42 years, TBR = 3.42) compared with a non-HIV FRS-matched control subject (age = 43 years, TBR = 2.01). Neither subject had known heart disease. For each subject, the FRS was low at 2, and calcium was not present on the cardiac CT. Neither subject was receiving a statin. A=Anterior-Posterior orientation, F=Foot-Head orientation.

Figure 2

Linear regression of Aortic Target-to-Background Ratio versus the natural log of sCD163 among HIV-infected patients with undetectable Viral Load (n=21) (rho = 0.44, P=0.03).