18FDG PET-CT imaging detects arterial inflammation and early atherosclerosis in HIV-infected adults with cardiovascular disease risk factors

Abstract

Background: Persistent vascular inflammation has been implicated as an important cause for a higher prevalence of cardiovascular disease (CVD) in HIV-infected adults. In several populations at high risk for CVD, vascular 18Fluorodeoxyglucose (18FDG) uptake quantified using 3D-positron emission-computed tomography (PET-CT) has been used as a molecular level biomarker for the presence of metabolically active proinflammatory macrophages in rupture-prone early atherosclerotic plaques. We hypothesized that 18FDG PET-CT imaging would detect arterial inflammation and early atherosclerosis in HIV-infected adults with modest CVD risk.

Methods: We studied 9 HIV-infected participants with fully suppressed HIV viremia on antiretroviral therapy (8 men, median age 52 yrs, median BMI 29 kg/m2, median CD4 count 655 cells/μL, 33% current smokers) and 5 HIV-negative participants (4 men, median age 44 yrs, median BMI 25 kg/m2, no current smokers). Mean Framingham Risk Scores were higher for HIV-infected persons (9% vs. 2%, p < 0.01). 18FDG (370 MBq) was administered intravenously. 3D-PET-CT images were obtained 3.5 hrs later. 18FDG uptake into both carotid arteries and the aorta was compared between the two groups.

Results: Right and left carotid 18FDG uptake was greater (P < 0.03) in the HIV group (1.77 ±0.26, 1.33 ±0.09 target to background ratio (TBR)) than the control group (1.05 ± 0.10, 1.03 ± 0.05 TBR). 18FDG uptake in the aorta was greater in HIV (1.50 ±0.16 TBR) vs control group (1.24 ± 0.05 TBR), but did not reach statistical significance (P = 0.18).

Conclusions: Carotid artery 18FDG PET-CT imaging detected differences in vascular inflammation and early atherosclerosis between HIV-infected adults with CVD risk factors and healthy HIV-seronegative controls. These findings confirm the utility of this molecular level imaging approach for detecting and quantifying glucose uptake into inflammatory macrophages present in metabolically active, rupture-prone atherosclerotic plaques in HIV infected adults; a population with increased CVD risk.

Figure 1

Representative co-registered 3-dimensional positron emission (PET) and contrast-enhanced computed tomography (CT) images of the right carotid artery of a healthy HIV-seronegative control male (Panel 1), and an HIV infected man with CVD risk factors (Panel 2). Transverse, sagittal, and coronal contrast CT images (A) and PET ¹⁸FDG uptake images (B) along with the corresponding carotid ultrasound images for these two men are shown. The anterior wall of the right carotid artery (upper portion of the carotid ultrasound image) is indicated with a yellow arrow and the posterior wall with a red arrow (lower portion of the image). In the HIV infected man (Panel 2), ultrasound imaging detected increased carotid artery intima media thickness in both the anterior and posterior walls and a non-obstructive plaque in the posterior wall of the right carotid artery. In the healthy control male (Panel 1), the intima media thickness was normal and no plaques were present in the anterior or posterior walls of the right carotid artery. Carotid PET imaging detected regions of higher ¹⁸FDG uptake (red nodules in blue, red and green ovals) in the HIV infected man (Panel 2B), while less ¹⁸FDG uptake was detected in the carotid artery of the healthy control male (Panel 1B).

Figure 2

Right and left carotid¹⁸FDG uptake (Mean ± SE) was greater (P < 0.03) in the HIV group (n = 9; 1.77 ± 0.26, 1.33 ± 0.09 target to background ratio-max (TBR_max)) than in the control group (n = 5; 1.05 ± 0.10, 1.03 ±0.05 TBR_max). Aorta ¹⁸FDG uptake tended (P = 0.18) to be greater in HIV (n = 5; 1.50 ±0.16 TBR_max) vs control group (n = 4; 1.24 ±0.05 TBR_max).