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ObjectivesThis study assessed 5 frequently applied arterial 18fluorodeoxyglucose (18F-FDG) uptake metrics in healthy control subjects, those with risk factors and patients with cardiovascular disease (CVD), to derive uptake thresholds in each subject group. Additionally, we tested the reproducibility of these measures and produced recommended sample sizes for interventional drug studies.Background18F-FDG positron emission tomography (PET) can identify plaque inflammation as a surrogate endpoint for vascular interventional drug trials. However, an overview of 18F-FDG uptake metrics, threshold values, and reproducibility in healthy compared with diseased subjects is not available.Methods18F-FDG PET/CT of the carotid arteries and ascending aorta was performed in 83 subjects (61 ± 8 years) comprising 3 groups: 25 healthy controls, 23 patients at increased CVD risk, and 35 patients with known CVD. We quantified 18F-FDG uptake across the whole artery, the most-diseased segment, and within all active segments over several pre-defined cutoffs. We report these data with and without background corrections. Finally, we determined measurement reproducibility and recommended sample sizes for future drug studies based on these results.ResultsAll 18F-FDG uptake metrics were significantly different between healthy and diseased subjects for both the carotids and aorta. Thresholds of physiological 18F-FDG uptake were derived from healthy controls using the 90th percentile of their target to background ratio (TBR) value (TBRmax); whole artery TBRmax is 1.84 for the carotids and 2.68 in the aorta. These were exceeded by >52% of risk factor patients and >67% of CVD patients. Reproducibility was excellent in all study groups (intraclass correlation coefficient >0.95). Using carotid TBRmax as a primary endpoint resulted in sample size estimates approximately 20% lower than aorta.ConclusionsWe report thresholds for physiological 18F-FDG uptake in the arterial wall in healthy subjects, which are exceeded by the majority of CVD patients. This remains true, independent of readout vessel, signal quantification method, or the use of background correction. We also confirm the high reproducibility of 18F-FDG PET measures of inflammation. Nevertheless, because of overlap between subject categories and the relatively small population studied, these data have limited generalizability until substantiated in larger, prospective event-driven studies. (Vascular Inflammation in Patients at Risk for Atherosclerotic Disease; NTR5006)

Collectively, these findings strengthen the case for a chronically affected haematopoietic system, potentially driving the low-grade inflammatory state in patients with atherosclerosis.

Background HIV infection is associated with a high risk of cardiovascular diseases (CVD) and increased arterial inflammation. In HIV, inflammation is also increased within lymph nodes (LN), tissues known to harbor the virus even among treated and suppressed individuals. We tested the hypothesis that arterial inflammation is linked to HIV disease activity and to inflammation within HIV-infected tissues (LN). Methods Seventy-four individuals were studied: 45 HIV-infected individuals and 29 uninfected controls. Arterial and LN inflammation were measured using 18F-fluorodeoxyglucose positron emission tomography, (FDG-PET). Detailed immunophenotyping was performed, along with measurement of viral activity/persistence, and circulating inflammatory biomarkers. Results Median age was 53 years, 100% male. Lymph node inflammation was higher in HIV-infected individuals and correlated with markers of viral disease activity (viral load, CD8+ T cells, CD4/CD8 ratio) and CD4+ T cell activation. Arterial inflammation was modestly increased in HIV-infected individuals and was positively correlated with circulating inflammatory biomarkers (hsCRP, IL-6) and activated monocytes (CD14dimCD16+; non-classical) but not to markers of HIV. While LN and arterial inflammation were increased in HIV, inflammatory activity in these tissues was not related (r=0.09, p=0.56). Conclusion While LN and to a lesser degree, the arterial wall are inflamed in HIV, inflammation in these tissues is not closely linked. Namely, measures of HIV disease activity strongly associate with LN inflammation but not arterial inflammation. These data suggest that LN and arterial inflammation do not share underlying pathways of immune activation and suggests therapeutic interventions that reduce viral disease activity may not predictably reduce arterial inflammation in HIV or its down-stream consequence (CVD).