Resveratrol treatment does not reduce arterial inflammation in males at risk of type 2 diabetes: a randomized crossover trial

Purpose Resveratrol has shown promising anti-inflammatory effects in in vitro and animal studies. We aimed to investigate this effect on arterial inflammation in vivo. Methods This was an additional analysis of a double-blind randomized crossover trial which included eight male subjects with decreased insulin sensitivity who underwent an 18F-fluoroxyglucose (18F-FDG) PET/CT after 34 days of placebo and resveratrol treatment (150 mg/day). 18F-FDG uptake was analyzed in the carotid arteries and the aorta, adipose tissue regions, spleen, and bone marrow as measures for arterial and systemic inflammation. Maximum target-to-background ratios (TBRmax) were compared between resveratrol and placebo treatment with the non-parametric Wilcoxon signed-rank test. Median values are shown with their interquartile range. Results Arterial 18F-FDG uptake was non-significantly higher after resveratrol treatment (TBRmax all vessels 1.7 (1.6–1.7)) in comparison to placebo treatment (1.5 (1.4–1.6); p=0.050). Only in visceral adipose tissue, the increase in 18F-FDG uptake after resveratrol reached statistical significance (p=0.024). Furthermore, CRP-levels were not significantly affected by resveratrol treatment (p=0.091). Conclusions Resveratrol failed to attenuate arterial or systemic inflammation as measured with 18F-FDG PET in subjects at risk of developing type 2 diabetes. However, validation of these findings in larger human studies is needed.

Time-Related Aortic Inflammatory Response, As Assessed With 18F-FDG PET/CT, in Patients Hospitalized With Severe or Critical COVID-19 The COVAIR Study

AimArterial involvement has been implicated in the coronavirus disease of 2019 (COVID-19). 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is a valuable tool for the assessment of disease severity in different types of vasculitis and is a predictor of outcome. We sought to prospectively assess the presence of aortic inflammation and its time-dependent trend by measuring the 18-FDG uptake in PET/CT in patients with severe or critical COVID-19.Methods In this pilot case control study, we recruited 20 patients, who were admitted with severe or critical COVID-19 illness. Patients underwent imaging between 20 to 120 days after hospital admission. Ten age- and sex-matched individuals with prior history of malignancy but free of active disease served as the control group. Arterial inflammation was assessed by measuring 18-FDG uptake in PET/CT and calculating aortic target to blood ratio (TBR).ResultsThere was a significant correlation between aortic TBR values and time distance from diagnosis to 18F-FDG PET/CT scan (-rho- =0.547, p=0.015) even after adjustment for confounders (p=0.002). Patients who were scanned less than 60 days (median) from diagnosis had significantly higher TBR values compared to patients examined more than 60 days post-diagnosis (1.55 [1.47-1.61] vs 1.40 [1.33-1.45], respectively, p=0.013).ConclusionThis is the first study suggesting that 18 FDG PET/CT imaging could be used for assessment of arterial inflammation in patients with severe/critical COVID-19. These findings may have important implications for the understanding of the pathophysiology and the course of the disease and for improving our preventive and therapeutic strategies.

Association of arterial inflammation as assessed by 18FDG-PET/CT and chemotherapy, in patients with lymphoma

Introduction Inflammation plays a pivotal role in the pathogenesis of both Hodgkin and non-Hodgkin's lymphoma and it has been shown recently that disease burden is associated with arterial inflammation. This can be captured by 18F-fluorodeoxyglucose (18F-FDG) positron emission computed tomography (PET/CT), a commonly used imaging modality for staging and treatment response of patients with lymphoma, which has also been established as a reliable marker of arterial inflammation. Chemotherapy remains the cornerstone of lymphoma treatment; however, its direct effect on arterial 18F-FDG uptake is unknown. Purpose To investigate the effect of chemotherapy on arterial inflammation using 18F-FDG PET/CT imaging, in patients with lymphoma. Methods Sixty-six patients (22 male, mean age 56 years) with Hodgkin (n=34) or non-Hodgkin's lymphoma (n=32) underwent 18F-FDG PET/CT imaging at baseline, during and after completion of chemotherapy as part of their routine protocol. Arterial 18F-FDG uptake was assessed at the same time points by measuring the metabolic activity (maximum standardized uptake value (SUVmax) and the arterial target to background ratio (TBR)) of the aortic wall along the entire aorta. Patients with Hodgkin lymphoma underwent therapy with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The interim scan was performed at 1 to 3 days prior to initiating the 3rd chemotherapy cycle. Patients with non-Hodgkin's lymphoma underwent therapy with cyclophosphamide, doxorubicin, vincristine and prednisone+rituximab (R-CHOP). Their interim scan was obtained at 2 weeks post the 4th chemotherapy cycle. All patients were re-assessed with 18F-FDG PET/CT imaging 6–8 weeks after chemotherapy completion. Results Baseline total aortic TBR was not associated with the presence of diabetes, dyslipidaemia or smoking (p=0.258, p=0.302 and p=0.452, respectively). Twelve patients were receiving statin therapy, however, there was no significant difference in baseline aortic TBR between patients on statins and patients who were not on statin therapy (p=0.265). In the whole study sample, the index vessel TBR progressively decreased by 0.17 from baseline to 6 weeks following the end of treatment (p=0.013 ANOVA with Bonferroni Correction, Figure 1). Conclusion Our findings suggest that arterial inflammation is reduced during and post chemotherapy in patients with lymphoma. In addition, they indicate a potential role of molecular imaging in cardio-oncology, providing a longitudinal evaluation of disease severity and its consequences to the arterial wall metabolic activity with a single examination. FUNDunding Acknowledgement Type of funding sources: None.

[18F]FDG and [18F]NaF as PET markers of systemic atherosclerosis progression: A longitudinal descriptive imaging study in patients with type 2 diabetes mellitus

Background While [18F]-fluordeoxyglucose ([18F]FDG) uptake is associated with arterial inflammation, [18F]-sodium fluoride ([18F]NaF) is a marker for arterial micro-calcification. We aimed to investigate the prospective correlation between both PET markers over time and whether they are prospectively ([18F]FDG) and retrospectively ([18F]NaF) related to progression of systemic arterial disease in a longitudinal study in patients with type 2 diabetes mellitus (T2DM). Methods Baseline [18F]FDG PET/Low Dose (LD) Computed Tomography (CT) scans of ten patients with early T2DM without cardiovascular history (70% men, median age 63 years) were compared with five-year follow-up [18F]NaF/LDCT scans. Systemic activity was expressed as mean target-to-background ratio (meanTBR) by dividing the maximal standardized uptake value (SUVmax) of ten arteries by SUVmean of the caval vein. CT-assessed macro-calcifications were scored visually and expressed as calcified plaque (CP) score. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (PWV). Five-year changes were expressed absolutely with delta (Δ) and relatively with %change. Results Baseline meanTBR[18F]FDG was strongly correlated with five-year follow-up meanTBR[18F]NaF (r = 0.709, P = .022). meanTBR[18F]NaF correlated positively with ΔCPscore, CPscore at baseline, and follow-up (r = 0.845, P = .002 and r = 0.855, P = .002, respectively), but not with %change in CPscore and PWV. Conclusion This proof-of-concept study demonstrated that systemic arterial inflammation is an important pathogenetic factor in systemic arterial micro-calcification development.

Pericoronary and periaortic adipose tissue density are associated with inflammatory disease activity in Takayasu arteritis and atherosclerosis

Aims To examine pericoronary (PCAT) and periaortic (PAAT) adipose tissue density on coronary computed tomography angiography (CCTA) for assessing arterial inflammation in Takayasu arteritis (TAK) and atherosclerosis. Methods and results PCAT and PAAT density was measured in coronary (n = 1016) and aortic (n = 108) segments from 108 subjects (TAK+coronary artery disease (CAD), n = 36; TAK, n = 18; atherosclerotic CAD, n = 32; matched controls, n = 22). Median PCAT and PAAT densities varied between groups (mPCAT: p < 0.0001; PAAT: p = 0.0002). PCAT density was 7.01 ± SEM 1.78 Hounsfield Unit (HU) higher in coronary segments from TAK+CAD patients than stable CAD patients (p = 0.0002), and 8.20 ± SEM 2.04 HU higher in TAK patients without CAD than controls (p = 0.0001). mPCAT density was correlated with Indian Takayasu Clinical Activity Score (r = 0.43, p = 0.001) and C-reactive protein (r = 0.41, p < 0.0001), and was higher in active versus inactive TAK (p = 0.002). mPCAT density above -74 HU had 100% sensitivity and 95% specificity for differentiating active TAK from controls (AUC=0.99 [95% CI 0.97-1]). The association of PCAT density and coronary arterial inflammation measured by 68Ga-DOTATATE positron emission tomography equated to an increase of 2.44 ± SEM 0.77 HU in PCAT density for each unit increase in 68Ga-DOTATATE maximum tissue-to-blood ratio (p = 0.002). These findings remained in multivariable sensitivity analyses adjusted for potential confounders. Conclusions PCAT and PAAT density are higher in TAK than atherosclerotic CAD or controls, and are associated with clinical, biochemical and PET markers of inflammation. Owing to excellent diagnostic accuracy, PCAT density could be useful as a clinical adjunct for assessing disease activity in TAK.

Home-Based Exercise Training in Childhood-Onset Takayasu Arteritis: A Multicenter, Randomized, Controlled Trial

IntroductionChildhood-onset Takayasu Arteritis (c-TA) is a rare, large-vessel vasculitis seen in children that could predisposing patients to a high risk of mortality. Exercise has the potential to improve overall health in several diseases, but evidence remains scant in c-TA. The main objective of this study was to investigate the safety and potential therapeutic effects of exercise in c-TA.MethodsThis was a 12-week, multicenter, randomized, controlled trial, to test the effects of a home-based, exercise intervention vs. standard of care in c-TA patients in remission. The primary outcomes were arterial inflammation, assessed by [18F] FDG- PET/MRI and systemic inflammatory markers. Secondary outcomes included, physical activity levels, functionality, body composition, disease-related parameters, and quality of life.ResultsThirty-seven patients were assessed for eligibility, which represents the total number of c-TA patients being followed by the three specialized medical ambulatory services in Sao Paulo. After exclusions, fourteen c-TA patients (71.4% females) aged 12-25 years were randomly allocated into exercised (n=5) and non-exercised groups (n=9). Exercise did not exacerbate arterial inflammation. In fact, exercised patients had a reduction in the frequency of vessel segments with severe inflammation, whereas the non-exercised patients had an opposite response (P=0.007). Greater improvements in visceral fat, steps per day, functionality and physical component SF-36 were observed in the exercised patients (P ≤ 0.05).ConclusionsExercise is safe and may improve visceral fat, physical activity levels, functionality, and physical component SF-36 in c-TA patients. Thus, exercise arises as a novel, evidence-based intervention to improve general health in c-TA.Clinical Trial Registrationhttps://www.clinicaltrials.gov/ct2/show/NCT03494062?term=NCT03494062&draw=2&rank=1, identifier NCT03494062.

Pattern of arterial inflammation and inflammatory markers in people living with HIV compared with uninfected people

Study Design To compare arterial inflammation (AI) between people living with HIV (PLWH) and uninfected people as assessed by 18F-Fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET). Methods We prospectively enrolled 20 PLWH and 20 uninfected people with no known cardiovascular disease and at least 3 traditional cardiovascular risk factors. All patients underwent 18F-FDG-PET/computed tomography (CT) of the thorax and neck. Biomarkers linked to inflammation and atherosclerosis were also determined. The primary outcome was AI in ascending aorta (AA) measured as mean maximum target-to-background ratio (TBRmax). The independent relationships between HIV status and both TBRmax and biomarkers were evaluated by multivariable linear regression adjusted for body mass index, creatinine, statin therapy, and atherosclerotic cardiovascular 10-year estimated risk (ASCVD). Results Unadjusted mean TBRmax in AA was slightly higher but not statistically different (P = .18) in PLWH (2.07; IQR 1.97, 2.32]) than uninfected people (2.01; IQR 1.85, 2.16]). On multivariable analysis, PLWH had an independent risk of increased mean log-TBRmax in AA (coef = 0.12; 95%CI 0.01,0.22; P = .032). HIV infection was independently associated with higher values of interleukin-10 (coef = 0.83; 95%CI 0.34, 1.32; P = .001), interferon-γ (coef. = 0.90; 95%CI 0.32, 1.47; P = .003), and vascular cell adhesion molecule-1 (VCAM-1) (coef. = 0.75; 95%CI: 0.42, 1.08, P < .001). Conclusions In patients with high cardiovascular risk, HIV status was an independent predictor of increased TBRmax in AA. PLWH also had an increased independent risk of IFN-γ, IL-10, and VCAM-1 levels.