Isabella Scotti

Non-invasive imaging of vascular inflammation

In large-vessel vasculitides, inflammatory infiltrates may cause thickening of the involved arterial vessel wall leading to progressive stenosis and occlusion. Dilatation, aneurysm formation, and thrombosis may also ensue. Activated macrophages and T lymphocytes are fundamental elements in vascular inflammation. The amount and density of the inflammatory infiltrate is directly linked to local disease activity. Additionally, patients with autoimmune disorders have an increased cardiovascular (CV) risk compared with age-matched healthy individuals as a consequence of accelerated atherosclerosis. Molecular imaging techniques targeting activated macrophages, neovascularization, or increased cellular metabolic activity can represent effective means of non-invasive detection of vascular inflammation. In the present review, novel non-invasive imaging tools that have been successfully tested in humans will be presented. These include contrast-enhanced ultrasonography, which allows detection of neovessels within the wall of inflamed arteries; contrast-enhanced CV magnetic resonance that can detect increased thickness of the arterial wall, usually associated with edema, or mural enhancement using T2 and post-contrast T1-weighted sequences, respectively; and positron emission tomography associated with radio-tracers such as [18F]-fluorodeoxyglucose and the new [11C]-PK11195 in combination with computed tomography angiography to detect activated macrophages within the vessel wall. Imaging techniques are useful in the diagnostic work-up of large- and medium-vessel vasculitides, to monitor disease activity and the response to treatments. Finally, molecular imaging targets can provide new clues about the pathogenesis and evolution of immune-mediated disorders involving arterial vessels.

Relation between characteristics of carotid atherosclerotic plaques and brain white matter hyperintensities in asymptomatic patients

White matter hyperintensities (WMH) can be incidentally found in patients with carotid atherosclerosis on brain magnetic resonance imaging (MRI). We investigated the relationship between WMH and characteristics of carotid plaques in asymptomatic patients without indication for carotid revascularization. We prospectively screened 235 consecutive patients with carotid stenosis <70%. After excluding patients with confounding causes of cerebral damage, 67 asymptomatic patients underwent carotid computed tomography angiography (CTA), contrast-enhanced ultrasound and brain MRI. Number and quantitative measurement of volume of WMH were associated with history of resistant hypertension, degree of stenosis (Doppler) and presence of an ulcerated plaque at CTA (p < 0.05). At multivariate regression analysis, resistant hypertension was independently associated with both number and volume of WMH, presence of an ulcer with number of WMH and degree of stenosis with WMH volume (p < 0.05), although WMH were equally distributed in both hemispheres irrespectively of plaque side. In conclusion, in asymptomatic patients with carotid plaques <70%, a higher burden of WMHs is associated with history of resistant hypertension that could be the expression of microvascular damage. Stenosis severity and presence of plaque ulceration are also associated with WMH burden although their causative relation is not supported by the bilateral distribution of WMH.

Carotid artery plaque uptake of 11C-PK11195 inversely correlates with circulating monocytes and classical CD14++CD16− monocytes expressing HLA-DR

Background We explored the relation between blood concentrations of monocyte/lymphocyte subsets and carotid artery plaque macrophage content, measured by positron emission tomography (PET) with 11C-PK11195. Methods and results In 9 patients with carotid plaques we performed 11C-PK11195-PET/computed tomography angiography imaging and measurement of absolute concentrations and frequencies of circulating monocytes and T-cell subsets. Plaque standardized uptake value (SUV) for 11C-PK11195 was negatively correlated with concentrations of total monocytes (r = −0.58, p = 0.05) and CD14++CD16−HLA-DR+ classical subset (r = −0.82, p = 0.005). These correlations hold true also in relation to plaque target to background ratio. No correlation was observed between plaque SUV and CD3+T lymphocytes, CD4+T lymphocytes nor with activated CD3+CD4+T cells expressing HLA-DR. Conclusions We first demonstrated a reduction in the absolute concentration of monocytes and particularly in classical monocytes expressing HLA-DR in the presence of an increased uptake of 11C-PK11195 in carotid plaques. The present work, despite being a pilot study comprising only a small number of subjects provides new insights in the search for specific cellular biomarkers with potential diagnostic and prognostic value in patients with a known carotid plaque.

SAT0302 Active Systemic Lupus Erythematosus Associates with Carotid Intima-Media Thickness Progression

Background A relationship between systemic inflammation and increased cardiovascular risk is often postulated. Simple and affordable clinical predictors of increased cardiovascular risk in patients with autoimmune disease, however, are not yet available in the clinical practice. Objectives To address the role of clinical, serological markers of disease activity, and of classical cardiovascular risk factors (CVRF) in predicting the carotid intima-media thickness (c-IMT) progression at 5 years (Δc-IMT) in patients with the prototypic autoimmune disease systemic lupus erythematosus (SLE). Methods Clinical and biochemical data including SLEDAI were collected at baseline and at five years of follow up from 50 patients with SLE and 50 age- and gender-matched healthy controls. C-IMT was also measured at baseline and at 5 years to evaluate progression. Results A higher SLEDAI score at baseline correlated with a faster Δc-IMT (0.007 (0.006) mm/year vs 0.003 (0.001) mm/year when compared to controls, P=0.026), irrespectively of the presence of CVRF and of the serological profile. Patients with higher SLEDAI score at baseline also experienced disease flares more frequently (p=0.037) than those with milder disease at baseline. Patients with a higher disease activity during follow up had also a faster Δc-IMT when compared to those with a persistently low disease activity (0.008 (0.004) mm/year vs -0.006 (0.004) mm/year, P=0.021). Elevated LDL-C levels were the only CVRF associated with disease flare-up; this might a consequence of the aggressive immunosuppressant therapy in those patients. Conclusions Patient with SLE show an increased cardiovascular risk as estimated by the c-IMT. Disease activity and in particular disease flares accelerate the progression of the vascular damage. Disclosure of Interest None declared