Specific features to differentiate Giant cell arteritis aortitis from aortic atheroma using FDG-PET/CT

Aortic wall 18F-fluorodeoxyglucose (FDG)-uptake does not allow differentiation of aortitis from atheroma, which is problematic in clinical practice for diagnosing large vessel vasculitis giant-cell arteritis (GCA) in elderly patients. The purpose of this study was to compare the FDG uptake characteristics of GCA aortitis and aortic atheroma using positron emission tomography/FDG computed tomography (FDG-PET/CT). This study compared FDG aortic uptake between patients with GCA aortitis and patients with aortic atheroma; previously defined by contrast enhanced CT. Visual grading according to standardized FDG-PET/CT interpretation criteria and semi-quantitative analyses (maximum standardized uptake value (SUVmax), delta SUV (∆SUV), target to background ratios (TBR)) of FDG aortic uptake were conducted. The aorta was divided into 5 segments for analysis. 29 GCA aortitis and 66 aortic atheroma patients were included. A grade 3 FDG uptake of the aortic wall was identified for 23 (79.3%) GCA aortitis patients and none in the atheroma patient group (p < 0.0001); grade 2 FDG uptake was as common in both populations. Of the 29 aortitis patients, FDG uptake of all 5 aortic segments was positive for 21 of them (72.4%, p < 0.0001). FDG uptake of the supra-aortic trunk was identified for 24 aortitis (82.8%) and no atheromatous cases (p < 0.0001). All semi-quantitative analyses of FDG aortic wall uptake (SUVmax, ∆SUV and TBRs) were significantly higher in the aortitis group. ∆SUV was the feature with the largest differential between aortitis and aortic atheroma. In this study, GCA aortitis could be distinguished from an aortic atheroma by the presence of an aortic wall FDG uptake grade 3, an FDG uptake of the 5 aortic segments, and FDG uptake of the peripheral arteries.

Expression of Cyr61 in ApoE−/− mice with chronic unilateral renal artery ligation

Cyr61 is a member of the CCN family of proteins that is expressed in atherosclerotic lesions and regulated by angiotensin II. It is unknown whether renal artery stenosis (RAS) increases Cyr61 expression. Male ApoE−/− mice were randomized to surgically induced RAS, RAS + treatment with either irbesartan, aliskiren or amlodipine or sham-surgery. RAS resulted in increased plasma angiotensin II levels, a mild, sustained increase in systolic blood pressure and increased aortic lipid deposition compared to sham-surgery. Surgically induced RAS led to the formation of atheroma in the infrarenal aorta and there was consistent and intense staining for Cyr61 within the atheroma. Treatment with irbesartan, aliskiren and amlodipine were associated with decreased aortic lipid deposition and decreased staining for Cyr61 in aortic atheroma. Serum levels of Cyr61 were not increased in mice or humans with RAS. In summary, Cyr61 expression in aortic atheroma but not serum is increased by RAS in ApoE−/− mice and is reduced by agents that lower blood pressure.

Risk factors for symptomatic vascular events in giant cell arteritis: a study of 254 patients with large-vessel imaging at diagnosis

Aims: To identify factors associated with vascular events in patients with giant cell arteritis (GCA). Methods: We performed a retrospective study of GCA patients diagnosed over a 20-year-period, who all underwent vascular imaging evaluation at diagnosis. Symptomatic vascular events were defined as the occurrence of any aortic event (aortic dissection or symptomatic aortic aneurysm), stroke, myocardial infarction, limb or mesenteric ischemia and de novo lower limbs arteritis stage 3 or 4. Patients with symptomatic vascular event (VE+) and without were compared, and risk factors were identified in a multivariable analysis. Results: Thirty-nine (15.4%) of the 254 included patients experienced at least one symptomatic vascular event during follow-up, with a median time of 21.5 months. Arterial hypertension, diabetes, lower limbs arteritis or vascular complication at diagnosis were more frequent in VE+ patients ( p < 0.05), as an abnormal computed tomography (CT)-scan at diagnosis ( p = 0.04), aortitis ( p = 0.01), particularly of the descending thoracic aorta ( p = 0.03) and atheroma ( p = 0.03). Deaths were more frequent in the VE+ group (37.1 versus 10.3%, p = 0.0003). In multivariable analysis, aortic surgery [hazard ratio (HR): 10.46 (1.41–77.80), p = 0.02], stroke [HR: 22.32 (3.69–135.05), p < 0.001], upper limb ischemia [HR: 20.27 (2.05–200.12), p = 0.01], lower limb ischemia [HR: 76.57 (2.89–2027.69), p = 0.009], aortic atheroma [HR: 3.06 (1.06–8.82), p = 0.04] and aortitis of the descending thoracic aorta on CT-scan at diagnosis [HR: 4.64 (1.56–13.75), p = 0.006] were independent predictive factors of a vascular event. Conclusion: In this study on GCA cases with large vessels imaging at diagnosis, aortic surgery, stroke, upper or lower limb ischemia, aortic atheroma and aortitis of the descending thoracic aorta on CT-scan, at GCA diagnosis, were independent predictive factors of a vascular event. Plain language summary Risk factors for symptomatic vascular events in giant cell arteritis This study was performed to identify the risk factors for developing symptomatic vascular event during giant cell arteritis (GCA) because these are poorly known. We performed a retrospective study of GCA patients diagnosed over a 20-year-period, who all underwent vascular imaging evaluation at diagnosis. Patients with symptomatic vascular event (VE+) and without (VE-) were compared, and risk factors were identified in a multivariable analysis. Thirty-nine patients experienced at least one symptomatic vascular event during follow-up, with a median time of 21.5 months. Arterial hypertension, diabetes, lower limbs arteritis or vascular complication at diagnosis were significantly more frequent in VE+ patients, as an abnormal CT-scan at diagnosis, aortitis, particularly of the descending thoracic aorta and atheroma. Deaths were more frequent in the VE+ group. Among 254 GCA patients, 39 experienced at least one vascular event during follow-up. Aortic surgery, stroke, upper and lower limb ischemia were vascular event risk factors. Aortic atheroma and descending thoracic aorta aortitis on CT-scan were vascular event risk factors. This study on GCA cases with large vessels imaging at diagnosis, showed that aortic surgery, stroke, upper or lower limb ischemia, aortic atheroma and aortitis of the descending thoracic aorta on CT-scan, at GCA diagnosis, were independent predictive factors of a vascular event.

Enterohepatic Transcription Factor CREB3L3 Protects Atherosclerosis via SREBP Competitive Inhibition

SummaryCREB3L3 is a membrane-bound transcription factor to maintain lipid metabolism in the liver and small intestine. CREB3L3 ablation in Ldlr-/- mice exacerbated hyperlipidemia with remnant ApoB-containing lipoprotein accumulation, developing enhanced aortic atheroma formation, whose extent was additive between liver- and intestine-specific deletion. Conversely, hepatic nuclear CREB3L3 overexpression markedly suppressed atherosclerosis with amelioration of hyperlipidemia. CREB3L3 directly upregulates anti-atherogenic FGF21 and ApoA4, whereas antagonizes hepatic SREBP-mediated lipogenic and cholesterogenic genes and regulates LXR-regulated genes involved in intestinal transport of cholesterol. CREB3L3 deficiency accumulates nuclear SREBP proteins. Because both transcriptional factors share the cleavage system for nuclear transactivation, full-length CREB3L3 and SREBPs on endoplasmic reticulum (ER) functionally inhibit each other. CREB3L3 competitively antagonizes SREBPs for ER-Golgi transport, resulting in ER retention and proteolytic activation inhibition at Golgi, and vice versa. Collectively, due to this new mechanistic interaction between CREB3L3 and SREBPs under atherogenic conditions, CREB3L3 has multi-potent protective effects against atherosclerosis.

Abstract WP265: Association Between Brachial-Ankle Pulse Wave Velocity and Aortic Atheroma in Acute Ischemic Stroke

Background and Purpose: Aortic plaques are associated with both larger artery and small artery atherosclerosis. However, association between aortic plaque and aortic stiffness in ischemic stroke is unknown. Brachial-ankle pulse wave velocity (baPWV) is a noninvasive technique to measure aortic stiffness. In the present study, we hypothesized that presence of aortic plaques is associated with increased baPWV. Methods: We reviewed 1099 patients diagnosed with acute ischemic stroke, who had both transesophageal echocardiography (TEE) and brachial-ankle pulse wave velocity (baPWV) measurements. Aortic plaques were classified as complex aortic plaques (CAP) or simple aortic plaques (SAP). CAP were defined as plaques protruding into the lumen ≥4 mm and of mobile lesions located in the proximal aorta. SAP represented plaques <4 mm in the proximal aorta and plaques located in the descending aorta of any sizes. Patients were classified into 4 groups; patients who have CAP only, those who have SAP only, those who have both CAP and SAP, and those without aortic plaques. Results: Among the 1099 patients, aortic atheroma was found in 689 (62.7%) patients. Twenty one (1.9%) patients had only CAP, 142 (12.9%) patients had both SAP and CAP, while 526 (47.9%) patients had SAP without CAP. Mean value of baPWV was 1982±580 cm/sec. baPWV was significantly increased in patients with any aortic atheromas than those without atheromas (2095±577 cm/sec vs. 1793±535 cm/sec, p <0.001). Analysis of variance showed that baPWV was significantly increased in patients with SAP only (p<0.001) and SAP and CAP (p<0.001) compared to those without any aortic atheroma, whereas CAP only patients were not associated with baPWV (p = 0.131). Conclusion: We found that baPWV was associated with SAP but not CAP in acute ischemic stroke patients. These feature suggests that SAP represent generalized atherosclerosis and aortic stiffness, whereas CAP represent the sole mechanism of stroke.

Abstract TP85: The Characteristics of Diffusion Weighted Image Patterns in Different Potential Embolic Source

Introduction: Few studies have focused on the characteristics of diffusion weighted image (DWI) pattern in different embolic stroke. Hypothesis: Studying the DWI pattern in patients with embolic stroke of determined source may help presume the cause of ESUS. Methods: From a prospective registry of 1,764 consecutive patients with acute ischemic strokes , we selected 422 patients with embolic stroke of determined source comprising of 4 groups as follows. 1: continuous atrial fibrillation (cAf) (n=232), 2: paroxysmal Af (pAf) (n=99), 3: paradoxical embolism associated with the foramen ovale (PXE) (n=48) and 4: aortogenic embolism associated with aortic atheroma (≥4mm, ulcer or mobile) (AoE) (n=56). The DWI patterns were classified as follows. First, cortical infarcts were classified according to the affected area of middle cerebral artery (MCA) segments such as M1: the horizontal segment, M2: after the bifurcation segments within the Sylvian fissure and M4: terminal cortical branch. Among patients with M1, pure striatocapsular infarction (SCI) was identified. Moreover, patients with the M2 and the M4 were divided into 2 groups including parietal ascending branches and temporal descending branches. Second, cortical and subcortical small multiple infarcts (<20mm) (sMI) were identified. Finally, infarcts in the anterior cerebral artery (AC) and the posterior circulation (PC) were identified. Results: The distribution of the DWI patterns in the 4 groups (cAf: pAf: PXE: AoE, %) are as follows: M1 (n=100) (76.0: 17.0: 7.0: 0), M2 (n=118) (59.3: 30.5: 7.6: 2.5), M4 (n=50) (50.0: 26.0: 18.0: 6.0), SCI (n=20) (2.1: 4.0: 14.5: 0), sMI (n=49) (18.3: 16.3: 18.3: 46.9), AC (n=13) (46.1: 46.1: 0: 7.6), and PC (n=92) (50.0: 20.6: 15.2: 14.1). Among 162 patients with M2 and M4 infarction, there were 57 involvements of descending branches (35.1%), comprising of 38 patients (41.7%) in cAf, 17 (34.6) in pAf, 1 (6.2) in PXE and 1(7.4) in AoE. Conclusions: Infarct sized was large in the Af groups. The involvement of inferior division of the MCA was exclusively found in the Af groups. The SCI was most prevalent in the PX. Multiple small scattered pattern was characteristically found in the AoE. The different DWI patterns relatively well associated with different embolic source.

Cryptogenic stroke

The paper considers the epidemiology and general etiological characteristics of cryptogenic stroke (CS). It discusses the concept of embolic stroke with an unknown source of embolism. It also characterizes the most significant causes of CS, such as paroxysmal atrial fibrillation, atrial cardiopathy, aortic atheroma, non-stenotic cerebral atherosclerotic plaques, and malignant neoplasms. The paper describes approaches to the diagnosis and secondary prevention of CS and proposes etiological and neuroimaging diagnostic algorithms for CI. Clinical cases are also presented.