Finasteride delays atherosclerosis progression in mice and is associated with a reduction in plasma cholesterol in men.

Finasteride is commonly prescribed to treat benign prostate hyperplasia and male-pattern baldness in cis men and, more recently, trans individuals. However, the effect of finasteride on cardiovascular disease remains elusive. We evaluated the role of finasteride on atherosclerosis using low-density lipoprotein (LDL) receptor-deficient (Ldlr-/-) mice. Next, we examined the relevance to humans by analyzing the data deposited between 2009 and 2016 in the National Health and Nutrition Examination Survey. We show that finasteride reduces total plasma cholesterol and delays the development of atherosclerosis in Ldlr-/- mice. Finasteride reduced monocytosis, monocyte recruitment to the lesion, macrophage lesion content, and necrotic core area, the latter of which is an indicator of plaque vulnerability in humans. RNA sequencing analysis revealed a downregulation of inflammatory pathways and an upregulation of bile acid metabolism, oxidative phosphorylation, and cholesterol pathways in the liver of mice taking finasteride. Men reporting the use of finasteride showed lower plasma levels of cholesterol and LDL-cholesterol than those not taking the drug. Our data unveil finasteride as a potential treatment to delay cardiovascular disease in people by improving the plasma lipid profile.

Rescue therapy of early neurological deterioration in lacunar stroke.

BACKGROUND: Early neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke. METHODS: This study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile. RESULTS: Among the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06-5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19-12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups. CONCLUSIONS: As a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban.

Incidental findings in cone beam computed tomography volumes: Calcified head-and-neck atheromas detected during dental evaluation.

PURPOSE: Atheromas can be detected incidentally in routine dental cone beam computed tomography (CBCT) images. This study aims to assess prevalence and risk factors associated with these vascular lesions. MATERIALS AND METHODS: The maxillofacial CBCTs of 458 subjects were evaluated and divided into 4 groups based on the presence of calcified atheroma: subjects with no calcified atheroma, subjects with intracranial calcified atheroma (ICA), subjects with extracranial calcified atheroma (ECA), and subjects exhibiting combined lesions. Age, sex, medical conditions, family history, and size were documented. Analysis of variance followed by a multiple comparison test was used for data satisfying parametric test assumptions. Chi-squared tests were used to assess categorical data. The Spearman Rho test was used to assess the correlation between the incidence of calcified atheroma and subjects' medical condition. RESULTS: Of the 458 CBCTs evaluated, 29.90% presented with calcified atheroma. Calcified atheroma prevalence was significantly higher in older patients versus younger patients (p = 0.004) and in males compared to females (p = 0.004). Males were more likely to have the combination of ICA and ECA, whereas females were more likely to have ICA alone (p ≤ 0.040). Patients with calcified atheroma were significantly more likely to have a history of hyperlipidemia (p = 0.001), hypertension (p = 0.001), and myocardial infarction/coronary artery diseases (p = 0.001). Overall, patients exhibiting both intracranial and extracranial lesions were more likely to have cardiovascular risk factors (p = 0.001). CONCLUSION: Incidentally detected calcified atheromas in CBCTs are common. Subjects with combined atheroma lesions are at higher risk for cardiovascular disease. The diagnosis of incidental calcified atheromas in CBCT's warrants early referral to medical specialists, especially if there is no medical history of existing cardiovascular disease.

Impact of aortic atheroma and distensibility on diastolic function and prognosis in patients with ischemic stroke.

BACKGROUND: Patients with ischemic stroke are vulnerable to heart failure with preserved ejection fraction (HFpEF) because these conditions share common risk factors. Although evaluation of the ascending aorta, aortic arch, and proximal descending thoracic aorta is an essential step to determine the source of the causative embolism, the relationship between the degree of aortic atheroma and left ventricular (LV) diastolic function has not been extensively investigated. METHODS: We analyzed the transesophageal and transthoracic echocardiography in ischemic stroke patients. Patients with previous coronary artery disease, valvular heart disease of more than moderate degree, and an LV ejection fraction of less than 50% were excluded. The relationships between the grade of the aortic atheroma, aortic stiffness indexes, and diastolic functional indexes were evaluated. RESULTS: In 295 patients, the atheroma grade was significantly correlated with aortic stiffness index, ratio of mitral annular and inflow velocities (E/e'), left atrial volume index, and LV diastolic elastance. With further adjustment for age, hypertension, diabetes, estimated glomerular filtration rate, left atrial volume index, and LV mass index, the significance of the atheroma grade was attenuated. In the subgroup analysis, the atheroma grade was significantly and independently related to E/e' in women (ß = 0.181, p = 0.032), but not in men. However, atheroma grade was not associated with poor clinical outcomes in either sex. CONCLUSIONS: Aortic atheroma grade was significantly and independently related to LV diastolic function, especially in women. This suggests that aortic atheroma is an index of arterial stiffness and a potential risk factor for HFpEF through ventricular-vascular interactions, especially in women.

A preliminary coronary computed tomography angiography-based study of perivascular fat attenuation index: relation with epicardial adipose tissue and its distribution over the entire coronary vasculature.

OBJECTIVES: To investigate the perivascular fat attenuation index (FAI) in association with epicardial adipose tissue (EAT) parameters and its distribution over the entire coronary vasculature in patients with known or suspected coronary artery disease (CAD). METHODS: Patients with known or suspected CAD who underwent coronary computed tomography angiography from January 1, 2019, to June 1, 2019, were retrospectively included. The perivascular FAI was quantified on four main epicardial coronary arteries and seven coronary segments. Moreover, EAT density and volume were measured. RESULTS: We included 192 consecutive patients (55 without coronary plaque [mean age 46.4 ± 13.2 years, 69.1% male] and 137 with coronary plaque [mean age 57.9 ± 13.0 years, 84.7% male]). EAT density was lower than perivascular FAI in both groups, but they exhibited substantial correlation (- 83.33 ± 4.54 vs. - 78.22 ± 6.52 HU, p < 0.001; r = 0.667 in plaque- patients and - 83.11 ± 4.48 vs. - 77.81 ± 5.63 HU, p < 0.001; r = 0.778 in plaque+ patients). The left main coronary artery had the highest perivascular FAI, followed by the left circumflex artery. The perivascular FAI in proximal segments was significantly higher compared to that in distal segments (all p < 0.05). Furthermore, the presence of plaque did not alter perivascular FAI on the patient or segmental level. CONCLUSION: The perivascular FAI was significantly higher than EAT density and correlated substantially with EAT density. The perivascular FAI distribution over the entire coronary tree varied and prompted for vessel-specific or segment-specific thresholds to determine abnormal perivascular FAI in practice. KEY POINTS: • The perivascular FAI correlated well with EAT density and had higher values than EAT density. • The distributions of perivascular FAI differ between coronary vessels or segments; considering segment and vessel confounding factors while conducting a perivascular FAI study is necessary. • No significant difference of perivascular FAI was observed between patients without and with coronary plaque, nor between coronary segments without plaque and those with plaque.

Accumulation of Plasma-Derived Lipids in the Lipid Core and Necrotic Core of Human Atheroma: Imaging Mass Spectrometry and Histopathological Analyses.

Objective: To clarify the pathogenesis of human atheroma, the origin of deposited lipids, the developmental mechanism of liponecrotic tissue, and the significance of the oxidation of phospholipids were investigated using mass spectrometry-aided imaging and immunohistochemistry.Atherosclerotic lesions in human coronary arteries were divided into 3 groups: pathologic intimal thickening with lipid pool, atheroma with lipid core, and atheroma with necrotic core. The lipid pool and lipid core were characterized by the deposition of extracellular lipids. The necrotic core comprised extracellular lipids and liponecrotic tissue. The proportion of cholesteryl linoleate in cholesteryl linoleate+cholesteryl oleate fraction in the extracellular lipid and liponecrotic regions differed significantly from that of the macrophage foam cell-dominant region, and the plasma-derived components (apolipoprotein B and fibrinogen) were localized in the regions. The liponecrotic region was devoid of elastic and collagen fibers and accompanied by macrophage infiltration in the surrounding tissue. Non-oxidized phospholipid (Non-OxPL), OxPL, and Mox macrophages were detected in the three lesions. In the atheroma with lipid core and atheroma with necrotic core, non-OxPL tended to localize in the superficial layer, whereas OxPL was distributed evenly. Mox macrophages were colocalized with OxPL epitopes.In human atherosclerosis, plasma-derived lipids accumulate to form the lipid pool of pathologic intimal thickening, lipid core of atheroma with lipid core, and necrotic core of atheroma with necrotic core. The liponecrotic tissue in the necrotic core appears to be developed by the loss of elastic and collagen fibers. Non-OxPL in the accumulated lipids is oxidized to form OxPL, which may contribute to the lesion development through Mox macrophages.

Serial analysis of coronary artery disease progression by artificial intelligence assisted coronary computed tomography angiography: early clinical experience.

BACKGROUND: Studies have shown that quantitative evaluation of coronary artery plaque on Coronary Computed Tomography Angiography (CCTA) can identify patients at risk of cardiac events. Recent demonstration of artificial intelligence (AI) assisted CCTA shows that it allows for evaluation of CAD and plaque characteristics. Based on publications to date, we are the first group to perform AI augmented CCTA serial analysis of changes in coronary plaque characteristics over 13 years. We evaluated whether AI assisted CCTA can accurately assess changes in coronary plaque progression, which has potential clinical prognostic value in CAD management. CASE PRESENTATION: 51-year-old male with hypertension, hyperlipidemia and family history of myocardial infarction, underwent CCTA exams for anginal symptom evaluation and CAD assessment. 5 CCTAs were performed between 2008 and 2021. Quantitative atherosclerosis plaque characterization (APC) using an AI platform (Cleerly), was performed to assess CAD burden. Total plaque volume (TPV) change-over-time demonstrated decreasing low-density non-calcified plaque (LD-NCP) with increasing overall NCP and calcified-plaque (CP). Examination of individual segments revealed a proximal-LAD lesion with decreasing NCP over-time and increasing CP. In contrast, although the D2/D1/ramus lesions showed increasing stenosis, CP, and total plaque, there were no significant differences in NCP over-time, with stable NCP and increased CP. Remarkably, we also consistently visualized small plaques, which typically readers may interpret as false positives due to artifacts. But in this case, they reappeared each study in the same locations, generally progressing in size and demonstrating expected plaque transformation over-time. CONCLUSIONS: We performed the first AI augmented CCTA based serial analysis of changes in coronary plaque characteristics over 13 years. We were able to consistently assess progression of plaque volumes, stenosis, and APCs with this novel methodology. We found a significant increase in TPV composed of decreasing LD-NCP, and increasing NCP and CP, with variations in the evolution of APCs between vessels. Although the significance of evolving APCs needs to be investigated, this case demonstrates AI-based CCTA analysis can serve as valuable clinical tool to accurately define unique CAD characteristics over time. Prospective trails are needed to assess whether quantification of APCs provides prognostic capabilities to improve clinical care.

Coexisting of aortic arch atheroma and atrial fibrillation for short-term recurrence and poor functional outcome in acute stroke.

BACKGROUND AND PURPOSE: Multiple embolic sources are sometimes observed simultaneously in patients with embolic stroke. The present study investigated the effects of coexisting aortic arch atheroma ≥ 4 mm thick and atrial fibrillation (AF) on short-term stroke recurrence and functional outcome. METHODS: Transesophageal echocardiography (TEE) was performed in consecutive embolic stroke patients, and 395 patients were classified into 4 groups according to the presence of aortic arch atheroma ≥ 4 mm thick and AF: AF - /ARCH - group, AF + /ARCH - group, AF - /ARCH + group, and AF + /ARCH + group. In accordance with these 4 groups, we evaluated stroke recurrence and all-cause death for 3 months after stroke onset, and also evaluated the 3-month functional outcome using the modified Rankin scale (mRS). RESULTS: Among the 128 AF patients, 39.1% also had aortic arch atheroma ≥ 4 mm thick. Of the 395 enrolled cases, the AF + /ARCH + group showed the highest frequencies of stroke recurrence and all-cause death during 3 months after onset. On multivariate analysis, stroke recurrence or all-cause death during 3 months after onset was relatively more frequent in the AF + /ARCH + group than in the AF + /ARCH - group (OR, 2.34; 95% CI, 0.82-6.69; p = 0.11), but that was not statistically significant, and poor functional outcome (mRS score 3-6) at 3 months was significantly more frequent in the AF + /ARCH + group than in the AF + /ARCH - group (OR, 2.59; 95% CI, 1.08-6.24; p = 0.0339). CONCLUSIONS: Aortic arch atheroma concomitant with AF is not rare and appears associated with increased risks of stroke recurrence and poor functional outcome.

Dual-energy CT plaque characteristics of post mortem thin-cap fibroatheroma in comparison to infarct-related culprit lesions.

Improvement of non-invasive identification of high-risk plaque may increase the preventive options of acute coronary syndrome. To describe the characteristics of thin-cap fibroatheroma (TCFA) in a post mortem model in comparison to characteristics of culprit lesions in patients with non-ST-elevation-myocardial-infarction (NSTEMI) using the dual energy computed tomography (DECT). Three post mortem hearts were prepared with iodine-contrast, inserted in a Kyoto phantom and scanned by DECT. Six TCFA were identified using histopathological analysis (cap thickness < 65 µm and necrotic core > 10% of the plaque area). In the NSTEMI group, 29 patients were scheduled to DECT prior to coronary angiography and invasive treatment. Culprit lesions were identified blinded for the patient history by two independent invasive cardiologists using the coronary angiography. The DECT analysis of TCFA and culprit lesions was performed retrospectively with determination of effective atomic number (Effective-Z), Hounsfield Unit (HU), plaque type (non-calcified, predominantly non-calcified, predominantly calcified or calcified), spotty calcification,, plaque length, plaque volume and plaque burden and the remodeling index. The Effective-Z, HU and plaqueburden were significantly different between TCFA and culprit lesions (P < 0.05).The TCFA plaques were more calcified in comparison to culprit lesions (P < 0.05). No significant difference in the other plaque characteristics was observed. The use of DECT demonstrated different Effective-Z values and different characteristics of post mortem TCFA in comparison to in vivo culprit lesions. This finding may highlight, that not all TCFA should be considered as vulnerable.

Aortic Fibrosis in Insulin-Sensitive Mice with Endothelial Cell-Specific Deletion of Ceacam1 Gene.

(1) Background: Mice with global Ceacam1 deletion developed plaque-like aortic lesions even on C57BL/6J background in the presence of increased endothelial cell permeability and insulin resistance. Loss of endothelial Ceacam1 gene caused endothelial dysfunction and reduced vascular integrity without affecting systemic insulin sensitivity. Because endothelial cell injury precedes atherosclerosis, we herein investigated whether the loss of endothelial Ceacam1 initiates atheroma formation in the absence of insulin resistance. (2) Methods: Endothelial cell-specific Ceacam1 null mice on C57BL/6J.Ldlr-/- background (Ldlr-/-VECadCre+Cc1fl/fl) were fed an atherogenic diet for 3-5 months before metabolic, histopathological, and en-face analysis of aortae were compared to their control littermates. Sirius Red stain was also performed on liver sections to analyze hepatic fibrosis. (3) Results: These mice displayed insulin sensitivity without significant fat deposition on aortic walls despite hypercholesterolemia. They also displayed increased inflammation and fibrosis. Deleting Ceacam1 in endothelial cells caused hyperactivation of VEGFR2/Shc/NF-κB pathway with resultant transcriptional induction of NF-κB targets. These include IL-6 that activates STAT3 inflammatory pathways, in addition to endothelin-1 and PDGF-B profibrogenic effectors. It also induced the association between SHP2 phosphatase and VEGFR2, downregulating the Akt/eNOS pathway and reducing nitric oxide production, a characteristic feature of endothelial dysfunction. Similarly, hepatic inflammation and fibrosis developed in Ldlr-/-VECadCre+Cc1fl/fl mice without an increase in hepatic steatosis. (4) Conclusions: Deleting endothelial cell Ceacam1 caused hepatic and aortic inflammation and fibrosis with increased endothelial dysfunction and oxidative stress in the presence of hypercholesterolemia. However, this did not progress into frank atheroma formation. Because these mice remained insulin sensitive, the study provides an in vivo demonstration that insulin resistance plays a critical role in the pathogenesis of frank atherosclerosis.

Pathophysiology of Atherosclerosis.

Atherosclerosis is the main risk factor for cardiovascular disease (CVD), which is the leading cause of mortality worldwide. Atherosclerosis is initiated by endothelium activation and, followed by a cascade of events (accumulation of lipids, fibrous elements, and calcification), triggers the vessel narrowing and activation of inflammatory pathways. The resultant atheroma plaque, along with these processes, results in cardiovascular complications. This review focuses on the different stages of atherosclerosis development, ranging from endothelial dysfunction to plaque rupture. In addition, the post-transcriptional regulation and modulation of atheroma plaque by microRNAs and lncRNAs, the role of microbiota, and the importance of sex as a crucial risk factor in atherosclerosis are covered here in order to provide a global view of the disease.

Semi-Quantitative [18F]FDG-PET/CT ROC-Analysis-Based Cut-Offs for Aortitis Definition in Giant Cell Arteritis.

[18F]fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) is used to diagnose large vessel vasculitis in giant cell arteritis (GCA). We aimed to define a semi-quantitative threshold for identifying GCA aortitis from aortic atheroma or the control. Contrast enhanced computed tomography (CECT) was used as the reference imaging for aortic evaluation and to define aortitis, aortic atheroma and control aortas. [18F]FDG-PET/CT was performed on 35 GCA patients and in two different control groups (aortic atheroma (n = 70) and normal control (n = 35)). Aortic semi-quantitative features were compared between the three groups. GCA patients without aortitis on CECT were excluded. Of the GCA patients, 19 (54.3%) were not on glucocorticoids (GC) prior to [18F]FDG-PET/CT. The SUVmax, TBRblood and TBRliver aortic values were significantly higher in the GCA aortitis group than in the aortic atheroma and control groups (p < 0.001). Receiver operating characteristic curve analyses brought to light quantitative cut-off values allowing GCA aortitis diagnosis with optimal sensitivity and specificity versus control or aortic atheroma patients for each PET-based feature analyzed. Considering the overall aorta, a SUVmax threshold of 3.25 and a TBRblood threshold of 1.75 had a specificity of 83% and 75%, respectively, a sensitivity of 81% and 81%, respectively, and the area under the ROC curve (AUC) was 0.86 and 0.83, respectively, for aortitis detection compared to control groups in GCA cases with GC. A SUVmax threshold of 3.45 and a TBRblood threshold of 1.97 had a specificity of 90% and 93%, respectively, a sensitivity of 89% and 89%, respectively, with an AUC of 0.89 and 0.96, respectively, for aortitis detection compared to the control in GC-free GCA cases. Discriminative thresholds of SUVmax and TBRblood for the diagnosis of GCA aortitis were established using CECT as the reference imaging.

Use of ADAM-C and CHA2DS2-VASc scores to predict complex aortic atheroma after brain ischemia: A prospective observational study.

BACKGROUND AND AIMS: Complex aortic atheroma (CAA) is a common cause of acute brain ischemia (BI), including ischemic stroke (IS) and transient ischemic attack (TIA), and is associated with recurrence. The CHA2DS2-VASc score is a useful tool for predicting stroke in patients with atrial fibrillation (AF), and can also predict cardiovascular events in other populations, including non-AF populations. The ADAM-C score is a new risk score for predicting the diagnostic yield of transesophageal echocardiography (TEE) after BI. We aimed to evaluate the ability of CHA2DS2-VASc and ADAM-C scores to predict CAA after BI. METHODS: This prospective, multicenter, observational study included 1479 patients aged over 18 years who were hospitalized for BI. CAA was defined as the presence of one or more of the following criteria: thrombus, ulcerated plaque, or plaque thickening ≥ 4 mm. RESULTS: CAA was diagnosed in 216 patients (14.6%). CHA2DS2-VASc and ADAM-C scores were significantly higher in the CAA group versus the non-CAA group (P < .0001 for both). The CHA2DS2-VASc and ADAM-C scores appear to be good predictors of CAA (AUC 0.699 [0.635, 0.761] and 0.759 [0.702, 0.814], respectively). The sensitivity, specificity, predictive positive value (PPV), and negative predictive value (NPV) of the scores for detecting CAA were 94%, 22%, 17%, and 96%, respectively, for a CHA2DS2-VASc score < 2, and 90%, 46%, 22%, and 96%, respectively, for an ADAM-C score < 3 CONCLUSIONS: CHA2DS2-VASc and ADAM-C scores are able to predict CAA after BI. CHA2DS2-VASc < 2 and ADAM-C < 3 both have an interesting NPV of 96%.

Can carotid artery calcifications on dental radiographs predict adverse vascular events? A systematic review.

OBJECTIVES: To investigate the predictive value of carotid artery calcifications (CACs) seen on dental imaging for future adverse events related to cerebrovascular and cardiovascular diseases. METHODS: Electronic databases (PubMed, Embase, SCOPUS and Cochrane) and selected grey literature were searched. Outcomes included stroke, transient ischaemic attack (TIA), myocardial infarction (MI), angina, heart failure, future interventional revascularization procedures and death. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: 5 studies were selected from 1011 records. All were of moderate to low risk of bias. Results were heterogeneous but showed that patients with CACs on panoramic radiographs (PANs) were more likely to experience strokes, TIA, MI and future revascularization procedures compared to control groups. The differences between groups were not all found to be statistically significant. Bilateral vessel-outlining CACs were an independent risk marker for future vascular events. Patients who are not currently being managed for cardiovascular risk factors should be referred for further evaluation. Those already being treated for atherosclerosis may not benefit from additional investigations. CONCLUSION: The evidence for the predictive value of CACs on PANs for adverse future vascular events is equivocal but can help to identify at-risk patients who require further evaluation. CLINICAL RELEVANCE: Dentists must be able to recognize CACs on PANs and make appropriate referrals for patients to be evaluated for cardiovascular risk factors, especially those who have not previously been assessed.

Morphohistological analysis of the prevalence and distribution of atheroma in the abdominal aorta and its branches: a cadaveric study.

BACKGROUND: Aneurysms and atheromatous processes are prominent pathological features that are commonly associated with significant morbidity and mortality. OBJECTIVES: This cadaveric study was conducted to evaluate the morphometric and histological aspects of atheromatous plaque formation in abdominal aortas and their branches and their associated morphological variations, if present, characterized by loops, kinking, or tortuosity. METHODS: The study was performed using 30 human cadavers (approx. 65-75 years). Frequency of occurrence of calcified plaques in the abdominal aorta and its branches and their morphometric measurements were noted and histological features were observed with the aid of Hematoxylin & Eosin staining. RESULTS: Variations in the abdominal aorta and the common iliac artery were observed in 16.6% of specimens. Atheromatous plaque formation was seen in 2 specimens (1 specimen was associated with kinking) while in 3 other specimens only variation in normal structure (kinking/ tortuous artery) was observed. Histological analysis showed foamy macrophages and dense calcification, giving an atheromatous appearance. CONCLUSIONS: Cadaveric reports of the location, nature, and degree of plaque formation in the abdominal aorta and its branches are extremely important in clinical settings and for choosing treatment options.

CONTEXTO: Aneurismas e processos ateromatosos são características patológicas perceptíveis que costumam estar associadas a morbidade e mortalidade significativas. OBJETIVOS: Este estudo em cadáveres teve como objetivo avaliar os aspectos morfométricos e histológicos da formação de placa ateromatosa na aorta abdominal e em seus ramos com suas subsequentes variações morfológicas caracterizadas por enrolamentos, acotovelamentos ou tortuosidades, se presentes. MÉTODOS: O estudo foi realizado com 30 cadáveres humanos (aproximadamente 65-75 anos). Foi descrita a frequência de ocorrência de placas calcificadas na aorta abdominal e em seus ramos com as respectivas medidas morfométricas e características histológicas com auxílio da coloração por hematoxilina e eosina. RESULTADOS: Variações na aorta abdominal e na artéria ilíaca comum foram observadas em 16,6% dos espécimes. A formação de placa ateromatosa foi observada em dois espécimes (um espécime foi associado a acotovelamento), enquanto em outros três espécimes houve apenas variação na estrutura normal (acotovelamento/artéria tortuosa). A análise histológica mostrou macrófagos espumosos e calcificação densa, o que gerou uma impressão ateromatosa. CONCLUSÕES: Os estudos em cadáveres sobre localização, natureza e grau de formação de placa na aorta abdominal e em seus ramos são extremamente importantes para os cenários clínicos e as opções de tratamento.

Diagnostic performance of perivascular fat attenuation index to predict hemodynamic significance of coronary stenosis: a preliminary coronary computed tomography angiography study.

OBJECTIVE: This study aimed to investigate the association between perivascular fat attenuation index (FAI) and hemodynamic significance of coronary lesions. METHODS: Patients with stable angina who underwent coronary computed tomography (CT) angiography and invasive fractional flow reserve (FFR) measurement within 2 weeks were retrospectively included. Lesion-based perivascular FAI, high-risk plaque features, total plaque volume (TPV), machine learning-based FFRCT, and other parameters were recorded. Lesions with invasive FFR ≤ 0.8 were considered functionally significant. RESULTS: This study included 167 patients with 219 lesions. Diameter stenosis (DS), lesion length, TPV, and perivascular FAI were significantly larger or longer in the group of hemodynamically significant lesions (FFR ≤ 0.8). In addition, smaller FFRCT value was associated with functionally significant lesions (0.720 ± 0.11 vs 0.846 ± 0.10, p < 0.001). No significant difference was found between the hemodynamically significant and insignificant subgroups with respect to CT-derived high-risk plaque features. According to multivariate analysis, DS, TPV, and perivascular FAI were significant predictors of lesion-specific ischemia. When integrating DS, TPV, and perivascular FAI, the area under the curve (AUC) of this combined method was 0.821, which was similar to that of FFRCT (AUC, 0.821 vs 0.850; p = 0.426). The diagnostic accuracy of FFRCT was higher than that of the combined approach, but the difference was statistically insignificant (79.0% vs 74.0%, p = 0.093). CONCLUSIONS: Perivascular FAI was significantly higher for flow-limiting lesions than for non-flow-limiting lesions. The combined use of FAI, TPV, and DS could predict ischemic coronary stenosis with high diagnostic accuracy. KEY POINTS: • Perivascular FAI was significantly higher for flow-limiting lesions than for non-flow-limiting lesions. • Combined use of FAI, plaque volume, and DS provided diagnostic performance comparable to that of machine learning-based FFR CTfor predicting ischemic coronary stenosis. • No significant difference was found between the hemodynamically significant and insignificant subgroups with respect to CT-derived high-risk plaque features.

Tooth loss is associated with atherosclerosis and a poorer functional outcome among stroke patients.

OBJECTIVES: The purpose of the study was twofold: (1) to test the hypothesis that tooth loss is independently associated with carotid atherosclerotic burden (CAB) among individuals with ischemic stroke (IS) or transient ischemic attack (TIA) and (2) to test the association between tooth loss and disability following the occurrence of cerebral ischemia. MATERIALS AND METHODS: This observational study included 418 patients with IS or TIA. Tooth loss and the CAB were measured through a head and neck multidetector computed tomography angiography. CAB was analyzed in both common, internal, and external carotid arteries and classified in five levels of vascular occlusion. The modified Rankin Scale (mRS) was used to evaluate the functional outcome at patient discharge. Health records provided information on sociodemographic and medical covariates. The association between CAB and tooth loss, as well as between tooth loss and subtypes of cerebral ischemia were estimated through Poisson regression. Cox regression was carried out to evaluate the association between tooth loss and the mRS, with α = 5%. RESULTS: Mean age was 65.6 ± 13.8 years, with 52.4% males. Multivariate analyses revealed that severe tooth loss (> 23 missing teeth) was independently associated with CAB ≥ 50% (PR = 2.86, 95% CI = 1.19-6.89) and mRS scores (> 2) (HR = 1.97, 95% CI = 1.10-3.75). CONCLUSION: Tooth loss was independently associated with CAB and predicted a poorer functional outcome among IS and TIA patients. CLINICAL RELEVANCE: Clinical assessment of tooth loss may provide important information on risk for CAB and poorer functional outcome among stroke patients.

Cholesterol Crystal in Thrombus Removed by Mechanical Thrombectomy Should be a Strong Marker for Aortogenic Embolic Stroke.

Aortogenic embolic stroke (AES) is an important stroke mechanism. However, as many stroke patients have aortic atheromatous lesions, it is unclear whether these lesions are the cause of these strokes. Cholesterol crystals are the solid, crystalline form of cholesterol that is found in atherosclerosis, but not in cardiac diseases such as atrial fibrillation, valvular diseases, and cardiomyopathy. Therefore, if a cholesterol crystal is found in a thrombus removed by mechanical thrombectomy (MT), this makes it possible to diagnose a patient as having an atheromatous lesion. Here, we report an AES case with a cholesterol crystal found in a thrombus removed by MT. A 67-year-old man was admitted due to consciousness disturbance, aphasia, and right hemiplegia. Diffusion-weighted imaging (DWI) showed a hyperintense area in the left frontal lobe, and magnetic resonance angiography demonstrated a branch occlusion of the left middle cerebral artery (MCA). MT was performed 1.5 h after stroke onset, with the thrombus removed and a left occluded MCA completely recanalized. Carotid duplex ultrasonography did not reveal any plaque in the carotid artery. Echocardiography did not show any abnormal function or findings, including thrombus. Transesophageal echocardiography showed a 4.9 mm atheromatous lesion at the aortic arch. Therefore, we suspected this patient as having an AES due to the embolic source of atheromatous lesion at the aortic arch. Pathological examination of the embolus revealed a cholesterol crystal cleft in the thrombus. Therefore, we diagnosed this patient as having AES caused by an atheromatous lesion at the aortic arch.

CCL4 Inhibition in Atherosclerosis: Effects on Plaque Stability, Endothelial Cell Adhesiveness, and Macrophages Activation.

Atherosclerosis is an arterial inflammatory disease. The circulating level of the C-C chemokine ligand (CCL4) is increased in atherosclerotic patients. This study aimed to investigate whether CCL4 inhibition could retard the progression of atherosclerosis. In ApoE knockout mice, CCL4 antibody treatment reduced circulating interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α levels and improved lipid profiles accompanied with upregulation of the liver X receptor. CCL4 inhibition reduced the atheroma areas and modified the progression of atheroma plaques, which consisted of a thicker fibrous cap with a reduced macrophage content and lower matrix metalloproteinase-2 and -9 expressions, suggesting the stabilization of atheroma plaques. Human coronary endothelial cells (HCAECs) and macrophages were stimulated with TNF-α or oxidized LDL (ox-LDL). The induced expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were attenuated by the CCL4 antibody or CCL4 si-RNA. CCL4 inhibition reduced the adhesiveness of HCAECs, which is an early sign of atherogenesis. CCL4 blockade reduced the activity of metalloproteinase-2 and -9 and the production of TNF-α and IL-6 in stimulated macrophages. The effects of CCL4 inhibition on down-regulating adhesion and inflammation proteins were obtained through the nuclear factor kappa B (NFκB) signaling pathway. The direct inhibition of CCL4 stabilized atheroma and reduced endothelial and macrophage activation. CCL4 may be a novel therapeutic target for modulating atherosclerosis.

Red Blood Cells and Hemoglobin in Human Atherosclerosis and Related Arterial Diseases.

As the main particulate component of the circulating blood, RBCs play major roles in physiological hemodynamics and impact all arterial wall pathologies. RBCs are the main determinant of blood viscosity, defining the frictional forces exerted by the blood on the arterial wall. This function is used in phylogeny and ontogeny of the cardiovascular (CV) system, allowing the acquisition of vasomotricity adapted to local metabolic demands, and systemic arterial pressure after birth. In pathology, RBCs collide with the arterial wall, inducing both local retention of their membranous lipids and local hemolysis, releasing heme-Fe++ with a high toxicity for arterial cells: endothelial and smooth muscle cells (SMCs) cardiomyocytes, neurons, etc. Specifically, overloading of cells by Fe++ promotes cell death. This local hemolysis is an event associated with early and advanced stages of human atherosclerosis. Similarly, the permanent renewal of mural RBC clotting is the major support of oxidation in abdominal aortic aneurysm. In parallel, calcifications promote intramural hemorrhages, and hemorrhages promote an osteoblastic phenotypic shift of arterial wall cells. Different plasma or tissue systems are able, at least in part, to limit this injury by acting at the different levels of this system.