Plaques In Femoral Arteries Research Articles

Determinants of vascular impairment in type 1 diabetes–impact of sex and connexin 37 gene polymorphism: A cross-sectional study

BackgroundThe associations of risk factors with vascular impairment in type 1 diabetes patients seem more complex than that in type 2 diabetes patients. Therefore, we analyzed the associations between traditional and novel cardiovascular risk factors and vascular parameters in individuals with T1D and modifications of these associations according to sex and genetic factors.MethodsIn a cross-sectional study, we analyzed the association of risk factors in T1D individuals younger than 65 years using vascular parameters, such as ankle brachial index (ABI) and toe brachial index (TBI), duplex ultrasound, measuring the presence of plaques in carotid and femoral arteries (Belcaro score) and intima media thickness of carotid arteries (CIMT). We also used photoplethysmography, which measured the interbranch index expressed as the Oliva-Roztocil index (ORI), and analyzed renal parameters, such as urine albumin/creatinine ratio (uACR) and glomerular filtration rate (GFR). We evaluated these associations using multivariate regression analysis, including interactions with sex and the gene for connexin 37 (Cx37) polymorphism (rs1764391).ResultsIn 235 men and 227 women (mean age 43.6 ± 13.6 years; mean duration of diabetes 22.1 ± 11.3 years), pulse pressure was strongly associated with unfavorable values of most of the vascular parameters under study (ABI, TBI, Belcaro scores, uACR and ORI), whereas plasma lipids, represented by remnant cholesterol (cholesterol – LDL-HDL cholesterol), the atherogenic index of plasma (log (triglycerides/HDL cholesterol) and Lp(a), were associated primarily with renal impairment (uACR, GFR and lipoprotein (a)). Plasma non-HDL cholesterol was not associated with any vascular parameter under study. In contrast to pulse pressure, the associations of lipid factors with kidney and vascular parameters were modified by sex and the Cx37 gene.ConclusionIn addition to known information, easily obtainable risk factor, such as pulse pressure, should be considered in individuals with T1D irrespective of sex and genetic background. The associations of plasma lipids with kidney function are complex and associated with sex and genetic factors. The decision of whether pulse pressure, remnant lipoproteins, Lp(a) and other determinants of vascular damage should become treatment targets in T1D should be based on the results of future clinical trials.Graphical

Abstract 3019: Piezo-1 Expression Decreases Under Disturbed Flow Model Of Femoral Atherosclerosis.

Background: Peripheral arterial disease (PAD) is often manifest by focal atherosclerotic plaque formation in the infra-inguinal arteries. However, murine models of atherosclerosis in the infra-inguinal arteries are lacking. It is well known that low and oscillatory wall shear stress, which occurs around blockages in PAD, promotes focal atherosclerotic plaque, but this has not been tested in vivo. Piezo1 is a mechanosensitive ion channel associated with hemodynamic changes in the arterial wall, but its role in flow-mediated atherosclerotic plaque deposition is not known. Objective: To develop a flow-mediated murine model of focal atherosclerotic plaque in the femoral arteries. Methods: 8 male and female S129 mice underwent partial femoral artery ligation (Figure A/B). Wall shear stress was calculated from duplex ultrasound imaging (Figure C/D). Atherogenic conditions were imposed with PCSK9 infection and high fat diet; this was initiated 1 week prior to partial femoral ligation. Histologic comparison of the left (partial femoral ligation) and right (normal stable flow) was performed. Results: Low wall shear stress was induced in this model (Figure C/D). Piezo1 expression was decreased in both male and female arteries under these conditions in this model (Figure E). Atherosclerotic plaque was induced by the partial femoral artery ligation but not on the normal stable flow side (Figure F). Conclusions: We have successfully developed a flow-mediated model of focal atherosclerotic plaque in murine femoral arteries. This is associated with downregulation of Piezo1 gene expression. Ongoing work is examining the causative role of Piezo1 on endothelial response to disturbed flow.

Impact of androgenic anabolic steroid use on cardiovascular and mental health in Danish recreational athletes: protocol for a nationwide cross-sectional cohort study as a part of the Fitness Doping in Denmark (FIDO-DK) study

IntroductionThe use of androgenic anabolic steroids (AASs) among recreational athletes is steadily increasing. However, knowledge regarding the potentially harmful effects of AAS primarily originates from case reports and small observational...

Association of immunologic findings of atheromatous plaques with subsequent cardiovascular events in patients with peripheral artery disease

Patients with peripheral artery disease (PAD) have a higher risk of cardiovascular events. We examined the histology of atheromatous plaques in the femoral artery and investigated their association with subsequent cardiovascular events in patients with PAD. Patients who underwent femoral artery endarterectomy between March 2010 and January 2021 were included. We analyzed the expression of myeloperoxidase (MPO), citrullinated histone, and programmed cell death ligand 1 (PD-L1) in femoral artery plaques by immunohistochemistry. Data on the subsequent occurrence of major adverse cardiovascular events (MACEs), major adverse limb events (MALEs), and all-cause mortality were retrospectively collected. A total of 37 patients were included. The median age was 71 (range, 42–90) years, and 25 patients (67.6%) were male. During the median follow-up of 24 months, 10 patients experienced MACEs and 16 patients had MALEs. Patients with MACEs had a higher number of MPO-stained cells (p = 0.044) and lower PD-L1 staining intensity (p = 0.021) in atheromatous plaques compared with those of patients with a stable prognosis. When the patients were grouped according to the immunologic score based on the MPO-stained cell number and PD-L1 staining intensity, those with a higher score had a significantly higher cumulative risk of MACEs (p = 0.014). The immunologic profile of excised peripheral artery plaques may be associated with future cardiovascular events in patients with PAD.

Validation and Reproducibility of Total Plaque Thickness in Carotid and Femoral Arteries Using Ultrasound

Plaque burden quantification by ultrasound improves cardiovascular (CV) risk prediction. However, measuring total plaque volume (TPV) with 3-D ultrasound, the current gold standard, is time consuming. In the present study we investigated the reproducibility of weighted total plaque thickness (wTPT) measured by 2-D ultrasound and its correlation with TPV. Participants in an ongoing study of subclinical atherosclerosis and CV risk with no known atherosclerotic CV disease but who were found to have one or more plaques in carotid or femoral arteries by 2-D ultrasound were included. A total of 34 women and 26 men (mean age: 59.4 y, standard deviation: 8.7) underwent primary 2-D and 3-D ultrasound examinations. Participants then underwent a 2-D ultrasound examination by another radiologist blinded to the first radiologist's findings. Finally, all participants underwent a follow-up 2-D ultrasound by the first radiologist. Comparison of wTPT measurements between the 2-D studies revealed no significant difference (mean difference: 0.29 mm, 95% confidence interval [CI]: -0.48 to 1.17). Inter-observer and intra-observer analyses revealed intraclass correlation coefficients of 0.97 (95% CI: 0.96-0.98) and 1.0 (95% CI: 0.99-1.00), respectively. wTPT correlated with TPV (Spearman's ρ=0.98, 95% CI: 0.96-0.99). Elapsed time for assessing wTPT was less than that for TPV (mean difference: 36.1 min, 95% CI: 26.0-46.3). wTPT had high reproducibility and correlation with TPV while requiring substantially less time. Future studies addressing the role of wTPT in predicting CV disease are needed.

Computed tomography defined femoral artery plaque composition predicts vascular complications during transcatheter aortic valve implantation.

Vascular and bleeding complications after transcatheter aortic valve implantation (TAVI) are common and lead to increased morbidity and mortality. Analysis of plaque at the arterial access site may improve prediction of complications. We investigated the association between demographic and procedural risk factors for Valve Academic Research Consortium (VARC-3) vascular complications in patients undergoing transfemoral TAVI with use of a vascular closure device (ProGlide® or MANTA®) in this retrospective cohort study. The ability of pre-procedure femoral CT angiography to predict complications was investigated including a novel method of quantifying plaque composition of the common femoral artery using plaque maps created with patient specific X-ray attenuation cut-offs. 23 vascular complications occurred in the 299 patients in the study group (7.7%). There were no demographic risk factors associated with vascular complications and no statistical difference between use of closure device (ProGlide® vs MANTA®) and vascular complications. Vascular complications after TAVI were associated with sheath size (OR 1.36, 95% CI 1.08-1.76, P 0.01) and strongly associated with CT-derived necrotic core volume in the common femoral artery of the procedural side (OR 17.49, 95% CI 1.21-226.60, P 0.03). Plaque map analysis of the common femoral artery by CT angiography reveals patients with greater necrotic core are at increased risk of VARC-3 vascular complications. The novel measurement of necrotic core volume in the common femoral artery on the procedural side by CT analysis was associated with post-TAVI vascular complications, which can be used to highlight increased risk.

Leech therapy and adjuvant Ayurveda treatment in the management of diabetic foot ulcer with atherosclerosis

Diabetic patients are more prevalent to atherosclerosis (29.1%); however, its pathophysiology is still unclear. Such cases mostly convert into either amputation due to rapid spread or lifelong anticoagulant. Ayurveda is famed to be a tool in prevention and management of such fatal or disabling surgeries by parasurgical procedure, i.e., leech therapy, Agnikarma, etc. This study presents a case of postdiabetic atherosclerosis (male/54 years old) with a complaint of blackening of the great toe of the right lower limb and and other associated symptoms such as intermittent claudication (Garde 4), Burning in sole, occasional numbness in the foot. this case was managed by the Ayurveda para-surgical procedure (Leech therapy). The patient was a known case of DM and taking medication for it for the last 1 year, but his blood sugar level was found to be uncontrolled (HB1Ac: 9.90). The patient had surgical history of coronary artery bypass graft before 8 years. His bilateral lower limb computed tomography angiography was suggestive of diffuse atherosclerotic fibrocalcified wall plaques in abdominal aorta, iliac, femoral, and both leg arteries. Clinical examination revealed black right greater toe with line of demarcation and on palpation, feeble femoral artery and downstream non-palpable arteries. As a part of treatment, leech application along with some rejuvenating oral drugs i.e. Sanjvani vati and pippali churna was given to the patient. On 2nd week of treatment protocol, black gangrenous great- toe was amputed which afterwards become open wound(approx.2cm x 2 cm). Afterward, daily wound dressing was done with Apamarga kshar taila or Thumari taila (As per the status of the wound) after cleaning with Triphala Kwath. After completion of treatment protocol, the patient got 85-90% relief in clinical symptoms and also previously feeble arteries were felt with full volume.

High relative amount of nodular calcification in femoral plaques is associated with milder lower extremity arterial disease

BackgroundClinical implications of different types of vascular calcification are poorly understood. The two most abundant forms of calcification, nodular and sheet calcification, have not been quantitatively analyzed in relation to the clinical presentation of lower extremity arterial disease (LEAD).MethodsThe study analyzed 51 femoral artery plaques collected during femoral endarterectomy, characterized by the presence of > 90% stenosis. Comprehensive clinical data was obtained from patient records, including magnetic resonance angiography (MRA) images, toe pressure and ankle brachial index measurements and laboratory values. The plaques were longitudinally sectioned, stained with Hematoxylin and Eosin and digitized in a deep learning platform for quantification of the relative area of nodular and sheet calcification to the plaque section area. A deep learning artificial intelligence algorithm was designed and independently validated to reliably quantify nodular calcification and sheet calcification. Vessel measurements and quantity of each calcification category was compared to the risk factors and clinical presentation.ResultsOn average, > 90% stenosed vessels contained 22.4 ± 12.3% of nodular and 14.5 ± 11.8% of sheet calcification. Nodular calcification area proportion in lesions with > 90% stenosis is associated with reduced risk of critically low toe pressure (< 30 mmHg) (OR = 0.910, 95% CI = 0.835–0.992, p < 0.05), severely lowered ankle brachial index (< 0.4) (OR = 0.912, 95% CI = 0.84–0.986, p < 0.05), and semi-urgent operation (OR = 0.882, 95% CI = 0.797–0.976, p < 0.05). Sheet calcification did not show any significant association.ConclusionsLarge amount of nodular calcification is associated with less severe LEAD. Patients with nodular calcification may have better flow reserves despite local obstruction.

A Single-Cell Atlas of the Atherosclerotic Plaque in the Femoral Artery and the Heterogeneity in Macrophage Subtypes between Carotid and Femoral Atherosclerosis.

Atherosclerosis of femoral arteries can cause the insufficient blood supply to the lower limbs and lead to gangrenous ulcers and other symptoms. Atherosclerosis and inflammatory factors are significantly different from other plaques. Therefore, it is crucial to observe the cellular composition of the femoral atherosclerotic plaque and identify plaque heterogeneity in other arteries. To this end, we performed single-cell sequencing of a human femoral artery plaque. We identified 14 cell types, including endothelial cells, smooth muscle cells, monocytes, three macrophages with four different subtypes of foam cells, three T cells, natural killer cells, and B cells. We then downloaded single-cell sequencing data of carotid atherosclerosis from GEO, which were compared with the one femoral sample. We identified similar cell types, but the femoral artery had significantly more nonspecific immune cells and fewer specific immune cells than the carotid artery. We further compared the differences in the proportion of inflammatory macrophages, and resident macrophages, and the proportion of inflammatory macrophages was greater within the carotid artery. Through comparing one femoral sequencing sample with carotid samples from public datasets, our study reveals the single-cell map of the femoral artery and the heterogeneity of carotid and femoral arteries at the cellular level, laying the foundation for mechanistic and pharmacological studies of the femoral artery.

Carotid and femoral artery plaques as predictors of cardiovascular and all-cause mortality in the middle-aged general population

Carotid and femoral artery plaques as predictors of cardiovascular and all-cause mortality in the middle-aged general population

Five-Year Experience With the Zenith Fenestrated Endovascular Graft for Treatment of Juxtarenal Abdominal Aortic Aneurysms at a Medium Volume Center

The use of fenestrated endovascular aortic repair (FEVAR) to treat abdominal aortic aneurysms involving the visceral arteries has increased worldwide with excellent results. The aim of this study was to evaluate the safety and effectiveness of the Zenith fenestrated endovascular graft (Cook Medical, Bloomington, IN) for the treatment of juxtarenal abdominal aortic aneurysms (AAAs) at a medium volume center. We performed a 5-year (2015-2020) retrospective analysis of all patients who had presented to our institution with juxtarenal AAAs and undergone FEVAR. Custom-made fenestrated stent grafts were designed with one to three fenestrations after analysis of computed tomography data sets. Renal alignment was performed with balloon-expandable stents. Follow-up included clinical examination, laboratory studies, mesenteric-renal duplex ultrasound, abdominal radiography, and computed tomography at hospital discharge, at 1, 6, and 12 months, and annually thereafter for ≤5 years. A total of 25 patients with juxtarenal AAAs had undergone FEVAR during the study period and were included in our analysis. Of the 25 patients, 18 were men and 7 were women, with a mean age of 71 ± 10 years. The mean aneurysm diameter was 60 ± 5 mm. A total of 53 visceral arteries required incorporation with fenestrations. Of these, 51 (96%) fenestrations were aligned by stents. Technical success was 100%. One intraoperative complication occurred. The patient developed bilateral common femoral artery plaque dissection and required common femoral artery endarterectomy. The mean length of hospital stay was 2.8 ± 1.5 days. No aneurysm ruptures or conversions were noted during a mean follow-up of 41 ± 15 months (range, 6-67 months). Of a total of 50 renal arteries targeted by fenestration, one renal artery occlusion (2%) and five cases of stenosis (10%) developed. Five patients (20%) required secondary interventions for renal artery stenosis or occlusion. One type I endoleak developed in 2 patients and one type II endoleak developed in 11 patients. One patient with a type II endoleak had experienced an increase in sac size at 1 year and underwent inferior mesenteric artery ligation. None of the patients died during the follow-up period. Our study has demonstrated that endovascular repair of juxtarenal AAAs with the Zenith fenestrated AAA stent graft at a medium volume center is safe and effective. Mortality and morbidity are low for properly selected patients treated at centers with experience in these procedures.

The intake of flavonoids, stilbenes, and tyrosols, mainly consumed through red wine and virgin olive oil, is associated with lower carotid and femoral subclinical atherosclerosis and coronary calcium

PurposeIt is suggested that polyphenols back the cardiovascular protection offered by the Mediterranean diet. This study evaluates the association of specific types of dietary polyphenols with prevalent subclinical atherosclerosis in middle-aged subjects.MethodsUltrasonography and TC were performed on 2318 men from the Aragon Workers Health Study, recruited between 2011 and 2014, to assess the presence of plaques in carotid and femoral arteries and coronary calcium. Polyphenol intake was assessed using a validated semi-quantitative 136-item food frequency questionnaire. The Phenol Explorer database was used to derive polyphenol class intake. Logistic and linear regressions were used to estimate the cross-sectional association of polyphenols intake with femoral and carotid subclinical atherosclerosis and coronary calcium.ResultsA higher intake of flavonoids (third vs. first tertile) was associated with a lower risk of both carotid (OR 0.80: CI 95% 0.62–1.02; P trend 0.094) and femoral (0.62: 0.48–0.80, P trend < 0.001) subclinical atherosclerosis. A higher intake of stilbenes was associated with a lower risk of femoral subclinical atherosclerosis (0.62: 0.46–0.83; P trend 0.009) and positive coronary calcium (0.75: 0.55–1.03; P trend 0.131). A higher intake of tyrosols was also associated with a lower risk of positive coronary calcium (0.80: 0.62–1.03; P trend 0.111). The associations remained similar when adjusted for blood lipids and blood pressure.ConclusionDietary flavonoids, stilbenes, and tyrosols, whose main sources are red wine and virgin olive oil, are associated with lower prevalence of subclinical atherosclerosis in middle-aged subjects.

Prevalence and correlates of vascular plaques and high intima thickness in a group of patients with high cardiovascular risk in Cameroon.

Introductioncarotid and femoral intima-media thickness (IMT) and atherosclerotic plaques are considered as markers of generalized atherosclerosis and as independent predictors of cardiovascular events and mortality. This study aimed to determine the prevalence and correlates between carotid and femoral intima-media thickness and plaques in patients with major cardiovascular risk factors (CVRFs).Methodswe carried out a cross-sectional study at the Yaoundé Central Hospital between December 2017 and May 2018. B-mode ultrasound was used to assess for the presence of plaques and also measure the IMT at the carotid and femoral arteries in patients with CVRFs. Logistic regression analysis was performed to examine the association between ultrasound findings (presence of plaques or IMT > 0.9mm) and cardiovascular risk factors. A p-value <0.05 was considered significant.Resultsamongst the 71 patients, 43.7% were male and 56.3% were female. The mean age was 61.6 ± 8.4 years and ranged from 40 to 75 years. Thirty-nine (54.9%) participants had carotid atherosclerotic plaques and 33 (46.5%) participants had femoral artery plaques. The plaque burden was higher in the carotid arteries. Plaques at one or more artery sites were seen in 67.6% of participants. An IMT ≥ 0.9 mm was seen in only 1.4 to 2.8% of participants. In the multivariable analysis using binary logistic regression, age > 50 years (males) or 60 years (females) (aOR: 11.3 [95% CI: 2.2 - 56.8], p=0.002) and presence of dyslipidemia (aOR: 3.6 [95% CI: 1.2 - 11], p=0.043) were associated with carotid artery plaques, while presence of dyslipidemia (aOR: 4.8 [95% CI1.8 - 13.3], p=0.004) and high cardiovascular risk profile (10-year risk> 20%) (aOR: 4.2 [95% CI: 1.2 - 13.2], p=0.0495) were associated with femoral artery plaques.Conclusionplaques were more frequent than an IMT > 0.9 mm, with a higher plaque burden in the carotid arteries. Plaques were associated with advanced age, dyslipidemia, and a high cardiovascular risk profile.

Prevalence of elevated serum fatty acid synthase in chronic limb-threatening ischemia

There are currently no serum-based evaluations that can corroborate the severity of peripheral artery disease (PAD). In this cross-sectional study, we assessed the prevalence of elevated serum fatty acid synthase (cFAS) in patients with chronic limb-threatening ischemia (CLTI) and evaluated the accuracy of its use in detecting this condition. Preoperative fasting serum samples from 87 patients undergoing vascular intervention were collected between October 2014 and September 2016. Median age was 62 years, with 56 (64%) men, and 32 (37%) with CLTI. We found that elevated cFAS content (OR 1.17; 95% CI 1.04–1.31), type 2 diabetes (T2D; OR 5.22; 95% CI 1.77–15.4), and smoking (OR 3.53; 95% CI 1.19–10.5) were independently associated with CLTI and could detect the presence of CLTI with 83% accuracy (95% CI 0.74–0.92). Furthermore, serum FAS content was positively correlated with FAS content in femoral artery plaque in patients with severe PAD ({R}^{2} = 0.22; P = 0.023). Finally, significantly higher co-localization of FAS and ApoB were observed within lower extremity arterial media (P < .001). Our findings indicate that serum FAS content is a marker for disease severity in patients with PAD, independent of concomitant T2D and smoking, and may play a key role in FAS and ApoB peripheral plaque progression.

Subclinical Liver Disease Is Associated with Subclinical Atherosclerosis in Psoriasis: Results from Two Observational Studies

Psoriasis is associated with a higher risk of liver diseases. We investigated the impact of hepatic steatosis (European cohort) and hepatic inflammation (United States cohort) on subclinical atherosclerosis. In the European cohort (n= 76 psoriasis participants and 76 controls), nonalcoholic fatty liver disease, assessed by the sonographic hepatorenal index, was more prevalent in psoriasis than in controls (61% vs. 45%; P= 0.04). Participants with psoriasis with nonalcoholic fatty liver disease had a higher prevalence of subclinical atherosclerosis (ultrasonographic presence of plaque in femoral or carotid arteries) than participants with psoriasis without nonalcoholic fatty liver disease (61% vs. 23%; P= 0.006) and controls with nonalcoholic fatty liver disease (61% vs. 32%; P < 0.05). Sonographic hepatorenal index was a determinant of subclinical atherosclerosis in psoriasis (OR= 3.5; P= 0.01). In the United States cohort (n= 162 participants with psoriasis who underwent positron emission tomography and coronary computed tomography angiography), those with high hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake had higher noncalcified (1.3 [0.49 mm2] vs. 1.0 [0.40 mm2]), fibrofatty (0.23 [0.15 mm2] vs. 0.11 [0.087 mm2]), and lipid-rich necrotic core (4.3 [2.3 mm2] vs. 3.0 [1.7 mm2]) coronary burden (all P < 0.001). Hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake associated with noncalcified (β= 0.28; P < 0.001), fibrofatty (β= 0.49; P < 0.001), and lipid-rich necrotic core (β= 0.28; P= 0.003) burden. These results show the downstream cardiovascular effects of subclinical liver disease in psoriasis.

Visual Scale as a Non-Invasive Method for Evaluation of Risk and Severity of Coronary Atherosclerosis.

Aim To evaluate quantitative and qualitative characteristics of atherosclerotic plaques (ASP) in carotid arteries (CA) and femoral arteries (FA) and to use these data for developing a visual scale (VS) for noninvasive diagnosis and determination of severity of coronary atherosclerosis.Material and methods This study included 216 patients (115 men and 101 women) aged 24 to 87 years (mean age, 61.5±10.73 years). All patients underwent coronary angiography (CAG) for detecting and determining severity of CA atherosclerosis and duplex scanning (DS) for detecting atherosclerosis of CA and FA.Results Analysis of ultrasound parameters of ASP in CA and FA showed that the maximal ASP height, moderate stenosis and maximal stenosis of the arterial bed had higher predictive values than other ultrasound parameters. These parameters were used for forming diagnostic complexes, on the basis of which two individual VSs for CA and FA were developed. Based on the high prognostic value of both scales, they were combined into one that was named VSCOMB. A ROC analysis determined cut-off points of the VSCOMB for diagnosis of CA atherosclerosis of various severity. VSCOMB scores &gt;4 indicated pronounced CA atherosclerosis with sensitivity of 86.1 % and specificity of 87.5 % whereas VSCOMB scores ≤4 excluded it. Thus, VSCOMB score 0-1 indicated the absence of CA atherosclerosis; score 2-4 indicated the presence of subclinical CA atherosclerosis; and score &gt;4 indicated severe CA atherosclerosis.Conclusion A VSCOMB was developed that includes a set of ultrasound parameters for CA and FA and is useful for noninvasive diagnosis of CA atherosclerosis of various severity. Simple and convenient use of VSCOMB allows it to be used at the screening stage to detect subclinical CA atherosclerosis and to prevent its progression.

Osteoid Metaplasia in Femoral Artery Plaques Is Associated With the Clinical Severity of Lower Extremity Artery Disease in Men

Lamellar metaplastic bone, osteoid metaplasia (OM), is found in atherosclerotic plaques, especially in the femoral arteries. In the carotid arteries, OM has been documented to be associated with plaque stability. This study investigated the clinical impact of OM load in femoral artery plaques of patients with lower extremity artery disease (LEAD) by using a deep learning-based image analysis algorithm. Plaques from 90 patients undergoing endarterectomy of the common femoral artery were collected and analyzed. After decalcification and fixation, 4-μm-thick longitudinal sections were stained with hematoxylin and eosin, digitized, and uploaded as whole-slide images on a cloud-based platform. A deep learning-based image analysis algorithm was trained to analyze the area percentage of OM in whole-slide images. Clinical data were extracted from electronic patient records, and the association with OM was analyzed. Fifty-one (56.7%) sections had OM. Females with diabetes had a higher area percentage of OM than females without diabetes. In male patients, the area percentage of OM inversely correlated with toe pressure and was significantly associated with severe symptoms of LEAD including rest pain, ulcer, or gangrene. According to our results, OM is a typical feature of femoral artery plaques and can be quantified using a deep learning-based image analysis method. The association of OM load with clinical features of LEAD appears to differ between male and female patients, highlighting the need for a gender-specific approach in the study of the mechanisms of atherosclerotic disease. In addition, the role of plaque characteristics in the treatment of atherosclerotic lesions warrants further consideration in the future.

Osteogenic differentiation and calcification of human aortic smooth muscle cells is induced by the RCN2/STAT3/miR-155-5p feedback loop

BackgroundVascular calcification (VC) is associated with the high morbidity and mortality of cardiovascular diseases in dialysis patients and is a process in which vascular smooth muscle cells (VSMCs) actively differentiate into osteoblast-like cells. Reticulocalbin-2 (RCN2) is involved in the process of osteogenic differentiation under diabetic conditions, but its regulatory role under hyperphosphatemic conditions and the related mechanisms remain unclear. In this study, the importance of the interactions among RCN2, STAT3 and miR-155-5p during the osteogenic differentiation and calcification of human aortic VSMCs (HASMCs) were investigated. MethodsRCN2 was measured in femoropopliteal artery plaque specimens from 6 peripheral arterial disease (PAD) patients with chronic kidney disease (CKD) and 6 PAD patients without CKD. RCN2 protein and mRNA expression were assessed in the high phosphate-induced aortic rings culture ex vivo model. In vitro calcification assays and molecular mechanism studies were performed in HASMCs. ResultsImmunohistochemical staining results revealed increased RCN2 expression in the calcified plaques of femoral arteries of patients with CKD and in a high phosphate-induced aortic culture ex vivo model. RCN2 promoted HASMCs osteogenic differentiation and calcification by inducing STAT3 phosphorylation. Furthermore, inhibition of STAT3 activation by cryptotanshinone (CT) promoted miR-155-5p expression in HASMCs. In turn, miR-155-5p inhibited RCN2 mRNA expression, while RCN2 overexpression partially offset the miR-155-5p-mediated inhibition of HASMC calcification, acting as a positive feedback loop. ConclusionThese results demonstrate that RCN2 is a crucial regulator of VC under hyperphosphatemic conditions. RCN2/STAT3/miR-155-5p feedback loop is important in VC and targeting each member of this feedback loop could potentially reverse high phosphate-induced VC.

Underperformance of clinical risk scores in identifying imaging-based high cardiovascular risk in psoriasis: results from two observational cohorts.

We aimed to evaluate whether traditional risk scores [short-term, 'psoriasis-modified' (multiplied by 1.5) and lifetime] were able to capture high cardiovascular disease (CVD) risk as defined by the presence of atherosclerotic plaques in coronary, femoral, or carotid arteries in psoriasis. We used two prospectives obseravational cohorts. European cohort: femoral and carotid atherosclerotic plaques were evaluated by ultrasound in 73 psoriasis patients. Lifetime CVD risk (LTCVR) was evaluated with QRISK-LT; short-term CVD risk was evaluated with SCORE and psoriasis-modified SCORE. American cohort: 165 patients underwent coronary computed tomography angiography to assess presence of coronary plaques. LTCVR was evaluated with atherosclerotic cardiovascular disease (ASCVD-LT) lifetime; short-term CVD risk was evaluated with ASCVD and psoriasis-modified ASCVD. European cohort: subclinical atherosclerosis was present in 51% of patients. QRISK-LT identified 64% of patients with atherosclerosis missing a high proportion (35%) with atheroma plaque (P < 0.05). The percentage of patients with atherosclerosis identified by QRISK-LT was significantly higher than those detected by SCORE (0%) and modified SCORE (10%). American cohort: subclinical atherosclerosis was present in 54% of patients. ASCVD-LT captured 54% of patients with coronary plaques missing a high proportion (46%) with coronary plaque (P < 0.05). The percentage of patients with atheroma plaques detected with ASCVD and modified ASCVD were only 20% and 45%, respectively. Application of lifetime, short-term and 'psoriasis-modified' risk scores did not accurately capture psoriasis patients at high CVD risk.

New three-dimensional volumetric ultrasound probe for accurate quantification of atherosclerotic plaque volume

Abstract Background Atherosclerosis burden is directly related with the development of clinical cardiovascular events. Recent ESC guidelines endorse carotid and/or femoral plaque burden assessment as a complement for conventional cardiovascular risk evaluation. Compared with previous 3D probes, new 3D-matrix transducers for vascular ultrasound imaging are designed to improve functionality and image quality for an accurate study of atherosclerosis burden. Purpose We aimed to validate a commercially available 3D-matrix transducer for plaque volume measurement in early disease stages (small plaques) when accurate plaque detection and quantification is challenging, and intermediate-advanced (medium-large size) plaques in carotid and femoral arteries. Methods We performed an ex vivo study using carotid and femoral arterial specimens from a pig model of early atherosclerosis in which actual 3D vascular ultrasound (3DVUS) volume measurements obtained using the new 3D-matrix transducer (XL14–3) were correlated against gold-standard histological measurements. Moreover, we performed a clinical experiment in a subset of intermediate-high risk patients from the “Athero-Brain: Head to Heart (H2H)” study with patent carotid and femoral atherosclerosis for comparing plaque volume evaluated by the new XL14–3 3D-matrix transducer, based on “electronic” 3D-sweep technology, with that measured by previously validated VL13–5 “mechanical” 3D-sweep transducer that uses a mechanically steered linear-array. Results In the ex vivo setting, we evaluated 11 atherosclerotic plaques (6 carotid and 5 femoral plaques, mean plaque volume 16.5±22.5 mm3 ranging in size from 1 to 56 mm3), finding a strong correlation between 3DVUS measures and the histological gold-standard with an intraclass correlation coefficient (ICC) of 0.994 (95% CI [0.976; 0.998]). In the clinical setting, we measured 25 plaques (14 carotid and 11 femoral plaques; mean plaque volume 273.4±216.5 mm3 ranging in size from 10 to 859 mm3) from 8 patients (mean age 75±5 years old, 45% men) finding again a strong correlation between 3DVUS electronic-based and mechanical-based volume measurements (ICC=0.996 95% CI [0.991; 0.998]). Correlation and Bland-Altman plots for the measurements of both experiments are displayed in the figure and showed good agreement (Slope close to 1 in the Passing Bablock analysis) with small or lower than clinically relevant differences between measurements. Conclusions 3DVUS using new matrix technology accurately measures plaque volumes of early (small-size) to intermediate-advanced plaques located in superficial arteries like carotid and femoral arteries. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Carlos III Institute through an Integrated Excellence Project Grant