Evento cardiovascular en una cohorte de pacientes con artritis reumatoide en Castilla-La Mancha, utilidad de la ecografía carotídea / Cardiovascular event in a cohort of rheumatoid arthritis patients in Castilla-La Mancha: Utility of carotid ultrasound

La artritis reumatoide (AR) presenta una mortalidad de 1,3-3 veces superior a la población general donde destaca la mortalidad de origen cardiovascular con un 40-50%. Actualmente se considera la enfermedad cardiovascular como una manifestación extraarticular de la AR, siendo un factor de riesgo independiente de los tradicionales, con un riesgo elevado de enfermedad cardiovascular (OR: 1,5-4,0). La medición ecográfica del grosor íntimo medial (GIM) de la arteria carótida común y la presencia de placas ateromatosas es un método no invasivo y marcador subrogado de arterioesclerosis subclínica. Objetivo: Establecer si los hallazgos de arterioesclerosis subclínica por ecografía carotídea pueden ser un buen predictor del desarrollo de eventos cardiovasculares (ECV) en una cohorte de pacientes con AR a 10 años. Metodología: Se evaluó una cohorte de pacientes con AR atendidos en consulta externa de Reumatología de una hospital de Castilla-La Mancha durante el año 2013. Se realizó una evaluación para el desarrollo de ECV a los 10 años siguientes de comenzado el estudio y se analizó su correlación con los hallazgos ecográficos previos de GIM y placas ateromatosas. Resultados: Ocho (24%) pacientes presentaron un ECV. Tres (9%), episodio de fallo cardiaco; 3 (9%) accidente cerebrovascular y 2 (6%) episodio de infarto agudo al miocardio. Los pacientes con AR que desarrollaron un ECV habían presentado un GIM mayor (0,97±0,08mm) en comparación con los pacientes con AR que no tuvieron complicaciones cardiovasculares (0,74±0,15mm) (p=0,003). La presencia de un GIM≥0,9mm y placas ateromatosas representó un riesgo relativo de 12,25 (p=0,012) y 18,66 (p=0,003), respectivamente, para el desarrollo de un ECV. Conclusiones: La ecografía carotídea en pacientes con AR nos podría permitir la detección precoz de aterosclerosis subclínica antes del desarrollo de ECV, siendo fundamentalmente el GIM≥0,9mm el hallazgo más asociado a ECV y no influenciado por la edad.(AU)

Rheumatoid arthritis (RA) has a mortality rate 1.3–3 times higher than the general population, with cardiovascular mortality accounting for 40%–50% of cases. Currently, cardiovascular disease is considered an extra-articular manifestation of RA (OR: 1.5–4.0). Ultrasound measurement of the intima-media thickness (IMT) of the common carotid artery and the presence of atherosclerotic plaques is a non-invasive method and a surrogate marker of subclinical arteriosclerosis. Objective: To determine if subclinical arteriosclerosis findings through carotid ultrasound can serve as a good predictor of cardiovascular events (CVE) development in a cohort of RA patients over a 10-year period. Methodology: A cohort of RA patients seen in the rheumatology outpatient clinic of a hospital in Castilla-La Mancha in 2013 was evaluated. A prospective evaluation for the development of CVE over the following 10 years was conducted, and its correlation with previous ultrasound findings of IMT and atherosclerotic plaques was analyzed. Results: Eight (24%) patients experienced a CVE. Three (9%) had heart failure, three (9%) had a stroke, and two (6%) experienced acute myocardial infarction. RA patients who developed a CVE had a higher IMT (0.97±0.08mm) compared to the RA patients without cardiovascular complications (0.74±0.15mm) (P=.003). The presence of IMT≥0.9mm and atherosclerotic plaques had a relative risk of 12.25 (P=.012) and 18.66 (P=.003), respectively, for the development of a CVE. Conclusions: Carotid ultrasound in RA patients may allow for early detection of subclinical atherosclerosis before the development of CVE, with IMT≥0.9mm being the most closely associated finding with CVE, unaffected by age.(AU)

Time-frequency analysis reveals an association between the specific nuclear magnetic resonance (NMR) signal properties of serum samples and arteriosclerotic lesion progression in a diabetes mouse model.

Diabetes causes arteriosclerosis, primarily due to persistent hyperglycemia, subsequently leading to various cardiovascular events. No method has been established for directly detecting and evaluating arteriosclerotic lesions from blood samples of diabetic patients, as the mechanism of arteriosclerotic lesion formation, which involves complex molecular biological processes, has not been elucidated. "NMR modal analysis" is a technology that enables visualization of specific nuclear magnetic resonance (NMR) signal properties of blood samples. We hypothesized that this technique could be used to identify changes in blood status associated with the progression of arteriosclerotic lesions in the context of diabetes. The study aimed to assess the possibility of early detection and evaluation of arteriosclerotic lesions by NMR modal analysis of serum samples from diabetes model mice. Diabetes model mice (BKS.Cg db/db) were bred in a clean room and fed a normal diet. Blood samples were collected and centrifuged. Carotid arteries were collected for histological examination by hematoxylin and eosin staining on weeks 10, 14, 18, 22, and 26. The serum was separated and subjected to NMR modal analysis and biochemical examination. Mice typically show hyperglycemia at an early stage (8 weeks old), and pathological findings of a previous study showed that more than half of mice had atheromatous plaques at 18 weeks old, and severe arteriosclerotic lesions were observed in almost all mice after 22 weeks. Partial least squares regression analysis was performed, which showed that the mice were clearly classified into two groups with positive and negative score values within 18 weeks of age. The findings of this study revealed that NMR modal properties of serum are associated with arteriosclerotic lesions. Thus, it may be worth exploring the possibility that the risk of cardiovascular events in diabetic patients could be assessed using serum samples.

Interaction Between Arteriosclerosis and Amyloid-ß on Cognitive Function.

BACKGROUND: Dementia is a multifactorial disease, with Alzheimer's disease (AD) and vascular pathology often co-occurring in many individuals with dementia. Yet, the interplay between AD and vascular pathology in cognitive decline is largely undetermined. OBJECTIVE: The aim of the present study was to examine the joint effect of arteriosclerosis and AD pathology on cognition in the general population without dementia. METHODS: We determined the interaction between blood-based AD biomarkers and CT-defined arteriosclerosis on cognition in 2,229 dementia-free participants of the population-based Rotterdam Study (mean age: 68.9 years, 52% women) cross-sectionally. RESULTS: Amyloid-ß (Aß)42 and arterial calcification were associated with cognitive performance. After further adjustment for confounders in a model that combined all biomarkers, only arterial calcification remained independently associated with cognition. There was a significant interaction between arterial calcification and Aß42 and between arterial calcification and the ratio of Aß42/40. Yet, estimates attenuated, and interactions were no longer statistically significant after adjustment for cardio metabolic risk factors. CONCLUSIONS: Arteriosclerosis and AD display additive interaction-effects on cognition in the general population, that are due in part to cardio metabolic risk factors. These findings suggest that joint assessment of arteriosclerosis and AD pathology is important for understanding of disease etiology in individuals with cognitive impairment.

Sex-specific association between carotid atherosclerosis and fundus arteriosclerosis in a Chinese population: a retrospective cross-sectional study.

OBJECTIVES: Vascular stiffening is highly predictive of major adverse cardiovascular events. It is not clear whether microangiopathy, such as fundus arteriosclerosis, is related to carotid atherosclerosis. Hence, this study was designed to investigate the relationship between carotid atherosclerosis and fundus arteriosclerosis among individuals of different sexes in the Chinese health-examination population. METHODS: This retrospective cross-sectional study involved 20,836 participants, including 13050 males and 7786 females. All participants underwent a detailed health examination, including medical history assessment, physical examination, assessment of lifestyle factors, fundus photography, Doppler ultrasound examination of the neck, and laboratory examinations. Two trained ophthalmologists analysed fundus arteriosclerosis based on fundus photographs, while carotid atherosclerosis was diagnosed using colour Doppler sonography of the neck. Binary logistic regression was used to analyse the relationship between carotid atherosclerosis and fundus arteriosclerosis. RESULTS: In participants with fundus arteriosclerosis, the incidence of carotid atherosclerosis was higher than that of participants without fundus arteriosclerosis (52.94% vs. 47.06%). After adjustments for potential confounding factors, fundus arteriosclerosis was significantly associated with the risk of carotid atherosclerosis. The OR with 95% CI for fundus arteriosclerosis was 1.17 (1.02, 1.34) with p = 0.0262, and individuals who did not have fundus arteriosclerosis were used as a reference in the total population. Fundus arteriosclerosis was associated with the incidence of carotid atherosclerosis in males (p = 0.0005) but not in females (p = 0.0746). CONCLUSIONS: Fundus arteriosclerosis was closely associated with carotid atherosclerosis in the Chinese population. This association was found in males but not in females.

Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion: The CMOSS Randomized Clinical Trial.

Importance: Prior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), but there have been subsequent improvements in surgical techniques and patient selection. Objective: To evaluate EC-IC bypass surgery in symptomatic patients with atherosclerotic occlusion of the ICA or MCA, using refined patient and operator selection. Design, Setting, and Participants: This was a randomized, open-label, outcome assessor-blinded trial conducted at 13 centers in China. A total of 324 patients with ICA or MCA occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency based on computed tomography perfusion imaging were recruited between June 2013 and March 2018 (final follow-up: March 18, 2020). Interventions: EC-IC bypass surgery plus medical therapy (surgical group; n = 161) or medical therapy alone (medical group; n = 163). Medical therapy included antiplatelet therapy and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. There were 9 secondary outcomes, including any stroke or death within 2 years and fatal stroke within 2 years. Results: Among 330 patients who were enrolled, 324 patients were confirmed eligible (median age, 52.7 years; 257 men [79.3%]) and 309 (95.4%) completed the trial. For the surgical group vs medical group, no significant difference was found for the composite primary outcome (8.6% [13/151] vs 12.3% [19/155]; incidence difference, -3.6% [95% CI, -10.1% to 2.9%]; hazard ratio [HR], 0.71 [95% CI, 0.33-1.54]; P = .39). The 30-day risk of stroke or death was 6.2% (10/161) in the surgical group and 1.8% (3/163) in the medical group, and the risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2.0% (3/151) and 10.3% (16/155), respectively. Of the 9 prespecified secondary end points, none showed a significant difference including any stroke or death within 2 years (9.9% [15/152] vs 15.3% [24/157]; incidence difference, -5.4% [95% CI, -12.5% to 1.7%]; HR, 0.69 [95% CI, 0.34-1.39]; P = .30) and fatal stroke within 2 years (2.0% [3/150] vs 0% [0/153]; incidence difference, 1.9% [95% CI, -0.2% to 4.0%]; P = .08). Conclusions and Relevance: Among patients with symptomatic ICA or MCA occlusion and hemodynamic insufficiency, the addition of bypass surgery to medical therapy did not significantly change the risk of the composite outcome of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01758614.

Mönckeberg Medial Arteriosclerosis in a Geriatric Patient with Chronic Kidney Disease and Poorly Controlled Diabetes Reporting for a Dental Recall Visit.

Mönckeberg medial arteriosclerosis is a condition characterized by the calcification of the tunica media layer of the blood vessels that are visible on plain radiography or sectional tomography. In dentistry, a properly acquired panoramic radiograph may show the condition incidentally. It is also known as medial arterial calcinosis and can be associated with diabetes mellitus or chronic kidney disease. This condition is different from the more common atherosclerosis where the tunica intima remains unaffected, and the diameter of the vessel lumen is preserved. Dental treatment can be performed when the patient is stable with medically controlled diabetes.

Novel Smart Assistance System for Arteriosclerosis Evaluation.

Arteriosclerosis is a cardiovascular disease that can cause calcification, sclerosis, stenosis, or obstruction of blood vessels and may further cause abnormal peripheral blood perfusion or other complications. In clinical settings, several approaches, such as computed tomography angiography and magnetic resonance angiography, can be used to evaluate arteriosclerosis status. However, these approaches are relatively expensive and require an experienced operator and often the injection of a contrast agent. In this article, a novel smart assistance system based on near-infrared spectroscopy was proposed that can noninvasively assess blood perfusion and thus indicate arteriosclerosis status. In this system, a wireless peripheral blood perfusion monitoring device simultaneously monitors changes in hemoglobin parameters and the cuff pressure applied by a sphygmomanometer. Several indexes extracted from changes in hemoglobin parameters and cuff pressure were defined and can be used to estimate blood perfusion status. A neural network model for arteriosclerosis evaluation was constructed using the proposed system. The relationship between the blood perfusion indexes and arteriosclerosis status was investigated, and the neural network model for arteriosclerosis evaluation was validated. Experimental results indicated that the differences in many blood perfusion indexes for different groups were significant and that the neural network model could effectively evaluate arteriosclerosis status (accuracy = 80.26%). By using a sphygmomanometer, the model can be employed for simple arteriosclerosis screening and blood pressure measurements. The model offers real-time noninvasive measurement, and the system is relatively inexpensive and easy to operate.

Clinical, laboratory and ultrasonographic risk factors for uterine artery arteriosclerosis: Insights for uterus transplantation.

OBJECTIVE: To assess uterine artery arteriosclerosis prevalence in women undergoing total hysterectomy for benign diseases, and any associations between clinical, laboratory, and ultrasound factors and uterine artery arteriosclerosis occurrence. METHODS: A single center, observational, prospective, cohort study was performed enrolling all symptomatic patients scheduled for total hysterectomy from May to December 2021. Our outcomes were: uterine artery arteriosclerosis prevalence and the difference in clinical, laboratory, and ultrasonographic factors between patients with and without uterine artery arteriosclerosis. RESULTS: Forty women were included. Uterine artery arteriosclerosis prevalence was 70%. Body mass index (BMI) (P = 0.04) and triglycerides (P = 0.04) were significantly higher in patients with uterine artery arteriosclerosis than in patients without; while high-density lipoprotein (HDL) (P = 0.02) was significantly lower. Uterine arteries with arteriosclerosis showed higher peak systolic velocity (PSV) values compared with vessels without arteriosclerosis (P = 0.05). CONCLUSIONS: Uterine artery arteriosclerosis shows a high prevalence in women undergoing total hysterectomy for benign diseases. Higher BMI, serum triglycerides, and PSV, and lower serum HDL appear as risk factors for uterine artery arteriosclerosis.

Mönckeberg's medial arteriosclerosis in the oral and maxillofacial region: A pilot study.

OBJECTIVE: To evaluate the prevalence of medial vascular calcifications in the oral and maxillofacial region and their association with systemic diseases. MATERIALS AND METHODS: The study included 211 consecutive patients with systemic diseases (January 2015-May 2016). Medical history and radiographic images were evaluated. Univariate analysis (t-test) was performed for continuous variables (age). The Chi square test was applied for the categorical variables (Mönckeberg medial arteriosclerosis [MMA], gender). RESULTS: There was a 6.2% prevalence of MMA. The mean age of patients with MMA was 65.46 ± 13.38. The prevalence of kidney disease in patients with MMA was significantly higher than in those without MMA (p < 0.001). This finding was maintained even after adjusting for other systemic diseases (OR = 31.84 [8.63-136.78]). CONCLUSION: A significant prevalence of MMA in kidney disease patients was observed in this pilot study.

Intracranial Carotid Arteriosclerosis Mediates the Association Between Blood Pressure and Cerebral Small Vessel Disease.

BACKGROUND: Intracranial arteriosclerosis could explain the association between blood pressure (BP) and cerebral small vessel disease (CSVD). Therefore, we tested whether intracranial carotid artery calcification (ICAC) mediates the association between BP and CSVD and determined pathophysiological mechanisms based on ICAC subtypes. METHODS: One thousand four hundred fifty-eight stroke-free participants from the Rotterdam Study (mean age, 68 years; 52% women) underwent nonenhanced computed tomography scans to quantify ICAC volume (mm3) between 2003 and 2015. ICAC was categorized into intimal and internal elastic lamina calcifications. CSVD included white matter hyperintensities volume, the presence of lacunes, and cerebral microbleeds visualized on magnetic resonance imaging. Office BP included systolic BP, diastolic BP, pulse pressure, and mean arterial pressure. Mediation analysis included a 2-way decomposition to determine the direct association between BP and CSVD and the indirect or mediated effect (negative or positive mediations expressed in %) of log-ICAC volume on such association. RESULTS: BP and log-ICAC were correlated and were also associated with CSVD. In all participants, total log-ICAC volume mediated the association of diastolic BP (-14.5%) and pulse pressure (16.5%) with log-white matter hyperintensities. Internal elastic lamina log-ICAC volume mediated -19.5% of the association between diastolic BP and log-white matter hyperintensities; intimal log-ICAC volume did not mediate associations. For lacunes, total and internal elastic lamina log-ICAC volume mediated the association of diastolic BP (-40% and -45.8%) and pulse pressure (26.9% and 18.2%). We did not observe mediations for cerebral microbleeds. CONCLUSIONS: Intracranial arteriosclerosis mediates the association between BP and CSVD. Internal elastic lamina calcification, considered a proxy of arterial stiffness, is the leading mechanism explaining the link between BP and CSVD.

OTNet: A CNN Method Based on Hierarchical Attention Maps for Grading Arteriosclerosis of Fundus Images with Small Samples.

The severity of fundus arteriosclerosis can be determined and divided into four grades according to fundus images. Automatically grading of the fundus arteriosclerosis is helpful in clinical practices, so this paper proposes a convolutional neural network (CNN) method based on hierarchical attention maps to solve the automatic grading problem. First, we use the retinal vessel segmentation model to separate the important vascular region and the non-vascular background region from the fundus image and obtain two attention maps. The two maps are regarded as inputs to construct a two-stream CNN (TSNet), to focus on feature information through mutual reference between the two regions. In addition, we use convex hull attention maps in the one-stream CNN (OSNet) to learn valuable areas where the retinal vessels are concentrated. Then, we design an integrated OTNet model which is composed of TSNet that learns image feature information and OSNet that learns discriminative areas. After obtaining the representation learning parts of the two networks, we can train the classification layer to achieve better results. Our proposed TSNet reaches the AUC value of 0.796 and the ACC value of 0.592 on the testing set, and the integrated model OTNet reaches the AUC value of 0.806 and the ACC value of 0.606, which are better than the results of other comparable models. As far as we know, this is the first attempt to use deep learning to classify the severity of atherosclerosis in fundus images. The prediction results of our proposed method can be accepted by doctors, which shows that our method has a certain application value.

Calcified facial and maxillary arteries: Incidental radiographic findings indicative of Mönckeberg arteriosclerosis.

BACKGROUND AND OVERVIEW: Mönckeberg arteriosclerosis is a disease of unknown etiology characterized by dystrophic calcifications within the tunica media of small- and medium-sized arteries, leading to reduced arterial compliance. The authors report a case discovered incidentally on dental radiographs. CASE DESCRIPTION: A 78-year-old man with a complex medical history was seen for routine oral health care. Panoramic and bite-wing radiographs revealed a tortuous, linear calcification in the area of the left mandibular first molar anterior to the angle of the mandible and suggestive of a calcified facial artery. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Medical radiologists have used the presence of arterial calcifications to determine the severity and prognosis of such diseases as primary hyperparathyroidism, secondary hyperparathyroidism, coronary artery disease, and diabetes. The presence of Mönckeberg arteriosclerosis on dental radiographs can help oral health care professionals identify patients with undiagnosed systemic disease.

Mönckeberg Arteriosclerosis of the Facial Vasculature Presentation on CBCT: A Case Report.

Mönckeberg arteriosclerosis, also known as Mönckeberg sclerosis or Mönckeberg medial calcinosis, is a well-documented phenomenon in medicine due to its association with a number of serious systemic conditions and aging. This article presents a unique case of Mönckeberg arteriosclerosis in the oral facial region demonstrated clearly on cone-beam computed tomography (CBCT). The reporting of Mönckeberg arteriosclerosis in dental literature is uncommon even though the radiographic features of the head and neck on plain film and CBCT are unique to the condition. As dentistry and medicine strive to move toward an integrated one-health model, it will be important for dental practitioners to recognize this condition during dental radiographic evaluation. A practitioner's understanding of the potential medical implications and the need for appropriate referral to a medical colleague could be lifesaving for a dental patient.

High-resolution MRI of the vessel wall helps to distinguish moyamoya disease from atherosclerotic moyamoya syndrome.

AIM: To evaluate the value of high-resolution magnetic resonance imaging of the vessel wall (VWI) for differentiating moyamoya disease (MMD) from atherosclerotic moyamoya syndrome (AS-MMS). MATERIALS AND METHODS: Twenty-one patients with MMD or AS-MMS were assessed retrospectively by two independent raters regarding and magnetic resonance angiography (MRA) stage grading score; collateral development in the lateral fissure and basal ganglia on MRA; and pattern of the thickening of the arterial wall; presence, degree, and pattern of enhancement; presence and distribution of deep tiny flow voids (DTFVs) and collateral development in the lateral fissure and basal ganglia on VWI. After univariate analysis between the two groups, logistic regression models based on imaging findings of MRA or VWI were implemented respectively, and receiver operating characteristic (ROC) curves were generated to compare the discriminatory power of the two imaging methods for diagnosis of MMD. Interrater agreement was analysed using an unweighted Cohen's κ or interclass correlation coefficient (ICC). RESULTS: MMD manifested as more concentric thickening, more homogeneous enhancement, higher presence of DTFV, smaller outer-wall boundary area of stenosis or occlusion, and smaller remodelling index on VWI. After Bonferroni-Holm correction for multiple comparisons, for AS-MMS, collaterals in both the lateral fissure and basal ganglia were not usually present on either MRA or VWI. The diagnostic performance of the multivariate logistic regression model based on VWI with an accuracy of 87.1% for classification was higher than MRA. Interrater agreement was moderate or substantial for all the imaging findings. CONCLUSIONS: VWI might be a useful and feasible method for differentiating MMD from AS-MMS and a prospective tool for guiding first-line treatment.

Dental caries status is associated with arteriosclerosis in patients on hemodialysis.

BACKGROUND: We previously found that worse dental caries status was associated with high pulse pressure among patients on hemodialysis, indicating that such patients might have arteriosclerosis. In this study, we used abdominal computed tomography to evaluate arteriosclerosis in patients on hemodialysis and investigated the association between arteriosclerosis and dental caries status. We also prospectively examined risk factors associated with 2-year prognosis. METHODS: The dental caries and periodontal disease statuses of 80 patients on hemodialysis were evaluated using the decayed, missing, or filled teeth (DMFT) index, and periodontal pocket depth, respectively. The aortic calcification index was semiquantitatively measured using computed tomography images of the abdominal aorta. Clinical data were also analyzed after all patients on hemodialysis provided written, informed consent to participate in the study. RESULTS: Regression analysis demonstrated a significant correlation between the DMFT and aortic calcification indexes. Multiple regression analysis showed that the DMFT index was significantly correlated with the aortic calcification index, following adjustment for age, sex, and dialysis period. Thirteen of the 80 patients died during the 2-year follow-up period; logistic regression analysis showed that mortality rate was significantly associated with the aortic calcification index, but not the DMFT index. However, periodontal pocket depth was not correlated with the aortic calcification index. CONCLUSION: These findings suggest that worse dental caries status could be associated with arteriosclerosis among patients on hemodialysis, which may indirectly affect the prognosis of arteriosclerosis in these patients.

Autologous adipose mesenchymal stem cell administration in arteriosclerosis and potential for anti-aging application: a retrospective cohort study.

OBJECTIVE: Arteriosclerosis is an age-related disease and a leading cause of cardiovascular disease. In animal experiments, mesenchymal stem cells and its culture-conditioned medium have been shown to be promising tools for prevention or treatment of arteriosclerosis. On the basis of these evidences, we aimed to assess whether administration of autologous adipose-derived mesenchymal stem cells (Ad-MSC) is safe and effective for treatment of arteriosclerosis. METHODS: We retrospectively reviewed clinical records of patients with arteriosclerosis who had received autologous Ad-MSC administration at our clinic. Patients' characteristics were recorded and data on lipid profile, intimal-media thickness (IMT), cardio-ankle vascular index (CAVI), and ankle-brachial index (ABI) before and after Ad-MSC administration were collected and compared. RESULTS: Treatment with Ad-MSC significantly improved HDL, LDL, and remnant-like particle (RLP) cholesterol levels. No adverse effect or toxicity was observed in relation to the treatment. Of the patients with abnormal HDL values before treatment, the vast majority showed improvement in the values. Overall, the measurements after treatment were significantly increased compared with those before treatment (p < 0.01). In addition, decreases in LDL cholesterol and RLP levels were observed after treatment in patients who had abnormal LDL cholesterol or RLP levels before treatment. The majority of patients with pre-treatment abnormal CAVI values had improved values after treatment. In patients with available IMT values, a significant decrease in the IMT values was found after therapy (p < 0.01). All patients with borderline arteriosclerosis disease had improved laboratory findings after treatment. In general, post-treatment values were significantly decreased as compared with pre-treatment values. Of the patients with normal ABI values before treatment at the same time as CAVI, the vast majority remained normal after treatment. CONCLUSIONS: These findings suggest that Ad-MSC administration is safe and effective in patients developing arteriosclerosis, thereby providing an attractive tool for anti-aging application.

Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells.

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystemic disorder with a variable clinical expressivity caused by biallelic variants in SMARCAL1. A phenotype-genotype correlation has been attempted and variable expressivity of biallelic SMARCAL1 variants may be associated with environmental and genetic disturbances of gene expression. We describe two siblings born from consanguineous parents with a diagnosis of SIOD revealed by whole exome sequencing (WES). Results: A homozygous missense variant in the SMARCAL1 gene (c.1682G>A; p.Arg561His) was identified in both patients. Despite carrying the same variant, the two patients showed substantial renal and immunological phenotypic differences. We describe features not previously associated with SIOD-both patients had congenital anomalies of the kidneys and of the urinary tract and one of them succumbed to a classical type congenital mesoblastic nephroma. We performed an extensive characterization of the immunophenotype showing combined immunodeficiency characterized by a profound lymphopenia, lack of thymic output, defective IL-7Rα expression, and disturbed B plasma cells differentiation and immunoglobulin production in addition to an altered NK-cell phenotype and function. Conclusions: Overall, our results contribute to extending the phenotypic spectrum of features associated with SMARCAL1 mutations and to better characterizing the underlying immunologic disorder with critical implications for therapeutic and management strategies.

Documento de consenso de un grupo de expertos de la Sociedad Española de Arteriosclerosis (SEA) sobre el uso clínico de la resonancia magnética nuclear en el estudio del metabolismo lipoproteico (Liposcale) / Consensus document of an expert group from the Spanish Society of Arteriosclerosis (SEA) on the clinical use of nuclear magnetic resonance to assess lipoprotein metabolism (Liposcale)

La evaluación y prevención del riesgo cardiovascular (RCV) que persiste en los pacientes con dislipidemia a pesar del tratamiento y de haber alcanzado los objetivos específicos de la concentración plasmática de colesterol unido a lipoproteínas de baja densidad (c-LDL) es un reto clínico en la actualidad, y sugiere que los biomarcadores lipídicos convencionales resultan insuficientes para una evaluación precisa del RCV. Más allá de su contenido lipídico, existen otras características propias de las partículas lipoproteicas que determinan su potencial aterogénico y su influencia en el RCV. Sin embargo, dichas características adicionales no pueden ser analizadas por las técnicas utilizadas habitualmente en los laboratorios clínicos. La espectroscopia por resonancia magnética nuclear (RMN) es una técnica que permite un análisis detallado de la cantidad, composición y tamaño de las lipoproteínas y proporciona información más detallada del estado del metabolismo lipídico y del RCV en los pacientes dislipémicos. En este artículo un grupo de lipidólogos de la Sociedad Española de Arteriosclerosis revisa la evidencia existente sobre los mecanismos aterogénicos de las partículas lipoproteicas y describen el fundamento técnico y la interpretación de los perfiles lipoproteicos obtenidos mediante RMN, haciendo especial referencia al test disponible en España (Liposcale®). Asimismo, se definen los principales perfiles de pacientes en los que dicho análisis aportaría una información de mayor interés clínico, los cuales son: a) sospecha de discordancia entre las concentraciones de lípidos y el número de partículas, situación frecuente en la diabetes, la obesidad, el síndrome metabólico y la hipertrigliceridemia; b) enfermedad cardiovascular aterotrombótica (ECVA) precoz o recurrente sin factores de RCV que la justifiquen; c) trastornos lipídicos infrecuentes o complejos como las concentraciones extremas de c-HDL, y d) situaciones clínicas en las que las técnicas analíticas clásicas no pueden aplicarse, como los valores de c-LDL muy bajos

The assessment and prevention of cardiovascular risk (CVR) that persists in patients with dyslipidaemia despite treatment and achievement of goals specific to the plasma concentration of cholesterol linked to low density (c-LDL) is a clinical challenge today, and suggests that conventional lipid biomarkers are insufficient for an accurate assessment of CVR. Apart from their lipid content, there are other lipid particle characteristics. The results of this study show that there are a number of lipoprotein compounds that determine atherogenic potential and its influence on the CVR. However, such additional characteristics cannot be analysed by the techniques commonly used in clinical laboratories. Nuclear Magnetic Resonance (NMR) is a technique that allows a detailed analysis to be made of the amount, composition, and size of lipoproteins, as well as providing more information about the detailed status of lipid metabolism and CVR in dyslipidaemia patients. In this article a group of lipidologists from the Spanish Society of Arteriosclerosis review the existing evidence on the atherogenic mechanisms of particles and describe the technical basis and interpretation of the profiles lipoproteins obtained by MRI, with special reference to the test available in Spain (Liposcale®). Likewise, the main patient profiles are defined as such that an analysis would provide information of greater clinical interest. These include: a) Suspected mismatch between lipid concentrations and particles, a common situation in diabetes, obesity, metabolic syndrome; b) Early atherothrombotic cardiovascular disease (ECVA) or recurrent without CVR factors to justify it; c) Lipid disorders, rare or complex, such as extreme concentrations of c-HDL, and d) Clinical situations where classical analytical techniques cannot be applied, such as very low c-LDL values

The association between carotid atherosclerosis and treatment with lithium and antipsychotics in patients with bipolar disorder.

OBJECTIVES: Patients with bipolar disorder are at high risk of cardiovascular diseases. Among cardiovascular diseases, coronary heart disease and stroke are the leading causes of premature death and both share the pathogenesis of arterial atherosclerosis. Increased carotid intima-media thickness is sensitive for detecting early atherosclerosis and a practical index for predicting cardiovascular diseases. However, few studies investigated carotid intima-media thickness in adults with bipolar disorder. We attempted to determine the factors associated with carotid intima-media thickness in adults with bipolar disorder. METHODS: The euthymic out-patients with bipolar I disorder aged over 20 years were recruited to measure the carotid intima-media thickness value through B-mode carotid ultrasound. Those with any psychiatric disorder, acute or life-threatening medical condition were excluded. All clinical information was obtained by reviewing medical records and directly interviewing patients with reliable others. RESULTS: Of the 106 participants with a mean age of 44.5 years, 40.6% (N = 43) had concurrent cardiovascular/endocrine/metabolic diseases. A multivariate regression indicated that higher assumed daily lithium dosage was significantly associated with a decreased carotid intima-media thickness in the whole sample. In the young subgroup (⩽45 years old, N = 63), higher current daily lithium dosage and lower body mass index were associated with lower carotid intima-media thickness. In those without concurrent cardiovascular/endocrine/metabolic diseases, higher ratio of first-generation antipsychotics exposure in relation to illness chronicity was associated with higher carotid intima-media thickness, after controlling for body mass index or age. CONCLUSION: Lithium treatment may be associated with less progression in carotid intima-media thickness and the reduced risk for atherosclerosis in adults with bipolar disorder, including those with high cardiovascular disease risk. In addition to age and body mass index, antipsychotics may increase carotid intima-media thickness even in the low cardiovascular disease-risk patients.

Ecografía clínica en el riesgo cardiovascular / Clinical ultrasonography in cardiovascular risk

En la prevención de la enfermedad cardiovascular, la estimación del riesgo cardiovascular es la piedra angular sobre la que se sustentan las intervenciones preventivas. En esta estimación del riesgo, la detección de daño cardiovascular subclínico supone una herramienta complementaria a la estratificación clásica basada en factores de riesgo. Por su versatilidad, disponibilidad, rapidez, bajo coste e inocuidad, la ecografía se ha situado con ventaja respecto a otras técnicas usadas en la detección de daño cardiovascular subclínico. Las guías de práctica clínica del ámbito de la prevención cardiovascular recomiendan su uso para la valoración de placas de ateroma e hipertrofia del ventrículo izquierdo como moduladores del riesgo cardiovascular. Además, la ecografía tiene otras aplicaciones relevantes en el ámbito del riesgo cardiovascular como son el diagnóstico del aneurisma de aorta abdominal, la valoración renal en pacientes con enfermedad renal crónica o sospecha de hipertensión arterial secundaria y la detección de esteatosis cuando se sospecha enfermedad por hígado graso no alcohólico

In the prevention of cardiovascular disease, determining the cardiovascular risk is the cornerstone of preventive interventions. In this risk estimation, detecting subclinical cardiovascular damage represents a complementary tool to classic stratification based on risk factors. The versatility, availability, speed, low cost and safety of ultrasonography place it ahead of other techniques employed in detecting subclinical cardiovascular damage. The clinical practice guidelines for cardiovascular risk prevention recommend the use of ultrasonography for assessing atheromatous plaques and left ventricular hypertrophy as modulators of cardiovascular risk. Ultrasonography also has other relevant applications in cardiovascular risk, including the diagnosis of abdominal aortic aneurysms, kidney assessments for patients with chronic kidney disease or suspected secondary arterial hypertension and the detection of steatosis when nonalcoholic fatty liver disease is suspected