Early Marker Of Atherosclerosis Research Articles

Aortic arterial stiffness associates with carotid intima-media thickness and carotid plaques in younger middle-aged healthy people

Purpose Aortic stiffness, assessed as estimated aortic pulse wave velocity (aPWV), and carotid intima-media thickness (cIMT) are markers of vascular age, and carotid plaques are a marker of early atherosclerosis. In this cross-sectional study we aimed to investigate the association between aPWV, cIMT and plaques across different age groups and in women and men, in a middle-aged healthy population. Materials and methods Participants in the 6.5-year follow-up of the VIPVIZA trial who were aged 47, 57 and 67 underwent an oscillometric measurement which estimates aPWV between 2020 and 2023. Carotid ultrasound examinations were also performed. Linear and ordinal regression models were used to investigate how aPWV associates with cIMT and with carotid plaques, for the overall study group and stratified for age groups and sex. Results A total of 1046 subjects were included in the analyses. Linear associations between aPWV and cIMT (β = 0.018, 95% CI: 0.006–0.030, p = 0.003), and between aPWV and plaques (OR: 1.19, 95% CI: 1.03–1.38, p = 0.018), were seen in the 57-year-olds. In the 47-year-olds a significant association was seen between aPWV and plaques (OR: 2.98 95% CI: 1.44–6.14, p = 0.003). No significant associations were seen in the 67-year-olds. For women, a significant association between aPWV and cIMT (β = 0.011, 95% CI: 0.004–0.017, p = 0.002) was shown. Conclusion Estimated aPWV was positively associated with increasing cIMT and the presence of carotid plaques in younger middle-aged individuals, and with cIMT in women, suggesting that measurement of estimated aPWV may improve cardiovascular risk assessment in younger middle-aged individuals and women. Clinical Trial Registration date 8 May 2013: URL: www.clinicaltrials.gov. Unique identifier: NCT01849575.

Cardiovascular Risk in People Living with Human Immunodeficiency (HIV) Viremia Suppression in a Young, Mid-Eastern European Population - Preliminary Study.

People living with HIV are twice as likely to develop cardiovascular diseases (CVDs) and myocardial infarction related to atherosclerosis than the uninfected population. This study aimed to evaluate the prevalence of subclinical atherosclerosis in a young, mid-eastern European population of PLWH receiving ART for undetectable viremia. This was a single-centre study. We included 34 patients below 50 years old, treated in Szczecin, Poland, with confirmed HIV-1 infection, treated with antiretroviral therapy (ART), and undetectable viremia. All patients underwent coronary artery computed tomography (CACT), carotid artery intima-media thickness (IMT) evaluation, and echocardiography. In the primary assessment, only two (5.8%) patients had an increased CVD risk calculated using the Framingham Risk Score (FRS), but we identified coronary or carotid plaques in 26.5% of the patients. Neither traditional risk factors nor those associated with HIV significantly influenced the presence of the plaque. IMT was significantly positively correlated with age and the FRS (R=0.38, p=0.04). Relative wall thickness assessed in echocardiography was higher in those with plaque (0.49 vs 0.44, p=0.04) and significantly correlated with IMT (R=0.38, p=0.04). In our population, more than a quarter of PLWH with undetectable viremia had subclinical atherosclerosis in either the coronary or carotid arteries. The FRS underpredicted atherosclerosis in this population. The role of RWT as a possible early marker of atherosclerosis needs further studies.

Evaluation of carotid intima media thickness as an early marker of atherosclerosis in children and adolescents with autism spectrum disorder: a case-control study

Evaluation of carotid intima media thickness as an early marker of atherosclerosis in children and adolescents with autism spectrum disorder: a case-control study

Higher levels of markers for early atherosclerosis in anti-citrullinated protein antibodies positive individuals at risk for RA, a cross sectional study

ObjectiveTo identify differences in levels of serum biomarkers associated with atherosclerosis between anti-citrullinated protein antibodies (ACPA) positive groups.MethodsCross-sectional data were used from the Dutch Lifelines Cohort Study combined with data derived from RA risk and early RA studies conducted at the University Medical Center Groningen (UMCG).Serum biomarkers of inflammation, endothelial cell activation, tissue remodeling and adipokine, which were previously associated with atherosclerosis, were measured with Luminex in four ACPA positive groups with different characteristics: without joint complaints, with joint complaints, RA risk and early RA groups.ResultsLevels of C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor Necrosis Factor Receptor 1 (TNFR1) and vascular endothelial growth factor (VEGF) were significantly higher in the RA risk and early RA groups compared to the joint complaints and the no joint complaints groups. The difference remained statistically significant after correcting for renal function, smoking and hypertension in multivariate logistic regression analysis, with focus on ACPA positive with joint complaints group versus RA risk group: CRP OR = 2.67, p = 0.033; IL-6 OR = 3.73, p = 0.019; TNFR1 OR = 1.003, p < 0.001; VGEF OR = 8.59, p = 0.019.ConclusionIndividuals at risk for RA have higher levels of inflammatory markers and VEGF, which suggests that they might also have a risk of higher cardiovascular disease (CVD); however, this does not apply to individuals with ACPA positivity with self-reported joint complaints or without joint complaints only. Therefore, it is important that individuals with RA risk are referred to a rheumatologist to rule in or out arthritis/development of RA and discuss CVD risk.

Ligustrazine alleviates the progression of coronary artery calcification by inhibiting caspase-3/GSDME mediated pyroptosis.

Coronary artery calcification (CAC) is an early marker for atherosclerosis and is mainly induced by the osteoblast-like phenotype conversion of vascular smooth muscle cells (VSMCs). Recent reports indicate that NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis plays a significant role in the calcification of vascular smooth muscle cells (VSMCs), making it a promising target for treating calcific aortic valve disease (CAC). Ligustrazine, or tetramethylpyrazine (TMP), has been found effective in various cardiovascular and cerebrovascular diseases and is suggested to inhibit NLRP3-mediated pyroptosis. However, the function of TMP in CAC is unknown. Herein, influences of TMP on β-glycerophosphate (β-GP)-stimulated VSMCs and OPG-/- mice were explored. Mouse Aortic Vascular Smooth Muscle (MOVAS-1) cells were stimulated by β-GP with si- caspase-3, si- Gasdermin E (GSDME) or TMP. Increased calcification, reactive oxygen species (ROS) level, Interleukin-1beta (IL-1β) and Interleukin-18 (IL-18) levels, lactate dehydrogenase (LDH) release, enhanced apoptosis, and activated cysteine-aspartic acid protease-3 (caspase-3)/GSDME signaling were observed in β-GP-stimulated MOVAS-1 cells, which was sharply alleviated by si-caspase-3, si-GSDME or TMP. Furthermore, the impact of TMP on the β-GP-induced calcification and injury in MOVAS-1 cells was abolished by raptinal, an activator of caspase-3. Subsequently, OPG-/- mice were dosed with TMP or TMP combined with raptinal. Calcium deposition, increased nodules, elevated IL-1β and IL-18 levels, upregulated CASP3 and actin alpha 2, smooth muscle (ACTA2), and activated caspase-3/GSDME signaling in OPG-/- mice were markedly alleviated by TMP, which were notably reversed by the co-administration of raptinal. Collectively, TMP mitigated CAC by inhibiting caspase-3/GSDME mediated pyroptosis.

Abstract P399: Cardiovascular Risk Factors and Measures of Early Atherosclerosis in Children With Down Syndrome

Background: Children with Down syndrome (DS) have unique cardiovascular (CV) risk profiles compared to the general population. Early markers of atherosclerosis can be measured and are associated with CV risk factors, although limited data are available for children with DS. Methods: A multicenter, cross-sectional study of children with DS between 8-18 years. CV risks assessed: BMI, blood pressure, diet, activity, smoke exposure, congenital heart disease, hypothyroid, cancer, apnea, family history of early coronary disease, lipids, lipoprotein subfractions, glucose, insulin, and HS-CRP. Vascular testing included pulse wave velocity (PWV) and carotid intimal medial thickness (CIMT). Prevalence of categorical CV risks were compared to population prevalence from NHANES data using Fisher’s exact or chi squared. Vascular measures were converted to Z scores using height and compared to population means with single sample t test, and linear regression evaluating associations between CV risks and vascular measures. Results: A total of 55 children with DS participated, 28 (51%) female, mean age 14.3 years (range 8.1-18.9). Compared to NHANES, DS children were more likely to have triglycerides &gt;90 mg/dL (63% DS vs. 10% NHANES, p=&lt;0.001) and non-HDL-cholesterol &gt;120 mg/dL (54% DS vs. 22% NHANES, p = &lt;0.001). PWV and CIMT Z scores were not significantly different from general population with mean (SD) of -0.1 (1.0) and 0.27 (1.5), respectively. Univariable analysis for PWV showed significant associations with systolic blood pressure [coefficient (95% CI): 0.04 (0.02, 0.06)] and smoke exposure [1.70 (0.35, 3.05)]. No associations were found for CIMT. Multivariable models are shown in Table 1. PWV was associated with BMI percentile and smoke exposure. No associations were found for CIMT. Conclusion: Children with DS had higher rates of lipid abnormalities compared to the general population. Lipid abnormalities were not associated with CIMT or PWV, and vascular measures adjusted for height were similar to children without DS.

Measurement of atherosclerosis markers in individuals with periodontitis.

The inflammatory response due to inflammatory cytokines, bacterial pathogens, and the altered lipoprotein metabolism in patients with periodontitis indicates that infection with periodontal anaerobic bacteria may influence atherogenesis in vitro and in vivo. We aimed to explore the effect of periodontitis concerning clinical and ultrasound markers of early atherosclerosis. In this case-control study, a total of 30 systemically healthy adults (15 with periodontitis and 15 without periodontitis) over 40 years of age were studied. Periodontitis was determined by measuring the clinical attachment level (CAL) and radiographic bone loss (RBL). Conventional cardiovascular risk factors, including body mass index, serum levels of total cholesterol (TCH), triglycerides (TG), and high-density and low-density lipoprotein (HDL and LDL, respectively) cholesterol were evaluated. Carotid artery intima-media thickness (IMT) was measured using ultrasonography. The mean values of the CAL and carotid IMT were 5.02±0.9 mm and 0.084±0.01 cm vs. 1.6±0.61 mm and 0.072±0.02 cm in the periodontitis and healthy groups, respectively, reflecting statistically significant differences (P=0.001 and P=0.037, respectively). There were statistically significant differences in the serum levels of TCH, TG, and LDL between the 2 groups (P=0.017). The CAL and RBL were positively associated with carotid IMT and serum cholesterol levels, except for HDL, whereas tooth loss was not associated with any markers (P<0.05). Compared to the healthy group, participants with periodontitis exhibited 2.09 times higher odds (95% confidence interval, 1.22-3.59) of having subclinical atherosclerosis. The presence of periodontitis increased the risk of atherosclerosis.

Hearing Loss As A Surrogate Marker For Early Atherosclerosis in A High-Risk Population: A Prospective Study

Hearing Loss As A Surrogate Marker For Early Atherosclerosis in A High-Risk Population: A Prospective Study

Nogo-B mediates endothelial oxidative stress and inflammation to promote coronary atherosclerosis in pressure-overloaded mouse hearts

AimsEndothelial dysfunction plays a pivotal role in atherosclerosis, but the detailed mechanism remains incomplete understood. Nogo-B is an endoplasmic reticulum (ER)-localized protein mediating ER-mitochondrial morphology. We previously showed endothelial Nogo-B as a key regulator of endothelial function in the setting of hypertension. Here, we aim to further assess the role of Nogo-B in coronary atherosclerosis in ApoE−/− mice with pressure overload. Methods and resultsWe generated double knockout (DKO) mouse models of systemically or endothelium-specifically excising Nogo-A/B gene on an ApoE−/− background. After 7 weeks of transverse aortic constriction (TAC) surgery, compared to ApoE−/− mice DKO mice were resistant to the development of coronary atherosclerotic lesions and plaque rapture. Sustained elevation of Nogo-B and adhesion molecules (VCAM-1/ICAM-1), early markers of atherosclerosis, was identified in heart tissues and endothelial cells (ECs) isolated from TAC ApoE−/− mice, changes that were significantly repressed by Nogo-B deficiency. In cultured human umbilical vein endothelial cells (HUVECs) exposure to inflammatory cytokines (TNF-α, IL-1β), Nogo-B was upregulated and activated reactive oxide species (ROS)-p38-p65 signaling axis. Mitofusin 2 (Mfn2) is a key protein tethering ER to mitochondria in ECs, and we showed that Nogo-B expression positively correlated with Mfn2 protein level. And Nogo-B deletion in ECs or in ApoE−/− mice reduced Mfn2 protein content and increased ER-mitochondria distance, reduced ER-mitochondrial Ca2+ transport and mitochondrial ROS generation, and prevented VCAM-1/ICAM-1 upregulation and EC dysfunction, eventually restrained atherosclerotic lesions development. ConclusionOur study revealed that Nogo-B is a critical modulator in promoting endothelial dysfunction and consequent pathogenesis of coronary atherosclerosis in pressure overloaded hearts of ApoE−/− mice. Nogo-B may hold the promise to be a common therapeutic target in the setting of hypertension.

New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death.

Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.

Non-Calcified Coronary Artery Plaque on Coronary Computed Tomography Angiogram: Prevalence and Significance.

We aimed to assess the prevalence of non-calcified plaque (NCP) on computed tomography angiography (CCTA) in symptomatic and asymptomatic individuals. In addition, we seek to compare plaque assessment on CCTA with intravascular ultrasound-virtual histology (IVUS-VH) and to assess the prognostic value of non-calcified plaques (NCPs). The CCTA can characterize coronary plaques and help quantify burden. Furthermore, it can provide additional prognostic information which can enable further risk stratification of patients. We performed a broad comprehensive review of the current literature pertaining to CCTA and primarily isolated NCP in symptomatic and asymptomatic patients. In addition, our review included studies correlating plaque on CT with IVUS-VH. NCP is the initial precursor of calcified plaque and serves as a prominent marker of early coronary atherosclerosis. By detecting NCP during early stages, several measures can be implemented which can alter the evolutionary course of the underlying disease. This can potentially lead to a lower incidence of cardiovascular events.

A multi-organ, lung-derived inflammatory response following in vitro airway exposure to cigarette smoke and next-generation nicotine delivery products

Despite increasing use of in vitro models that closely resemble in vivo human biology, their application in understanding downstream effects of airway toxicity, such as inflammation, are at an early stage. In this study, we used various assays to examine the inflammatory response induced in MucilAir™ tissues and A549 cells exposed to three products known to induce toxicity. Reduced barrier integrity was observed in tissues following exposure to each product, with reduced viability and increased cytotoxicity also shown. Similar changes in viability were also observed in A549 cells. Furthermore, whole cigarette smoke (CS) induced downstream phenotypic THP-1 changes and endothelial cell adhesion, an early marker of atherosclerosis. In contrast, exposure to next-generation delivery product (NGP) aerosol did not induce this response. Cytokine, histological and RNA analysis highlighted increased biomarkers linked to inflammatory pathways and immune cell differentiation following exposure to whole cigarette smoke, including GM-CSF, IL-1β, cleaved caspase-3 and cytochrome P450 enzymes. As a result of similar observations in human airway inflammation, we propose that our exposure platform could act as a representative model for studying such events in vitro. Furthermore, this model could be used to test the inflammatory or anti-inflammatory impact posed by inhaled compounds delivered to the lung.

Ethanolic Extract of Moringa oleifera Leaves Reduces The Expression of ICAM-1 in Aortic Tissues of Metabolic Syndrome Induced Rattus norvegicus

Introduction: Metabolic syndrome poses a risk for the development of atherosclerotic lesions, which are associated with various cardiovascular diseases. Moringa leaves are known for their antioxidant and anti-inflammatory properties. ICAM-1 serves as an early marker of atherosclerosis. This study aims to investigate how the dosage of ethanolic extract from Moringa leaves affects the expression of ICAM-1 in the aortic tissue of Wistar rats with metabolic syndrome. Methods: This study employed a laboratory experimental design with a posttest only control group. The research involved 30 Wistar rats, divided into five groups: the normal control group (G1), the positive control group (G2), and three experimental groups (G3, G4, and G5). The experimental groups (G3, G4, and G5) were induced with metabolic syndrome and administered ethanolic extract of Moringa leaves at doses of 150 mg/kg, 250 mg/kg, and 350 mg/kg, respectively. The expression of aortic ICAM-1 was evaluated using the Intensity Distribution Score (IDS) and analyzed using one-way ANOVA and Post-hoc Tukey HSD test. Results: Increasing the dosage of ethanolic leaf extract of Moringa oleifera reduces the IDS value of ICAM-1 in the aortic tissue of Wistar rats with a significance of p&lt;0.05.. Conclusion: The higher dosage of ethanolic leaf extract from Moringa oleifera Lamk has the potential to decrease ICAM-1 expression in the aortic tissue of Wistar rats with metabolic syndrome. The author hopes that Moringa leaf extract can be utilized as a supplement to prevent the formation of atherosclerotic plaques and cardiovascular diseases resulting from atherosclerotic plaques, such as thromboembolism and stroke.

O-222 Functional characterization and clinical implications of patient-specific iPSC-derived endothelial cells to unravel the pathogenesis associated with androgen-mediated endothelial dysfunction in polycystic ovarian syndrome

Abstract Study question Whether and how the endothelial cell (EC) dysfunction is involved in the pathogenesis of PCOS revealed by iPSC-based disease modeling? Summary answer PCOS-specific iPSC-derived ECs were successfully established and the results showed that EC proliferation and function were impaired in PCOS through the androgen receptor(AR)-mediated signaling pathway. What is known already ECs have been shown to play critical biological roles in the regulation of vascular tone and inflammatory process and any injury to ECs or disturbance in their homeostasis is called EC dysfunction, which has been recognized as an early marker of atherosclerosis and cardiovascular diseases. Several studies have also revealed indirect evidence of EC dysfunction among women with PCOS, including elevated circulatory markers of endothelial damage and impaired vascular structure. But whether and how EC dysfunction is involved in the pathogenesis of PCOS is still unclear. Study design, size, duration This is an experimental study at tertiary university hospital. iPSCs were established from skin fibroblasts and peripheral blood mononuclear cells from two patients with PCOS and two control participants. Participants/materials, setting, methods iPSCs were differentiated into ECs through monoculture with chemically defined conditions. Single cell RNA sequencing (scRNA-seq) was performed on the iPSCs-derived ECs to compare the differences between PCOS and control. iPSCs-derived ECs were treated with different dosages (1, 10 and 100 nM) of dihydrotestosterone (DHT). Cell cycle phases were analyzed by flow cytometry with BrdU incorporation assay. The expression of AR, cyclin-dependent kinase 1 (CDK1) and vascular endothelial growth factor (VEGF) were analyzed using rtPCR. Main results and the role of chance Up to 90% of iPSC-derived ECs successfully expressed EC markers, including CD31, CD144 and von Willebrand Factor in both PCOS and control groups, showing a high differentiation efficiency in the present study. The pathway enrichment analysis of transcriptomic data of iPSC-derived ECs showed functional differences involving cell cycle process, VEGF signaling and apoptotic process between PCOS and control. Analysis using sc-RNA seq revealed decreased cellular proliferation in the PCOS iPSC-derived ECs compared to control group, which was due to cell cycle arrest revealed by flow cytometry. The modulating effects of androgen on the proliferation and gene expression of iPSC-derived ECs were further investigated. DHT at doses ranging from 1 to 100 nM stimulated iPSC-derived ECs proliferation in the control group through upregulation of AR, CDK1 and VEGF gene expression. In contrast, DHT did not promote the cellular proliferation of PCOS iPSC-derived ECs at physiological concentrations of 1 and 10 nM and the expression of AR, CDK1, and VEGF remained unchanged. These data suggest that DHT-induced cellular proliferation and the expression of associated genes were more sensitive and dose-dependent in the control iPSC-derived ECs and blunted in the PCOS iPSC-derived ECs. Limitations, reasons for caution One of the major limitations of our study was the limited number of cases during the establishment of iPSCs, which was unable to reflect the heterogeneity and complexity of PCOS. Wider implications of the findings Impaired cellular proliferation and differentially expressed genes involved in cell proliferation, immune responses, cardiovascular functions, and apoptosis were observed among PCOS iPSC-derived ECs. Additionally, androgen-induced ECs proliferation was blunted in PCOS through a diminished AR/VEGF/cyclin D1 signaling pathway, which might hinder VEGF-dependent vascular repair and probably increase cardiovascular risks. Trial registration number not applicable

Decaffeinated coffee and green tea extract inhibit foam cell atherosclerosis by lowering inflammation and improving cholesterol influx/efflux balance through upregulation of PPARγ and miR-155

Background: Foam cells, the markers of early atherosclerosis and characterise the advanced atherosclerotic plaque, are stimulated by inflammation due to the excess of lipid in macrophages. The combination of decaffeinated coffee and green tea extract (DCGTE) has been suggested to have a role in foam cell inhibition. Objective: to investigate the role of DCGTE against foam cell formation, through modulation of the inflammation process and cholesterol metabolism in macrophage colony stimulating factor (M-CSF) and oxidized low-density lipoprotein (oxLDL)-exposed macrophages. Methods: Coffee and green tea were extracted by filtration and infusion respectively. Both of coffee and green tea underwent decaffeination using active carbon and blanching methods, respectively. Raw 264.7 Cells were administered with 160/160 and 320/320 μg/ml of DCGTE. Foam cell formation was observed using a light microscope after staining with Oil Red O (ORO), and quantified with ELISA. The expression of cluster differentiation 36 (CD36) ( lipid influx) and ATP binding cassette transporter A1 (ABCA1) ( cholesterol efflux) were determined through immunofluorescence. Tumor Necrosis Factor α (TNFα) and Interleukin10 (IL10) were quantified with ELISA. Peroxisome proliferator activated response γ (PPARγ) expression and activity were assessed with Polymerase Chain Reaction (PCR) and ELISA, respectively. The expression of microRNA 155 (miR-155) was examined using qPCR. Results: DCGTE at the above concentrations tended to reduce foam cell numbers, significantly inhibited lipid accumulation (p=0.000), reduced CD36 expression (p=0.000) and TNFα secretion (p=0.000) in Raw264.7 exposed to M-CSF 50 ng/ml and oxLDL 50 μg/ml. The PPARγ expression (p=0.000), PPARγ activity (p=0.001), ABCA1 (p=0.002), miR-155 relative expression (p=0.000), and IL10 production (p=0.000) also increased in DCGTE groups. Conclusion: DCGTE lowered foam cell possibly through attenuation of the inflammatory process and improvement of lipid/efflux mechanisms via upregulation of PPARγ and miR-155 in M-CSF and oxLDL-stimulated Raw264.7 cells. Our results suggest DCGTE might help to prevent atherosclerosis-based diseases.

Effects of Hypoglycemia on Cardiovascular Function in Patients with Diabetes.

Hypoglycemia is common in patients with type 1 and type 2 diabetes (T1D, T2D), treated with insulin or sulfonylureas, and has multiple short- and long-term clinical implications. Whether acute or recurrent, hypoglycemia significantly affects the cardiovascular system with the potential to cause cardiovascular dysfunction. Several pathophysiological mechanisms have been proposed linking hypoglycemia to increased cardiovascular risk, including hemodynamic changes, myocardial ischemia, abnormal cardiac repolarization, cardiac arrhythmias, prothrombotic and proinflammatory effects, and induction of oxidative stress. Hypoglycemia-induced changes can promote the development of endothelial dysfunction, which is an early marker of atherosclerosis. Although data from clinical trials and real-world studies suggest an association between hypoglycemia and cardiovascular events in patients with diabetes, it remains uncertain whether this association is causal. New therapeutic agents for patients with T2D do not cause hypoglycemia and have cardioprotective benefits, whereas increasing the use of new technologies, such as continuous glucose monitoring devices and insulin pumps, has the potential to reduce hypoglycemia and its adverse cardiovascular outcomes in patients with T1D.

Elderberry extract improves molecular markers of endothelial dysfunction linked to atherosclerosis.

Endothelial dysfunction (ED), secondary to diminished nitric oxide (NO) production and oxidative stress, is an early subclinical marker of atherosclerosis. Reduced NO bioavailability enhances the adhesion of monocytes to endothelial cells and promotes atherosclerosis. Elderberry extract (EB) is known to contain high levels of anthocyanins which could exert vascular protective effects. Specifically, we investigated the functional capacity of EB on various markers of ED. Human umbilical vein endothelial cells (HUVEC) were pretreated with EB 50 μg/mL and stimulated with TNF-α 10 ng/mL. Cell viability, apoptosis, oxidative stress; eNOS, Akt, Nrf2, NOX-4, and NF-κB at the protein level were measured. A co-culture model was used to determine whether EB could prevent the adhesion of monocytes (THP-1) to HUVECs. Moreover, the expression of adhesion molecules and pro-inflammatory cytokines were also measured. It wasdemonstrated that EB prevented TNF-α induced apoptosis and reactive oxygen species production in HUVECs. Additionally, EB upregulated Akt and eNOS activity, and Nrf2 expression in response to TNF-α, whereas it decreased NOX-4 expression and NF-κB activity. EB prevented the adhesion of monocytes to HUVECs, as well as reduced IL-6 and MCP-1 levels, which was associated with inhibition of VCAM-1 expression. Our results demonstrate that EB upregulates key cellular markers of endothelial function and ameliorates markers of ED. EB could be used as a potential nutritional aid for preventing atherosclerosis progression.

Measuring Carotid Intima-Media Thickness in Young Adults Born Preterm: Comparison of Manual Versus Semi-automated B-Mode Ultrasound

Introduction: Young adults born very preterm have increased cardiovascular risks. While intima-media thickness of the common carotid artery is an early marker of atherosclerosis in adults, the most reliable method of its measurement is not established in this population. The purpose of this study is to compare manual and semi-automated B-mode ultrasound intima-media thickness measurement techniques in adults born very preterm and full-term. Methods: Intima-media thickness was measured in adults 18 to 29 years born very preterm (&lt;30 weeks’ gestation) or full-term (≥37 weeks’ gestation) using B-mode ultrasound. Analyses included intraclass correlation coefficient (ICC) and relationships with prematurity status, age, body mass index, and metabolic and respiratory comorbidities. Results: There were 86 preterm-born participants (58% women) and 85 full-term (56% women), mean age 23 ± 2 years. Intra-observer agreement was better using semi-automated (ICC = 0.89; 95% confidence interval (CI) = [0.86-0.91]) than manual measurement (ICC = 0.73; 95% CI = [0.65-0.79]). Measures obtained using both techniques did not detect any differences according to prematurity status, did not correlate with age, and moderately correlated with body mass index. The semi-automated technique showed higher intima-media thickness values in men vs women and overall gave higher values. Results obtained through both techniques moderately correlated with each other when looking at subgroups: preterm group ICC of 0.53, full-term group ICC of 0.62. Conclusion: Manual and semi-automated intima-media thickness measurements moderately correlate in young adults. The semi-automated technique is more reproducible. Both techniques are useful in discriminating intima-media thickness according to weight. This study identifies variance of results according to different techniques of measurements. Adherence to a single technique is recommended in young adults born prematurely. Clinical implication includes adherence to the same technique for risk stratification and for follow-up of these patients.

Carotid Intimomedial Thickness (CIMT) in Patients with Rheumatoid Arthritis; the Need for More Aggressive Cardiovascular Screening in RA.

To use carotid intimal medial thickness as a marker of early atherosclerosis in patients with rheumatoid arthritis. Cross-sectional descriptive study. Place and Duration of the Study: Rheumatology Unit of Federal Government Polyclinic Hospital, Islamabad, from 1st June 2019 till 30th January 2022. The study included 190 patients divided equally into cases of rheumatoid arthritis and healthy control groups. Carotid intimal medial thickness was measured using the carotid doppler ultrasound. The mean values of both the study groups were evaluated using the independent sample t-tests. Different statistical tests for correlation were also used where appropriate. This study included a total of 190 patients, 95 each in case and control groups. There were 15 (15.8%) males and 80 (84.2%) females with mean age of 43.5±12.8 years among cases, while 27 (28.4%) males and 68 (71.6%) females with mean age of 43.1±10.1 years in the control group. A significantly higher number of cases had a carotid intima-media thickness of more than 0.6 mm as compared to controls (43.2% vs. 25.3%, p=0.009). Cases with seropositive status were 1.98 times more likely to have higher carotid intima-medial thickness compared with controls. Carotid intima-media thickness measurement is important as a surrogate marker of atherosclerotic process in patients with rheumatoid arthritis. Rheumatoid arthritis (RA), Carotid intimal medial thickness (CIMT), Atherosclerosis, Cardiovascular disease (CVD).

Assessment of Sonographic Carotid Parameters in Autism Spectrum Disorder: A Comparative Case Control Study

ABSTRACT Objective To compare carotid intima-media thickness (cIMT), systolic and diastolic diameters (D), intima-media thickness/diameter ratio (IDR) values in children with ASD, and control groups, and to analyze the correlation of these parameters with the Childhood Autism Rating Scale (CARS) scores. Methods This prospective case-control study included 37 children diagnosed with ASD and 38 individuals without ASD in the control group. Correlation assessments of sonographic measurements with CARS scores in the ASD group were also performed. Results Diastolic diameters of the right (median of ASD group:5.5 mm, control group:5.1 mm) and left (median of ASD group: 5.5 mm, in control group: 5.1 mm) side were higher in the ASD group (p = .015 and p = .032 respectively). A statistically significant correlation was detected between CARS score and left cIMT, right cIMT, right cIMT/systolic D, right cIMT/diastolic D, left cIMT/systolic D, and left cIMT/diastolic D (p < .05). Conclusion Vascular diameters, cIMT, and IDR values of children with ASD positively correlated with CARS scores, and these findings could be interpreted as a marker of early atherosclerosis in children with ASD.