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Objective Patients with Behçet's disease (BD) may experience long-term morbidity caused by various forms of cardiovascular disease. This study aimed to assess the risk for cardiovascular comorbidity in paediatric BD patients with and without vascular involvement, independent of the contribution of traditional risk factors. Methods Paediatric patients classified as having BD according to the 2015 Peadiatric BD (PEDBD) criteria were included in the study. Twenty-four-hour ambulatory blood pressure monitoring (ABPM), transthoracic echocardiography, and carotid intima-media thickness (cIMT) measurements were performed. Patients with an active disease or those who have other known risk factors for cardiovascular disease were not included in the study. Results Thirty-one children and adolescents with paediatric BD (16 female, 51.6%; F/M: 1.06) were enrolled in the study. Among the BD patients, 10 patients (34.4%) had abnormal ABPM. Carotid IMT values, mean arterial pressure, systolic and diastolic blood pressure by ABPM and the prevalence of abnormal ABPM, non-dipping, and ambulatory hypertension were similar between patients with and without vascular involvement. The echocardiography measurements showed that BD patients with vascular involvement had a significantly higher velocity and velocity time integral of the left ventricle outflow tract, which may indicate increased stiffness of the aorta. Conclusion Paediatric BD patients with vascular involvement may tend to have more cardiovascular risk factors. However, cardiovascular assessment should be considered in all BD patients, regardless of the involved systems. We suggest that ABPM may accurately define hypertension and cardiovascular risk in BD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Type 1 diabetes (T1D) carries a significant risk of atherosclerosis as the main driver for cardiovascular events. Atherosclerosis is initiated by the activation of the endothelium by various risk factors through the inflammation process. The anti-inflammatory cytokine TGF-β1 may inhibit the development of atherosclerosis. METHODS: In a cross-sectional study, a total of 40 patients aged 14.5±3.16 years old with T1D and 40 healthy controls aged 14.7±0.99 years old were involved. Common carotid artery IMT (CIMT) was measured by real-time M-echocardiography mode (Affinity 50G Philips) and Flow Mediated Dilatation (FMD), using high-resolution ultrasonography and Doppler flow characteristics. The TGF-B1 level was measured by indirect ELISA at Saiful Anwar Hospital Laboratory. RESULTS: There were no differences in age, gender, Body Mass Index (BMI), duration of diabetes, renal function, or nutritional status between the T1D and healthy groups (p > 0.05) A significant difference in cIMT was observed between the T1D group and the healthy group (0.567 ± 0.87 mm vs. 0.387 ± 0.57 mm, P = 0 ), FMD (7.17 ± 3.98 mm vs. 11.22 ± 5.48 mm, p = 0 ), and the level of TGF-β1 cytokine (39.83±13.51 vs. 73.67±15.34 pg/ml, P = 0 ) A significantly negative correlation between TGF-β1 and cIMT ( p = 0 ; r = - 0.685 ) a significantly positive correlation between TGF-β1 and FMD ( p = 0 ; r = 0.55 ) were found. CONCLUSION: Atherosclerosis is an inflammatory disease accelerated by diabetes. The inflammation process is more prominent in T1D patients. T1D patients show a decreased level of TGF-ẞ1, increased measurement of cIMT (>0.5 mm), and a decreased measurement of FMD. [ABSTRACT FROM AUTHOR]

Cardiovascular risk factors are the cause of atherosclerotic disease, which can involve all the elastic and muscolo-elastic arteries. The etiopathogenesis of atherosclerosis is multifactorial since genetics, lifestyle, and comorbidities can be simultaneously involved. Clinical manifestations can be heterogeneous and include myocardial infarction, stroke, aortic aneurysms, renal artery stenosis, renal insufficiency, peripheral artery disease, etc. Currently, 70% of clinical events cannot be prevented with available drug therapy, statins included, and at least 10% of coronary events occur in apparently healthy individuals in the absence of major traditional risk factors. The case of a young male with a history of coronary artery disease and multiple atherosclerotic risk factors not properly treated who was admitted to the emergency department for pulmonary edema and high blood pressure is presented. During the diagnostic workup, a dramatic atherosclerotic involvement of all arterial trees emerged. Moreover, the patient presented with thrombosis of the right subclavian artery, which was treated with a heparin infusion and later complicated by cerebral hemorrhage with residual hemiplegia.

BackgroundCoronary artery calcium (CAC) is a measure of atherosclerotic burden and is well-validated for risk stratification in middle- to older-aged adults. Few studies have investigated CAC in younger adults, and there is no calculator for determining age-, sex-, and race-based percentiles among individuals aged 0 and develop age-sex-race percentiles for U.S. adults aged 30-45 years.MethodsWe harmonized 3 datasets-CARDIA (Coronary Artery Risk Development in Young Adults), the CAC Consortium, and the Walter Reed Cohort-to study CAC in 19,725 asymptomatic Black and White individuals aged 30-45 years without known atherosclerotic cardiovascular disease. After weighting each cohort equally, the probability of CAC >0 and age-sex-race percentiles of CAC distributions were estimated using nonparametric techniques.ResultsThe prevalence of CAC >0 was 26% among White males, 16% among Black males, 10% among White females, and 7% among Black females. CAC >0 automatically placed all females at >90th percentile. CAC >0 placed White males at the 90th percentile at age 34 years compared with Black males at age 37 years. An interactive webpage allows one to enter an age, sex, race, and CAC score to obtain the corresponding estimated percentile.ConclusionsIn a large cohort of U.S. adults aged 30-45 years without symptomatic atherosclerotic cardiovascular disease, the probability of CAC >0 varied by age, sex, and race. Estimated percentiles may help interpretation of CAC scores among young adults relative to their age-sex-race matched peers and can henceforth be included in CAC score reporting.

BackgroundThere are currently no recommendations guiding when best to perform coronary artery calcium (CAC) scanning among young adults to identify those susceptible for developing premature atherosclerosis.ObjectivesThe purpose of this study was to determine the ideal age at which a first CAC scan has the highest utility according to atherosclerotic cardiovascular disease (ASCVD) risk factor profile.MethodsWe included 22,346 CAC Consortium participants aged 30-50 years who underwent noncontrast computed tomography. Sex-specific equations were derived from multivariable logistic modeling to estimate the expected probability of CAC >0 according to age and the presence of ASCVD risk factors.ResultsParticipants were on average 43.5 years of age, 25% were women, and 34% had CAC >0, in whom the median CAC score was 20. Compared with individuals without risk factors, those with diabetes developed CAC 6.4 years earlier on average, whereas smoking, hypertension, dyslipidemia, and a family history of coronary heart disease were individually associated with developing CAC 3.3-4.3 years earlier. Using a testing yield of 25% for detecting CAC >0, the optimal age for a potential first scan would be at 36.8 years (95% CI: 35.5-38.4 years) in men and 50.3 years (95% CI: 48.7-52.1 years) in women with diabetes, and 42.3 years (95% CI: 41.0-43.9 years) in men and 57.6 years (95% CI: 56.0-59.5 years) in women without risk factors.ConclusionsOur derived risk equations among health-seeking young adults enriched in ASCVD risk factors inform the expected prevalence of CAC >0 and can be used to determine an appropriate age to initiate clinical CAC testing to identify individuals most susceptible for early/premature atherosclerosis.

Abstract Objectives To perform a systematic literature review and meta-analysis on endothelial cell (EC) markers that are involved and dysregulated in systemic lupus erythematosus (SLE) in relation to disease activity, as EC dysregulation plays a major role in the development of premature atherosclerosis in SLE. Methods Search terms were entered into Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) studies published after 2000 reporting measurements of EC markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles, and 3) disease activity measurement. For meta-analysis calculations, the Meta-Essentials tool by Erasmus Research Institute and of Management (ERIM) was used. Only those EC markers, which were 1) reported in at least two articles and 2) reported a correlation coefficient (i.e. Spearman’s rank or Pearson’s) between the measured levels of the EC marker and disease activity were included. For meta-analyses, a fixed effect model was used. Results From 2133 hits, 123 eligible articles were selected. The identified SLE-related endothelial markers were involved in EC activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. Meta-analyses of primarily cross-sectional studies showed significant associations between marker levels and disease activity for the following endothelial markers: Pentraxin-3, Thrombomodulin, VEGF, VCAM-1, ICAM-1, IP-10 and MCP-1. Dysregulated EC markers without associations with disease activity were: Angiopoeitin-2, vWF, P-Selectin, TWEAK and E-Selectin. Conclusions We provide a complete literature overview for dysregulated EC markers in SLE comprising a wide range of different EC functions. SLE-induced EC marker dysregulation was seen with, but also without, association with disease activity. This study provides some clarity in the eminent complex field of EC markers as biomarkers for SLE. Longitudinal data on EC markers in SLE are now needed to guide us more in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE patients.

Purpose of Review: South Asia has around 1/6th of the current global population. Epidemiological studies suggest that South Asians living in South Asia and diaspora are at an increased risk of premature atherosclerotic cardiovascular diseases (ASCVDs). This is due to an interplay of genetic, acquired, and environmental risk factors. Due to its increasing share of the global population, clinicians need to know the reasons for this early predisposition, and strategies for early identification and mitigation. Recent Findings: South Asians have earlier onset of cardiometabolic risk factors such as insulin resistance, hypertension, and central adiposity. This increased risk is seen in both native South Asians and the diaspora. Summary: South Asians have earlier onset of ASCVD due to an earlier onset of cardiometabolic risk factors. Health promotion and early identification of these risk factors are essential to mitigate this ongoing crisis. [ABSTRACT FROM AUTHOR]

Objectives: To perform a systematic literature review and meta-analysis on endothelial cell (EC) markers that are involved and dysregulated in systemic lupus erythematosus (SLE) in relation to disease activity, as EC dysregulation plays a major role in the development of premature atherosclerosis in SLE. Methods: Search terms were entered into Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) studies published after 2000 reporting measurements of EC markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles, and 3) disease activity measurement. For meta-analysis calculations, the Meta-Essentials tool by Erasmus Research Institute and of Management (ERIM) was used. Only those EC markers, which were 1) reported in at least two articles and 2) reported a correlation coefficient (i.e. Spearman's rank or Pearson's) between the measured levels of the EC marker and disease activity were included. For meta-analyses, a fixed effect model was used. Results: From 2133 hits, 123 eligible articles were selected. The identified SLE-related endothelial markers were involved in EC activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. Meta-analyses of primarily cross-sectional studies showed significant associations between marker levels and disease activity for the following endothelial markers: Pentraxin-3, Thrombomodulin, VEGF, VCAM-1, ICAM-1, IP-10 and MCP-1. Dysregulated EC markers without associations with disease activity were: Angiopoeitin-2, vWF, P-Selectin, TWEAK and E-Selectin. Conclusions: We provide a complete literature overview for dysregulated EC markers in SLE comprising a wide range of different EC functions. SLE-induced EC marker dysregulation was seen with, but also without, association with disease activity. This study provides some clarity in the eminent complex field of EC markers as biomarkers for SLE. Longitudinal data on EC markers in SLE are now needed to guide us more in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE patients. [ABSTRACT FROM AUTHOR]

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Background: Several non-traditional factors are associated with increased risk of atherosclerosis among patients with acute coronary syndrome (ACS). Objective: This study aimed to detect predictors for the premature atherosclerosis in patients less or equal than 45 years old in men and less than 55 years old in female and severity of premature atherosclerosis in acute coronary syndrome. Patients and methods: This cross-sectional study included 105 patients with acute coronary syndrome attended for angiography at Cardiology Department, Zagazig University Hospitals. Patients were divided equally into: Group (I) included young patient having traditional risk factors only with acute coronary syndrome, group (II) included young patients having nontraditional risk factors only such as Apo A-I and Apo B and increased lymphocyte to monocyte ratio with acute coronary syndrome and group (III) that included young patient having both traditional and non- traditional risk factors such as ApoA-I, m Apo B and increased lymphocyte to monocyte ratio with acute coronary syndrome. In all groups severity of atherosclerosis was assessed by Gensini score system. Results: About 2/3 of acute coronary syndrome with traditional risk factors group (62.9%) had severe atherosclerosis, with high statistically significant difference between the 3 groups. Hypertension was the only significant traditional factor in relation to severity of atherosclerosis. Also, obese patients had severe atherosclerosis 5 times more than non- obese. Odds of having severe atherosclerosis was 2.66 times more among males than females. Conclusion: A variety of significant non-traditional risk factors place patients at higher risk for ACS. We recommend taking these factors in consideration as regards assessment of occurrence and severity of premature atherosclerosis and ACS. [ABSTRACT FROM AUTHOR]

Adult growth hormone deficiency (AGHD) is considered a rare endocrine disorder involving patients with childhood-onset and adult-onset growth hormone deficiency (AoGHD) and characterized by adverse cardiometabolic risk profile. Besides traditional cardiovascular risk factors, endothelial dysfunction, low-grade inflammation, impaired adipokine profile, oxidative stress and hypovitaminosis D may also contribute to the development of premature atherosclerosis and higher cardiovascular risk in patients with AGHD. Growth hormone replacement has been proved to exert beneficial effects on several cardiovascular risk factors, but it is also apparent that hormone substitution in itself does not eliminate all cardiometabolic abnormalities associated with the disease. Novel biomarkers and diagnostic techniques discussed in this review may help to evaluate individual cardiovascular risk and identify patients with adverse cardiometabolic risk profile. In the absence of disease-specific guidelines detailing how to assess the cardiovascular status of these patients, we generally recommend close follow-up of the cardiovascular status as well as low threshold for a more detailed evaluation. [ABSTRACT FROM AUTHOR]

Abstract Background Children with juvenile dermatomyositis (JDM), the most common inflammatory myopathy of childhood, may be at increased risk of premature atherosclerosis given a host of traditional and non-traditional risk factors. The primary aim of this study was to determine the underlying frequency of premature atherosclerosis in children with JDM compared to pediatric controls using flow-mediated dilation as a measure of endothelial function. Methods Children and adolescents with and without JDM were evaluated for traditional atherosclerotic risk factors and assessment of endothelial function, using Endothelial Pulse Amplitude Testing (Endo-PAT). Results In this study, 75% of pediatric controls were of Black or Hispanic descent (compared to 55% in the JDM group) and 70% were found to live in a household with a medium income less than $50,000/year (compared to 45% in the JDM group). Among traditional atherogenic risk factors, lipoprotein A appeared to be different between controls and JDM patients (66 nmol/L and 16.5 nmol/L, respectively). Using a reactive hyperemia index (RHI)

The aim of this review was to examine the literature regarding younger individuals without classical risk factors for atherosclerosis who develop coronary artery disease (CAD) prematurely at an early age. An extensive literature review was undertaken in Pubmed, Scopus, and Google Scholar regarding early-onset or premature atherosclerosis, CAD, its diagnosis, management, and prophylaxis. There are individuals of both genders, particularly in the younger age group of 20-40 years of age, who lack the traditional/ classical risk factors and still develop CAD and other manifestations of atherosclerosis. Even the 10-year age gap in manifesting CAD that is noted between women and men ascribable to a cardioprotective effect of sex hormones may not be noted under these circumstances. This indicates that the risk profile differs in young patients with non-- classical atherosclerotic risk factors, and factors such as genetics, inflammation, thrombosis, psychosocial, environmental, and other parameters play an important role in atherosclerosis and other mechanisms that lead to CAD in younger individuals. These patients are at risk of major adverse cardiac events, which determine their prognosis. Unfortunately, current major guidelines do not acknowledge that many patients who manifest premature CAD are at high risk, and as a consequence, many of these patients may not be receiving guideline-directed hypolipidemic and other therapies before they present with symptoms of CAD. Caretakers need to be more vigilant in offering efficacious screening and strategies of prevention for early-onset or premature CAD to younger individuals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background Early identification of healthy arterial aging versus premature atherosclerosis is important for optimal atherosclerotic cardiovascular disease risk stratification and prevention. We sought to identify predictors for the long‐term absence of carotid plaque among young adults. Methods and Results We included 508 participants from the Bogalusa Heart Study without clinical atherosclerotic cardiovascular disease who were free of carotid plaque at baseline (2001–2002) and underwent ultrasound imaging at follow‐up (2013–2016). Modified Poisson regression estimated the persistent absence of plaque over 12.8 years. Participants were on average age 36.2 years at baseline, 64% were women, and 29% were Black. Although nearly all participants (97%) had a 10‐year atherosclerotic cardiovascular disease risk

Abstract Background Familial hypercholesterolaemia (FH) is the most common inherited metabolic disease with an autosomal dominant mode of inheritance. It is characterised by raised serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c), leading to premature coronary artery disease. Children with FH are subjected to early and enhanced atherosclerosis, leading to greater risk of coronary events, including premature coronary artery disease. To the best of our knowledge, this is the first report of a pair of monochorionic diamniotic identical twins with a diagnosis of heterozygous FH, resulting from mutations in both LDLR and ABCG8 genes. Case presentation This is a rare case of a pair of 8-year-old monochorionic diamniotic identical twin, who on family cascade screening were diagnosed as definite FH, according to the Dutch Lipid Clinic Criteria (DLCC) with a score of 10. There were no lipid stigmata noted. Baseline lipid profiles revealed severe hypercholesterolaemia, (TC = 10.5 mmol/L, 10.6 mmol/L; LDL-c = 8.8 mmol/L, 8.6 mmol/L respectively). Their father is the index case who initially presented with premature CAD, and subsequently diagnosed as FH. Family cascade screening identified clinical FH in other family members including their paternal grandfather who also had premature CAD, and another elder brother, aged 10 years. Genetic analysis by targeted next-generation sequencing using MiSeq platform (Illumina) was performed to detect mutations in LDLR, APOB100, PCSK9, ABCG5, ABCG8, APOE and LDLRAP1 genes. Results revealed that the twin, their elder brother, father and grandfather are heterozygous for a missense mutation (c.530C > T) in LDLR that was previously reported as a pathogenic mutation. In addition, the twin has heterozygous ABCG8 gene mutation (c.55G > C). Their eldest brother aged 12 years and their mother both had normal lipid profiles with absence of LDLR gene mutation. Conclusion A rare case of Asian monochorionic diamniotic identical twin, with clinically diagnosed and molecularly confirmed heterozygous FH, due to LDLR and ABCG8 gene mutations have been reported. Childhood FH may not present with the classical physical manifestations including the pathognomonic lipid stigmata as in adults. Therefore, childhood FH can be diagnosed early using a combination of clinical criteria and molecular analyses.

Objectives: The coronavirus-disease-2019 (COVID-19) pandemic has led to the restructuring of health-services to prioritize the treatment of COVID-19. The severe restrictions on daily life affected the management of chronic diseases. Patients with a previous history of premature myocardial infarction (MI) are a vulnerable group requiring frequent and continued medical attention both in the pandemic and non-pandemic era. The present study was conducted to provide insight into the impact of COVID-19 outbreak on heart-healthy lifestyle and management of patients with a history of premature MI. Methods: This cross-sectional study included 170 consecutive patients with a history of premature MI who were already in regular follow-up in a tertiary out-patient prevention clinic before the pandemic. Inclusion criteria included age ≥18 years and being on regular follow up with the diagnosis of premature MI (documented MI before the age of 55 years) at least for one year. All patients were contacted by phone-call and replied to a 23-item questionnaire measuring the impact of the pandemic on the management, healthy lifestyle habits, and anxiety level. Results: One patient died due to COVID-19 infection; therefore the analyses were conducted in 169 patients (age: 47.67 ​± ​11.84 years, 21.3% women). The median age at first MI was 39 (IQR 10) years and the median time elapsed since the first MI was 7 years (IQR 10). The study population was highly compliant with the follow-up visits (78.1%) and pharmacological therapy (97%) before the pandemic according to the medical files. The majority (82.2%) of the patients were aware that having a history of premature MI would increase the risk and harm of COVID-19. Anxiety level increased in 62.7% of the study patients. Overall, 65.7% of the patient group reported a disruption at least in ≥1 component(s) of healthy life-behaviors (non-compliance with the heart-healthy diet, an increase in alcohol intake, an increase in smoking, and/or reduced physical activity) since the emergence of the outbreak. The anxiety level (p ​= ​0.001) and the prevalence of appetite change (p ​

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We aimed to identify plasma protein biomarkers related to inflammation that correlated with physiological measurements of vascular function and structure in healthy individuals. We used the OLINK proteomics panel, which measures 92 inflammatory proteins, in 834 young, healthy non-smokers (ages 18–26). Principal component analysis (PCA) was employed to identify patterns of proteins. The following measurements were used: pulse-wave velocity (PWV), carotid intima-media thickness (cIMT) and augmentation index (AIX). Established cardiovascular risk factors were included in multivariable models. PCA showed four principal components (PC 1, PC 2, PC 3, PC 4). PC 3, comprising proteins related to hemostasis, was significantly and inversely correlated with PWV. Among the proteins with the highest factor loadings on PC 3, uPA was negatively correlated with PWV in multivariable regression models. AIX was significantly correlated with PC 2, comprising inflammatory cytokines. Among the proteins with the highest factor loadings on PC 2, interleukin-6 was significantly correlated with AIX in the multivariable model. cIMT was significantly correlated with PC 4, comprising proteins related to chemotaxis. Among the proteins with the highest factor loadings on PC 4, fractalkine was significantly correlated with cIMT in the multivariable model. In young, healthy individuals, OLINK inflammatory proteins correlated with measures of vascular status. Each of the three measures PWV, AIX, and cIMT, which target different parts of the vasculature, correlated with its own specific protein signature, indicating that different subsets of inflammatory mediators affect different parts of the vasculature and are detectable already in young healthy adults. Image 1 • In healthy young adults, vascular physiology correlates with the expression of inflammatory proteins. • Pulse-wave velocity correlates with urokinase-type plasminogen activator (uPA). • Augmentation index correlates with interleukin-6 (IL6). • Carotid intima media thickness correlates with fractalkine. [ABSTRACT FROM AUTHOR]

Genetic factors partly determine the risk for premature myocardial infarction (MI). We report the identification of a novel rare genetic variant in a kindred with an autosomal dominant trait for premature MI and atherosclerosis and explored the association of a common nonsynonymous variant in the same gene with the risk of ischemic heart disease (IHD) in a population-based study. Next-generation sequencing was performed in a small pedigree with premature MI or subclinical atherosclerosis. A common variant, rs8141797 A>G (p.Asn466Ser), in sushi domain–containing protein 2 (SUSD2) was studied in the prospective Copenhagen General Population Studies (N = 105,408) for association with IHD. A novel heterozygous nonsense mutation in SUSD2 (c.G583T; p.Glu195Ter) was associated with the disease phenotype in the pedigree. SUSD2 protein was expressed in aortic specimens in the subendothelial cell layer and around the vasa vasorum. Furthermore, the minor G-allele of rs8141797 was associated with per allele higher levels of SUSD2 mRNA expression in the heart and vasculature. In the Copenhagen General Population Study, hazard ratios for IHD were 0.92 (95% CI: 0.87–0.97) in AG heterozygotes and 0.86 (0.62–1.19) in GG homozygotes vs noncarrriers (P -trend =.002). Finally, in meta-analysis including 73,983 IHD cases and 215,730 controls, the odds ratio for IHD per G-allele vs A-allele was 0.93 (0.90–0.96) (P = 4.6 × 10−7). The identification of a truncating mutation in SUSD2 , which was associated with premature MI and subclinical atherosclerosis, combined with the finding that a common missense variant in SUSD2 was strongly associated with a lower risk of IHD, suggest that SUSD2 may alter the risk of atherosclerosis. • A nonsense mutation in sushi domain–containing protein 2 (SUSD2) was associated with the coronary artery disease phenotype in the family. • In meta-analysis, a common variant in SUSD2 was strongly associated with the risk of ischemic heart disease. • This suggests that SUSD2 may alter the risk of coronary artery disease. • Further experimental work in animal models is needed to support these observations. [ABSTRACT FROM AUTHOR]

Background: Children with juvenile dermatomyositis (JDM), the most common inflammatory myopathy of childhood, may be at increased risk of premature atherosclerosis given a host of traditional and non-traditional risk factors. The primary aim of this study was to determine the underlying frequency of premature atherosclerosis in children with JDM compared to pediatric controls using flow-mediated dilation as a measure of endothelial function. Methods: Children and adolescents with and without JDM were evaluated for traditional atherosclerotic risk factors and assessment of endothelial function, using Endothelial Pulse Amplitude Testing (Endo-PAT). Results: In this study, 75% of pediatric controls were of Black or Hispanic descent (compared to 55% in the JDM group) and 70% were found to live in a household with a medium income less than $50,000/year (compared to 45% in the JDM group). Among traditional atherogenic risk factors, lipoprotein A appeared to be different between controls and JDM patients (66 nmol/L and 16.5 nmol/L, respectively). Using a reactive hyperemia index (RHI) < 1.67 as evidence of endothelial dysfunction, 75% of controls were defined as having endothelial dysfunction compared to 50% in JDM group. When controlled for lipoprotein A as an atherogenic confounder, JDM patients were found to have a 41% increase in RHI, thus indicating less endothelial dysfunction compared to controls. Conclusions: In this study, we have shown that atherogenic risk factors are present in the pediatric population and may be associated with endothelial dysfunction, even at very young ages. Despite increasing concerns that children with rheumatologic disorders may be at increased risk of developing premature atherosclerosis, traditional and sociodemographic features may play a greater role in the ultimate development of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Despite improved treatment, premature cardiovascular (CV) events remain a major health problem. Aim of this study was to evaluate the patterns of risk factors in patients with premature CV events. CV risk factors (CVRF) were evaluated in 130 patients with a history of CV events (myocardial infarction, stroke, limb ischemia, stent and bypass intervention in any vessel bed) under 50 years of age attending our lipid clinic. Patients were also stratified according to their Lp(a) concentrations: group 1: 0–45 nmol/l (<18 mg/dl); group 2: >45–120 nmol/l (>18–50 mg/dl); group 3: >120 nmol/l (>50 mg/dl). The most common risk factors in our patients were male sex (75%), current (61%) and previous smoking (9%), arterial hypertension (70%), and a positive family history of early CV events (54%) and hyperlipidemia (69%). Only 27% had a BMI >30 kg/m2 and 14% had diabetes mellitus. 69% of patients with premature CV disease (CVD) showed Lp(a) levels > 120 nmol/l (>50 mg/dl). Patients with the highest Lp(a) showed a tendency of more frequent positive family histories of hyperlipidemia. They had experienced their first CV event on average 3 years earlier than those with low Lp(a). CV events predominantly involved coronary arteries. 85% of patients experienced at least one coronary event. In patients with premature CV disease male sex, smoking, hypertension, a positive family history and elevated Lp(a) are the most important CV risk factors. Lp(a) should be considered in the management of young patients with CV disease. [ABSTRACT FROM AUTHOR]

Familial Hypercholesterolaemia is a common genetic cause of premature Coronary heart Disease (CHD). It is an autosomal, dominant, inherited disorder of lipoprotein metabolism that results in a raised Low Density Lipoprotein Cholesterol (LDL-C) plasma concentration. The current study presented a 36 year old female having angina on exertion class 2 for past 1 year. She had large xanthomas over dorsal aspect of both the hands and feet and xanthelasma over eyelid. She was diagnosed as case of familial hypercholesterolemia. Her vascular profile revealed aortic root calcification, left main with triple vessel disease, right common carotid artery stenosis and atherosclerotic narrowing of aorta distal to left subclavian artery.

Objective: The purpose of this study was to evaluate the association between V103V, 6140AG, TGA-Stop-TAA Stop, and 6016CA polymorphisms of the apelin (APLN) gene detected for the first time among young patients with acute coronary syndrome (ACS) and coronary artery disease (CAD). Methods: This was a prospective cross-sectional study. The study population was divided into 2 groups. The first group included 132 patients who were found to have critical lesions in their coronary arteries, while the control group consisted of 41 patients who were found to have normal coronary arteries or non-critical atherosclerotic lesions. Results: Among the gene polymorphisms, V103V was found to be more common in the critical CAD patients with the GG genotype compared with the control group (67.4% vs. 46.3%). On the other hand, the GT genotype was more common in the control group (53.7% vs. 32.6%). Univariate and multivariate logistic regression analysis revealed that the GG genotype of V103V was an independent predictor for the presence of critical CAD (odds ratio: 2.397; 95% confidence interval, 1.174–4.892; p=0.016). Conclusion: In cases of V103V polymorphism of the APLN gene, patients with the GG genotype were at a greater risk for the presence of atherosclerotic critical lesions compared with the control group.

Introduction: Atherosclerosis in young and premenopausal women with systemic lupus erythematosus (SLE) is frequent, premature and progressive. Although asymptomatic or with atypical clinical presentation, the patients are at high risk of cardiac events. Aim of this study is to estimate the risk profile for atherogenesis and the prevalence of myocardial perfusion abnormalities with 99mTc myocardial perfusion scintigraphy (MPS) in young and premenopausal women. Material and methods: Sixty female patients, aged 30-72 years (divided into two subgroups - patients under 45 years of age and patients over 45 years), diagnosed with SLE for over of 5 years, in active phase of the disease were analyzed for disease activity scores (SLEDAI), the immunologic status of the disease (ANA and a-DNA antibodies in the serum), procoagulant tendency (antiphospholipid antibodies -APhL and lupus- anticoagulant-LAC), the activity of the inflammatory process (hsCRP), the anti-SLE therapeutic approach and the presence of traditional risk factors for atherosclerosis (BMI, smoking, hypertension, hyperlipidemia, diabetes, and familial history for the CAD). Using one-day Dipyridamol - Rest 99mTc SPECT Gated MPS SPECT the extent, severity and reversibility of myocardial perfusion abnormalities were estimated, along with summed scores at stress, rest and summed difference scores and left ventricle volumes and ejection fraction. Results: Abnormal MPS SPECT were detected in 27/60 or in 45% of patients, with one vessel affection of 66.7% (18/27pts) of LAD and 14.8% (4/27pts) o RCA and with two vessel disease of LAD/RCA in 2/27 pts (7.4%) and LAD/Cx in 3/27pts (11.1%). Myocardial perfusion abnormalities were equally prevalent in subgroups of patients younger than 45 years (44,4%) and in patients older than 45 years (45.5%) (ns). The subgroups did not differ significantly concerning the extent of perfusion abnormalities (9,8±3.2% of LV myocardial mass vs. 9,8±7.1%,ns), their severity (with predominance of mild perfusion defects, 48,6% vs. 51,3%,ns) and reversibility (reversible in 41.3% and 58.6%, ns). The differences between the summed scores of severity and the extent of ischemia in the two subgroups were statistically nonsignificant. Younger patients had significantly higher end-diastolic, end-systolic and stroke volumes during stress and rest conditions, compared to older patients (p<0,01) although there were no differences in systolic function, which was not affected in either of the groups as expressed threw ejection fraction. Although nonsignificant, younger patients had higher values of hsCRP and higher procoagulant activity (positive aPhL, LAC) while they were with more active disease activity, with higher SLEDAI score compared to older patients (p=0.028). Higher SLEDAI score and LV volumes, especially EDV at stress were identified as predictor of abnormal MPS in younger groups and more aggressive multidrug anti SLE treatment as predictor of normal MPS. Conclusion: The prevalence and characteristics of myocardial perfusion abnormalities in young SLE are equal as the same in older SLE patients, which indicates the presence of premature, accelerated atherosclerosis in young cohort of patients with SLE. Younger SLE patients with pure disease control (higher SLEDAI score, less aggressive treatment, high hsCRP values and pronounced procoagulant tendency) should undergo screening for myocardial perfusion abnormalities s using 99mTc MIBI MPS). [ABSTRACT FROM AUTHOR]

Background: Sitosterolemia is a rare lipid metabolism disorder that involves storage of plant sterols. This disease is associated with atherosclerosis, but detailed vascular endothelial assessment is difficult. Case presentation: We report a 5-year-old girl with sitosterolemia who presented with xanthomas at 23 months of age. Her total cholesterol was 868 mg/dL, and her plasma sitosterol level was 9.48 mg/dL. Direct sequencing detected a homozygous mutation in gene ABCG5 (p.Arg389His). Echocardiographic examination revealed that the carotid artery intima media thickness (cIMT) was 0.4 mm with heterogenous hyperechogenicity inside the arterial wall. She was treated using dietary therapy and ezetimibe, which effectively lowered her sitosterol levels. After 3 years of treatment, her cIMT was stable in diameter and arterial wall echogenicity had improved. Conclusions: Sitosterolemia is a unique disorder in which it is difficult to avoid premature atherosclerosis because of high sitosterol levels. cIMT measurement with arterial wall assessment may improve management. [ABSTRACT FROM AUTHOR]

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Background: Early vascular alteration, atherosclerosis and coronary artery disease have emerged as important cardiovascular complications among beta-thalassemia major (B-TM) patients. The aims of the current study were to assess the prevalence of premature atherosclerosis among our B-TM patients, and to investigate the diagnostic value of serum Osteoprotegerin assay as an early biomarker for atherosclerosis.Methods: This cross-sectional study was conducted at Hematology unit - Pediatric Department, Zagazig University Children Hospital- Egypt in the period from March 2014 to March 2015. A total of 115 children were enrolled in the current study; as sixty-five (65) children with beta thalassemia major aged 5-18 years, on regular blood transfusion regimen represented the patient group. While fifty (50) healthy children, with comparable age and gender, were assigned as control group. All participants were subjected to history taking, thorough clinical examination and laboratory investigations including; complete blood count, liver and kidney function tests, C- reactive protein, lipid profile, serum ferritin and serum Osteoprotegerin (OPG) assay. Also, carotid artery intima media thickness (CAIMT) was performed by duplex ultrasound for patients and controls.Results: Our B-TM patients were transfusion-dependent for as long as 8.5 ± 3.8 years with significantly higher serum ferritin levels (2490 ± 1579 ng/dl vs 83 ± 32 ng/dl, p = 0.001), C-reactive protein (5.7 ± 5.7 vs 0.9 ± 0.9), liver enzymes and bilirubin when compared to controls. Significantly higher serum triglyceride (128 ± 20 vs 101 ± 7 mg/dL, p = 0.009) and atherogenic index of plasma (0.45 ± 0.12 vs 0.22 ± 0.04, p = 0.001) were recorded in patients than comparisons. On the contrary, total serum cholesterol (116 ± 16 vs 143 ± 5, p < 0.001), low density lipoprotein-cholesterol (LDL-C) (44 ± 9 vs 73 ± 6, p < 0.001) and high density lipoprotein cholesterol (HDL-C) (39 ± 2 vs 61 ± 5, p < 0.001), were significantly lowered in patients versus normal peers. Carotid arteries intima media thickness (CAIMT) of both side were significantly increased for patients (Rt 0.62 ± 0.2 vs. 0.29 ± 0.07 mm, p = 0.001 & Lt 0.66 ± 0.17 vs 0.29 ± 0.05 mm, p = 0.001) when compared with healthy controls, and showed positive correlation with, serum triglyceride, atherogenic index of plasma, and serum Osteoprotegerin levels. ELISA assay of serum Osteoprotegerin (OPG) revealed significantly higher levels for thalassemia patients than matched healthy controls (427 ± 102 vs. 324 ± 126 pg/ml, p = 0.02). Of particular interest is the obvious positive correlation between OPG levels and CAIMT of both sides (Rt r 0.54, p = 0.001 &Lt r 0.479, p = 0.001) and also with serum triglycerides (r 0.374, p = 0.03).Conclusions: Subclinical atherosclerosis started prematurely in children with beta- thalassemia. Carotid artery intima media thickness represented a simple, accurate and non-invasivemodality for early detection ofatherosclerosis. It was correlated well with serum Osteoprotegerin; this finding highlighted the possible validity of OPG assay as an early predictor of atherosclerosis in thalassemia children. [ABSTRACT FROM AUTHOR]

The effect of human cholesteryl ester transfer protein (CETP) expression on atherogenesis is still under debate. The rs5882 (I405V) polymorphism affect CETP function. We aimed to examine the relationship between the rs5882 polymorphism and the risk of angiographically determined coronary artery disease (CAD). To define premature CAD (PCAD), an age cutoff of 55 years for women and 45 years for men was used. An age- and sex-matched case-control study was conducted in 560 patients with newly diagnosed angiographically documented PCAD (≥50% luminal stenosis of any coronary vessel) and an equal number of control patients with normal coronary arteries (no luminal stenosis at coronary arteries). The severity of CAD was determined by vessel score and Gensini score. A real-time polymerase chain reaction (PCR) and high resolution melting analysis were used to distinguish between genotypes. The I405V genotype distributions were not statistically different in CAD and non-CAD groups in univariate and multivariable-adjusted logistic regression analyzes. The median and inter-quartile range for Gensini score was not significantly different among the AA (43, 24 to 73), AG (40, 20 to 66), and GG (45, 25 to 72) genotypes (p = 0.097). Furthermore, the distribution of vessel score did not statistically differ between these genotypes (p = 0.691). Our results suggest that there is no significant association between CETP I405V polymorphism and the risk of PCAD presence and severity. Larger prospective studies are needed to investigate such associations in different populations.

Subnormal HDL-cholesterol (HDL-C) and apolipoprotein (apo)AI levels are characteristic of familial hypercholesterolemia (FH), reflecting perturbed intravascular metabolism with compositional anomalies in HDL particles, including apoE enrichment. Does LDL-apheresis, which reduces HDL-cholesterol, apoAI, and apoE by adsorption, induce selective changes in HDL subpopulations, with relevance to atheroprotection? Five HDL subpopulations were fractionated from pre- and post-LDL-apheresis plasmas of normotriglyceridemic FH subjects (n = 11) on regular LDL-apheresis (>2 years). Apheresis lowered both plasma apoE (−62%) and apoAI (−16%) levels, with preferential, genotype-independent reduction in apoE. The mass ratio of HDL2:HDL3 was lowered from ∼1:1 to 0.72:1 by apheresis, reflecting selective removal of HDL2 mass (80% of total HDL adsorbed). Pre-LDL-apheresis, HDL2 subpopulations were markedly enriched in apoE, consistent with ∼1 copy of apoE per 4 HDL particles. Large amounts (50-66%) of apoE-HDL were removed by apheresis, preferentially in the HDL2b subfraction (−50%); minor absolute amounts of apoE-HDL were removed from HDL3 subfractions. Furthermore, pre-β1-HDL particle levels were subnormal following removal (−53%) upon apheresis, suggesting that cellular cholesterol efflux may be defective in the immediate postapheresis period. In LDL-receptor (LDL-R) deficiency, LDL-apheresis may enhance flux through the reverse cholesterol transport pathway and equally attenuate potential biglycan-mediated deposition of apoE-HDL in the arterial matrix.

Background: Hutchinson-Gilford Progeria Syndrome (HGPS) is a very rare genetic disorder with a frequency of 1 in 8 million live births. It is characterised by premature aging phenotype. The median age at death is 13.4 years. It is an autosomal dominat disease due to a de novo point mutation in the Lamin A gene exon 11 in the majority of cases. More than 100 cases have been reported world wide."nCase report: We describe here an exceptionally long-lived patient with HGPS, who is alive at age 36. She was referred by a cardiologist to our endocrinology clinic to be worked up for presence of a metabolic or genetic disorder before a heart surgery."nResults: Having more attention of clinicians about very rare diseases and referring the patients to geneticist are the main goals of this case report as well as describing the disease.

Background: The purpose of the study is to determine levels of total cholesterol (TC), low-density, and high-density lipoprotein fractions of cholesterol (LDLc and HDLc), in patients with juvenile idiopathic arthritis (JIA), and relate those to disease activity, overweight, and physical activity (PA), testing the hypothesis that the levels of cholesterol fractions are associated with inflammation as well as with overweight and low PA. Methods: Two hundred ten patients with JIA were included in this descriptive cross-sectional study. TC, LDLc, HDLc were measured, and associations with clinical disease activity (JADAS27), biomarkers of inflammation (myelo-related protein complex 8/14 (MRP8/14), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR)), body mass index (BMI), waist-to-height ratio (WtH ratio), and PA were explored. Results: Mean values for TC, LDLc, and HDLc in the patients were within the normal range for Danish Children. HDLc was negatively correlated with MRP8/14 (r = -0.343, CI -0.474 to -0.201, p < 0.0005) but was not related to overweight or PA. Neither TC nor LDLc showed any association with inflammation, overweight, or PA. MRP8/14 correlated positively with CRP, JADAS27 and WtH ratio (r = 0.277, CI 0.142 to 0.413, p = 0.001). Conclusions: Levels of cholesterol fractions in patients with JIA were found within the normal range. Nonetheless, the level of HDLc was negatively associated with the level of the inflammatory marker MRP8/14, which is in accordance with the concept of inflammation as an important driver for premature development of atherosclerosis in JIA. WtH ratio (a measure of central fatness) was not associated to HDLc, but to MRP8/14, suggestive of central fatness as an additional driving factor for the chronic inflammation in JIA. [ABSTRACT FROM AUTHOR]

Background Risk of subclinical atherosclerosis is increased in patients with systemic lupus erythematosus (SLE). We correlated carotid intima media thickness (CIMT) and endothelial dysfunction through flow-mediated dilation (FMD) in SLE patients with the SLE Disease Activity Index (SLEDAI). Methods This single-centre cross-sectional study recruited 100 consenting SLE outpatients (ACR 1997 criteria) out of which 50 had nephritis, with disease duration of ≥2 years for SLE and ≥6 months for lupus nephritis. We measured baseline laboratory levels, CIMT and FMD (after brachial BP cuff inflation up to 200 mmHg for five minutes), and calculated SLEDAI. Results Mean age was 29.88 ± 6.53 years; 95/100 were female. CIMT showed positive correlation (p = 0.037; rho = 0.209), and FMD showed inverse correlation with patient’s age (p = 0.011; rho = –0.252). CIMT and FMD were more deranged in patients aged ≥25 years (p < 0.05). CIMT was not significantly different between SLE patients with and without nephritis (p > 0.05), whereas SLEDAI and FMD were more deranged in nephritis patients (p < 0.05). In patients without nephritis, FMD showed significant inverse correlation with disease duration (p = 0.043; rho = –0.288) and urine albumin (p = 0.045; rho = –0.285). In nephritis patients, the correlation between age of the patient was significantly positive with CIMT (p = 0.001; rho = 0.441) and significantly inverse with FMD (p = 0.028; rho = –0.312). Conclusion SLE patients with nephritis are at a higher risk to develop arterial stiffening, leading to early end-organ damage. Early aggressive treatment may prevent endothelial dysfunction. FMD using vascular ultrasonography on the brachial artery represents a non-invasive, repeatable and useful method for the assessment of endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Background: Several single nucleotide polymorphisms (SNPs) in lipid transport genes have been shown to be associated with premature coronary artery disease (PCAD). The scavenger receptor BI (SCARB1) is a key component of the reverse cholesterol transport and lipid metabolism. We aimed to examine the relationship between the rs5888 SNP within SCARB1 and the risk of angiographically determined PCAD. Methods: We used an age cut-off of 55 years for women and 45 years for men to define PCAD. Five-hundred and five patients with newly diagnosed angiographically documented PCAD (=50 % luminal stenosis of any coronary vessel) as case group compared with 546 controls (subjects with no luminal stenosis at coronary arteries). The severity of CAD was determined by vessel score as well as Gensini score. A real-time polymerase chain reaction (PCR) and High Resolution Melting (HRM) analysis was used to distinguish between genotypes. Results: T allele as compared to C allele was associated with increased odds of PCAD in total population (adjusted OR = 1.3, 95 % CI = 1.0 to 1.5; p = 0.020), and in women (adjusted OR = 1.3, 95 % CI = 1.0 to 1.8; p = 0.037), but not in men (adjusted OR = 1.2, 95 % CI = 0.9 to 1.5; p = 0.311). There was also no significant association between the examined polymorphism and the severity of CAD in whole or in men or women subgroups. Conclusions: Our findings suggest that the SNP (rs5888) within SCARB1 is independently associated with PCAD in a sex-dependent manner. [ABSTRACT FROM AUTHOR]

Many studies show that Juvenile Idiopathic Arthritis (JIA) is associated with early subclinical signs of atherosclerosis. Chronic inflammation per se may be an important driver but other known risk factors, such as dyslipidemia, hypertension, insulin insensitivity, a physically inactive lifestyle, obesity, and tobacco smoking may also contribute substantially. We performed a systematic review of studies through the last 20 years on early signs of subclinical atherosclerosis in children and adolescents with JIA with the purpose of investigating whether possible risk factors, other than inflammation, were considered. We found 13 descriptive cross sectional studies with healthy controls, one intervention study and two studies on adults diagnosed with JIA. Only one study addressed obesity, and physical activity (PA) has only been assessed in one study on adults with JIA and only by self-reporting. This is important as studies on PA in children with JIA have shown that most patients are less physically active than their healthy peers, and as physical inactivity in several large studies of normal schoolchildren is found to be associated with increased clustering of risk factors for cardiovascular disease. It is thus possible that an inactive lifestyle in patients with JIA is an important contributor to development of the subclinical signs of atherosclerosis seen in children with JIA, and that promotion of an active lifestyle in childhood and adolescence may diminish the risk for premature atherosclerotic events in adulthood. [ABSTRACT FROM AUTHOR]

Background: Vascular health is of concern in patients with Juvenile Idiopathic Arthritis (JIA) since Rheumatoid Arthritis (RA) epidemiologically has a well-described association with premature development of atherosclerosis. Chronic inflammation with persisting systemic circulating inflammatory proteins may be a cause of vascular damage, but general physical inactivity could be an important contributor. Pain and fatigue are common complaints in patients with JIA and may well lead to an inactive sedentary lifestyle. For this reason we assessed the physical activity (PA) objectively in patients with moderate to severe Juvenile Idiopathic Arthritis (JIA) in comparison with gender and age matched healthy schoolchildren, and looked for associations between PA and features of JIA. Methods: One hundred thirty-three patients, 7-20 years of age, participated. Disease activity, disability, functional ability, and pain were assessed and PA was measured by accelerometry through 7 days and compared to PA in age- and gender-matched healthy schoolchildren. Results: We found a significantly lower level of PA in patients compared to gender- and age-matched healthy schoolchildren both in average activity (counts per minute, cpm) (475.6 vs. 522.7, p = 0.0000018) and in minutes per day spent with cpm >1500 (67.9 vs. 76.4, p = 0.0000014), with cpm >2000 (moderate physical activity) (48.4 vs. 52.8, p = 0.0001, and with cpm >3000 (high physical activity) (24.7 vs. 26.5, p = 0.00015). A negative association (β = -0.213, p = 0.014) between active disease in weight bearing joints and high physical activity remained the only significant association between disease related factors and PA. Of the girls 19 % and of the boys 45 % (vs. 39 % and 61 % in the reference group) met standards set by Danish Health Authorities for daily PA in childhood. Conclusion: Children and adolescents with JIA are less physically active than their healthy peers and less active than recommended for general health by the Danish Health Authorities. This is not explained by pain or objective signs of inflammation. When inflammation has been curbed, restoration of an active healthy lifestyle should be highly prioritized. [ABSTRACT FROM AUTHOR]