Atherosclerotic Manifestations Research Articles

Atherosclerosis in patients with cervical artery dissection.

Cervical artery dissection (CeAD) is considered a non-atherosclerotic arteriopathy, but atherosclerosis of the cervical arteries may co-exist. We explored the frequency and clinical importance of co-existent atherosclerosis in patients with CeAD. Single-center exploratory study from the Stroke Center Basel, Switzerland. We re-reviewed duplex ultrasound images at (i) baseline and (ii) last follow-up visit for the presence versus absence of the following atherosclerotic manifestations in the carotid arteries: (i) abnormal carotid intima-media thickness, (ii) plaques, and (iii) atherosclerotic stenosis. We investigated whether CeAD patients with versus without co-existing atherosclerosis differ regarding (a) recurrence of CeAD and (b) occurrence of vascular events (myocardial infarction, peripheral artery disease, or ischemic stroke) using logistic regression with adjustment for age and follow-up time. Among 294 CeAD patients (median age 46 [IQR 37-53], 41.8% women), 35 (12%) had any atherosclerotic signs at baseline. Among 196 patients with available follow-up, another 21/196 (11%) patients developed atherosclerosis during a median follow-up of 55.7 months. Patients with atherosclerosis had decreased odds of recurrent CeADs when compared to patients without atherosclerosis (OR 0.03, 95% CI = 0.00-0.30). During follow-up, 6 (15%) vascular events occurred among 40 CeAD patients with atherosclerosis and 13 (8.5%) among 153 patients without atherosclerosis (OR 1.38, 95% CI = 0.39-4.55, data for 3 patients were missing). Signs of atherosclerosis in the carotid artery were detectable in 12% of CeAD patient at baseline. Additionally, 11% of CeAD patients developed new signs of atherosclerosis within the following 5 years. The presence of atherosclerosis may suggest a lower risk for recurrent CeAD. Whether it might indicate an increased risk for late clinical vascular events deserves further studies.

MiRNA in the Diagnosis and Treatment of Critical Limb Ischemia.

Chronic threatening limb ischemia of the inferior limbs (CLTI) is the final stage of peripheral arterial disease (PAD) and is one of the most feared atherosclerotic manifestations because if left untreated, in time, it can lead to amputation. Although there are currently numerous treatment techniques, both open and endovascular, it is a pathology that has no underlying treatment. Therefore, current studies are very much focused on new therapeutic possibilities that can be applied in the early stages of the atherosclerotic process. In numerous studies in the literature, miRNAs have been identified as important markers of atherosclerosis. The present study aims to identify the expression of three miRNAs-miR-199a, miR-20a, and miR-30c-in patients with chronic limb-threatening ischemia in the pre- and post-revascularization periods. The aim of the study is to identify whether these three markers play a role in critical ischemia and whether they have the potential for future use in new treatments of this pathology.

ATHEROSCLEROTIC CHANGES OF BRACHIOCEPHALIC ARTERIES IN DIFFERENT AGE GROUPS ACCORDING TO SONOGRAPHY

Background. One of the most frequent causes of death is considered to be stroke on the back of atherosclerosis of the extracranial carotid arteries. Detection of atherosclerosis at an early stage facilitates timely prevention and reduces the risk of developing of an acute cardiovascular event in the future. Purpose. To evaluate the clinical significance of ultrasound in the diagnosis of atherosclerotic changes in the brachiocephalic arteries in people of different age groups. Materials and methods. Echography of brachiocephalic arteries was performed among 155 people aged 45 to 89 years, who were randomized into 3 age groups. The middle–aged group included 56 people; the elderly group – 54 people; the senile group - 45 people. The processing of the results of the study was carried out in the programs Statistica 10 (StatSoft, USA). Results. According to the data of sonography, atherosclerotic plaques were detected in 62.5% of the middle–aged group, 83.3% of the elderly group and 88.9% of senile age. Heterogeneous hypoechoic and calcified plaques are found only among people who are over 60 years old. Moderate stenosis was observed at the bifurcation of the common carotid artery in all age groups. Pronounced stenosis and critical vascular stenosis in the proximal part of the internal carotid artery are observed in senile age. The index of the maximum systolic velocity among people with atherosclerosis decreases with age. With increasing age, the level of vascular resistance increases. Conclusion. Considering significant changes in the indicators of atherosclerotic manifestations already in middle age, in order to reduce the increase in population mortality from cardiovascular diseases, the healthcare system should introduce early ultrasound screening of brachiocephalic arteries for patients from 18 years of age.

#673 Predictive value of insulin resistance and GFR-adjusted uricemia on all-cause mortality: the URRAH study

Abstract Background and Aims Uric acid (UA) and insulin resistance (IR) are interlinked: UA contributes to adversely affects the insulin signaling pathway, while IR predicts the development of hyperuricemia. Both UA and IR are related to metabolic syndrome, which is nowadays one of the most prevalent risk factors for mortality. In the clinical scenario, the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been proved to have a high correlation with IR. Lipoprotein-based markers of IR are at least as strongly associated with subclinical atherosclerosis and with newly developing atherosclerotic manifestations than Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The aim of the research was to explore the extent of interaction between IR and GFR-adjusted uricemia in determining mortality risk in a large population cohort study. Method data from 18,694 subjects were included from Uric acid Right foR heArt Healt (URRAH) database. Differences between TG/HDL-C ratio quintiles were evaluated by t-test or chi-square test. We evaluated the association between TG/HDL-C ratio and GFR-adjusted uricemia, and the development of outcomes during the follow-up study period. The primary endpoint was all-cause mortality. The Kaplan-Meier method was used to calculate the cumulative survival rate. Cox proportional hazard regression models were used to analyze the prognosis associated with IR. Results after a mean follow-up of 124 ± 64 months, there were 2,665 (14.2%) deaths for all causes. The incidence of fatal, non-fatal cardiovascular events, and all-cause mortality increased in parallel with the increase of TG/HDL-C quintiles. In both diabetic and non-diabetic patients, TG/HDL-C ratio showed a positive association with increasing of GFR-adjusted uricemia (UA/GFR ratio). TG/HDL-C ratio and GFR-adjusted uricemia significantly interact in determining all-cause mortality, even in non-diabetic patients (P < 0.0001). Subjects with higher TG/HDL-C ratio quintile had a statistically significantly higher rate of mortality than patients with lower quintiles (Fig. 1, log rank test P < 0.0001), independently by uricemia, GFR, the presence of diabetes and body mass index (BMI). Multivariate analysis showed that the TG/HDL-C ratio increase the mortality risk even after adjustment for potential confounding factors included age, diabetes, UA/GFR, BMI and statins treatment (Table 1). Conclusion For practical purposes, the easily obtainable TG/HDL-C ratio may suffice to determine the impact of insulin resistance as a risk factor. TG/HDL-C ratio interacts with GFR-adjusted uricemia in predicting mortality, even in non-diabetic patients. In conclusion, Both IR and GFR-adjusted UA levels seems to have an important predictive role on all-cause mortality, independently of age, gender, diabetes, hypertension and statins.

LDL cholesterol target attainment in a representative German cohort of high- and very-high-CV risk patients with statin intolerance: a simulation study

Abstract Background The LDL cholesterol (LDL-C) treatment goals recommended by the 2019 ESC/EAS guidelines are only achieved in a minority of patients. Reasons include the inability to tolerate sufficient doses of statins. To reduce cardiovascular risk in these patients, alternative lipid-lowering therapies (LLT) are required. Purpose Simulation of LDL-C target attainment and achievable LDL-C reductions with oral LLT including ezetimibe and bempedoic acid in patients with statin intolerance (SI) using electronic health records. Methods Data were obtained from the IQVIATM Disease Analyzer database containing a representative sample of German outpatients. We selected patients with high or very-high cardiovascular risk based on ESC/EAS guidelines and diagnosed hypercholesterolaemia. Within this cohort, statin-intolerant patients were classified by applying the following literature-informed definitions pointing towards SI with high confidence (among others): patients with LLT only consisting of non-statins, long-term discontinuation of statin therapy, down-titration of statins, and documented side effects in the electronic health records. We used a Monte Carlo approach to simulate sequentially escalating oral LLT, by adding ezetimibe and bempedoic acid in patients with uncontrolled LDL-C in this population. Results Of the total study population (n=130,778 patients), 33.9% had high and 66.1% had very-high cardiovascular risk. Within this cohort, 11,286 patients (8.6%) met the criteria of SI. Compared to the total study population, in the SI group, there were higher proportions of patients who exhibited atherosclerotic manifestations and who were classified as "very-high cardiovascular risk" (73.7% vs. 66.1%). Their LDL-C levels were slightly higher (105.6 vs. 103.6 mg/dL). 46.5% received a low-intensity statin monotherapy. Ezetimibe, both as monotherapy or in combination, was more frequently prescribed. 12.3% did not receive any LLT (Table). Patients classified as statin-intolerant entered into the simulation model. At baseline, 7.7% were at LDL-C target. In patients without ezetimibe, consecutive treatment with ezetimibe and bempedoic acid increased the calculated proportion of patients at goal to 22.6% and 52.0%. A higher proportion of patients classified as high risk achieved the target compared to those at very-high risk (58.1% vs. 49.9%). The median LDL-C (IQR) after simulation of ezetimibe and bempedoic acid treatment was 62 (48–84) mg/dL (Figure). Conclusions Patients meeting the definition of SI based on their electronic health records represented 8.6% of the total cohort of the patients with high or very-high cardiovascular risk. In this population, oral combination LLT with ezetimibe and bempedoic acid has the potential to substantially increase the proportion of patients achieving clinically relevant LDL-C reductions.

Cardiometabolic outcomes of sitagliptin-enhanced metformin treatment in uncontrolled type 2 diabetes patients without atherosclerotic manifestations

Cardiometabolic outcomes of sitagliptin-enhanced metformin treatment in uncontrolled type 2 diabetes patients without atherosclerotic manifestations

CORRELATION OF LIPOPROTEIN(a) AND CORONARY ARTERY DISEASES

<div><p><strong>INTRODUCTION:</strong> Cardiovascular diseases (CVD) continue to be one of the leading causes of mortality worldwide. While factors such as diabetes, sedentariness, psychostress, genetic predisposition, hypertension, smoking, and hyperlipidemia are well-known in the etiology of atherosclerosis (Ath) of coronary arteries. Recent studies have also identified high concentrations of lipoproteins (a) [Lp(a)] as a risk factor. In fact, high concentrations of Lp(a) above 30mg/dl (reference value-30mg/dl) have been found to be a risk factor for Ath, leading experts to develop medications aimed at reducing Lp(a) concentrations and preventing atherosclerotic manifestations. <a href="https://eas-society.org/"><em>The European Atherosclerosis Society</em></a> has also released clinical guidelines for testing and treating high concentrations of Lp(a) as part of the global assessment of cardiovascular risk.</p><p><strong>THE GOAL OF THE STUDY:</strong> The goal of this study is to investigate the concentration of Lp(a) in patients with coronary disease and its connection to the presentation of atherosclerosis of the coronary arteries in patients with CVD compared to a control group of healthy individuals. Through this study, we hope to gain a better understanding of the role of Lp(a) in CVD and its potential as a target for prevention and treatment. By identifying and addressing risk factors like high Lp(a) concentrations, we can work towards reducing the global burden of CVD and improving health outcomes for individuals around the world.</p><p><strong>THE AIM OF THE STUDY:</strong> The aim of this study is to determine the concentration of lipoprotein(a) in patients with coronary disease, its connectivity and role in the presentation of atherosclerosis of the coronary arteries in patients with CVD compared to the control group of healthy individuals.</p><p><strong>MATERIAL AND METHODS:</strong> As working material, the blood taken from the vein of patients with coronary disease was used - N0=80, (with an identical average age of 55.70±6.00 years old, of which 35 were female while 45 were male. In the study, there was also a control group: N0=80 healthy volunteers (45 were male and 35 female) with the same age as the patients. Blood for analysis was taken at 8 o'clock in the morning, at room temperature of 19-24°C, every three months in a period of 12 months.</p><p>Echocardiography and EKG were also performed on all the patients with Toshiba SSH-140A machine, color Doppler probe 3.7Hz, sectorial type, taking into account as key parameters the thickness of the back wall of the left ventricle and the thickness of-Left ventricular internal diameter end diastole (LVPVd) and interventricular septal end diastole (IVSd>12 mm). Together with the examination of Lp(a) concentrations, the lipid profile was also analyzed. The analyzes were done at the Clinical Laboratory Institute at the University Clinical Center of the Faculty of Medicine – Skopje, North Macedonia.</p><p><strong>STATISTICAL PROCESSING OF THE MATERIAL:</strong> From the statistical methods, arithmetic mean value, standard deviation X±SD were used. The comparative statistics of the lipid parameters between the analyzed groups were analyzed with students ‘t’ dependent and independent samples according to the Mann-Whitney U-test and Wilcoxon - test. The results of the lipid fractions will be shown tabularly (see table 3) with the statistical program SPSS V26.</p><p><strong>RESULTS:</strong> The obtained values of lipids (Col.Total, TG, HDL-ch, LDL-ch) and lipoprotein (a) in both groups are presented with mean values and standard deviation X-SD. Due to the fact that in the obtained results of Lp(a) in both sexes, in patients with coronary disease, we did not notice any significant difference, we will present them as common for both groups, with CVD with maximum values of 78.00-16,00 mg/dl while in the control group =15.20-4.30 mg/dl, with a statistically significant difference with p<0.000. The same difference was found from the obtained results of lipid concentrations between the two groups with p <0.0001 (as presented in the tables below).</p><p><strong>CONCLUSION:</strong> The results obtained in the paper proved that high concentrations of Lp(a) > 30 mg/dl are risk factors for the occurrence of Ath of the coronary arteries and that these patients are at a 5-8 times higher risk for the development of Ath of coronary arteries, compared to individuals with normal Lp(a) values, therefore the treatment of high concentrations of Lp(a) should be started at the beginning of their appearance. In conclusion, we can suggest that the adequate treatment of high Lp(a) concentrations and the balancing of the lipid profile can apparently affect the prevention of atherosclerotic processes of the coronary arteries, therefore we prefer that in individuals with a history of CAD and those with coronary disease, the examination of Lp(a) and lipid profile should be one of the initial examinations during the management of patients with CAD.</p><p><strong>Keywords: </strong>Lipoprotein (a), atherosclerosis, Cardiovascular Arterial Diseases (CAD), lipid profile.</p></div>

Clinical and Pre-Clinical Pharmacokinetics and Pharmacodynamics of Bentracimab.

Antiplatelet agents are among the most frequently used medications in cardiovascular medicine. Although in patients with atherosclerotic disease manifestations, in particular those treated by percutaneous coronary intervention, antiplatelet agents are beneficial for the prevention of ischemic events, they inevitably increase the risk of bleeding. Furthermore, 5-15% of patients treated by percutaneous coronary intervention may need a surgical procedure within 2 years, creating challenges to safe and effective antiplatelet drug management. Importantly, major spontaneous or procedural-related bleedings are associated with increased hospital admission, length, costs, and poor prognosis. Although the effects of other antithrombotic therapies, such as direct oral anticoagulants, can be reversed by approved specific agents, there are no approved reversal agents for any antiplatelet drugs. The fact that many antiplatelet agents, such as aspirin and thienopyridines (i.e., clopidogrel and prasugrel), bind irreversibly to their targets represents a challenge for the development of a drug-specific reversal agent. In contrast, ticagrelor is a non-thienopyridine with a plasma half-life of 7-9 h that reversely binds the P2Y12 receptor producing potent signaling blockage. In 2015, bentracimab (also known as PB2452 or MEDI2452), a neutralizing monoclonal antibody fragment that binds free plasma ticagrelor and its major active metabolite, was identified. This systematic overview provides a comprehensive summary of the drug development program of bentracimab, focusing on its pharmacodynamic, pharmacokinetic, and safety profiles.

Asymmetric Dimethylarginine as a Biomarker in Coronary Artery Disease.

As atherosclerosis remains a leading cause of morbidity and mortality worldwide despite the advances in its medical and interventional management, the identification of markers associated with its incidence and prognosis constitutes an appealing prospect. In this regard, asymmetric dimethylarginine (ADMA), a well-studied endogenous endothelial nitric oxide synthase inhibitor, represents a core mediator of endothelial dysfunction in atherosclerotic diseases. Given the pathophysiologic background of this molecule, its importance in the most frequent atherosclerotic manifestation, coronary artery disease (CAD), has been extensively studied in the past decades. The available evidence suggests elevation of ADMA in the presence of common cardiovascular risk factors, namely diabetes mellitus, arterial hypertension, and hypertriglyceridemia, being related to endothelial dysfunction and incident major adverse cardiovascular events in these groups of patients. Moreover, ADMA is associated with CAD occurrence and severity, as well as its prognosis, especially in populations with renal impairment. Interestingly, even in the absence of obstructive CAD, increased ADMA may indicate coronary endothelial dysfunction and epicardial vasomotor dysfunction, which are prognostication markers for incident cardiovascular events. In the case of acute coronary syndromes, high ADMA levels signify an augmented risk of incomplete ST-segment elevation resolution and poorer prognosis. Abnormal ADMA elevations may indicate adverse outcomes following percutaneous or surgical coronary revascularization, such as in-stent restenosis, graft patency, and hard cardiovascular endpoints. Finally, since its association with inflammation is significant, chronic inflammatory conditions may present with coronary endothelial dysfunction and subclinical coronary atherosclerosis by means of increased coronary artery calcium, with augmented ADMA acting as a biomarker.

Prevalence of Subclinical Cardiovascular Disease in Patients with Nonalcoholic Fatty Liver Disease: Analysis of the Paracelsus 10,000 Cohort Study

Background: In patients with nonalcoholic fatty liver disease (NAFLD), cardiovascular diseases are more often the cause of death than the liver disease itself. However, the prevalence of atherosclerotic manifestations in individuals with NAFLD is still uncertain. This study aimed to explore the association between NAFLD and coronary artery calcification (CAC) in a Central European population. Methods: A total of 1,743 participants from the Paracelsus 10,000 study were included. The participants underwent CAC scoring and were assessed for fatty liver index (FLI), fibrosing nonalcoholic steatohepatitis (NASH) index (FNI), and fibrosis-4 index (FIB-4 score), which are indicators for steatosis and fibrosis. Multivariable logistic regression models were calculated. Results: Results revealed an association between liver steatosis/fibrosis and CAC. An FLI >60 was associated with higher odds of NAFLD (odds ratio [OR] 3.38, 95% CI: 2.61–4.39, p < 0.01) and increased prevalence of CAC score >300 compared to FLI <30 (9% vs. 3%, p < 0.01), even after adjusting for traditional cardiometabolic risk factors. While the crude ORs of the FIB-4 scores ≥ 1.3 and FNI score were significantly associated with increased odds of CAC, they became nonsignificant after adjusting for age, sex, and MetS. Conclusion: This study reveals a significant association between NAFLD and CAC. The findings suggest that assessing liver fat and fibrosis could enhance the assessment of cardiovascular risk, but further research is needed to determine whether hepatic fat plays an independent role in the development of atherosclerosis and whether targeting liver steatosis can mitigate vascular risk.

Leukotrienes in the atherosclerotic cardiovascular diseases — a systematic review

Introduction: The role of inflammation in the pathogenesis of atherosclerotic diseases is strongly suggested. There are multiple studies indicating the possibility of a pathophysiological connection between atherosclerotic changes and leukotrienes (LTs) — the products of arachidonic acid metabolism. The goal of this systematic review, performed in line with the PRISMA statement, was to investigate the potential role of LTs in the pathophysiology of atherosclerotic cardiovascular diseases (CVD). Material and methods: The MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews were searched to identify the potentially eligible studies. Publications that contained information on any type of LTs identified in blood or urine were included in the review. A database search identified 2082 records. Reliable LTs identification in patients with CVD was used in 30 publications. Results: Stable and acute forms of coronary artery disease are characterized by the overproduction of different types of LTs. The level of LTB4 and LTC4 in the blood is elevated in patients with cerebral ischemia. Patients with acute and chronic peripheral artery disease have elevated levels of LTE4 in urine. Conclusions: The findings of this systematic review show that there is a clear tendency to indicate the association of cardiovascular atherosclerotic diseases with increased production of LTs. This dependency detailed characteristic remains unclear and the question on the impact of elevated leukotrienes on clinical atherosclerotic disease manifestations is still open.

Association of Inflammatory and Metabolic Biomarkers with Mitral Annular Calcification in Type 2 Diabetes Patients.

(1) Background: Type 2 diabetes mellitus (T2DM) contributes to cardiovascular disease and related mortality through the insidious effects of insulin resistance and chronic inflammation. Mitral annular calcification (MAC) is one such degenerative process promoted by T2DM. (2) Methods: This is a post hoc analysis of insulin resistance, inflammation, and hepatic steatosis markers in T2DM patients without atherosclerotic manifestations, but with incidental echocardiographic detection of mild MAC. (3) Results: 138 consenting patients were 49.3% men, 57.86 years old, with a history of T2DM of 6.16 years and HbA1c 8.06%, of whom sixty had mild MAC (43.47%). The statistically significant differences between patients with/without MAC were higher HOMA C-peptide and C-peptide index for insulin resistance, higher TNF-α for inflammation, and lower estimated glomerular filtration rate. High-sensitive C-reactive protein (hsCRP) was significantly associated with insulin resistance and the strength of the relationship was higher in the MAC group. Predictive of MAC were TNF-α, HOMA C-peptide, and especially hepatic steatosis and hypertension. (4) Conclusions: MAC was more prevalent than reported in the literature. Insulin resistance and inflammation were predictive of MAC, but significant markers differ across studies. Widely available routine tests and echocardiographic assessments are useful in the early identification of mitral annular calcifications in diabetes patients.

Abstract No. 78 Coral reef aorta: an increasingly recognized atherosclerotic manifestation with varied symptomatology

Abstract No. 78 Coral reef aorta: an increasingly recognized atherosclerotic manifestation with varied symptomatology

Population-based screening in children for early diagnosis and treatment of familial hypercholesterolemia: design of the VRONI study.

Familial hypercholesterolemia (FH) is the most frequent monogenic disorder (prevalence 1:250) in the general population. Early diagnosis during childhood enables pre-emptive treatment, thus reducing the risk of severe atherosclerotic manifestations later in life. Nonetheless, FH screening programs are scarce. VRONI offers all children aged 5-14 years in Bavaria a FH screening in the context of regular pediatric visits. LDL-cholesterol (LDL-C) is measured centrally, followed by genetic analysis for FH if exceeding the age-specific 95th percentile (130 mg/dl, 3.34 mmol/l). Children with FH pathogenic variants are treated by specialized pediatricians and offered a FH-focused training course by a qualified training center. Reverse cascade screening is recommended for all first-degree relatives. VRONI aims to prove the feasibility of a population-based FH screening in children and to lay the foundation for a nationwide screening program.

Elevated Serum Cystatin C and Decreased Cathepsin S/Cystatin C Ratio Are Associated with Severe Peripheral Arterial Disease and Polyvascular Involvement.

Peripheral arterial disease (PAD) is frequently associated with atherosclerotic manifestations of the carotids and coronaries. Polyvascular involvement and low ankle–brachial index predict major cardiovascular events and high mortality. Cathepsin S (Cat S) promotes the inflammatory pathways of the arterial wall, while Cystatin C (Cys C) functions as its inhibitor; therefore, Cys C was proposed to be a biomarker of progression in PAD. In a single-center observational study, we investigated the correlations of serum Cys C and Cat S/Cys C ratio in a group of 90 PAD patients, predominantly with polyvascular involvement. Cys C and Cat S/Cys C were associated with ankle–brachial index (ABI) scores <0.4 in univariate and multiple regression models. Furthermore, both markers correlated positively with the plasma Von Willebrand Factor Antigen (VWF: Ag) and Von Willebrand Factor collagen-binding activity (VWF: CB). In addition, Cat S/Cys C was significantly decreased, whereas Cys C increased in subjects with three-bed atherosclerotic involvement. According to our results, high serum Cys C and low Cat S/Cys C ratios may indicate severe peripheral arterial disease and polyvascular atherosclerotic involvement.

Population-based screening in children for early diagnosis and treatment of familial hypercholesterolemia: design of the VRONI study.

BackgroundHeterozygous familial hypercholesterolemia (FH) represents the most frequent monogenic disorder with an estimated prevalence of 1:250 in the general population. Diagnosis during childhood enables early initiation of preventive measures, reducing the risk of severe consecutive atherosclerotic manifestations. Nevertheless, population-based screening programs for FH are scarce.MethodsIn the VRONI study, children aged 5–14 years in Bavaria are invited to participate in an FH screening program during regular pediatric visits. The screening is based on low-density lipoprotein cholesterol measurements from capillary blood. If exceeding 130 mg/dl (3.34 mmol/l), i.e. the expected 95th percentile in this age group, subsequent molecular genetic analysis for FH is performed. Children with FH pathogenic variants enter a registry and are treated by specialized pediatricians. Furthermore, qualified training centers offer FH-focused training courses to affected families. For first-degree relatives, reverse cascade screening is recommended to identify and treat affected family members.ResultsImplementation of VRONI required intensive prearrangements for addressing ethical, educational, data safety, legal and organizational aspects, which will be outlined in this article. Recruitment started in early 2021, within the first months, more than 380 pediatricians screened over 5200 children. Approximately 50 000 children are expected to be enrolled in the VRONI study until 2024.ConclusionsVRONI aims to test the feasibility of a population-based screening for FH in children in Bavaria, intending to set the stage for a nationwide FH screening infrastructure. Furthermore, we aim to validate genetic variants of unclear significance, detect novel causative mutations and contribute to polygenic risk indices (DRKS00022140; August 2020).

Savremeni tretman pacijenata sa karotidnom stenozom

Narrowing of the carotid arteries, carotid stenosis, (CS) is a frequent manifestation of atherosclerosis. It can be associated with other diseases of peripheral blood vessels, stenotic occlusive or aneurysmal, but also coronary arteries. Almost 15% of ischemic strokes are caused by this disease, which shares common risk factors with other atherosclerotic manifestations (age, male gender, hypertension, diabetes, smoking). The disease is progressive and with progression comes the progression of the degree of stenosis, the volume and morphological characteristics of the plaque. As these features progress, they increase the risk of clinical manifestations. Ischemic stroke, transient ischemic attack or transient blindness in the ipsilateral eye (amaurosis fugax) are the only clinical manifestations that can be directly related to carotid stenosis. Ischemic changes in the brain parenchyma, which can be seen on magnetic resonance imaging or computed tomography, are also associated with carotid stenosis. All the mentioned parameters are taken into account when making decisions about further treatment. Available drug therapy includes antiplatelet and statin therapy with control of risk factors (body weight correction, smoking cessation) and associated diseases (hypertension, diabetes, etc.). Invasive treatment includes carotid endarterectomy (CEA) as vascular or carotid stenting (CAS) as endovascular treatment. KEA is performed under local or general anesthesia, increasingly under local anesthesia, and after accessing the carotid arteries through a cervicotomy, they are clamped, the flow is interrupted, and after the artery is opened, plaque removal and endarterectomy are performed. In addition to the anesthesiological management of the patient and the performance of the surgical technique, the monitoring of cerebral perfusion during clamping is an important technical detail in these operations. KAS is performed through a percutaneous transfemoral approach under local anesthesia when a stent is implanted in the carotid artery at the site of the carotid stenosis. To perform this procedure, adequate access is required in terms of the quality of the femoral and iliac blood vessels, i.e. the aortic arch. KAS was introduced into practice much later, and in the last 20 years, there has been a significant improvement both in terms of performance and technology with the development of modern stents and the materials used in their installation. A special contribution to this technique was the introduction of embolization protection. KAS is a complementary method to CEA and an individual approach to the patient enables the choice of method, taking into account the advantages and disadvantages of one and the other method. When it comes to symptomatic patients, CEA certainly has a significantly greater advantage and when the use of CAS should be avoided. Complications of both methods are general, local and neurological, with the latter being the most important. Current recommendations state that performing these procedures is beneficial for the patient if the risk of neurological complications is less than 3% in asymptomatic patients, or less than 6% in symptomatic patients. At the Clinic for Vascular and Univascular Surgery of the Clinical Center of Serbia, in the last fifteen years, almost 9.000 procedures have been performed due to carotid stenosis, of which about 10% (960) were CAS. We opt for this method in patients who are at cardiorespiratory risk for CEA or in whom access to the carotid bifurcation is difficult. All, the CEA procedures are performed under conditions of the cervical block. The improvement of patient stratification and the use of artificial intelligence should in the future help doctors decide on the method of examination and treatment of these patients.

Stability of the aneurysmatic sac post-EVAR could no longer be a reliable criterion of healing.

Evaluation of the impact of aneurysm sac behavior in terms of either stability or shrinkage after endovascular aneurysm repair (EVAR) on long-term clinical outcomes. A retrospective study was conducted on 1483 consecutive patients who underwent EVAR from 1999 to 2021 at our institution. 1037 patients met inclusion criteria (1037/1483, 69.9%): abdominal aortic or aorto-iliac aneurysm, elective surgery, follow-up (FU) ≥12 months. Patients who had sac stability (330/1037, 31.8%) and patients who demonstrated sac shrinkage (542/1037, 52.2%) at FU were compared; patients who presented sac increase at FU were excluded (165/1037, 16%). rupture rates, need for surgical conversion, and long-term aneurysm-related mortality. Secondary endpoints: all type endoleak rates and long-term reintervention rates. Mean FU was 61.2 months (IQ 26-85.7 months). In terms of comorbidities, the group of patients with stable sac showed greater association with polidistrectual atherosclerotic manifestations. Estimated 12-year survival was 42.9% in the stable sac group and 65% in the shrinked group (P<0.001), although there were no significant differences in terms of freedom from aneurysm-related death (97.3% vs. 95.4% estimated at 12 years, P=0.493). Patients with sac stability had higher rates of rupture (2.1% vs. 0.6%, P=0.035) and surgical conversion (2.1% vs. 0.6%, P=0.035). The stable sac group had significantly higher rates of all type endoleak during FU (45.8% vs. 24%, P<0.001). Estimated 12-year freedom from reintervention rates were 56.2% and 83.9% respectively (P<0.001). After more than 20 years of EVAR experience it is probably time to reconsider the procedure clinical success parameters as a patient with a stable sac cannot be considered healed.

Detection of Atherosclerosis by Small RNA-Sequencing Analysis of Extracellular Vesicle Enriched Serum Samples.

Atherosclerosis can occur throughout the arterial vascular system and lead to various diseases. Early diagnosis of atherosclerotic processes and of individual disease patterns would be more likely to be successful if targeted therapies were available. For this, it is important to find reliable biomarkers that are easily accessible and with little inconvenience for patients. There are many cell culture, animal model or tissue studies that found biomarkers at the microRNA (miRNA) and mRNA level describing atherosclerotic processes. However, little is known about their potential as circulating and liquid biopsy markers in patients. In this study, we examined serum-derived miRNA – profiles from 129 patients and 28 volunteers to identify potential biomarkers. The patients had four different atherosclerotic manifestations: abdominal aneurysm (n = 35), coronary heart disease (n = 34), carotid artery stenosis (n = 24) and peripheral arterial disease (n = 36). The samples were processed with an extracellular vesicle enrichment protocol, total-RNA extraction and small RNA-sequencing were performed. A differential expression analysis was performed bioinformatically to find potentially regulated miRNA biomarkers. Resulting miRNA candidates served as a starting point for an overrepresentation analysis in which relevant target mRNAs were identified. The Gene Ontology database revealed relevant biological functions in relation to atherosclerotic processes. In patients, expression of specific miRNAs changed significantly compared to healthy volunteers; 27 differentially expressed miRNAs were identified. We were able to detect a group-specific miRNA fingerprint: miR-122-5p, miR-2110 and miR-483-5p for abdominal aortic aneurysm, miR-370-3p and miR-409-3p for coronary heart disease, miR-335-3p, miR-381-3p, miR493-5p and miR654-3p for carotid artery stenosis, miR-199a-5p, miR-215-5p, miR-3168, miR-582-3p and miR-769-5p for peripheral arterial disease. The results of the study show that some of the identified miRNAs have already been associated with atherosclerosis in previous studies. Overrepresentation analysis on this data detected biological processes that are clearly relevant for atherosclerosis, its development and progression showing the potential of these miRNAs as biomarker candidates. In a next step, the relevance of these findings on the mRNA level is to be investigated and substantiated.

Intracranial aneurysm is predicted by abdominal aortic calcification index: A retrospective case-control study

Background and aimsPatients with intracranial aneurysms (IA) have excess mortality for cardiovascular diseases, but little is known on whether atherosclerotic manifestations and IA coexist. We investigated abdominal aortic calcification index (ACI) association with unruptured and ruptured IAs. MethodsThis retrospective case-control study reviews all tertiary centers patients (n = 24,660) who had undergone head computed tomography angiography (CTA), magnetic resonance angiography (MRA) or digital subtraction angiography (DSA) for any reason between January 2003 and May 2018. Patients (n = 2020) with unruptured or ruptured IAs were identified, and patients with available abdominal CT were included. IA patients were matched by sex and age to controls (available abdomen CT, no IAs) in ratio of 1:3. ACI was measured from abdomen CT scans and patient records were reviewed. Results1720 patients (216 ruptured IA (rIA), 246 unruptured IA (UIA) and 1258 control) were included. Mean age was 62.9 ± 11.9 years and 58.2% were female. ACI (OR 1.02 per increment, 95%CI 1.01–1.03) and ACI>3 (OR 5.77, 95%CI 3.29–10.11) increased risk for rIA compared to matched controls. UIA patients' ACI was significantly higher but ACI did not increase odds for UIA compared to matched controls. History of coronary artery disease was less frequent in rIA patients. There was no calcification in aorta in 8.8% rIA and 13.6% UIA patients (matched controls 25.7% and 22.6% respectively, p < 0.01). ConclusionsAortic calcification is greater in rIA and UIA patients than matched controls. ACI increases risk for rIAs.