Establishing the Mutational Spectrum of Hungarian Patients with Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) is one of the most common autosomal, dominantly inherited diseases affecting cholesterol metabolism, which, in the absence of treatment, leads to the development of cardiovascular complications. The disease is still underdiagnosed, even though an early diagnosis would be of great importance for the patient to receive proper treatment and to prevent further complications. No studies are available describing the genetic background of Hungarian FH patients. In this work, we present the clinical and molecular data of 44 unrelated individuals with suspected FH. Sequencing of five FH-causing genes (LDLR, APOB, PCSK9, LDLRAP1 and STAP1) has been performed by next-generation sequencing (NGS). In cases where a copy number variation (CNV) has been detected by NGS, confirmation by multiplex ligation-dependent probe amplification (MLPA) has also been performed. We identified 47 causal or potentially causal (including variants of uncertain significance) LDLR and APOB variants in 44 index patients. The most common variant in the APOB gene was the c.10580G>A p.(Arg3527Gln) missense alteration, this being in accordance with literature data. Several missense variants in the LDLR gene were detected in more than one index patient. LDLR variants in the Hungarian population largely overlap with variants detected in neighboring countries.

The effect of non-invasively obtained central blood pressure on cardiovascular outcome in diabetic patients in Assiut University Hospitals

Background The major cause of morbidity and mortality in diabetes is cardiovascular disease, which is exacerbated by the presence of hypertension. Therefore, proper control of BP in diabetic hypertensive patients is essential. Few studies have specifically investigated the prognostic significance of central BP in Egyptian populations with diabetes and hypertension and its relation with cardiovascular outcome. This study aims to evaluate relation between central BP and diabetic composite cardiovascular complications. Results Diabetic patients with CVD were significantly older (p value < 0.01), obese (p value < 0.01) with long duration of diabetes (p value < 0.001) and had significantly higher peripheral and central systolic and diastolic BP and higher AIx@75(p values < 0.01) than those without CVD. Regarding the metabolic parameters, they had significantly higher fasting blood glucose, HbA1c, and higher blood cholesterol levels (p values < 0.001), higher LDL (p value < 0.01), triglycerides levels (p value = 0.014), and microalbuminuria (p value = 0.028). Logistic regression analysis found increased BMI, central systolic BP, and AIx@75 were independent predictors of composite CVD (p values < 0.05). Conclusions There is a pattern of favorability towards central rather than peripheral BP indices to predict the occurrence of CVD in diabetic patients.

Management of Patients with Left Ventricular Assist Device during the COVID-19 Pandemic

The novel coronavirus disease 2019 (COVID-19) is an infectious disease with multi-organ involvement, including the cardiovascular system. The disease may cause several cardiovascular complications, and may increase morbidity and mortality among patients with background cardiovascular disease. Patients with advanced heart failure are often treated with left ventricular assist device (LVAD), and represent a unique population mandating multi-disciplinary approach. Several aspects of COVID-19 should be taken into account in LVAD implants, including right ventricular involvement, hemodynamic alterations, thromboembolic and haemorrhagic complications, and the psychological effects of social isolation. Patients with VAD and suspected COVID-19 should be transferred to specialized centers for better management of complications. Here, we review the implications of COVID-19 pandemic on LVAD patients with our recommendations for appropriate management.

Current issues of disability and rehabilitation of elderly and senile patients with lower limb loss due to vascular pathology

Большинство пациентов с ампутационным дефектом нижних конечностей являются гражданами пожилого возраста с высокой ко- и полиморбидностью, наличием нескольких гериатрических синдромов, что неблагоприятно влияет на прогноз, снижает реабилитационный потенциал, в ряде случаев приводит к развитию сердечно-сосудистых осложнений, ампутации второй конечности, тяжелой инвалидизации и высокой послеоперационной летальности. Ключевым звеном процесса реабилитации инвалидов с культей нижней конечности является обеспечение их функциональным протезом. В статье приведен анализ заболеваемости, первичной инвалидности в период 2015-2019 гг., гендерных, возрастных и клинических характеристик пациентов, проживающих в Санкт-Петербурге, которым выполнена ампутация нижней конечности вследствие сосудистой патологии. Установлено, что отсутствует информация о выживаемости пациентов после проведения ампутации в различные сроки постгоспитального периода в Санкт-Петербурге. Выявлен выраженный дисбаланс между количеством выполняемых ампутаций нижних конечностей ежегодно и количеством обращений инвалидов в бюро медико-социальной экспертизы для обеспечения техническими средствами реабилитации и направлением на первичное протезирование, реабилитацию. The majority of patients with amputation defect of the lower extremities are elderly citizens with high co- and polymorbidity, the presence of several geriatric syndromes, which adversely affects the prognosis, reduces the rehabilitation potential, in some cases leads to the development of cardiovascular complications, amputation of the second limb, severe disability and high postoperative mortality. The key link in the rehabilitation process of disabled people with a lower limb stump is to provide them with a functional prosthesis. The article provides an analysis of morbidity, primary disability in the period from 2015 to 2019, gender, age and clinical characteristics of patients living in St. Petersburg who underwent amputation of the lower limb due to obliterating artery diseases is presented. It was found that there is no information on the survival rate of patients after amputation at various times of the post-hospital period in St. Petersburg. We have identified a pronounced imbalance between the number of lower limb amputations performed and the number of applications of disabled people to the bureau of medical and social expertise for providing technical means of rehabilitation and referral to primary prosthetics.

Cardiovascular manifestations of Hutchinson–Gilford progeria syndrome

Cardiovascular complications are the most frequent cause of death in patients with the Hutchinson–Gilford progeria syndrome. However, due to its rarity, studying the course of cardiac abnormalities has been a challenge. The cardiovascular phenotype helps to provide greater insight into the natural history of these abnormalities.

Association of dietary inflammatory potential (DIP) and endothelial function biomarkers among females

Purpose Dietary inflammatory potential (DIP) is a novel dietary index designed to evaluate individuals’ diets with considering inflammation and anti-inflammation score. In addition, adhesion molecules including soluble intracellular adhesion molecules-1 (sICAM-1), soluble cellular adhesion molecules-1 (sVCAM-1) and E-selectin are important biomarkers to assess endothelium dysfunction which are related to atherosclerosis and cardiovascular complications. Also, there is no study for assessing the association between adhesion molecules and DIP until now as well as other studies that assessed the relationship between dietary inflammatory index or DIP has controversy. The purpose of this cross-sectional study was to determine the correlation between DIP and endothelial markers such as E-selectin, sICAM-1 and sVCAM-1 among female nurses from Isfahan. In this study, DIP was used instead of DII. Design/methodology/approach This study was performed on 420 healthy nurses. The nurses were selected by random cluster sampling method from private and public Isfahan hospitals. A validated food frequency questionnaire (FFQ) was applied to assess the DIP. A fasting blood sample was collected for measuring the plasma levels of the endothelial markers and other variables. Findings After adjusting different potential confounders, no statistical association was found between DIP and sICAM-1, E–selectin and sVCAM-1 in Model I (P = 0.57, 0.98 and 0.45), Model II (P = 0.57, 0.98 and 0.45) and Model III (P = 0.67, 0.92 and 0.50) in comparison to the crude group (P = 0.35, 0.83 and 0.49, respectively). Originality/value The results revealed that the plasma levels of endothelial markers including E-selectin, sICAM-1 and sVCAM-1 were not significantly associated with DIP in female nurses.

Golden Syrian hamster as a model to study cardiovascular complications associated with SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in the Golden Syrian hamster causes lung pathology that resembles human coronavirus disease (COVID-19). However, extra-pulmonary pathologies associated with SARS-CoV-2 infection and post COVID sequelae remain to be understood. Here we show, using a hamster model, that the early phase of SARS-CoV-2 infection leads to an acute inflammatory response and lung pathologies, while the late phase of infection causes cardiovascular complications (CVC) characterized by ventricular wall thickening associated with increased ventricular mass/ body mass ratio and interstitial coronary fibrosis. Molecular profiling further substantiated our findings of CVC, as SARS-CoV-2-infected hamsters showed elevated levels of serum cardiac Troponin-I (cTnI), cholesterol, low-density lipoprotein and long-chain fatty acid triglycerides. Serum metabolomics profiling of SARS-CoV-2-infected hamsters identified N-acetylneuraminate, a functional metabolite found to be associated with CVC, as a metabolic marker was found to be common between SARS-CoV-2-infected hamsters and COVID-19 patients. Together, we propose hamsters as a suitable animal model to study post-COVID sequelae associated with CVC which could be extended to therapeutic interventions.

Renal Function Protection as an Important Component of a Comprehensive Approach to the Management of Patients with Atrial Fibrillation

The increase in the life expectancy of the population is accompanied by an increase in the prevalence of diseases for which old and senile age are risk factors. Atrial fibrillation (AF) and chronic kidney disease (CKD) are two diseases that can coexist in a patient. The risk of ac thromboembolic and hemorrhagic events in this case increases due to the mutual aggravating influence of these diseases. In addition, these patients have a high incidence of coronary events, and cardiovascular complications are the main cause of death in patients with AF and CKD. Consequently, such patients require an integrated approach to treatment, and their management is a complex clinical task. The direct oral anticoagulant rivaroxaban has been most studied in a population of comorbid AF and CKD patients and has proven a high efficacy and safety profile in these patients in randomized controlled trials. In addition, rivaroxaban has shown a significant reduction in the risk of myocardial infarction in various patients, as well as the possibility of preserving renal function to a greater extent compared with warfarin therapy, and a possible positive effect on reducing the risk of cognitive impairment. A single dosing regimen can improve adherence to treatment, which is one of the key conditions for achieving the above effects. Thus, these factors make it possible to achieve comprehensive protection of comorbid patients with AF and CKD.

Neutrophil Cathepsin G Enhances Thrombogenicity of Mildly Injured Arteries via ADP-Mediated Platelet Sensitization

Inhalation of particulate matter in polluted air causes direct, size-restricted passage in the circulation and pronounced lung inflammation, provoking platelet activation and (non)-fatal cardiovascular complications. To determine potency and mechanism of platelet sensitization via neutrophil enzymes, we performed in vitro aggregation studies in washed human platelets and in murine and human blood, in the presence of elastase, cathepsin G and regular platelet agonists, present in damaged arteries. The impact of both enzymes on in vivo thrombogenicity was studied in the same thrombosis mouse model, previously having demonstrated that neutrophil activation enhances peripheral thrombogenicity. At 0.05 U/mL, cathepsin G activated washed human platelets via PAR1, whereas at 0.35 U/mL, aggregation occurred via PAR4. In Swiss mouse platelet-rich plasma no aggregation occurred by cathepsin G at 0.4 U/mL. In human and murine blood, aggregations by 0.05–0.1 U/mL cathepsin G were similar and not PAR-mediated, but platelet aggregation was inhibited by ADP antagonists, advocating cathepsin G-released ADP in blood as the true agonist of sustained platelet activation. In the mouse thrombosis model, cathepsin G and elastase amplified mild thrombogenicity at blood concentrations that activated platelets in vitro. This study shows that cathepsin G and elastase secreted in the circulation during mild air pollution-induced lung inflammation lyse red blood cell membrane proteins, leading to ADP-leakage into plasma, sensitizing platelets and amplifying their contribution to cardiovascular complications of ambient particle inhalation.

Mesenchymal Stem Cell Therapy in Diabetic Cardiomyopathy

The incidence and prevalence of diabetes mellitus (DM) are increasing worldwide, and the resulting cardiac complications are the leading cause of death. Among these complications is diabetes-induced cardiomyopathy (DCM), which is the consequence of a pro-inflammatory condition, oxidative stress and fibrosis caused by hyperglycemia. Cardiac remodeling will lead to an imbalance in cell survival and death, which can promote cardiac dysfunction. Since the conventional treatment of DM generally does not address the prevention of cardiac remodeling, it is important to develop new alternatives for the treatment of cardiovascular complications induced by DM. Thus, therapy with mesenchymal stem cells has been shown to be a promising approach for the prevention of DCM because of their anti-apoptotic, anti-fibrotic and anti-inflammatory effects, which could improve cardiac function in patients with DM.