Cardiovascular Risk in Patients with Inflammatory Bowel Diseases-The Role of Endothelial Dysfunction.

Inflammatory bowel disease (IBD) is associated with an increased risk of cardiovascular disease (CVD). Cardiovascular pathology in people with IBD has not been well studied to date, and a direct link between cardiovascular events and IBD has not been established. The mechanisms underlying this association include the parallel and dynamic interaction of inflammation, modulation of the composition of the gut microbiota, endothelial dysfunction, thrombogenicity, and increased endothelial and epithelial permeability. Endothelial dysfunction is a common aspect of the pathogenesis of IBD and atherosclerotic CVD and can be considered one of the most important factors leading to the development and progression of cardiovascular pathology in patients with IBD. The purpose of this literature review is to describe the mechanisms underlying the development of endothelial dysfunction and disorders of the structure and function of the gut-vascular barrier in the pathogenesis of the cardiovascular manifestation of IBD.

Sonographic Features of Rectus Femoris Muscle in Patients with Metabolic Dysfunction-Associated Fatty Liver Disease and Their Correlation with Body Composition Parameters and Muscle Strength: Results of a Single-Center Cross-Sectional Study.

This study aimed to describe sonographic features of rectus femoris muscle (RFM) in patients with metabolic dysfunction-associated fatty liver disease (MASLD) and their correlation with body composition parameters and muscle strength. A total of 67 patients with MASLD underwent dual-energy X-ray absorptiometry (DEXA), bioimpedance analysis (BIA), muscle strength measurement (grip strength [GS] and chair stand test [CST]), and ultrasound (US) investigation of the RFM in the dominant thigh using a 4 to 18 MHz linear probe. MASLD patients exhibited increased RFM echogenicity, possibly due to fatty infiltration. We confirmed that the greater the subcutaneous fat thickness, the smaller was the muscle mass (p < 0.001), and the lower was the muscle strength (p < 0.001 for GS and p = 0.002 for CST). On the contrary, the greater the anteroposterior diameter (APD) of RFM, the higher was the muscle mass (p < 0.001), and the greater was the muscle strength (p < 0.001 for GS and p = 0.007 for CST). In addition, APD of the RFM and stiffness of RFM exhibited direct correlation with bone mineral density values of the lumbar spine (p = 0.005 for both GS and CST). We concluded that US investigation of the RFM in the dominant thigh can be helpful in identifying MASLD patients at a high risk of musculoskeletal disorders given repeated point-of-care clinical evaluations.

Atrial fibrillation recurrence after catheter ablation is associated with RAD51 and p63 proteins.

Catheter ablation has been demonstrated to reduce atrial fibrillation (AF) recurrence. The mechanisms of AF recurrence after catheter ablation are unknown, and the present study aimed to identify serum proteins associated with AF recurrence. The present prospective study comprised a cohort of patients with AF, which was divided into two groups after one-year follow-up: group 1 included patients with compensated AF after catheter ablation and group 2 included patients with AF recurrence after catheter ablation. Initial microarray profiling of the serum proteins was performed in small subgroups M1 and M2 recruited from groups 1 and 2, respectively, by an antibody microarray to evaluate potentially relevant proteins. The data of initial proteomic profiling identified candidate proteins in groups 1 and 2, and their levels were then measured by ELISA. The data of profiling suggested an overall increase in the levels of RAD51 and p63 proteins in the M2 subgroup versus that in the M1 subgroup, indicating potential relevance of these two proteins to AF recurrence. The results of ELISA of the levels of RAD51 and p63 in the groups 1 and 2 demonstrated an increase in the levels of RAD51 (11.11 ± 4.36 vs 8.45 ± 4.85 ng/mL; P = 0.009) and p63 (165.73 ± 113.75 vs 100.05 ± 37.56 units of normalized optical density; P = 0.0007) in the group 2 (with AF recurrence or substrate AF) compared with that in the group 1 (compensated AF). Thus, RAD51 and p63 were associated with AF recurrence after catheter ablation and may represent possible etiological factors for subsequent outcomes.

Validation of SCORE2 on a sample from the Russian population and adaptation for the very high cardiovascular disease risk region.

SCORE2 (Systematic COronary Risk Evaluation 2) is a risk assessment scale for cardiovascular events, presented in 2021 by the European Society of Cardiology. Both for training and validation of the SCORE2 model, representative samples from the Russian population were not used. Therefore, we aimed to validate SCORE2 on a such sample. For this purpose, we used a sample from the ESSE-RF epidemiological study consisting of 7251 participants aged 40-69 years without history of CVDs. We performed the validation by comparing SCORE2 risk estimates for ESSE-RF participants with the observed incidence of cardiovascular events in the study, adjusted for event information losses. The validation demonstrated that SCORE2 risk estimates were accurate for Russian men and inaccurate for Russian women. Together with the quantitative assessment of risk, SCORE2 offers its interpretation in terms of 10-year CVD risk group: low-moderate, high, and very high. For Russian men we considered the original interpretation of the SCORE2 estimates to be questionable because almost none of the men would be categorized as having "low-to-moderate" 10-year CVD risk. This problem would be typical for all countries of the very high CVD risk region. Therefore, we proposed a new interpretation of the SCORE2 risk estimates for men from the very high risk region. According to the proposed interpretation, the fraction of men in ESSE-RF in "low-to-moderate" 10-year CVD risk increased from 2% to 18% and the fraction of men in "very high" CVD risk decreased from 63% to 20% as compared to the original interpretation. The proposed interpretation would allow a more personalized approach to CVD treatment and optimize the burden on primary healthcare in the very high risk region countries.

Heat Shock Proteins (HSPs) and Cardiovascular Complications of Obesity: Searching for Potential Biomarkers.

Heat shock proteins (HSPs), a family of proteins that support cellular proteostasis and perform a protective function under various stress conditions, such as high temperature, intoxication, inflammation, or tissue hypoxia, constitute a promising group of possible biochemical markers for obesity and cardiovascular diseases. HSP27 is involved in essential cellular processes occurring in conditions of obesity and its cardiometabolic complications; it has protective properties, and its secretion may indicate a cellular response to stress. HSP40 plays a controversial role in the pathogenesis of obesity. HSP60 is involved in various pathological processes of the cardiovascular, immune, excretory, and nervous systems and is associated with obesity and concomitant diseases. The hypersecretion of HSP60 is associated with poor prognosis; hence, this protein may become a target for further research on obesity and its cardiovascular complications. According to most studies, intracellular HSP70 is an obesity-promoting factor, whereas extracellular HSP70 exhibited inconsistent dynamics across different patient groups and diagnoses. HSPs are involved in the pathogenesis of cardiovascular pathology. However, in the context of cardiovascular and metabolic pathology, these proteins require further investigation.

Gut Microbiota Patterns in Patients with Non-Alcoholic Fatty Liver Disease: A Comprehensive Assessment Using Three Analysis Methods.

Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing evidence suggests that functional and compositional changes in the gut microbiota may contribute to the development and promote the progression of NAFLD. 16S rRNA gene next-generation sequencing is widely used to determine specific features of the NAFLD microbiome, but a complex system such as the gut microbiota requires a comprehensive approach. We used three different approaches: MALDI-TOF-MS of bacterial cultures, qPCR, and 16S NGS sequencing, as well as a wide variety of statistical methods to assess the differences in gut microbiota composition between NAFLD patients without significant fibrosis and the control group. The listed methods showed enrichment in Collinsella sp. and Oscillospiraceae for the control samples and enrichment in Lachnospiraceae (and in particular Dorea sp.) and Veillonellaceae in NAFLD. The families, Bifidobacteriaceae, Lactobacillaceae, and Enterococcaceae (particularly Enterococcus faecium and Enterococcus faecalis), were also found to be important taxa for NAFLD microbiome evaluation. Considering individual method observations, an increase in Candida krusei and a decrease in Bacteroides uniformis for NAFLD patients were detected using MALDI-TOF-MS. An increase in Gracilibacteraceae, Chitinophagaceae, Pirellulaceae, Erysipelatoclostridiaceae, Muribaculaceae, and Comamonadaceae, and a decrease in Acidaminococcaceae in NAFLD were observed with 16S NGS, and enrichment in Fusobacterium nucleatum was shown using qPCR analysis. These findings confirm that NAFLD is associated with changes in gut microbiota composition. Further investigations are required to determine the cause-and-effect relationships and the impact of microbiota-derived compounds on the development and progression of NAFLD.

Applicability of Diagnostic Criteria and High Prevalence of Familial Dysbetalipoproteinemia in Russia: A Pilot Study.

Familial dysbetalipoproteinemia (FD) is a highly atherogenic genetically based lipid disorder with an underestimated actual prevalence. In recent years, several biochemical algorithms have been developed to diagnose FD using available laboratory tests. The practical applicability of FD diagnostic criteria and the prevalence of FD in Russia have not been previously assessed. We demonstrated that the diagnostic algorithms of FD, including the diagnostic apoB levels, require correction, taking into account the distribution of apoB levels in the population. At the same time, a triglycerides cutoff ≥ 1.5 mmol/L may be a useful tool in identifying subjects with FD. In this study, a high prevalence of FD was detected: 0.67% (one in 150) based on the ε2ε2 haplotype and triglycerides levels ≥ 1.5 mmol/L. We also analyzed the presence and pathogenicity of APOE variants associated with autosomal dominant FD in a large research sample.

Which Comes First, Nonalcoholic Fatty Liver Disease or Arterial Hypertension?

Non-alcoholic fatty liver disease (NAFLD) and arterial hypertension (AH) are widespread noncommunicable diseases in the global population. Since hypertension and NAFLD are diseases associated with metabolic syndrome, they are often comorbid. In fact, many contemporary published studies confirm the association of these diseases with each other, regardless of whether other metabolic factors, such as obesity, dyslipidemia, and type 2 diabetes mellites, are present. This narrative review considers the features of the association between NAFLD and AH, as well as possible pathophysiological mechanisms.

Lipoprotein(a) in an adult sample from the Russian population: distribution and association with atherosclerotic cardiovascular diseases.

Introduction: Lipoprotein(a) (Lp(a)) is recognized as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to estimate the distribution of Lp(a) levels in working age adults from the Russian population and to assess its association with ischemic heart disease (IHD), myocardial infarction (MI), stroke, diabetes mellitus (DM), and arterial hypertension (AH). Material and methods: This substudy of the population-based study "Epidemiology of Cardiovascular Diseases and their Risk Factors in Some Regions of the Russian Federation" (ESSE-RF) included 8461 subjects aged 25-64 years (63.7% women) without lipid-lowering drugs. Atherosclerotic cardiovascular disease was self-reported. Lp(a), apolipoproteins AI and B, and lipid and glucose levels in blood serum were determined. Results: The prevalence of Lp(a) ≥ 30 mg/dl was 20.5% and 23.0%, and prevalence of Lp(a) ≥ 50 mg/dl was 13.3% and 15.2%, in men and women, respectively. An association of Lp(a) with IHD, MI, and AH, but not with stroke and DM, was shown. A cut-off level of Lp(a) of 9 mg/dl was determined, above which there was increased frequency of MI (by 59.2%, p = 0.02), IHD (by 33.4%, p < 0.001), and AH (by 11.6%, p < 0.001). In the multivariate analysis only the association of Lp(a) with IHD (1.19 (1.01-1.41), p = 0.038) and MI (1.57 (1.06-2.38), p = 0.028) remained significant. Conclusions: Lipoprotein(a) level ≥ 30 mg/dl was detected in every fifth adult aged 25-64 years. Increased risk of MI and IHD starts at an Lp(a) serum level above 9 mg/dl.

Clinically Meaningful Fatigue and Depression Are Associated with Sarcopenia in Patients with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Sarcopenia is thought to be related to an increased risk of non-alcoholic steatohepatitis and advanced liver fibrosis. Our cross-sectional single-center study was designed to analyze the prevalence of sarcopenia in patients with NAFLD and possible influencing factors. METHODS: A survey on the presence of sarcopenia, fatigue, anxiety, and depression, along with a quality-of-life (QoL) assessment, was forwarded by email to 189 outpatients. Demographics, anthropometric and clinical data (laboratory test results and abdomen complete ultrasound protocol), performed within 2-4 weeks prior to the enrollment, were obtained. RESULTS: Sarcopenia (defined as SARC-F score ≥ 4) was identified in 17 (15.7%) patients, all of them (100%) females, with median age (interquartile range) 56 (51-64) years. These patients had a poorer metabolic state (greater values of waist and hip circumferences, body mass index, and HOMA-IR) and significantly poorer QoL, specifically, regarding the physical component of health, compared with NAFLD patients without sarcopenia. Multivariate analysis showed that depression (OR = 1.25, 95% CI: 1.02-1.53, p = 0.035) and clinically meaningful fatigue (OR = 1.14, 95% CI: 1.04-1.26, p = 0.008) were the factors independently associated with sarcopenia in patients with NAFLD. CONCLUSION: Sarcopenia is associated with depression and fatigue rather than with the severity of liver disease alone and may negatively affect QoL in patients with NAFLD.

Possible Mechanisms Linking Obesity, Steroidogenesis, and Skeletal Muscle Dysfunction.

Increasing evidence suggests that skeletal muscles may play a role in the pathogenesis of obesity and associated conditions due to their impact on insulin resistance and systemic inflammation. Skeletal muscles, as well as adipose tissue, are largely recognized as endocrine organs, producing biologically active substances, such as myokines and adipokines. They may have either beneficial or harmful effects on the organism and its functions, acting through the endocrine, paracrine, and autocrine pathways. Moreover, the collocation of adipose tissue and skeletal muscles, i.e., the amount of intramuscular, intermuscular, and visceral adipose depots, may be of major importance for metabolic health. Traditionally, the generalized and progressive loss of skeletal muscle mass and strength or physical function, named sarcopenia, has been thought to be associated with age. That is why most recently published papers are focused on the investigation of the effect of obesity on skeletal muscle function in older adults. However, accumulated data indicate that sarcopenia may arise in individuals with obesity at any age, so it seems important to clarify the possible mechanisms linking obesity and skeletal muscle dysfunction regardless of age. Since steroids, namely, glucocorticoids (GCs) and sex steroids, have a major impact on the amount and function of both adipose tissue and skeletal muscles, and are involved in the pathogenesis of obesity, in this review, we will also discuss the role of steroids in the interaction of these two metabolically active tissues in the course of obesity.

Genetic landscape in Russian patients with familial left ventricular noncompaction.

Background: Left ventricular noncompaction (LVNC) cardiomyopathy is a disorder that can be complicated by heart failure, arrhythmias, thromboembolism, and sudden cardiac death. The aim of this study is to clarify the genetic landscape of LVNC in a large cohort of well-phenotyped Russian patients with LVNC, including 48 families (n=214). Methods: All index patients underwent clinical examination and genetic analysis, as well as family members who agreed to participate in the clinical study and/or in the genetic testing. The genetic testing included next generation sequencing and genetic classification according to ACMG guidelines. Results: A total of 55 alleles of 54 pathogenic and likely pathogenic variants in 24 genes were identified, with the largest number in the MYH7 and TTN genes. A significant proportion of variants -8 of 54 (14.8%) -have not been described earlier in other populations and may be specific to LVNC patients in Russia. In LVNC patients, the presence of each subsequent variant is associated with increased odds of having more severe LVNC subtypes than isolated LVNC with preserved ejection fraction. The corresponding odds ratio is 2.77 (1.37 -7.37; p <0.001) per variant after adjustment for sex, age, and family. Conclusion: Overall, the genetic analysis of LVNC patients, accompanied by cardiomyopathy-related family history analysis, resulted in a high diagnostic yield of 89.6%. These results suggest that genetic screening should be applied to the diagnosis and prognosis of LVNC patients.

Non-Alcoholic Fatty Liver Disease and Bone Tissue Metabolism: Current Findings and Future Perspectives.

Non-alcoholic fatty liver disease (NAFLD) is reaching epidemic proportions worldwide. Moreover, the prevalence of this liver disease is expected to increase rapidly in the near future, aligning with the rise in obesity and the aging of the population. The pathogenesis of NAFLD is considered to be complex and to include the interaction between genetic, metabolic, inflammatory, and environmental factors. It is now well documented that NAFLD is linked to the other conditions common to insulin resistance, such as abnormal lipid levels, metabolic syndrome, and type 2 diabetes mellitus. Additionally, it is considered that the insulin resistance may be one of the main mechanisms determining the disturbances in both bone tissue metabolism and skeletal muscles quality and functions in patients with NAFLD. To date, the association between NAFLD and osteoporosis has been described in several studies, though it worth noting that most of them included postmenopausal women or elderly patients and originated from Asia. However, taking into account the health and economic burdens of NAFLD, and the increasing prevalence of obesity in children and adolescents worldwide, further investigation of the relationship between osteopenia, osteoporosis and sarcopenia in NAFLD, including in young and middle-aged patients, is of great importance. In addition, this will help to justify active screening and surveillance of osteopenia and osteoporosis in patients with NAFLD. In this review, we will discuss various pathophysiological mechanisms and possible biologically active molecules that may interplay between NAFLD and bone tissue metabolism.

Examining time-frequency mechanisms of full-fledged deep sleep development in newborns of different gestational age in the first days of their postnatal development.

Early age-related changes in EEG time-frequency characteristics during the restful sleep of newborns of different gestational ages result in the development of conventional EEG signs of deep sleep already during the first postnatal week of their life. Allocating newborns to different groups based on their gestational age and duration of postnatal period allowed demonstrating substantial intergroup differences in brain activity during sleep and wakefulness, along with significant variability in the time-frequency characteristics of brain activity. The process of conventional deep sleep development in infants born prior to the week 35 of gestation is associated with an increase in the power of alpha activity in the sensorimotor cortex of the brain.

Diversities in the Gut Microbial Patterns in Patients with Atherosclerotic Cardiovascular Diseases and Certain Heart Failure Phenotypes.

To continue progress in the treatment of cardiovascular disease, there is a need to improve the overall understanding of the processes that contribute to the pathogenesis of cardiovascular disease (CVD). Exploring the role of gut microbiota in various heart diseases is a topic of great interest since it is not so easy to find such reliable connections despite the fact that microbiota undoubtedly affect all body systems. The present study was conducted to investigate the composition of gut microbiota in patients with atherosclerotic cardiovascular disease (ASCVD) and heart failure syndromes with reduced ejection fraction (HFrEF) and HF with preserved EF (HFpEF), and to compare these results with the microbiota of individuals without those diseases (control group). Fecal microbiota were evaluated by three methods: living organisms were determined using bacterial cultures, total DNA taxonomic composition was estimated by next generation sequencing (NGS) of 16S rRNA gene (V3-V4) and quantitative assessment of several taxa was performed using qPCR (quantitative polymerase chain reaction). Regarding the bacterial culture method, all disease groups demonstrated a decrease in abundance of Enterococcus faecium and Enterococcus faecalis in comparison to the control group. The HFrEF group was characterized by an increased abundance of Streptococcus sanguinus and Streptococcus parasanguinis. NGS analysis was conducted at the family level. No significant differences between patient's groups were observed in alpha-diversity indices (Shannon, Faith, Pielou, Chao1, Simpson, and Strong) with the exception of the Faith index for the HFrEF and control groups. Erysipelotrichaceae were significantly increased in all three groups; Streptococcaceae and Lactobacillaceae were significantly increased in ASCVD and HFrEF groups. These observations were indirectly confirmed with the culture method: two species of Streptococcus were significantly increased in the HFrEF group and Lactobacillus plantarum was significantly increased in the ASCVD group. The latter observation was also confirmed with qPCR of Lactobacillus sp. Acidaminococcaceae and Odoribacteraceae were significantly decreased in the ASCVD and HFrEF groups. Participants from the HFpEF group showed the least difference compared to the control group in all three study methods. The patterns found expand the knowledge base on possible correlations of gut microbiota with cardiovascular diseases. The similarities and differences in conclusions obtained by the three methods of this study demonstrate the need for a comprehensive approach to the analysis of microbiota.

Analysis of Adverse Events in the Treatment of Patients with Non-Valvular Atrial Fibrillation with Oral Anticoagulants: Data from the "ANTEY" Observational Study.

Rationale. Therapy with oral anticoagulants (OACs) in patients with atrial fibrillation (AF) is based on finding the optimal balance of efficacy and safety of these drugs. Data from observational studies are an additional source of information for the adverse events (AEs) of pharmacotherapy. Objective: To investigate pharmacotherapy AEs with OACs in the "ANTEY" prospective observational study in patients with non-valvular atrial fibrillation (AF). Material and Methods: A total of 201 people were enrolled (83 (41.3%) were women). The age of subjects was 71.1 ± 8.7 years (data presented as mean with standard deviation). The study protocol included two face-to-face visits (contacts V0 and V1) and one follow-up (FU) phone contact which were made with the patient at an interval of 6 months. At V0, all patients were recommended to take one of the non-vitamin K antagonist oral anticoagulants (NOACs); starting from V1, warfarin could have been prescribed or NOAC could have been changed. Information about AEs and OACsadministration was collected at V0, V1, and FU. Results. During 1 year of observation, 15 out of 201 patients refused to take OACs, and 186 initiated the recommended drug. Rivaroxaban was initiated in 93 patients, dabigatran in 46, apixaban in 40, and warfarin in 7 patients. There were 55 AEs, 25 of which were serious (SAEs), including 4 deaths. Of the 30 AEs, there were 18 bleedings: eight (8.6%) occurred with the administration of rivaroxaban; four (8.5%) with dabigatran, three (7.5%) with apixaban, and three (42.9%) with warfarin. Differences in the incidence of bleeding events between NOACs and warfarin are statistically significant (p = 0.025). Any AEs increased the chance of nonadherence to treatment nine-fold: OR = 9.2 (CI95%: 3.6−23.5), p < 0.0001. Conclusions. The most typical and common AEs in real-world clinical practice settings treatment with OACs were bleedings, the incidence of which was approximately 8% to 9% in the treatment with NOACs and was much higher with warfarin, bleedings in the treatment with OACs are statistically significantly associated with nonadherence to the use of these drugs in the future.

A Splice Variant of the MYH7 Gene Is Causative in a Family with Isolated Left Ventricular Noncompaction Cardiomyopathy.

Variants of the MYH7 gene have been associated with a number of primary cardiac conditions, including left ventricular noncompaction cardiomyopathy (LVNC). Most cases of MYH7-related diseases are associated with such variant types as missense substitutions and in-frame indels. Thus, truncating variants in MYH7 (MYH7tv) and associated mechanism of haploinsufficiency are usually considered not pathogenic in these disorders. However, recent large-scale studies demonstrated evidence of the significance of MYH7tv for LVNC and gave rise to an assumption that haploinsufficiency may be the causal mechanism for LVNC. In this article, we present a family with isolated LVNC and a heterozygous splice variant of the MYH7 gene, analyze possible consequences of this variant and conclude that not all variants that are predicted truncating really act through haploinsufficiency. This study can highlight the importance of a precise assessment of MYH7 splicing variants and their participation in the development of LVNC.

Reduced Quality of Life in Patients with Non-Alcoholic Fatty Liver Disease May Be Associated with Depression and Fatigue.

Non-alcoholic fatty liver disease (NAFLD) is often thought of as clinically asymptomatic. However, many NAFLD patients complain of fatigue and low mood, which may affect their quality of life (QoL). This may create a barrier to weight loss and hinder the achievement of NAFLD therapy goals. Our study aimed to evaluate the QoL in NAFLD patients vs. healthy volunteers, and to analyze likely influencing factors. From March 2021 through December 2021, we enrolled 140 consecutive adult subjects (100 NAFLD patients and 40 controls). Overall, 95 patients with NAFLD and 37 controls were included in the final analysis. Fatty liver was diagnosed based on ultrasonographic findings. We employed 36-Item Short Form Health Survey (SF-36) to evaluate QoL, Hospital Anxiety and Depression Scale (HADS) to identify anxiety and/or depression, and Fatigue Assessment Scale (FAS) to measure fatigue. NAFLD patients had significantly lower physical component summary scores, as well as significantly higher HADS-D scores, compared with the control group (Mann-Whitney U criterion = 1140.0, p = 0.001 and U = 1294.5, p = 0.022, respectively). Likewise, fatigue was more common in NAFLD patients (χ2 = 4.008, p = 0.045). Impaired QoL was significantly associated with fatigue (FAS score ≥ 22, p < 0.001) and depression (HADS-D ≥ 8, p < 0.001). In conclusion, NAFLD patients had significantly poorer QoL vs. controls, in particular with respect to the physical component of health. Impaired QoL may be associated with fatigue and depression, and together they may interfere with increased physical activity and lifestyle modifications in patients with NAFLD.

Phenotypic vs. genetic cascade screening for familial hypercholesterolemia: A case report.

One of the most common autosomal dominant disorders is familial hypercholesterolemia (FH), causing premature atherosclerotic cardiovascular diseases and a high risk of death due to lifelong exposure to elevated low-density lipoprotein cholesterol (LDL-C) levels. FH has a proven arsenal of treatments and the opportunity for genetic diagnosis. Despite this, FH remains largely underdiagnosed worldwide. Cascade screening is a cost-effective method for the identification of new patients with FH and the prevention of cardiovascular diseases. It is usually based only on clinical data. We describe a 48-year-old index patient with a very high LDL-C level without controlled guidelines-based medication, premature atherosclerosis, and a rare variant in the low-density lipoprotein receptor (LDLR) gene. Phenotypic cascade screening identified three additional FH relatives, namely the proband's daughter, and two young grandsons. The genetic screening made it possible to rule out FH in the proband's younger grandson. This clinical case demonstrates that genetic cascade screening is the most effective way of identifying new FH cases. We also first described in detail the phenotype of patients with a likely pathogenic variant LDLR-p.K223_D227dup.

Targeting Gut Microbiota as a Novel Strategy for Prevention and Treatment of Hypertension, Atrial Fibrillation and Heart Failure: Current Knowledge and Future Perspectives.

Cardiovascular diseases (CVDs) remain the major public health concern worldwide. Over the last two decades, a considerable amount of literature has been published on gut microbiota (GMB) composition and its metabolites, involved in the pathophysiology of CVDs, including arterial hypertension, atrial fibrillation, and congestive heart failure. Although many types of medicines are available to treat CVD, new therapeutic tools are needed to improve clinical outcomes. A challenge that often arises in the researchers' community is how to manipulate the GMB to manage cardiovascular risk factors. Therapeutic strategies designed to manipulate GMB composition and/or its metabolites include dietary approaches, prebiotics/probiotics supplementation, and fecal microbiota transplantation (FMT). In this review, we have focused on three main cardiovascular pathologies (arterial hypertension, atrial fibrillation and heart failure) due to their shared common pathophysiological pathways and structural changes in myocardium, such as inflammation, hypertrophy, fibrosis, and myocardial remodeling. The main aims of the review are: (1) to summarize current knowledge on the key pathophysiologic links between GMB and CVDs, and (2) discuss the results of the studies on GMB modulation for the prevention and treatment of selected CVDs.