Development Of Atherosclerotic Cardiovascular Disease Research Articles

Lipid Profile in Olympic Athletes: Proposal for a “Lipid Athlete Score” as a Clinical Tool to Identify High-Risk Athletes

Dyslipidemia is a major risk factor for atherosclerosis. Identification of dyslipidemia in athletes has raised interest in establishing preventive strategies and reducing cardiovascular (CV) events. Nowadays, targets or “scores” for athletes are undefined. The aim of our study was to create a “Lipid Athlete Score” based on lipid parameters and derive score indexes to identify high-risk athletes. We retrospectively enrolled 957 Olympic athletes practicing different sporting disciplines (power, skills, endurance, and mixed), analyzing their CV profiles and anthropometrics; 55.4% were male, the mean age was 27.1 ± 5 years, and the mean body mass index (BMI) was 23.1 ± 3.2 kg/m2. Three hundred and forty-three athletes (35.8%) were dyslipidemic (LDL ≥ 115 mg/dL or LDL/HDL ≥ 1.90). Multivariate analysis revealed the following: male p = 0.001, OR 1.88 [0.41–2.51], familiarity for dyslipidemia p = 0.001, OR 2.82 [1.72–4.59], BMI ≥ 30 kg/m2 p = 0.001, OR 2.53 [1.46–4.38], and fat mass p = 0.001, OR 2.29 [1.38–3.80] were significant. Endurance athletes presented the lowest CV risk. We proposed a lipid athlete score including major (LDL ≥ 115 mg/dL and LDL/HDL ≥ 1.90) and minor criteria (male, BMI > 30 kg/m2 or fat mass >22% for males and 32% for females, familiarity for dyslipidemia, and conventional CV risk factors). Twelve athletes (1.2%) were at high risk, 150 athletes (15.7%) at medium risk, 171 athletes (17.9%) at low risk, and 624 (65.2%) were at no risk. Dyslipidemia is very common in elite athletes. We have defined a specific lipid athlete score based on lipid parameters and derived score indexes for the stratification of risk. In accordance with this tool, a substantial proportion of athletes (16.9%) were at medium-to-high risk and need early preventive strategies to improve their lipid profiles and reduce the future development of atherosclerotic CV diseases.

Prevención cardiovascular en la diabetes mellitus. ¿Es adecuado hablar de riesgo moderado o intermedio?

Diabetes, especially type 2, is considered a risk situation for atherosclerotic cardiovascular disease (ASCVD). Subjects with diabetes type 2 have a mortality rate due to ASCVD 3 times higher than that found in the general population, attributed to hyperglycemia and the frequent association of other cardiovascular risk factors, such as atherogenic dyslipidemia.Numerous scientific societies have established a risk classification for ASCVD in diabetes based on 3 degrees (moderate, high and very high). The objectives of dyslipidemia control are clearly defined and accepted, and vary depending on the previously established cardiovascular risk.In moderate or intermediate risk, the guidelines propose a less intensive intervention, maintaining LDL-C levels<100mg/dL and NO-HDL-C levels<130mg/dL, and waiting 10 years until reaching the high-risk category to initiate more intensive treatment. However, during the decade of follow-up recommended in the guidelines, cholesterol deposition in the arterial wall increases, facilitating the development of an unstable and inflammatory atheromatous plaque, and the development of ASCVD. Alternatively, diabetes could be considered from the outset to be a high-risk situation and the goal should be LDL-C<70mg/dL. Furthermore, maintaining LDL-C levels<70mg/dL contributes to reducing and stabilizing atheromatous plaque, avoiding or reducing mortality episodes due to ASCVD during those years of diabetes evolution.Should we maintain the proposed objectives in subjects with diabetes and moderate risk for a decade until reaching the high cardiovascular risk phase or, on the contrary, should we adopt a more intensive stance from the beginning seeking to reduce cardiovascular risk in the majority of patients with diabetes? Is it better to wait or prevent with effective therapeutic measures from the first moment?

Effectiveness and safety of bempedoic acid in routine clinical practice: 1-year follow-up snapshot of the MILOS German cohort

Abstract Background Low-density lipoprotein cholesterol (LDL-C) has an established role in the development of atherosclerotic cardiovascular disease. The 2019 ESC/EAS dyslipidaemia guidelines recommended more intensive treatment goals, however, many patients do not reach them. Bempedoic acid (BA) is a first-in-class ATP citrate lyase inhibitor that lowers LDL-C levels. There is limited data on the use of BA and BA + ezetimibe (EZE) fixed-dose combination (FDC) in clinical practice. Purpose The purpose of this snapshot of 1-year follow-up data from the MILOS study is to evaluate the effectiveness and safety of BA and its FDC in routine clinical practice in Germany. Methods MILOS is a European, prospective, observational, non-interventional study in adult patients with primary hypercholesterolaemia or mixed dyslipidaemia. Patients were recruited from 126 sites in Germany between January 2021 and January 2022, and are followed up for 1–2 years after baseline measurements. Here, we summarise 1-year follow-up data from a snapshot taken on January 13th, 2023. Results Of 992 patients enrolled in Germany, 714 had either completed their 1-year follow-up or discontinued the study prematurely, and 524 of these 714 patients attended their 1-year follow-up visit. For this snapshot, 714 patients are used when determining cardiovascular (CV) outcomes and safety endpoints, and 524 patients are used when reporting efficacy data. The overall mean (SD) age of the population (n=524) was 64.7 (10.0) years, and 60.7% were male. Patients treated with BA/BA+EZE FDC had an overall mean LDL-C level of 2.18 mmol/L (84.1 mg/dL) at 1 year compared with 3.20 mmol/L (123.6 mg/dL) pre-treatment, representing a mean relative LDL-C reduction of 27.3%. Overall, 25.8% (135/524) of patients had reached their LDL-C goal after 1 year of treatment compared with 4.0% (21/524) pre-treatment (Figure 1A and 1B). The overall incidence rate of the composite endpoint of major adverse cardiovascular event (4-component MACE) including CV death, non-fatal myocardial infarction, non-fatal stroke, and coronary revascularisation (n=714) was 3.36%. At 1-year follow-up, 19% (136/714) of patients had an adverse drug reaction (ADR) suspected to be related to BA/BA+EZE FDC, and 0.8% (6/714) had serious ADRs, as deemed by the investigator. Conclusion This snapshot analysis of 1-year follow-up data suggests that the addition of BA to other lipid-lowering therapies increases the proportion of patients at LDL-C goal by ∼6-fold in the observed cohort. The safety and tolerability profile of bempedoic acid are in line with data from randomised controlled trials.

The role of transient receptor potential canonical 7 (TRPC7) in western diet-induced aortic damage via abnormal lipid production

Abstract Background The Western lifestyle, characterized by a diet rich in fat and fructose (HFHF), has been linked to metabolic disorders that accelerate aortic aging and damage, ultimately leading to the development of atherosclerotic cardiovascular diseases (ASCVD). Signaling pathways that promote cellular aging are associated with pathological changes. Our previous research has shown that activating TRPC7, a protein responsible for regulating cellular calcium homeostasis, leads to elevated levels of reactive oxygen species, DNA damage, and cellular aging, thereby initiating age-related pathogenesis. Metabolic disorders have also been linked to myocardial aging and damage. Therefore, investigating the impact of TRPC7 on the pathogenesis of metabolic disorder-associated aortic damage is of utmost importance. Purpose We aimed to examine the involvement of TRPC7 in the pathogenesis of metabolic disorders associated with aortic damage, which ultimately contributes to the development of ASCVD. Methods The study involved feeding mice an HFHF diet for 10 weeks, after which their body weight was recorded, and their aortas were harvested for analysis. Aortic thickness, lipid accumulation, and collagen content were measured. Immunohistochemistry staining was used to detect various markers, including DNA damage, senescence, senescence-associated secretory phenotype, and cell death. In addition, abnormal lipid production was screened using a lipidomic approach and bioinformatics tool. Results The study revealed that TRPC7 deficiency inhibited HFHF-induced increases in body weight and the ratio of adventitia to tunica media thicknesses, lipid accumulation, and collagen content in the aorta. Interestingly, lacking TRPC7 significantly reduced aortic pathogenesis induced by HFHF while upregulating DNA damage, senescence, SASP, and cell death in the mice fed with HFHF. In contrast, mice fed a regular diet, with or without TRPC7, showed no significant effects on body weight, aortic morphology, lipid droplets, DNA damage, senescence, and cell death in their aortas. Additionally, the study revealed that abnormal lipids, such as PC(18:0/20:4), PC(16:0/20:4), LacCer(d18:1/12:0), and PC(18:0/18:2), which can cause aortic aging and damage, were produced in mice fed with HFHF. However, in mice with deficient TRPC7, these abnormal lipids were not detected in their plasma. Conclusion Our study demonstrates that TRPC7 plays a crucial role in regulating metabolic disorder-associated aortic pathogenesis, leading to the progression of ASCVD. By inhibiting HFHF-induced aortic damage and aging, TRPC7 blockage shows promising effectiveness. Furthermore, the observed abnormal lipids production suggests TRPC7's involvement in lipid metabolism. These findings underscore the significance of investigating TRPC7 as a potential therapeutic target for preventing or treating metabolic disorder-associated aortic damage and related cardiovascular diseases.fig 1fig 2

The Relationship Between Smoking Cessation and Atherosclerotic Cardiovascular Disease Development Among Patients with CKD

The Relationship Between Smoking Cessation and Atherosclerotic Cardiovascular Disease Development Among Patients with CKD

Lp(a) and inflammation: a new insight into atherosclerosis

AbstractBackgroundLipid‐lowering therapy is of utmost importance in both primary and secondary prevention of atherosclerotic cardio vascular disease (ASCVD). However, the presence of residual risk allows cardiovascular events to occur even when low‐density lipoprotein cholesterol (LDL‐C) levels are very low. A large number of clinical studies have provided evidence confirming the association between elevated plasma Lp(a) and the development of ASCVD. Clinical studies have also suggested that reducing Lp(a) may help decrease the occurrence of cardiovascular events.MainLp(a) consists of LDL‐like particles, apo(a) and OxPL. The level of Lp(a) in thehuman body is predominantly determined by genetics, with external factorshaving minimal impact. Additionally, Lp(a) levels have been found to vary among different ethnicities. There is a notable correlation between elevated levels of Lp(a) and coronary artery disease (CAD), which is independent of other lipoproteins. Furthermore, there exists a linear relationship between Lp(a) levels and the risk of developing ASCVD. It is now wildly believed that Lp(a) primarily contributes to the development of cardiovascular events through pro‐inflammation, pro‐thrombosis and pro‐atherosclerosis. From the perspective of Lp(a) influencing inflammation, it primarily promotes the release of inflammatoryfactors. This, in turn, increases levels of vascular inflammation and facilitates the recruitment of monocytes‐macrophages. Moreover, it also affects the function of endothelial cells during the development process of atherosclerosis. All these aspects complement each other and contribute to the progression of at herosclerosis. Currently, the lipid‐lowering treatment used inclinical practice can partially reduce the levels of Lp(a), but its impact on inflammation is not significant.ConclusionLp(a) is an independent risk factor for CAD, as it promotes inflammation in the body and accelerates theprogression of atherosclerosis. Further research on effective methods to reduce Lp(a) levels can provide new insights for the treatment of atherosclerosis.

A virus-like particle-based bivalent PCSK9 vaccine lowers LDL-cholesterol levels in non-human primates

Elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor in the development of atherosclerotic cardiovascular disease (ASCVD). Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), a negative regulator of LDL-C metabolism, have emerged as promising approaches for reducing elevated LDL-C levels. Here, we evaluated the cholesterol-lowering efficacy of virus-like particle (VLP) based vaccines that target epitopes found within the LDL receptor (LDL-R) binding domain of PCSK9. In both mice and non-human primates, a bivalent VLP vaccine targeting two distinct epitopes on PCSK9 elicited strong and durable antibody responses and lowered cholesterol levels. In macaques, a VLP vaccine targeting a single PCSK9 epitope was only effective at lowering LDL-C levels in combination with statins, whereas immunization with the bivalent vaccine lowered LDL-C without requiring statin co-administration. These data highlight the efficacy of an alternative, vaccine-based approach for lowering LDL-C.

LDL Cholesterol Variability Impacts the Prognosis of Patients with Chronic Ischemic Heart Disease: A Real-World Italian Experience.

Epidemiologic, genetic, and clinical intervention studies have indisputably shown that low-density lipoprotein cholesterol (LDL-C) is causal in the development of atherosclerotic cardiovascular disease (ASCVD). However, LDL-C variability could be related to increased ASCVD risk in patients already treated with statins. The aim of the present retrospective real-life study was to assess the prognostic impact of LDL-C variability on all-cause mortality and cardiovascular hospitalizations in patients with stable cardiovascular artery disease. A total of 3398 patients were enrolled and followed up for a median of 56 months. Considering LDL-C < 70 mg/dL as the therapeutical target, during follow-up, the percentage of patients who achieved this goal raised from 20.7% to 31.9%. In total, 1988 events were recorded, of which 428 were all-cause deaths and 1560 were cardiovascular hospitalizations. At the last medical examination, each increase in LDL-C levels of 20 mg/dL corresponded to a 6% raise in the risk of any event (HR 1.06; 95%CI, 1.03 to 1.09). In conclusion, our real-world study supports the hypothesis that a continuous and progressive downward trend in LDL-C levels is needed to achieve and maintain a cardiovascular benefit, at least in secondary prevention.

Serum branch-chained amino acids are increased in type 2 diabetes and associated with atherosclerotic cardiovascular disease

Background and aimCirculating biomarkers of metabolic and cardiovascular diseases can help in the early detection and prevention of those diseases. Using proton nuclear magnetic resonance (1H-NMR), we aimed to study the plasma levels of low-molecular-weight metabolites (LMWMs) in a cohort of 307 patients with metabolic diseases to assess their relationships with type-2 diabetes (T2D) and incident atherosclerotic cardiovascular disease (ASCVD).MethodsWe conducted a cross-sectional and prospective study. We included 307 patients attending the Lipid Unit of our University Hospital for the treatment of the following metabolic disturbances and associated disorders: T2D (73.9%), obesity (58.7%), and hypertension (55.1%). 1H-NMR was used to study the plasma levels of 13 LMWMs. LMWM serum concentrations were evaluated in patients with and without T2D. and the correlations with several parameters and their associations with T2D were analyzed. The association between LMWM levels at baseline and the development of ASCVD in patients with T2D after 10 years of follow-up was also evaluated.ResultsAmong the LMWMs measured, the branched-chain amino acids (BCAAs) valine, leucine and isoleucine showed a positive association with several clinical and lipid-related biochemical parameters and inflammatory markers (p < 0.05). Likewise, these three BCAAS were associated with diabetes even after adjusting for covariates (p < 0.05). During the follow-up period of 10 years, 29 of the 185 patients with diabetes at baseline (15.68%) developed ASCVD. After adjusting for clinical covariates, baseline levels of valine and alanine were associated with the development of ASCVD (p < 0.05).ConclusionOverall, our results indicated that plasma levels of LMWMs measured by 1H-NMR could be potential biomarkers associated with T2D. Moreover, alanine and valine can help in the early detection of the cardiovascular risk associated with this metabolic disease.

Postprandial Hyperlipidemia: Its Pathophysiology, Diagnosis, Atherogenesis, and Treatments.

Postprandial hyperlipidemia showing postprandial increases in serum triglyceride (TG) is associated with the development of atherosclerotic cardiovascular disease (ASCVD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed; however, this test is very time-consuming and is difficult to perform. Elevated serum TG levels reflect an increase in TG-rich lipoproteins (TRLs), such as chylomicrons (CM), very low-density lipoproteins (VLDL), and their remnants (CM remnants [CMRs] and VLDL remnants [VLDLRs]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurement of apo B48, which is a constituent of CM and CMR; non-fasting TG, which includes TG content in all lipoproteins including CM and CMR; non-high-density lipoprotein cholesterol (non-HDL-C), which includes TRLs and low-density lipoprotein; and remnant cholesterol are useful to reveal the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an inducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with postprandial hyperlipidemia have various atherogenic properties such as induction of inflammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss, and exercise positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, fenofibrate, bezafibrate, ezetimibe, and eicosapentaenoic acid have been shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide 1 analogues have been shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments. However, there are some problems with the diagnosis for postprandial hyperlipidemia. Postprandial hyperlipidemia cannot be specifically defined by measures such as TG levels 2 h after a meal. To study interventions for postprandial hyperlipidemia with the outcome of preventing the onset of ASCVD, it is necessary to define postprandial hyperlipidemia using reference values such as IGT.

Association between the Composite Dietary Antioxidant Index and Atherosclerotic Cardiovascular Disease in Postmenopausal Women: A Cross-Sectional Study of NHANES Data, 2013-2018.

The relationship between composite dietary antioxidant index (CDAI) levels and the risk of atherosclerotic cardiovascular disease (ASCVD) in postmenopausal women is unknown. In total, 3109 women from the National Health and Nutrition Examination Survey 2013-2018 were included in this cross-sectional study. We evaluated the association between CDAI levels and the risk of ASCVD by using three logistic regression models and restricted cubic splines. A stratified analysis and sensitivity analysis were also conducted. The restricted cubic splines exhibited an L-shaped dose-response association between CDAI levels and the ASCVD risk. Logistic regression analysis found that CDAI levels were negatively associated with the occurrence of ASCVD. The ORs associated with a per-SD increase in CDAI were 0.67 (95% CI: 0.51-0.88) for ASCVD risk. Similarly, women in the group with high CDAI levels were less likely to have ASCVD (OR = 0.71, 95% CI: 0.50-0.98) compared to those in the group with low CDAI levels. When the CDAI levels were divided into quartiles, it was found that the ORs for ASCVD with CDAI levels in Q2 (-1.04-1.11), Q3 (1.11-3.72), and Q4 (3.72-43.87) were 0.63 (0.44, 0.90), 0.64 (0.42, 0.94), and 0.51 (0.27, 0.97), respectively, compared to those with CDAI levels in Q1 (-6.83--1.04). In addition, age, high-density lipoprotein cholesterol levels, and smoking behaviors acted as potential modifiers, and ORs were more significant in women aged 40-69 years, in individuals with low high-density lipoprotein cholesterol levels, and in smokers (p for interaction <0.05). These findings may offer valuable insights into the role of CDAI levels in the development of ASCVD among postmenopausal women.

Circulating Th17/Treg as a promising biomarker for patients with rheumatoid arthritis in indicating comorbidity with atherosclerotic cardiovascular disease.

Immune and inflammatory responses have a pivotal role in the pathogenesis of rheumatoid arthritis (RA) and atherosclerotic cardiovascular disease (ASCVD). This study aims to explore the change of peripheral lymphocytes, especially the absolute and relative changes in peripheral T cells in RA patients with and without ASCVD. The changes in the lymphocyte subsets were assessed to provide a novel insight in diagnosing and preventing ASCVD in patients with RA. A propensity score matching system (1:1) was conducted to perform a matched case-control study with 169 pairs RA-ASCVD and RA participants. Univariate and multivariate analyses were performed to determine the association between peripheral lymphocytes and RA-ASCVD. Multivariate logistic regression analysis demonstrated that Th17 cell absolute, Th17 cell Ratio, Th17/Treg were associated with a significantly higher risk of ASCVD after model adjustment. Then we focused on Th17/Treg, multivariate logistic analyses in tri-sectional Th17/Treg groups showed that the odds of ASCVD is gradually increasing with Th17/Treg rank's rising after model adjustment. Finally, the restricted cubic spline of Th17/Treg and odds ratio of RA-ASCVD was conducted. Interestingly, we found a critical point of Th17/Treg (critical point = 0.2399). Th17/Treg shows a protective role in the odds of ASCVD when Th17/Treg < 0.2399. With smaller Th17/Treg, the protective efficiency is more obvious when Th17/Treg < 0.2399. Our study suggested that increasing absolute and percentage of Th17 cells in the peripheral blood of patients with RA was associated with the development of ASCVD. And Th17/Treg may be a promising biomarker for patients with RA in indicating comorbidity with ASCVD.

Protein tyrosine phosphatase non-receptor type 2 as the therapeutic target of atherosclerotic diseases: past, present and future.

Tyrosine-protein phosphatase non-receptor type 2(PTPN2), an important member of the protein tyrosine phosphatase family, can regulate various signaling pathways and biological processes by dephosphorylating receptor protein tyrosine kinases. Accumulating evidence has demonstrated that PTPN2 is involved in the occurrence and development of atherosclerotic cardiovascular disease. Recently, it has been reported that PTPN2 exerts an anti-atherosclerotic effect by regulating vascular endothelial injury, monocyte proliferation and migration, macrophage polarization, T cell polarization, autophagy, pyroptosis, and insulin resistance. In this review, we summarize the latest findings on the role of PTPN2 in the pathogenesis of atherosclerosis to provide a rationale for better future research and therapeutic interventions.

КЛИНИКО-ЛАБОРАТОРНЫЕ ХАРАКТЕРИСТИКИ ЖЕНЩИН – ПАЦИЕНТОК АМБУЛАТОРНОГО ПРИЕМА ЛИПИДОЛОГА

Introduction. Lipid metabolism disorders are one of the most important factors contributing significantly to the probability of developing cardiovascular diseases, death from coronary heart disease and mortality of the population. Aim. To identify the features of anamnestic, clinical and laboratory parameters in female patients of the lipid cabinet and to determine the frequency of detection of familial hypercholesterolemia in them. Material and methods. The study included 777 female patients of the outpatient appointment of a doctor of the lipid cabinet. The examination of patients with dyslipidemia included an examination by a cardiologist-lipidologist (with the calculation of the risk of cardiovascular complications on the Systemic COronary Risk Evaluation scale, the probability of familial hypercholesterolemia on the British Simon Broom scale and the criteria of the Dutch lipid clinics. Results and discussion. The total number of 777 patients were 63% of the total number of patients in the lipid cabinet; aged 19-90 years old, average age 58.49±9.48. The average level of total cholesterol was 7.74±1.98 mmol/l, low-density lipoprotein cholesterol 4.84±1.4 mmol/l, high-density lipoprotein cholesterol 1.46±0.44 mmol/l, triglycerides 1.61±1.42 mmol/l, non-high-density lipoprotein cholesterol 6.32±1.97 mmol/l. In 23% of patients, lipid metabolism disorders are secondary. Atherosclerosis of brachiocephalic arteries was diagnosed in 68.4% of patients, hypertension was in 41.4%. 15.1% of patients were diagnosed with atherosclerotic cardiovascular disease. Conclusions. The most significant for the development of atherosclerotic cardiovascular disease in women with lipid metabolism disorders were body mass index, burdened family history, duration of menopause and level of physical activity. Smoking, diabetes mellitus, hypertension, external signs of dyslipidemia were not associated with atherosclerotic cardiovascular diseases.

Fecal microbiota transplantation in patients with metabolic syndrome and obesity: A randomized controlled trial.

Metabolic syndrome is a multifactorial disease, and the gut microbiota may play a role in its pathogenesis. Obesity, especially abdominal obesity, is associated with insulin resistance, often increasing the risk of type two diabetes mellitus, vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation, all of which promote the development of atherosclerotic cardiovascular disease. To evaluate the outcomes of fecal microbiota transplantation (FMT) in patients with metabolic syndrome. This was a randomized, single-blind placebo-controlled trial comparing FMT and a sham procedure in patients with metabolic syndrome. We selected 32 female patients, who were divided into eight groups of four patients each. All of the patients were submitted to upper gastrointestinal endoscopy. In each group, two patients were randomly allocated to undergo FMT, and the other two patients received saline infusion. The patients were followed for one year after the procedures, during which time anthropometric, bioimpedance, and biochemical data were collected. The patients also had periodic consultations with a nutritionist and an endocrinologist. The primary end point was a change in the gut microbiota. There was evidence of a postprocedural change in microbiota composition in the patients who underwent FMT in relation to that observed in those who underwent the sham procedure. However, we found no difference between the two groups in terms of the clinical parameters evaluated. There were no significant differences in biochemical or anthropometric parameters, between the two groups evaluated. Nevertheless, there were significant postprocedural differences in the microbiota composition between the placebo group. To date, clinical outcomes related to FMT remain uncertain.

Major roles of the gut microbiota and microRNAs in cardiovascular disease events: a systematic review

Introduction: Gut microbiota (GM) is an essential mediator in the health of GM and has been identified as the origin of several diseases by influencing cell signaling and T cell receptor pathways in the central nervous system. Several microRNAs participate in signaling networks through GM intervention. The interaction between GM and miRNAs plays a crucial role in vascular dysfunction. GM can metabolize L-carnitine, choline, and phosphatidylcholine and produce vascular-toxic metabolites such as trimethylamine-Noxide (TMAO), which is associated with the atherosclerotic process. Nutrology and dietary therapy represent important strategies, especially with the use of plant-derived miRNAs to modify GM. Objective: To carry out a systematic review to highlight the main roles of the gut microbiota and microRNAs in cardiovascular disease events. Methods: The present study followed a concise systematic review model (PRISMA). The literary search process was carried out from March to May 2023 and was developed based on Scopus, PubMed, Science Direct, Scielo, and Google Scholar, using scientific articles from 2002 to 2022. The low quality of evidence was attributed to reports of cases, editorials, and brief communications, according to the GRADE instrument. The risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: The total of 126 studies were found for eligibility analysis, and then 42 of the 64 total studies were selected for this systematic review. According to the GRADE instrument, most studies showed homogeneity in their results, with X2 =88.7%&gt;50%. It was concluded that the gut microbiota can be influenced by diet, genetics, and environmental factors. Changes in the microbial population can lead to multiple diseases, including cardiovascular disease. miRNAs have been known as important regulators of several biological functions, and are also involved in the pathogenesis of cardiovascular diseases. There is evidence that disturbances in the gut microbiota and derived metabolites impair the development of atherosclerotic cardiovascular disease. Studies have shown that YRNAs belonging to extracellular vesicles and their fragments play important roles in the initiation, progression, and diagnosis of atherosclerosis.

CircSnd1 promotes atherosclerosis progression through the miR-485-3p/Olr1 signaling pathway

BackgroundCircular RNAs (circRNAs) participate in the development of atherosclerotic cardiovascular disease. Identifying and verifying the key competing endogenous RNA (ceRNA) network related to atherosclerosis (AS) is significant for understanding the development of AS. The aim of this study was to investigate the circRNA-miRNA‒mRNA network, identify a key circRNA and explore its role in the development of atherosclerosis. MethodsDifferentially expressed mRNAs (DEMs) and circRNAs (DECs) in the AS model were obtained from datasets in the Gene Expression Omnibus (GEO) database. R software and Cytoscape software were used to construct and visualize the ceRNA network. The dual-luciferase reporter experiment and the RNA pull-down experiment were used to verify the selected ceRNA axis. siRNA targeting circRNA, miRNA mimic, miRNA inhibitor, or gene overexpression plasmid was used for in vitro functional studies. ELISA and western blotting were used to detect inflammation and lipid transport-related proteins. Furthermore, an AS mouse model was established and treated with recombinant adeno-associated viral vectors to further verify the influence of the selected ceRNA axis on the occurrence and/or development of AS. ResultsA total of 497 DEMs were enriched in 25 pathways, based on which the circ_0082139 (circSnd1)/miR-485-3p/Olr1 axis was selected. In vitro, the interaction among the three molecules of this axis was validated and it was found to affect inflammation and lipid transport, which were characterized by the significant change of inflammatory factors (Il-6, Il-8, Tnf-α, Mcp-1, Vcam-1, and Icam-1), and lipid transport-related genes, including Abca1, Abcg1, Ldlr, Hdlbp, Lp-pla2, and Srebp-1c. Through animal experiments, we further verified that the circSnd1/miR-485-3p/Olr1 axis regulated these molecules and participated in the formation and/or development of AS in vivo. ConclusionsThe circSnd1/miR-485-3p/Olr1 axis participates in the formation and development of atherosclerosis by regulating inflammation and lipid transport.

The Physics of Stroke

Flow of fluids in channels obey the natural law of Physics. It is dependent on force of propulsion, length of channel, caliber of channel and viscosity of fluid flowing through. In humans, blood flow to the brain obeys these laws. When perturbed by disease, flow and oxygen delivery are compromised resulting in cerebrovascular disease or stroke. Flow to the human brain depends on the force generated by the heart, viscosity of blood, length of the vessels, and diameter of the vascular channels with their variability. In normal situation, the cerebrovascular vessels can automatically regulate itself to ensure adequate cerebral perfusion. With Atherosclerotic Cardiovascular disease in the cerebral vasculature, flow dynamics is deranged and the result is the disease called stroke. Atherosclerotic cardiovascular diseases make the vessels stiff thus increasing intraluminal pressure. This damages the inner lining, the endothelium, and prepares grounds for the development of plaques. Plaques narrow vascular caliber increasing flow pressure at the narrow point but decreasing it beyond that point. The flow ceases to be laminar and becomes turbulent. When the plaques are ruptured by the high pressure at the points of narrowing, the blood coagulation cascade is activated and blood viscosity rises. These predispose to thrombus formation. The vessels thin out having lost elasticity of the walls rupturing easily with sudden blood pressure surges. In this state, the vessels lose their intrinsic ability to vary their diameters to cushion these effects. Blood flow becomes precarious. Cerebral tissue beyond such points suffer from ischemia and may actually have blood egress into them. Metabolism is impaired and higher cerebral function suffers resulting in cerebrovascular disease or stroke. Understanding how disease alters flow dynamics will equip clinicians better with the knowledge required to counter development of atherosclerotic cardiovascular diseases that result in stroke.

Shared inflammatory pathways of rheumatoid arthritis and atherosclerotic cardiovascular disease.

The association between chronic inflammation and increased risk of cardiovascular disease in rheumatoid arthritis (RA) is well established. In the general population, inflammation is an established independent risk factor for cardiovascular disease, and much interest is placed on controlling inflammation to reduce cardiovascular events. As inflammation encompasses numerous pathways, the development of targeted therapies in RA provides an opportunity to understand the downstream effect of inhibiting specific pathways on cardiovascular risk. Data from these studies can inform cardiovascular risk management in patients with RA, and in the general population. This Review focuses on pro-inflammatory pathways targeted by existing therapies in RA and with mechanistic data from the general population on cardiovascular risk. Specifically, the discussions include the IL-1, IL-6 and TNF pathways, aswell as theJanus kinase (JAK)-signal transducer and activator of transcription (STAT) signalling pathway, and the role of these pathways in RA pathogenesis in the joint alongside the development of atherosclerotic cardiovascular disease. Overall, some robust data support inhibition of IL-1 and IL-6 in decreasing the risk of cardiovascular disease, with growing data supporting IL-6 inhibition in both patients withRA and the general population to reduce the risk of cardiovascular disease.

Spatial analysis of 10-year predicted risk and incident cardiovascular atherosclerotic diseases in a swiss urban population

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Swiss National Science Foundation GlaxoSmithKline. Introduction Whether cardiovascular risk score geographically aggregates and informs on spatial development of atherosclerotic cardiovascular disease (ASCVD) remains unknown. Aims We first determined the spatial distribution of cardiovascular risk predicted in an urban population. Second, we compared risk maps with clustering of incident ASCVD over a 10-year follow-up. Sensitivity analyses were conducted to identify explanatory risk factors for both clusters of predicted risk and observed ASCVD. Methods Using data from a population-based cohort study, we computed the Systematic Coronary Risk Evaluation Score 2 (SCORE2 and SCORE2-OP) in participants free from ASCVD at baseline (2003-2006). Geographical distributions of predicted risk and incident ASCVD were determined using global and local spatial autocorrelation statistics. Different models were tested to identify explanatory variables (alcohol consumption, body mass index, socio-economic status, anxiety disorder, major depressive disorder, Mediterranean diet, sport activity, polygenic risk score, mean noise, concentration of PM2.5, normalized difference vegetation index, land surface temperature). Results 6203 individuals (56% women, mean age 52.5 ± SD 10.7) with a median follow-up of 10 years (IQR, 6-10) were included in the analyses. Over the period, there was persistent geographical clustering of predicted risk and ASCVD (Figures 1 and 2). Predicted risk and incident ASCVD marginally overlapped spatially. Body-mass index (BMI) and alcohol consumption explained most of the spatial distribution of predicted risk, reducing high-risk clusters from 286 to 5 and low-risk clusters from 391 to 44. For ASCVD, high clusters either persisted or were reinforced depending upon locations, after adjustment for potential risk factors, with an increase from 100 to 118. Low clusters reduced from 293 to 76 after the adjustment. Incidence rate of ASCVD was 2.5% (IC95%, 3.7-2.4%]) in high-risk clusters compared to the rest of the population. Conclusions Using a population-based cohort, we showed that in an urban area there exists clusters of high and low incidence of ASCVD. Geographical distribution of clusters of high clinical risk score was not congruent with that of incident ASCVD, limiting the use of clinical risk scores in identifying areas where ASCVD may develop.