Plasma Exosomal Mir-423-5p Is Involved in the Occurrence and Development of Bicuspid Aortopathy via TGF-β/SMAD2 Pathway

Objectives: Patients with bicuspid aortic valve (BAV) are at increased risk for ascending aortic dilation (AAD). Our study was aimed at systemically analyzing the expression profile and mechanism of circulating plasma exosomal microRNAs (miRNAs) related to BAV and AAD.Methods: We isolated plasma exosomes from BAV patients (n=19), BAV patients with AAD (BAVAD, n=26), and healthy tricuspid aortic valve individuals with low cardiovascular risk (TAVnon, n=16). We applied a small RNA sequencing approach to identify the specific plasma exosomal miRNAs associated with BAV (n=8) and BAVAD (n=10) patients compared with healthy TAVnon (n=6) individuals. The candidate differentially expressed (DE) miRNAs were selected and validated by RT-qPCR in the remaining samples. GO and KEGG pathway enrichment analyses were performed to illustrate the functions of target genes. Western blot analysis and luciferase reporter assay were conducted in human aortic vascular smooth muscle cells (VSMCs) to verify the results of target gene prediction in vitro.Results: The expression levels of three up-regulated (miR-151a-3p, miR-423-5p, and miR-361-3p) and two down-regulated (miR-16-5p and miR-15a-5p) exosomal miRNAs were significantly altered in BAV disease. Additionally, miR-423-5p could be functionally involved in the occurrence and development of BAV and its complication BAVAD by regulating TGF-β signaling. miR-423-5p could target to SMAD2 and decreased the protein levels of SMAD2 and P-SMAD2.Conclusion: Plasma exosomal miR-423-5p regulated TGF-β signaling by targeting SMAD2, thus exerting functions in the occurrence and development of BAV disease and its complication bicuspid aortopathy.

152 Effects of nutraceuticals on the control of the lipid-glycaemic structure and on endothelial protection, in patients with low cardiovascular risk profile

Aims Nutraceuticals are dietary supplements that contain a concentrated form of a presumed bioactive substance originally derived from a food. There is a relationship between the consumption of monacolin K from red yeast rice and maintenance of normal blood low density lipoprotein cholesterol (LDL-C) concentrations recognized by the European Agency on Food Safety. The present study evaluates the effects of a therapeutical association of nutraceuticals (a combination of containing fermented red rice, named Monacolin K and Coenzyme Q10) on lipo-glycaemic profile and on the vascular function evaluated as endothelial function and arterial stiffness (using the non-invasive methods of EndoPAT and SphygmoCOR). Methods The present is a single-centre prospective study enrolling 30 patients with low cardiovascular risk profile (SCORE risk, cardiovascular disease risk <10% at 10 years). Patients were consecutive enrolled from March 2019 to February 2020 (recruitment period). The average follow-up was 14 weeks, from intaking monacolin K 10 mg + Coenzyme Q10 10 mg. The scheduled evaluations of the enrolled population were: before the beginning of the therapy and after a period of 14 weeks. Results After 14 weeks of treatment we demonstrated a statistically significant reduction in total cholesterol (P 0.015) and LDL (P 0.003). An important effect on the inflammatory profile was highlighted, resulting in a decrease in Hs-CRP at 12-weeks (P 0.052), associated with a progressive reduction of arterial stiffness (P 0.063) and an improvement in endothelial function (P 0.048). Conclusions Data obtained suggest that formulations with natural nutraceuticals, especially fermented red rice, have a protective cardiovascular effect, not also through reduction of plasma lipids but in endothelial function and arterial stiffness improvement.

Heart failure in low risk patients with atrial fibrillation, nationwide registry case-control study based on 227811 patients

Background Heart failure (HF) is common in patients with atrial fibrillation (AF), and also associated with worse outcome. Consequently, it is commonly included in risk prediction models for AF, used in daily clinical praxis. However, knowledge about the association between solely AF and incidental HF is limited. Aim This study aims to evaluate the short and long-term risks for onset of HF in patients with AF and low cardiovascular risk profile. Methods All patients with first recorded hospitalization for AF in the Swedish National Patient Register, were included from the 1St January 1987 to 31st December 2018. Each patient with AF was matched by age, sex and county with two controls from the Swedish Total Population Register. Patients <18 years, or with concomitant hypertension, diabetes mellitus, coronary and periphery artery disease, previous stroke or transitory ischemic attack, cardiomyopathy, pulmonary arterial hypertension, congenital heart disease, valvular heart disease and renal failure prior or at baseline were excluded. Results In total 227 811 patients and 452 712 controls met the inclusion and exclusion criteria and were included in the study. The incidence rate for incidental HF per 1000 person-year within one year after AF diagnosis was 6.2 (95% CI: 4.5–8.6) among patient 18–34, increased with increasing age and was 142.8 (95% CI: 139.4–146.3) among those >80 years. Within five years the incidence rate decreased in all age categories and was 2.4 (95% CI: 1.8–3.0) among the youngest and 94.0 (95% CI: 92.4–95.6) in the oldest age group. When compared to matched controls from the general population patients with AF had a hazard ratio (HR) and CI 95% to develop HF within one year at 103.9 (46.3–233.1), 34.9 (26.5–45.9), 17.5 (15.5–19.8), 10.3 (9.6–11.1) and 6.1 (5.8–6.4) among patients aged 18–34, 35–49, 50–59, 60–69, 70–79 and >80 years, respectively. Conclusion Despite low cardiovascular risk profile AF still carries high risk for developing incidental HF in particular during the first observation year with increasing tendency along with increasing age. Younger patients with AF and without other cardiovascular comorbidities had more than 100 times higher relative risk to develop HF within one year when compared to matched controls. FUNDunding Acknowledgement Type of funding sources: None.

Prevalence of carotid and femoral artery atherosclerosis among the Ivanovo Oblast population: data from the ATEROGEN-Ivanovo study

Aim. To study the prevalence of carotid (CA) and femoral artery (FA) atherosclerosis among Russian population, mainly in middle age group, using a representative sample of one of the Central Russian regions.Material and methods. The analysis included participants of the ATEROGEN-Ivanovo study (sub-study of the ESSE-RF conducted in the Ivanovo region) aged 40-67 years, who were invited for CA and FA ultrasound to assess plaque presence. A total 1102 people were examined, which was >80% of the original sample.Results. The age of subjects was 54 [48; 60] years (men, 28%). Only 11,2% of participants took statins; 30,9% had low cardiovascular risk (CVR), 35,6% — moderate CVR, 21,8% — high CVR, and 11,8% — very high CVR. The incidence of at least one plaque in CA or FA was 73,6%. The prevalence of CA atherosclerosis was 76,4% in men and 59,1% in women, FA atherosclerosis — 54,9% and 28,3%, respectively. Furthermore, plaques were detected already at the age of 40. The incidence of plaques significantly increased with age, with the exception of carotid atherosclerosis in men, a significant increase in the incidence of which stopped at 45 years of age.Conclusion. Among the Ivanovo population aged 40-67 with a predominance of low-to-moderate CVR patients, there is a high prevalence of carotid and femoral atherosclerosis, which indicates a high potential for using ultrasound for diagnosing subclinical atherosclerosis in assessing CVR in people of this age range.

Nutraceuticals in the Management of Dyslipidemia: Which, When, and for Whom? Could Nutraceuticals Help Low-Risk Individuals with Non-optimal Lipid Levels?

Purpose of Review The aim of this review is to summarize the available clinical efficacy and safety data related to the most studied and used lipid-lowering nutraceuticals. Recent Findings A growing number of meta-analyses of randomized clinical trials supports the effectiveness and tolerability of some lipid-lowering nutraceuticals such as red yeast rice, plant sterols and stanols, soluble fibers, berberine, artichoke extracts, bergamot polyphenol fraction, garlic, green tea, and spiruline. No significant safety concern has been raised for the use of such products. Association of more lipid-lowering nutraceuticals and of some nutraceuticals with lipid-lowering drugs has been tested as well. Summary Current evidence suggests that some clinically tested lipid-lowering nutraceuticals could be safely used to improve plasma lipid levels in subjects affected by mild-to-moderate dyslipidaemia with low cardiovascular risk.

Myocardial remodeling in NSTEMI patients with intermediate and low cardiovascular risk exposed to delayed revascularization

Background: Nowadays, the impact of the delayed myocardial revascularization (DMR) (>72h) in patients with myocardium infarction without STsegment elevation (NSTEMI) having either intermediate or low cardiovascular risk (ILCR) on quality of post-infarction myocardial remodeling is not well established. Aim of the study: The comparative evaluation of cardiac functional recovery of NSTEMI patients undergoing either revascularization <72h or DMR (72h–30 days) in a follow-up of 6 months. Material and methods: The study was realized in 2 homogenic series of NSTEMI patients with ILCR exposed to revascularization: <72h (control) or to DMR (72h–30 days). The echocardiographic and physical test indices were registered at the 2nd day since revascularization and after 6 months. Results: The increasing ratio of ejection fraction was significantly higher in patients with DMR compared to control (5.24% vs 1.73%). Likewise, the contractility ability of left ventricle improved better, proven by systolic volume diminution, lower value of akinetic areas, and less patients with class III of heart failure according to New York Heart Association (4 vs 29%). More than that, DMR was associated with higher physical endurance. Conclusions: NSTEMI patients with ILCR exposed to delayed myocardial revascularization (72h–30 days) had a better post-infarction recovery after 6 months according to dynamics of echocardiographic and physical tolerance indices in comparison with patients revascularized <72h.

The combination of diclofenac and B vitamins – effectiveness and safety in clinical practice

Diclofenac is one of the most commonly used non-steroidal anti-inflammatory drugs in the World, eagerly chosen for the therapy of skeletal, joint and muscle pain. However, the use of diclofenac is associated with side effects common for the entire class of drugs, including enhancement of cardiovascular risk. It has been shown that B vitamins are involved in many processes essential for the nervous system activity, as well as in the mechanism of initiating and transmitting pain stimuli. Besides, they have a synergistic analgesic effect when combined with diclofenac. Application of both drugs in analgesic therapy resulted in more effective pain relief, but also allowed for the reduction of diclofenac doses, leading to minimize the risk of side effects. The combination of B vitamins has a positive effect on the efficacy and safety of the therapy, which is important especially for low cardiovascular risk patients.

Characteristics of Populations Excluded From Clinical Trials Supporting Intensive Blood Pressure Control Guidelines

Background Only one third of patients recommended intensified treatment by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline for high blood pressure would have been eligible for the clinical trials on which recommendations were largely based. We sought to identify characteristics of adults who would have been trial‐ineligible in order to inform clinical practice and research priorities. Methods and Results We examined the proportion of adults diagnosed with hypertension who met trial inclusion and exclusion criteria, stratified by age, diabetes mellitus status, and guideline recommendations in a cross‐sectional study of the National Health and Nutrition Examination Survey, 2013–2016. Of the 107.7 million adults (95% CI, 99.3–116.0 million) classified as having hypertension by the ACC/AHA guideline, 23.1% (95% CI, 20.8%–25.5%) were below the target blood pressure of 130/80 mm Hg, 22.2% (95% CI, 20.1%–24.4%) would be recommended nonpharmacologic treatment, and 54.6% (95% CI, 52.5%–56.7%) would be recommended additional pharmacotherapy. Only 20.6% (95% CI, 18.8%–22.4%) of adults with hypertension would be trial‐eligible. The majority of adults <50 years were excluded because of low cardiovascular risk and lack of access to primary care. The majority of adults aged ≥70 years were excluded because of multimorbidity and limited life expectancy. Reasons for trial exclusion were similar for patients with and without diabetes mellitus. Conclusions Intensive blood pressure treatment trials were not representative of many younger adults with low cardiovascular risk and older adults with multimorbidity who are now recommended more intensive blood pressure goals.