Abstract MicroRNAs (miRNAs) are tiny non-coding RNA molecules that regulate gene expression predominantly at the post-transcriptional level. Far from being simple intracellular regulators, miRNAs ...have recently been involved in intercellular communication and have been shown to circulate in the bloodstream in stable forms. In the past years specific miRNA expression patterns have been linked to the development of atherosclerosis and coronary artery disease, two closely related conditions. The study of miRNAs has promoted our understanding of the processes involved in the pathogenesis of atherosclerosis and innovative diagnostic and therapeutic approaches have emerged. In this review, we present the role of miRNAs in the development of atherosclerosis, on coronary artery disease progression and we assess their role as diagnostic biomarkers. Finally we evaluate the therapeutic and preventive opportunities that arise from the study of miRNAs in coronary artery disease and especially in myocardial infarction.
Myocardial redox state is a critical determinant of atrial biology, regulating cardiomyocyte apoptosis, ion channel function, and cardiac hypertrophy/fibrosis and function. Nevertheless, it remains ...unclear whether the targeting of atrial redox state is a rational therapeutic strategy for atrial fibrillation prevention.
To review the role of atrial redox state and anti-oxidant therapies in atrial fibrillation.
Published literature in Medline was searched for experimental and clinical evidence linking myocardial redox state with atrial fibrillation pathogenesis as well as studies looking into the role of redoxtargeting therapies in the prevention of atrial fibrillation.
Data from animal models have shown that altered myocardial nitroso-redox balance and NADPH oxidases activity are causally involved in the pathogenesis of atrial fibrillation. Similarly experimental animal data supports that increased reactive oxygen / nitrogen species formation in the atrial tissue is associated with altered electrophysiological properties of atrial myocytes and electrical remodeling, favoring atrial fibrillation development. In humans, randomized clinical studies using redox-related therapeutic approaches (e.g. statins or antioxidant agents) have not documented any benefits in the prevention of atrial fibrillation development (mainly post-operative atrial fibrillation risk).
Despite strong experimental and translational data supporting the role of atrial redox state in atrial fibrillation pathogenesis, such mechanistic evidence has not been translated to clinical benefits in atrial fibrillation risk in randomized clinical studies using redox-related therapies.
Abstract Contrast-induced nephropathy (CIN) following percutaneous coronary interventions (PCI) in patients with acute myocardial infarction (AMI) is associated with high morbidity and mortality ...while there are no reliable predictive tools easy to use. We evaluated the association of pre-procedural high sensitivity C-reactive protein (hsCRP) with the development of CIN, and integrated this variable in a new risk CIN prediction model. Consecutive patients (348 AMI subjects) undergoing PCI were recruited. Creatinine levels were detected on admission, at 24, 48, and 72 hours after PCI. CIN was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. In our study population (348 subjects) CIN developed in 54 (15.5%) patients. Patients with CIN were older and had higher hsCRP at admission, whereas their ejection fraction (EF) and glomerular filtration rate (GFR) were lower. In multivariate analysis after incorporating potential confounders, hsCRP at admission was an independent predictor of CIN (OR for logCRP: 2.00, p=0.01). In ROC curve analysis, a model incorporating hsCRP, age, GFR and EF, showed good accuracy in predicting the development of CIN (c-statistic: 0.84, 95%CI: 0.793-0.879). A total risk score derived from the proposed model yielded significant positive and negative predictive value and classified 85.8% of our patients correctly for CIN. In conclusion measuring hsCRP levels at admission in patients undergoing PCI for AMI may offer additional assistance in predicting the development of CIN. A model incorporating age and admission hsCRP, EF and GFR emerged as an accurate tool for predicting CIN in this context.
To estimate the incidence of hemorrhagic events in patients with atrial fibrillation (AF) treated with acenocoumarol, and the management cost of those requiring hospitalization in Greece.
A ...nationwide telephone survey was conducted between December 2017 and January 2018, to identify cardiologists who treat AF patients with acenocoumarol. A total of 300 cardiologists were selected and reported the number of AF acenocoumarol-treated patients during the past 12 months and the number of those who experienced a hemorrhagic event. The hospital charges to sickness fund and the cost of resource utilization of AF patients hospitalized between January 2013 and June 2017 at a tertiary hospital in Athens due to acenocoumarol-related bleedings were retrieved.
Out of 48,255 AF patients, 12,633 (26.2%) were treated with acenocoumarol. In all, 5.1% of patients experienced a hemorrhagic event with the incidence of bleeding requiring hospitalization being 1.7%. The most common bleeding site was the gastrointestinal system (51.5%). The mean (95% CI) management cost per bleeding event requiring hospitalization was €1,202 (€1,058–€1,420). The higher cost was that of intracranial bleeding €3,887 (€2,700–€5,046). The expected annual economic burden for the management of bleedings related to acenocoumarol and requiring hospitalization was estimated at €1,463,955.
The incidence of bleeding events in AF acenocoumarol-treated patients in Greece as well as the estimated annual economic burden for the management of bleeding events requiring hospitalization, emphasize the need to comply with the current guidelines and to optimize therapeutic strategies for the management of AF side effects with oral anticoagulants, particularly in patients with high bleeding risk.
Clopidogrel's ability to inhibit platelet function determined its clinical usefulness. The role of CYP2C19*2 genotype on antiplatelet treatment is recently under question. Arterial wall properties ...and inflammation are key players in atherosclerosis development. Hence, we evaluated the impact of CYP2C19*2 genetic polymorphism on endothelial function, arterial stiffness and inflammation in coronary artery disease (CAD) patients receiving clopidogrel treatment.
In this study we enrolled 408 consecutive patients with stable CAD under dual antiplatelet therapy (clopidogrel 75mg/day, aspirin 100mg/day), 30 days after percutaneous coronary intervention. Measurement of flow-mediated dilation (FMD) of the brachial artery was used to evaluate endothelial function. Carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) was measured to estimate arterial stiffness. Real time polymerase chain reaction was used for the genotyping of CYP2C19*2. Levels of tumor necrosis factor alpha (TNF-a) and interleukin 6 (IL-6) were measured with ELISA. We found no difference in basic clinical and demographic characteristics nor in FMD, PWV, AIx and inflammatory status (p=NS for all) between CYP2C19 homozygotes for the wild type; carriers of reduced function allele and homozygotes for the reduced function allele.
CYP2C19*2 loss of action polymorphism causes no impact on vascular function and inflammatory status in stable CAD patients receiving clopidogrel treatment.
Atherosclerosis is the main underlying pathology of cardiovascular disease and is precipitated by various hereditary and non-hereditary risk factors. Inflammation is considered an important step in ...the progression of atherosclerosis and involves numerous cells, mediators and cellular procedures. Therefore, a biomarker able to determine the vascular inflammatory status is imperative as the combination of inflammatory biomarkers with the classic risk factors might provide further information about atherosclerosis progression and cardiovascular risk. The identification of novel inflammatory molecules and the improvement in analytical methods allows the potential implementation of these tests in every day clinical practice. In the current article, we focus on the role of established and novel biomarkers in atherosclerosis progression and in the determination of cardiovascular risk. We also present recent data concerning the risk stratification of patients according to their inflammatory status and the possible anti-inflammatory treatment strategies.
Abstract only
Background:
Transcatheter PFO closure has been established as a safe and effective approach for secondary prevention in patients with ESUS. The Amplatzer® PFO occluder and Gore Helex® ...septal occluder are two FDA-approved devices, which consist of a nickel-titanium alloy frame. While nickel is the first cause of hypersensitivity reaction worldwide, the potential occurrence of nickel hypersensitivity following PFO closure is still under investigation.
Aim:
Our aim is to investigate whether patients with nickel allergy are more susceptible to experiencing adverse events after device implantation and to explore the potential role of device selection.
Methods:
We prospectively enrolled patients undergoing PFO closure. Before the procedure, nickel skin patch tests were performed in all the patients. The patients were randomized to receive either Amplatzer® or Gore® device. During a three-month follow-up period, we evaluated the primary endpoint, which was a composite outcome including patient-reported chest pain, palpitations, headaches, and rash. We used the chi-squared test to evaluate the primary endpoint and performed multivariate binary logistic regression analysis to assess the effect of device selection on the primary endpoint.
Results:
A total of 50 patients (50% female, 45.4±10.3 years old) completed the follow-up and were included in the present analysis. Among them, 29 patients received the Gore device, while the remaining 21 patients received the Amplatzer device. Fourteen patients were diagnosed with nickel hypersensitivity. The primary endpoint was reached in 40% of the analyzed patients. The occurrence of the primary endpoint was significantly higher in patients with nickel hypersensitivity compared to those without (50% vs. 13.3%, p=0.005). Additionally, multivariate binary logistic regression analysis demonstrated no association between device selection and the composite outcome (p=0.892).
Conclusions:
Our preliminary results indicate that patients with nickel hypersensitivity are more likely to develop symptoms such as chest pain, palpitations, headaches, and rash following the procedure. However, the completion of our study is necessary to obtain more reliable and conclusive results.
Objective: Increased resting heart rate as well as increased arterial stiffness are both independent predictors of cardiovascular events and mortality. Results of previous studies have failed to ...converge concerning the association between heart rate and arterial stiffness, regardless of other potential confounders, such as age, gender and particularly blood pressure (BP). We aimed to investigate: (a) the degree of association (if any) between resting heart rate and carotid-to-femoral pulse wave velocity (PWV), the gold standard index of arterial stiffness, (b) if the relationship between heart rate and PWV is mediated by BP levels and (c) whether their association is affected by the levels of aortic stiffening. Approach: Demographic, hemodynamic, laboratory and clinical data of 1566 subjects from the cross-sectional observational 'Corinthia' study were analyzed using univariate and multivariate regression models. Mediation analysis was performed to test whether mean arterial pressure (MAP) is a significant mediator in the heart rate-PWV relationship. The total population was divided in two groups of low and high arterial stiffness according to the median PWV value (8.6 m s−1). Main results: We found that (i) there is a significant association between heart rate and PWV, regardless of other confounding factors. An increase in heart rate by 20 b.p.m. can increase PWV by 0.5 m s−1. However, this association was significant only for subjects with increased aortic stiffness (PWV > 8.6 m s−1) and not for those with PWV 8.6 m s−1. Further, (ii) heart rate-PWV association was partially mediated by MAP. Significance: Increased resting heart rate is related to increased aortic stiffness, only in subjects with stiffer aortas, regardless of BP and other risk factors and subjects' characteristics. The synergistic prognostic effect of increased arterial stiffness and elevated heart rate on target organ damage, cardiovascular events and mortality should be explored in future studies.
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