Circulating progenitor cells and their interaction with platelets in patients with an acute coronary syndrome.

CD34+ cells expressing KDR (CD34+/KDR+) represent a small proportion of circulating progenitor cells that have the capacity to interact with platelets and to differentiate into mature endothelial cells, thus contributing to vascular homeostasis and regeneration as well as to re-endothelialization. We investigated the levels of CD34+ and CD34+/KDR+ progenitor cells as well as their interaction with platelets in acute coronary syndrome (ACS) patients before the initiation (baseline) of their treatment with a P2Y12 receptor antagonist, and at 5-days post-treatment (follow-up). Sixty-seven consecutive ACS patients and thirty healthy subjects (controls) participated in the study. On admission, all patients received 325 mg aspirin, followed by 100 mg/day and then were loaded either with 600 mg clopidogrel or 180 mg ticagrelor, followed by 75 mg/day (n = 36) or 90 mg × 2/day (n = 31), respectively. The levels of circulating CD34+ and CD34+/KDR+ progenitor cells, as well as their interaction with platelets, were determined by flow cytometry, before and after activation with ADP, in vitro. The circulating levels of CD34+ and CD34+/KDR+ cells in both patient groups at baseline were lower compared with controls while they were significantly increased at 5-days of follow-up in both groups, this increase being more pronounced in the ticagrelor group. The platelet/CD34+ (CD61+/CD34+) conjugates were higher at baseline and reduced at follow-up while the platelet/KDR+ (CD61+/KDR+) conjugates were lower at baseline and increased at follow-up, both changes being more pronounced in the ticagrelor group. ADP activation of control samples significantly increased the KDR expression by CD34+ cells and the CD61+/KDR+ conjugates, these parameters being unaffected in patients at baseline but increased at follow-up. Short-term dual antiplatelet therapy in ACS patients restores the low platelet/KDR+ conjugates and CD34+ cell levels and improves the low membrane expression levels of KDR in these cells, an effect being more pronounced in ticagrelor-treated patients. This may represent a pleiotropic effect of antiplatelet therapy towards vascular endothelial regeneration.

Comparison of Triflusal with Aspirin in the Secondary Prevention of Atherothrombotic Events; Α Randomised Clinical Trial.

BACKGROUND: Triflusal has demonstrated an efficacy similar to aspirin in the prevention of vascular events in patients with acute myocardial infarction (ΜΙ) and ischaemic stroke but with less bleeding events. OBJECTIVE: We performed a randomised, multicentre, phase 4 clinical trial to compare the clinical efficacy and safety of triflusal versus aspirin, administered for 12 months in patients eligible to receive a cyclooxygenase-1 (COX-1) inhibitor. METHODS: Patients with stable coronary artery disease or with a history of non-cardioembolic ischaemic stroke were randomly assigned to receive either triflusal 300 mg twice or 600 mg once daily or aspirin 100 mg once daily for 12 months. The primary efficacy endpoint was the composite of: (a) ΜΙ, (b) stroke (ischaemic or haemorrhagic), or, (c) death from vascular causes for the entire follow-up period. The primary safety endpoints were the rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria. RESULTS: At 12-month follow-up, an equivalent result was revealed between the triflusal (n=559) and aspirin (n=560) in primary efficacy endpoint. Specifically, the combined efficacy outcome rate (i.e. MI, stroke or death from vascular causes) difference was equal to -1.3% (95% confidence interval -1.1 to 3.5) and lied within the a-priori defined equivalence interval (p<0.001). Regarding the primary safety endpoints, patients on triflusal treatment were 50% less likely to develop bleeding events according to the BARC criteria, and especially any clinically overt sign of haemorrhage that requires diagnostic studies, hospitalisation or special treatment (BARC type 2). CONCLUSION: The efficacy of triflusal in the secondary prevention of vascular events is similar to aspirin when administered for 12 months. Importantly, triflusal significantly reduced the incidence of ΜΙ and showed a better safety profile compared with aspirin. (ASpirin versus Triflusal for Event Reduction In Atherothrombosis Secondary prevention, ASTERIAS trial; Clinical Trials.gov Identifier: NCT02616497).

Electrocardiographic abnormalities and arrhythmic risk markers in adult patients with beta thalassemia major.

BACKGROUND: There seems to be a significant arrhythmia burden in ß-thalassemia major (TM) patients without overt cardiomyopathy. Apart from conventional electrocardiographic (ECG) and arrhythmic risk markers we studied novel markers of ventricular repolarization and autonomic imbalance both at rest and after exercise testing. METHODS: We studied 47 adult TM patients without systolic heart failure and 47 age and sex-matched healthy control subjects. The median age of the studied population was 36 [32-43] years, 57% men. Baseline demographic and clinical characteristics were recorded while 12-lead electrocardiograms, 24-hour ECG Holter recordings, and treadmill exercise stress tests were analyzed. RESULTS: TM patients exhibited increased QTc intervals in both 12-lead ECG recordings and in 24-hour Holter recordings. In addition, they had increased indexes of ventricular repolarization heterogeneity such as QT dispersion, and T peak-to-end/QT ratios. Furthermore, TM patients had decreased indexes of heart rate variability while the heart rate recovery after exercise was significantly attenuated compared to controls. Also, they had increased P wave and QRS duration while the QRS fragmentation was very prevalent. Finally, premature atrial extrasystoles and paroxysmal atrial fibrillation episodes were more frequent in TM patients. CONCLUSIONS: TM patients with preserved left ventricular systolic function have several ECG abnormalities including alterations in ventricular depolarization and repolarization. Also, cardiac autonomic dysfunction is evident in 24-hour ECG monitoring as well as in the recovery phase after exercise testing. The prognostic value of specific arrhythmic risk indexes in this setting remains to be elucidated.

Dynamic platelet adhesion in patients with an acute coronary syndrome: The effect of antiplatelet therapy.

Platelet adhesion and aggregation are key functions leading to thrombus formation. The effect of aspirin, clopidogrel, and ticagrelor on platelet aggregation has been well established, however, there is limited data on the effect of these drugs on platelet adhesion. We therefore evaluated the effect of these drugs on platelet adhesion in acute coronary syndrome (ACS) patients. Citrated blood was collected from 50 ACS patients loaded with 325 mg of aspirin (baseline) and at 5 days after the administration of aspirin 100 mg/day and clopidogrel (600 mg loading dose, 75 mg/day) (n = 26) or ticagrelor (180 mg loading dose, 90 mg × 2/day) (n = 24). High on-treatment platelet reactivity (HTPR) to clopidogrel was estimated by vasodilator stimulated phosphoprotein (VASP) phosphorylation assay. Platelet adhesion to collagen was studied for 6 min under high shear stress and was evaluated using the time to platelet recruitment (TPR), the perimeter and average area of each adherent object, number of adherent objects, and the total percent of surface coverage (SC%). Six ACS patients exhibited HTPR to clopidogrel and excluded from the platelet adhesion assays. TPR and SC% values were similar among patient groups at baseline and controls. However, all other adhesion parameters were different in ACS patients, indicating the formation of more aggregates in regard to controls. At 5 days post-treatment with either clopidogrel or ticagrelor, the TPR values were increased and the SC% values were reduced to a similar extent compared with baseline. However, significant differences were observed in the ticagrelor group in the perimeter, number of adherent objects, and the average area of each adherent object indicating a more potent inhibition of adherence-induced platelet aggregation than clopidogrel. In conclusion, aspirin does not affect platelet adherence to collagen, whereas clopidogrel and ticagrelor inhibit to a similar extent dynamic platelet adhesion at 5 days post-treatment in ACS patients. However, ticagrelor exhibits a greater inhibitory effect on reducing adhesion-induced platelet aggregation.

Acute myocardial infarction in a young bodybuilder taking anabolic androgenic steroids: A case report and critical review of the literature.

We describe a case report of a 30-year-old bodybuilder suffering acute myocardial infarction (AMI). He had been taking stanozolol and testosterone for two months. The coronary angiogram showed high thrombotic burden in the left anterior descending artery without underlying atherosclerosis. Few case reports of AMI in athletes taking anabolic androgenic steroids (AASs) have been reported so far. AAS-related AMI is possibly underreported in the medical literature due to the desire of the affected individuals to hide AAS use. Physicians should always consider the possibility of AAS abuse in the context of a young athlete suffering AMI. AASs can predispose to AMI through the acceleration of coronary atherosclerosis. Additionally, thrombosis without underlying atherosclerosis or vasospasm is highly possible to cause AMI in AAS users. Complications after AMI may be more frequent in AAS users.

Salts of Clopidogrel: Investigation to Ensure Clinical Equivalence: A 12-Month Randomized Clinical Trial.

BACKGROUND: In the present clinical trial, we compared the efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulfate (CHS) salt in patients eligible to receive clopidogrel. METHODS: A prospective 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n = 1864) were screened and 1800 were enrolled in the trial and randomized to CHS or CB. Primary efficacy end point was the composite of myocardial infarction, stroke, or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium criteria. RESULTS: At 12-month follow-up, no differences were observed between CB (n = 759) and CHS (n = 798) in primary efficacy and safety end points (age, sex, history of percutaneous coronary intervention adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.41-1.21 and OR, 0.81; 95% CI, 0.51-1.29, respectively) between CHS and CB. Analyses of efficacy and safety in subgroups that were defined according to the qualifying diagnosis revealed that there was no difference between CHS and CB. CONCLUSION: The efficacy and safety of CB administered for 12 months for the secondary prevention of atherothrombotic events are similar to that of CHS. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE trial; ClinicalTrials.gov Identifier:NCT02126982).

Infection control in implantation of cardiac implantable electronic devices: current evidence, controversial points, and unresolved issues.

A significant increase in the implantation of cardiac implantable electronic devices (CIEDs) is evident over the past years, while there is evidence for a disproportionate increase in CIED-related infections. The cumulative probability of device infection seems to be higher in implantable cardioverter defibrillator and in cardiac resynchronization therapy patients compared with permanent pacemaker patients. Given that more than a half of CIED infections are possibly related to the operative procedure, there is a need for effective periprocedural infection control. However, many of the current recommendations are empirical and not evidence-based, while questions, unresolved issues, and conflicting evidence arise. The perioperative systemic use of antibiotics confers significant benefit in prevention of CIED infections. However, there are no conclusive data regarding the specific value of each agent in different clinical settings, the value of post-operative antibiotic treatment as well as the optimal duration of therapy. The merit of local pocket irrigation with antibiotic and/or antiseptic agents remains unproved. Of note, recent evidence indicates that the application of antibacterial envelopes into the device pocket markedly decreases the infection risk. In addition, limited reports on strict integrated infection control protocols show a dramatic reduction in infection rates in this setting and therefore deserve further attention. Finally, the relative impact of particular factors on the infection risk, including the type of the CIED, patients' individual characteristics and comorbidities, should be further examined since it may facilitate the development of tailored prophylactic interventions for each patient.

Red blood cell distribution width and atrial fibrillation in patients with sick sinus syndrome.

BACKGROUND: Sick sinus syndrome (SSS) is associated with atrial fibrillation (AF). Red blood cell distribution width (RDW) is a marker of anisocytosis of erythrocytes and is related to inflammatory stress. Recently, RDW has been associated with AF. The aim of the present study was to evaluate the potential association of RDW with AF history in patients with SSS. METHODS: Consecutive patients with symptomatic SSS undergoing dual-chamber pacemaker implantation were screened. Baseline clinical, laboratory, echocardiographic, and electrocardiographic parameters were recorded. Conventional inflammatory indexes were also assessed. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis for parameters associated with AF were performed. RESULTS: The final study population consisted of 101 patients (47 men); median age: 77 [73-82] years. The demographic and clinical characteristics were comparable between tachy-brady (AF history) patients (n=32) and patients with other forms of SSS (n=69). Left atrial diameter was increased in tachy-brady patients [44 (39-48)mm vs. 39 (36-44)mm; p=0.05]. Also, the RDW was greater in these patients [14.7 (13.6-15.4)% vs. 13.7 (13.4-14.3)%; p=0.02]. Multivariate analysis showed that RDW is independently associated with AF (OR: 1.58; 95% CI: 1.06-2.85; p=0.04). The ROC curve analysis showed that the area under the curve was 0.69 (p=0.028). A RDW cut-off point of 14 was related to AF with a sensitivity of 70% and a specificity of 69%. CONCLUSION: RDW is associated with AF history in patients with SSS. The prognostic value of RDW in terms of future AF development and arrhythmia perpetuation in these patients should be further examined.

The Current Role of Omega-3 Fatty Acids in the Management of Atrial Fibrillation.

BACKGROUND: The main dietary source of omega-3 polyunsaturated fatty acids (n-3 PUFA) is fish, which contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the present manuscript, we aimed to review the current evidence regarding the clinical role of n-3 PUFA in the prevention of atrial fibrillation (AF) and the possible underlying mechanisms. METHODS: A literature search based on PubMed listings was performed using "Omega-3 fatty acids" and "atrial fibrilation" as key search terms. RESULTS: n-3 PUFA have been shown to attenuate structural atrial remodeling, prolong atrial effective refractory period through the prevention of reentry and suppress ectopic firing from pulmonary veins. Dietary fish intake has been found to have no effect on the incidence of AF in the majority of studies. Circulating DHA has been consistently reported to be inversely associated with AF risk, whereas EPA has no such effect. The majority of studies investigating the impact of n-3 PUFA supplementation on the incidence of AF following cardiac surgery reported no benefit, though most of them did not use n-3 PUFA pretreatment for adequate duration. Studies using adequate four-week pretreatment with n-3 PUFA before cardioversion of AF showed a reduction of the AF incidence. CONCLUSIONS: Although n-3 PUFA have antiarrhythmogenic properties, their clinical efficacy on the prevention of AF is not consistently supported. Further well-designed studies are needed to overcome the limitations of the existing studies and provide robust conclusions.

Defining the Path Between Social and Economic Factors, Clinical and Lifestyle Determinants, and Cardiovascular Disease.

BACKGROUND: Low socioeconomic status is associated with poorer cardiovascular health. OBJECTIVES: The aim of the present work was to evaluate how social and economic factors influence modifiable cardiovascular disease risk factors and thus, acute coronary syndrome or ischemic stroke presence. METHODS: One thousand participants were enrolled; 250 consecutive patients with a first acute coronary syndrome (83% were male, 60 ± 12 years old) and 250 control subjects, as well as 250 consecutive patients with a first ischemic stroke (56% were male, 77 ± 9 years old) and 250 control subjects. The control subjects were population-based and age-sex matched with the patients. Detailed information regarding their medical records, lifestyle characteristics, education level, financial status satisfaction, and type of occupation were recorded. RESULTS: After controlling for potential confounding factors, significant inverse associations were observed regarding financial status satisfaction and sedentary/mental type occupation with acute coronary syndrome or stroke presence, but not with the educational level. Nevertheless, further evaluation using path analysis, revealed quite different results, indicating that the education level influenced the type of occupation and financial satisfaction, hence affecting indirectly the likelihood of developing a cardiovascular disease event. CONCLUSIONS: Social and economic parameters interact with modifiable cardiovascular disease risk factors through multiple pathways.

Generic Clopidogrel Besylate in the Secondary Prevention of Atherothrombotic Events: A 6-month Follow-up of a Randomised Clinical Trial.

BACKGROUND: The aim of the present interim analysis was to compare the clinical efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulphate (CHS) salt in patient groups eligible to receive clopidogrel. METHODS: A 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n=1,864) were screened and 1,800 were enrolled in the trial and randomized to CHS (n=759) or CB (n=798). Primary efficacy end point was the composite of myocardial infarction, stroke or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria. RESULTS: At 6-months follow-up no differences were observed between CB and CHS in primary efficacy end point (OR, 0.80; 95% CI, 0.37 to 1.71; p=0.57). Rates of BARC-1,-2,-3a and -5b bleeding were similar between the two study groups whereas no bleeding events according to BARC-3b, -3c, -4 and -5a were observed in either CHS or CB group. CONCLUSION: The clinical efficacy and safety of the generic CB is similar to that of the innovator CHS salt, thus, it can be routinely used in the secondary prevention of atherothrombotic events for a period of at least 6 months. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE study Clinical Trials.gov Identifier: NCT02126982).

Eating behaviors and their relationship with cardiovascular disease. A case/case-control study.

The aim of the present work was to evaluate the combined role of eating behaviors and to investigate their effect on the likelihood of developing an acute coronary syndrome (ACS) or an ischemic stroke. During 2009-2010, 1000 participants were enrolled; 250 consecutive patients with a first ACS (83% males, 60 ± 12 years) and 250 control subjects, as well as 250 consecutive patients with a first ischemic stroke (56% males, 77 ± 9 years) and 250 controls. The controls were population-based and age-sex matched with the patients. Detailed information regarding their anthropometric data, medical records and lifestyle characteristics (dietary and smoking habits, physical activity, psychological state and eating practices -using a special questionnaire-) were recorded. Five eating behaviors were selected to compose an eating behavior score for the purposes of this work: adherence to the Mediterranean diet (using the MedDietScore), frequency of breakfast consumption, eating while being stressed, eating while working and skipping meals. Eating behaviors with beneficial health effects were scored with 0, while those with negative effects were assigned score 1. The total range of the score was between 0 and 5. Higher scores reveal "unhealthier" eating practices. After controlling for potential confounding factors, each unit increase of the eating behavior score was associated with 70% (95% CI: 1.29-2.22) higher likelihood of developing an ACS. Insignificant associations were observed regarding ischemic stroke. The overall adoption of specific "unhealthy" eating practices seems to have a detrimental effect on cardiovascular health, and especially coronary heart disease.

Bivalirudin use and one-month outcome in the context of contemporary antiplatelet treatment: insights from the Greek Antiplatelet Registry.

AIMS: Little is known about the use of bivalirudin in "real life". In the context of contemporary antiplatelet treatment, we aimed to assess bivalirudin treatment patterns and short-term (one-month) outcome. METHODS: Greek Antiplatelet Registry (GRAPE) is a prospective, observational, multicenter cohort study of consecutive, moderate-to-high-risk acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI). We assessed bivalirudin treatment patterns and predictive factors for its use. Combined in-hospital and one-month major adverse cardiovascular events (MACE, including death, myocardial infarction, urgent revascularization, and stroke), and bleeding events according to Bleeding Academic Research Consortium (BARC) criteria were analyzed after propensity matching. RESULTS: Of 2047 registered patients, 480 (23.4%) were treated with bivalirudin. Multivariate analysis (C statistic 0.77, 0.75-0.80 95% CIs, P < 0.001) revealed as factors favoring bivalirudin use primary PCI, radial arterial access, presentation with positive biomarkers and use of novel P2Y12 inhibitor, whereas IIb/IIIa inhibitor administration did not. Regional trends also affected bivalirudin's choice. In 370 propensity-matched pairs of patients who received or not bivalirudin, MACE, BARC type 1, 2 and 3 did not differ between groups: 4.1%, 21.9%, 3.2%, 3.5% and 5.1%, 18.9%, 2.7%, 4.3%, respectively, P = nonsignificant for all. CONCLUSIONS: In a "real life", contemporary antiplatelet treatment registry, clinical, laboratory and logistic factors affect bivalirudin's choice, while there are no differences in one-month outcome between bivalirudin-treated and non-bivalirudin-treated patients.