IntroductionKinetics of stress-related biological parameters were determined in acute coronary syndrome (ACS) patients undergoing complex cardiovascular rehabilitation.MethodsWe determined platelet functionality in the absence/presence of a selective alpha-2 adrenergic receptor inhibitor, atipemazole parallel with salivary cortisol levels at enrolment, and at 3- and 12-months follow-up in 75 ACS patients with percutaneous coronary intervention.ResultsPharmacological/non-pharmacological secondary prevention methods have been efficiently applied. Baseline aggregometry indicated platelet hyperactivity, decreasing gradually and being significantly reduced late, at 12 months (p < 0.05). Cortisol levels followed similar kinetics (p < 0.05). Baseline epinephrine-induced aggregations (EIA) significantly correlated with most of the other platelet agonists, even at subsequent time-points. Patients with upper-quartile EIA at enrolment (EIA-UQ) had significantly higher ADP- and collagen-induced aggregations at enrolment, at 3- and 12-months follow-up as well, indicating that high adrenergic response in the acute phase is accompanied by general platelet hyperactivity and predicts sustained platelet activation. In the EIA-UQ group higher cardiac biomarker release, elevated C-reactive protein and cortisol levels, and lower baseline left ventricular ejection fraction were detected.Atipemazole significantly reduced platelet aggregation induced by several platelet agonists, being most potent and comparable to full in vitro P2Y12 inhibition on collagen-induced aggregations (p < 0.05), indicating that catecholamines might serve as promt/long-term modulators of platelet function.DiscussionDespite effective CCR programme and dual antiplatelet therapy, prolonged activation of sympathetic neuroendocrine system and general platelet hyperactivity can be detected up to one year in ACS patients with high adrenergic platelet activity. Moreover, initial high adrenergic activity is accompanied by clinical parameters associated to increased cardiovascular risk, therefore early identification of these patients might support complex optimal long-term therapy.

Over the past two decades, transcatheter aortic valve implantation (TAVI) for the treatment of degenerative severe aortic valve stenosis has become a well-established therapeutic option with increasing scientific evidence. TAVI procedure indications are not determined purely by the risk of cardiac surgery and progressively, more and more consider patient’s life expectancy. Current guidelines leave "grey zones" alongside the first class recommendations for TAVI and surgical aortic valve replacement (SAVR), providing an opportunity to make optimal decision between different therapies, taking into account advantages and disadvantages of both interventions, patient's interests and local circumstances. Since patients treated with TAVI have come to be younger, several factors and different characteristics of the intervention must be considered individually (lifetime management). In addition to intraventricular conduction disturbances, pacemaker implantation, paravalvular leak, valve durability, the feasibility of percutaneous coronary interventions after TAVI and potential aortic valve reinterventions are the most important issues. The choice of the first intervention – whether it is TAVI or SAVR – is crucial, as it can determine the patient's quality of life, valve durability and the feasibility of subsequent invasive procedures.

A transzkatéteres aortabillentyű-implantáció (TAVI) az elmúlt két évtizedben egyre erősebb evidenciákkal rendelkező terápiás lehetősége lett a degeneratív súlyos aortabillentyű-stenosis kezelésének. Az indikációs kör függetlenné vált a szívsebészeti beavatkozás kockázatától, és egyre inkább a várható életkilátásokhoz igazodik. Az aktuális irányelvek a TAVI és a szívsebészeti aortabillentyű-csere (SAVR) egyértelmű javaslatai mellett hagynak „szürke zónákat” is, amelyek lehetőséget teremtenek a két beavatkozás előnyeinek és hátrányainak, valamint a beteg érdekeinek és a helyi viszonyoknak a figyelembevételével az optimális döntés meghozatalára. Minél fiatalabb betegcsoportra terjesztjük ki a TAVI-t, annál inkább figyelembe kell venni azokat a tényezőket és hosszú távú hatásokat, amelyek ezzel az intervenciótípussal együtt járnak. Az intraventrikuláris vezetési zavarok, a pacemakerimplantáció, a paravalvuláris leak mellett fontos kérdés a billentyű élettartama, valamint a TAVI utáni perkután koronáriaintervenciók és az esetleges aortabillentyű-reintervenciók elvégezhetősége. Az első intervenció – akár TAVI, akár SAVR – kiválasztása kulcsfontosságú, ugyanis meghatározhatja a beteg életminőségét, a billentyű élettartamát, valamint a későbbi, ismételt invazív beavatkozások lehetőségét.

Our aim was to introduce more homogenous phenotypes for studying genetic variations in the clinically heterogeneous obsessive compulsive disorder (OCD) beside classical case-control analysis. Symptoms were assessed with Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and principle component analysis of the lifetime symptom categories yielded four factors (Cleaning, Obsessive, Compulsive, Sexual). The comparison of serotonin transporter linked polymorphic region (5-HTTLPR) in 102 OCD patients and 223 controls showed an increased L-allele frequency but no difference was observed when rs25531 was included. Intronic variants of the serotonin transporter gene did not show association with either OCD, nor with the obtained factors.

Aims: Methylphenidate (MPH) is the most frequently prescribed drug in Attention Deficit Hyperactivity Disorder (ADHD). Hitherto mostly the dopamine transporter gene has been studied in MPH-response and only a few studies analyzed the norepinephrine transporter (NET, SLC6A2) gene, although MPH is a potent inhibitor of both dopamine and norepinephrine transporters. We aimed to analyze this monoamine transporter gene in relation to ADHD per se and MPH-response in particular to gain further knowledge in ADHD pharmacogenetics using a Caucasian sample. Methods: Six single nucleotide polymorphisms (rs28386840, rs2242446, rs3785143, rs3785157, rs5569, rs7194256 SNP) were studied across the NET gene in 163 ADHD children (age: 9.3 +/- 2.6; 86.5% male) using ADHD-RS hyperactivity-impulsivity and inattention scales. For case-control analysis 486 control subjects were also genotyped. At the MPH-response analysis responders had minimum 25% decrease of ADHD-RS total score after 2 months of treatment, and chi-square test compared 90 responders and 32 non-responders, whereas ANOVA was used to assess symptom improvement after the first month among the 122 ADHD patients. Results: The classical case-control analysis did not yield any association with ADHD diagnosis, which was supported by meta-analysis conducted on the available genetic data (combining previously published and the present studies). On the other hand, the intronic rs3785143 showed nominal association with inattention symptoms (p = 0.01). The haplotype analysis supported this association, and indicated the importance of the first haploblock encompassing the intronic and 2 promoter SNPs. With MPH-response only the promoter rs28386840 showed nominal association: Those with at least one T-allele were overrepresented in the responder group (42% vs 19%, p = 0.08), and they had better improvement on the hyperactivity-impulsivity scale compared to the AA genotype (p = 0.04). Conclusion: Although none of our single SNP findings remained significant after correcting for multiple testing, our results from the MPH-response analysis indicate the potential importance of promoter variants in the NET gene.

Background Acute coronary syndrome is associated with platelet hyperactivity, which in its persistent form, promotes recurrent thrombotic events. Complex cardiac rehabilitation after acute coronary syndrome improves clinical outcome; however, its effect on platelet hyperactivity is unknown.Design and methods We enrolled 84 acute coronary syndrome patients on dual antiplatelet therapy, who underwent a new complex cardiac rehabilitation programme (NovaCord physiotherapy, lifestyle counselling, strict diet, stress management and regular coaching) and 51 control acute coronary syndrome patients with traditional cardiac rehabilitation. Platelet functionality was determined at enrolment and at three months follow-up by aggregometry, serum platelet-derived growth factor levels, total- and platelet-derived microvesicle counts (PMV; CD41a+/CD61+, CD62P+).Results Platelet aggregation parameters and platelet-derived growth factor levels were significantly decreased in the complex cardiac rehabilitation group at three months (1 mu g/ml collagen, median (interquartile range): 22 (10-45) vs 14 (7.5-25.5)%, p=0.0015; 2 mu g/ml collagen: 36 (22-60) vs 26.5 (16-37)%, p=0.0019; 1.25 mu M adenosine-diphosphate: 4.5 (1-10) vs 1 (0-3)%, p=0.0006; 5 mu M adenosine-diphosphate: 27 (16-38) vs 22 (12-31)%, p=0.0078; epinephrine: 33 (15-57) vs 27 (12-43)%, p=0.01; platelet-derived growth factor: 434.6 (256.0-622.7) vs 224.8 (148.5-374.1) pg/ml, p=0.0001). In contrast, these changes were absent or did not reach statistical significance in the traditional cardiac rehabilitation group. Platelet-derived microvesicle counts were significantly decreased in both groups, while total microvesicle count was significantly reduced only in the complex cardiac rehabilitation group (median (interquartile range): 3945.5 (2138-5661) vs 1739 (780-2303) count/mu l; p=0.0001).Conclusions Platelet hyperactivity three months after acute coronary syndrome significantly decreased in patients undergoing complex cardiac rehabilitation. Besides dual antiplatelet therapy, effective management and comprehensive control of cardiovascular risk factors might represent a new, non-pharmacological approach to influence platelet functionality.

In patients with typical angina pectoris, inducible myocardial ischaemia and macroscopically normal coronaries (cardiac syndrome X (CSX)), a significantly elevated plasma level of terminal complement complex (TCC), the common end product of complement activation, has been observed without accompanying activation of the classical or the alternative pathways. Therefore, our aim was to clarify the role of the ficolin-lectin pathway in CSX. Eighteen patients with CSX, 37 stable angina patients with significant coronary stenosis (CHD) and 54 healthy volunteers (HC) were enrolled. Serum levels of ficolin-2 and ficolin-3, ficolin-3/MASP-2 complex and ficolin-3-mediated TCC deposition (FCN3-TCC) were determined. Plasma level of TCC was significantly higher in the CSX than in the HC or CHD group (5.45 versus 1.30 versus 2.04 AU/ml, P < 0.001). Serum levels of ficolin-2 and ficolin-3 were significantly lower in the CSX compared to the HC or CHD group (3.60 versus 5.80 or 5.20 mu g/ml, P < 0.05; 17.80 versus 24.10 or 26.80 mu g/ml, P < 0.05). The ficolin-3/MASP-2 complex was significantly lower in the CSX group compared to the HC group (92.90 versus 144.90 AU/ml, P = 0.006). FCN3-TCC deposition was significantly lower in the CSX group compared to the HC and CHD groups (67.8% versus 143.3% or 159.7%, P < 0.05). In the CSX group, a significant correlation was found between TCC and FCN3-TCC level (r = 0.507, P = 0.032) and between ficolin-3/MASP-2 complex level and FCN3-TCC deposition (r = 0.651, P = 0.003). In conclusion, in patients with typical angina and myocardial ischaemia despite macroscopically normal coronary arteries, low levels of several lectin pathway parameters were observed, indicating complement activation and consumption. Complement activation through the ficolin-lectin pathway might play a role in the complex pathomechanism of CSX.

The effect of invasive percutaneous coronary procedures on complement activation has not been elucidated. We enrolled stable angina patients with elective percutaneous coronary intervention (SA-PCI, n=24), diagnostic coronary angiography (CA, n=52) and 23 patients with ST segment elevation myocardial infarction and primary PCI (STEMI-PCI). Complement activation products (C1rC1sC1inh, C3bBbP and SC5b-9) were measured on admission, 6 and 24h after coronary procedures. The alternative pathway product, C3bBbP significantly and reversibly increased 6h after elective PCI (baseline: 7.81AU/ml, 6h: 16.09AU/ml, 24h: 4.27AU/ml, p<0.01, n=23) and diagnostic angiography (baseline: 6.13AU/ml, 6h: 12.08AU/ml, 24h: 5.4AU/ml, p<0.01, n=52). Six hour C3bBbP values correlated with post-procedural CK, creatinine level and the applied contrast material volume (r=0.41, r=0.4, r=0.3, p<0.05, respectively). In STEMI-PCI, baseline C3bBbP level was higher, compared to SA-PCI or CA patients (11.33AU/ml vs. 7.81AU/ml or 6.13AU/ml, p<0.001). Similarly, the terminal complex (SC5b-9) level was already elevated at baseline compared to SA-PCI group (3.49AU/ml vs. 1.87AU/ml, p=0.011). Complement pathway products did not increase further after primary PCI. Elective coronary procedures induced transient alternative complement pathway activation, influenced by the applied contrast volume. In STEMI, the alternative complement pathway is promptly activated during the atherothrombotic event and PCI itself had no further detectable effect.

Flow is a special mental state characterized by deep concentration that occurs during the performance of optimally challenging tasks. In prior studies, proneness to experience flow has been found to be moderately heritable. In the present study, we investigated whether individual differences in flow proneness are related to a polymorphism of the dopamine D2 receptor coding gene (DRD2 C957T rs6277). This polymorphism affects striatal D2 receptor availability, a factor that has been shown to be related to flow proneness. To our knowledge, this is the first study to investigate the association between this trait and a specific gene variant. In a sample of 236 healthy Hungarian adults, we found that CC homozygotes report higher flow proneness than do T allele carriers, but only during mandatory activities (i.e., studying and working), not during leisure time. We discuss implications of this result, e.g., the potential mediators of the relationship.

Objective: We examined the vascular system, from the microvasculature to the aorta, in diabetes mellitus, using non-invasive methods.Methods: We enrolled patients with type 1 diabetes: 17 patients without complications (DMW) and 19 patients with clinically manifest complications (DMC). Control group was represented by 34 healthy volunteers (C). We examined microvascular function with laser-Doppler flowmetry, using post-occlusive reactive hyperemia test and local heating. Arterial stiffness was studied by arteriograph, determining augmentation index and pulse wave velocity. We measured serum levels of sE-selectin and sICAM-1, markers of endothelial dysfunction.Results: Microvascular reactivity was significantly reduced in DMC-, and tendentiously in DMW groups. sE-selectin level was significantly higher in DMC group than in controls. Arterial stiffness was the highest in the DMC group and the lowest in the DMW group. Heart rate was significantly higher in both diabetic groups compared to controls. Time to maximum flow during PORH test tended to be the shortest in DMW group.Conclusions: Our results confirm impairment of the microvascular system in diabetic patients, even in early, uncomplicated stage of the disease, and might demonstrate diffuse hyperkinesis in the vascular system, resulting from the insulin effect or refering to the "vasodilation phase" of diabetes mellitus.

Recovering helpers play an increasing role in addiction treatment. In this study, we assessed the process of how addicts become recovering helpers. Semi-structured interviews were conducted with six recovering helpers, and the transcribed interviews were analyzed using interpretative phenomenological analysis. Four turning points were identified during the interviews: starting using drugs or gambling, becoming an addict, hitting bottom, and becoming a helper. In addition, four themes related to being a helper were identified: the recovering self and the helping self, the wounded helper, the skilled helper and the experience of helping. Understanding the dynamics and background of recovering helpers’ work may contribute to their training, to finding the most appropriate place for them in addiction treatment, and in drug and alcohol policy.

Abstract High on-clopidogrel platelet reactivity (HPR) is a predictor of ischemic events after percutaneous coronary intervention. We conducted a prospective cohort study to identify variables related to HPR in acute coronary syndrome patients who are at high thrombotic risk. We enrolled 463 patients undergoing urgent coronary angiography. Platelet reactivity was measured 12–36 hours after 600 mg clopidogrel loading with multiple electrode aggregometry (Multiplate® analyzer, Roche, Basel, Switzerland, 6.4 µM ADP). HPR was defined by the consensus cut-off area under the curve >46 U. The rate of HPR was 16.0%. We analyzed simple clinical and laboratory parameters with backward multivariate logistic regression and identified the following predictors of HPR: platelet count (per G/L, OR: 1.0073, 95% CI: 1.0035–1.0112, p = 0.0002), CRP level (per mg/L, OR: 1.0077, 95% CI: 1.0016–1.01372, p = 0.01), and active smoking (OR: 0.51, 95% CI: 0.29–0.89, p = 0.02). We developed and internally validated a risk prediction model demonstrating moderate discriminative capacity (area-under-the-receiver operating characteristic curve = 0.67). In conclusion, we found a relatively low rate of high on-clopidogrel platelet reactivity (16.0%) even in an acute patient cohort. HPR measured by Multiplate was associated with high platelet count and CRP level on admission and was inversely related to active smoking. The model with rapidly available simple parameters might help to identify individuals at risk for HPR in the acute setting.

The benefit of adjusted antiplatelet therapy in patients with myocardial infarction after primary percutaneous coronary intervention is not well elucidated. We aimed to identify patients with high on treatment platelet reactivity and to gradually adjust antiplatelet therapy.Materials and Methods: We enrolled 133 acute myocardial infarction and 67 stable angina patients undergoing intracoronary stenting into our study. Maximal aggregation was determined with light transmission aggregometry. Aggregation >50% induced by 5 mu M ADP was indexed with high on-clopidogrel treatment platelet reactivity. In these cases 75 mg clopidogrel was doubled and control test was performed. Patients effectively inhibited with 150 mg clopidogrel were defined as clopidogrel pseudo non-responders. Patients with high platelet reactivity even on 150 mg clopidogrel were considered as clopidogrel real non-responders and were switched to ticlopidine.Results: Aggregations (5ADP; p = 0.046) and the ratio of real non-responders (p = 0.013) were significantly higher in the myocardial infarction group. Most real non-responders were effectively treated with switch of therapy. The ratio of pseudo non-responders also tended to be higher in myocardial infarction. Platelet reactivity remained constant during follow-up; however, a new appearance of high platelet reactivity was observed at 6 and at 12 months.Conclusions: Patients with acute myocardial infarction undergoing percutaneous coronary intervention may benefit from prospective platelet function testing, because of higher platelet reactivity and much higher ratio of clopidogrel real non-response. Switch of therapy may effectively overcome clopidogrel non-response. A new appearance of high platelet reactivity with unknown clinical significance is observed in both groups among the patients on clopidogrel. (C) 2013 Elsevier Ltd. All rights reserved.

Clinical studies as well as animal models emphasized the importance of the complement system in the pathogenesis of coronary atherosclerosis and cardiovascular diseases. Our aim was to examine the extent and clinical implication of complement system activation in patients with stable atherosclerotic coronary heart disease (ACHD).Seventy-six patients with stable angina pectoris (SAP) scheduled for elective coronary angiography were enrolled into the study. Percutaneous coronary intervention (PCI) was performed in 24 patients, in 27 patients (NOPCI group) the coronary angiography showed significant stenosis and bypass surgery (CABG) or optimal medical therapy (OMT) were advised, whereas in 25 patients the coronary angiography was negative (NC group). 115 volunteers served as healthy controls (HC). In all individuals, the plasma level of several complement activation products - C1rC1sC1inh, C3bBbP and SC5b-9 - were determined on admission, strictly before the coronary angiography.In patients with angiographically proven ACHD (PCI and NOPCI groups), the baseline C1rC1sC1inh levels were significantly higher compared to NC group and HC (p <0.0001, for both comparisons). According to the multiple logistic regression analysis, high C1rC1sC1inh level proved to be an independent biomarker of coronary heart disease (p <0.026, OR: 65.3, CI: 1.628-2616.284).Conclusion: Activation of the classical complement pathway can be observed in angiographically proven coronary atherosclerosis. Elevated C1rC1sC1inh-levels might represent an useful biomarker for coronary artery disease. (C) 2012 Elsevier Ltd. All rights reserved.