Biomedical subjects

Gergely Feher

Publications and source records attributed to Gergely Feher.

7 recordsLinked to original sources

PubMed2006

Clopidogrel resistance: role of body mass and concomitant medications.

INTRODUCTION: Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this has made antiplatelet therapy the cornerstone of cardiovascular disease management. Recent studies have described the phenomenon of clopidogrel resistance but the possible mechanisms are still unclear. PATIENTS AND METHODS: The aim of this study was to compare the characteristics (risk profile, previous diseases, medications, hemorheological variables and plasma von Willebrand factor and soluble P-selectin levels) of patients in whom clopidogrel provided effective platelet inhibition with those in whom clopidogrel was not effective in providing platelet inhibition. 157 patients with chronic cardio- and cerebrovascular diseases (83 males, mean age 61+/-11 yrs, 74 females, 63+/-13 yrs) taking 75 mg clopidogrel daily (not combined with aspirin) were included in the study. RESULTS: Compared with clopidogrel-resistant patients (35 patients (22%), patients who demonstrated effective clopidogrel inhibition had a significantly lower BMI (26.1 vs. 28.8 kg/m2, p<0.05). Patients with ineffective platelet aggregation were significantly more likely to be taking benzodiazepines (25% vs. 10%) and selective serotonin reuptake inhibitors (28% vs. 12%) (p<0.05). After an adjustment to the risk factors and medications BMI (OR 2.62; 95% CI: 1.71 to 3.6; p<0.01), benzodiazepines (OR 5.83; 95% CI: 2.53 to 7.1; p<0.05) and SSRIs (OR 5.22; 95% CI: 2.46 to 6.83; p<0.05) remained independently associated with CLP resistance. There was no significant difference in the rheological parameters and in the plasma levels of adhesive molecules between the two examined groups. CONCLUSION: The background of ineffective clopidogrel medication is complex. Drug interactions may play a role on clopidogrel bioavailability, on the other hand, the significant difference in BMI between the two examined groups suggests that clopidogrel therapy should be weight-adjusted.

Benzodiazepines↗

PubMed2006

Aspirin resistance: possible roles of cardiovascular risk factors, previous disease history, concomitant medications and haemorrheological variables.

BACKGROUND AND OBJECTIVE: Recent studies have described the incidence (approximately one in eight high-risk patients will experience a further atherothrombotic event over a 2-year period) of aspirin (acetylsalicylic acid) resistance and its possible background. The aim of this study was to compare the characteristics (risk profile, previous diseases, medications and haemorrheological variables) of patients in whom aspirin provided effective platelet inhibition with those in whom aspirin was not effective in providing platelet inhibition. METHODS: 599 patients with chronic cardio- and cerebrovascular diseases (355 men, mean age 64 +/- 11 years; 244 women, mean age 63 +/- 10 years) taking aspirin 100-325 mg/day were included in the study. Blood was collected between 8:00am and 9:00am from these patients after an overnight fast. The cardiovascular risk profiles, history of previous diseases, medication history and haemorrheological parameters of patients who responded to aspirin and those who did not were compared. Platelet and red blood cell (RBC) aggregation were measured by aggregometry, haematocrit by a microhaematocrit centrifuge, and plasma fibrinogen by Clauss' method. Plasma and whole blood viscosities were measured using a capillary viscosimeter. RESULTS: Compared with aspirin-resistant patients, patients who demonstrated effective aspirin inhibition had a significantly lower plasma fibrinogen level (3.3 g/L vs 3.8 g/L; p < 0.05) and significantly lower RBC aggregation values (24.3 vs 28.2; p < 0.01). In addition, significantly more patients with effective aspirin inhibition were hypertensive (80% vs 62%; p < 0.05). Patients who had effective platelet aggregation were significantly more likely to be taking beta-adrenoceptor antagonists (75% vs 55%; p < 0.05) and ACE inhibitors (70% vs 50%; p < 0.05), whereas patients with ineffective platelet aggregation were significantly more likely to be taking HMG-CoA reductase inhibitors (statins) [52% vs 38%; p < 0.05]. Use of statins remained an independent predictor of aspirin resistance even after adjustment for risk factors and medication use (odds ratio 5.92; 95% CI 1.83, 16.9; p < 0.001). CONCLUSIONS: The mechanisms underlying aspirin resistance are multifactorial. Higher fibrinogen concentrations increase RBC aggregation and can also result in increased platelet aggregation. The higher rate of hypertension in patients with effective platelet aggregation on aspirin could explain the differences in beta-adrenoceptor antagonist and ACE inhibitor use between these patients and aspirin-resistant patients. Furthermore, an additive effect of these drugs may contribute to effective antiplatelet therapy. It is also possible that drug interactions with statins might reduce aspirin bioavailability and/or activity, thereby reducing platelet inhibition in aspirin-resistant patients.

Adrenergic beta-Antagonists↗

PubMed2006

Hemorheological parameters and aging.

BACKGROUND: There is increasing evidence that impaired hemorheological parameters are associated with increased risk of cardio- and cerebrovascular events. The aim of our present study was to examine the relationship of these parameters to the advancing age. METHODS: The data of 6236 cardio- and cerebrovascular patients (3774 males, mean age 59.8 +/- 13.2 years and 2462 females, mean age 60.9 +/- 12.8 years) were included into this analysis. Males and females were divided into three groups, A < 45 years of age (young), B 45-65 years (middle-aged), C > 65 years (old). To exclude the effect of risk profile, previous diseases and medication, 623 patients (397 males, mean age 60.2 +/- 12.7 yrs and 226 females, mean age 60.5 +/- 12.4 yrs) were selected from the examined group with matching parameters. Blood was collected after an overnight fasting. Hematocrit, fibrinogen, red blood cell aggregation, plasma and whole blood viscosity were determined. RESULTS: All the measured parameters correlated significantly with advancing age in the whole population (p < 0.01), however the values of the correlation coefficients were very low. On the other hand, examining the different age-groups we found that these parameters did not consequently correlate with age, in fact hematocrit, red blood cell aggregation and whole blood viscosity values were negatively correlated with age in old males (p < 0.05). In the selected population these parameters did not correlate with advancing age. CONCLUSIONS: In the whole population the correlation of hemorheological parameters and advancing age may be just of statistical, but not clinical significance because of the high number of subjects. In the selected population these parameters did not correlate with advancing age. Our results suggest that these parameters are mostly independent of aging, increased values are not associated with older age but the more frequently occurring diseases.

Adult↗

PubMed2006

The effect of blood glucose levels on hemorheological parameters, platelet activation and aggregation in oral glucose tolerance tests.

Rheological factors and increased platelet aggregation are convincingly implicated in the development of micro- and macrovascular disease associated with diabetes mellitus. The present examination has been designed to describe the effects of a standard oral glucose load on hemorheological parameters, platelet activation and aggregation in patients with normal and pathologic glucose tolerance. Oral glucose tolerance test (OGTT) was performed in 30 patients suspected to have diabetes mellitus. Hematocrit, erythrocyte aggregation, red blood cell filterability, plasma and whole blood viscosity, soluble P-selectin levels and platelet aggregation were tested paralelly with blood glucose measurements 1, 2, and 3 hours after glucose consumption. Patients were divided into two groups based on glucose tolerance. Patients with abnormal glucose tolerance (IGT/DM) showed significant elevation in red blood cell aggregability (Myrenne indices M and M1) at the 2- and 3-hour samplings (p<0.01 and p<0.001, respectively). Patients with normal glucose tolerance (NGT) showed significant elevation only in M1 index (p=0.01). Plasma viscosity decreased significantly compared to fasting values in IGT/DM patients in all samples, but remained unchanged in NGT patients. Hematocrit decreased in IGT/DM patients significantly from the 2-hour samplings on (p<0.05), in normoglycaemic patients its decrease reached a borderline significance at 3-hour measurements. No significant changes were detected in whole blood viscosity, red blood cell filterability and sP-selectin levels during OGTT in either examined groups. No examined parameters were significantly correlated to blood glucose levels at any sampling. Erythrocyte aggregation showed significant correlation with BMI (p<0.01). Our results demonstrate that after the intake of a standard amount of glucose the development of rheological alterations is not simultaneous with the elevation of blood glucose levels, and our data suggest that the observed elevation in erythrocyte aggregation during OGTT might be associated with hyperinsulinemia.

Aged↗

PubMed2005

Glycoprotein IIIA gene (PlA) polymorphism and aspirin resistance: is there any correlation?

BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa receptors play an inevitable role in platelet aggregation. The GP IIIa gene is polymorphic (PlA1/PlA2) and the presence of a PlA2 allele might be associated with an increased risk for acute coronary syndrome (ACS). OBJECTIVE: To examine the prevalence of the PlA2 allele in patients with ACS and in subjects with or without aspirin resistance. METHODS: The prevalence of the PlA2 allele was assessed in 158 patients with ACS and PlA2 compared with its prevalence in 199 healthy volunteers. The antiplatelet efficacy of aspirin was examined in all patients with ACS, as well as in 69 individuals who had suffered ischemic stroke and in 58 high-risk subjects without any known ischemic vascular events. RESULTS: PlA2 prevalence was significantly higher in patients with ACS (59/158) than in the control group (51/199; p < 0.05). Carriers of the PlA2 allele had a significantly higher risk of developing ACS, even after an adjustment to the risk factors (OR 5.74; 95% CI 1.75 to 18.8; p = 0.004). The occurrence of the PlA2 allele was significantly higher among patients with aspirin resistance than in subjects who demonstrated an appropriate response to the drug (allele frequencies, 0.21 vs 0.14; p < 0.05). All patients homozygous for the PlA2 allele had an inadequate platelet response to aspirin. CONCLUSIONS: Our results support the hypothesis that carriers of the PlA2 allele might have an increased risk for ACS. PlA2 homozygosity was associated with an inadequate response to aspirin therapy. Our data further suggest that patients with PlA2 allele homozygosity might benefit from antiplatelet therapy based on adenosine diphosphate antagonists throughout secondary treatment for prevention of ACS.

Adult↗

PubMed2004

Inhibition of ADP-evoked platelet aggregation by selected poly(ADP-ribose) polymerase inhibitors.

Pathologic platelet activation has been implicated in the pathogenesis of ischemic heart disease. Since cardiomyocytes can be protected from ischemia-reoxygenation injury by poly(ADP-ribose) polymerase (PARP) inhibitors mimicking the adenine/ADP part of NAD, their structural resemblance to ADP may also enable the blockade of platelet aggregation via binding to ADP receptors. Blood samples drawn from healthy volunteers were pre-incubated with different concentrations of PARP inhibitors: 4-hydroxyquinazoline, 2-mercapto-4(3 H)-quinazolinone, or HO-3089. ADP-, collagen- and epinephrine-induced platelet aggregation was evaluated according to the method described by Born. The effect of PARP inhibitors on thrombocyte aggregation was also examined when platelets were sensitized by heparin and in the presence of incremental concentrations of ADP. All examined PARP inhibitors reduced the ADP-induced platelet aggregation in a dose-dependent manner (significant inhibition at 20 microM for HO-3089 and at 500 microM for the other agents; P < 0.05), even if platelets were sensitized with heparin. However, their hindrance on platelet aggregation waned as the concentration of ADP rose (no effect at 40 microM ADP). PARP inhibitors had minimal effect on both collagen- and epinephrine-induced platelet aggregation. Our study first demonstrates the feasibility of a design for PARP inhibitors that does not only protect against ischemia-reperfusion-induced cardiac damage but may also prevent thrombotic events.

Blood Platelets↗

PubMed2004

Hemorheological methods in drug research.

Development of new drugs is a sophisticated process that requires several, different methods. In our experiments we have applied two rheological models to study experimental and clinically used drugs. The antioxidant properties of several agents were estimated by erythrocyte filtration technique. The known antioxidant compound vitamin E was used to validate our measurements. An experimental cardioprotective agent, H-2545 provided significant protection against oxidative changes in red blood cell filterability (p<0.001). Although some of the examined, known cardiovascular drugs also showed significant antioxidant effect, they were less efficient than H-2545 and the scavenger effect of this novel agent exceeded the antioxidant properties of vitamin E. Modification of mexiletine with a pyrroline ring improved significantly its antioxidant capacity suggesting this molecular segment to be responsible for the antioxidant effect. In our second model the antiplatelet effect of experimental poly(ADP-ribose) polymerase (PARP) inhibitors was evaluated. Two widely used antiplatelet agents: acetyl salicylic acid and eptifibatide served as controls in the validation of the measurements. PARP inhibitors reduced ADP-induced platelet aggregation in a dose-dependent manner (p<0.05). However, their hindrance on platelet aggregation waned as the concentration of ADP rose. Regarding the platelets' role in the development of ischemic vascular diseases, the antiaggregating property of PARP inhibitors may exert additional beneficial effects on tissue blood supply under conditions of compromised vascular flow.

Adenosine Diphosphate↗