Biomedical subjects

Katalin Koltai

Publications and source records attributed to Katalin Koltai.

11 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

Viscosity, hemostasis and inflammation in atherosclerotic heart diseases.

BACKGROUND: In atherosclerotic diseases vascular reserve is impaired and pressure gradient is decreased, therefore the reduced blood fluidity can lead to tissue ischemia more rapidly. In previous investigations we demonstrated the deterioration of plasma and whole blood viscosities in patients with acute ischemic coronary syndromes, chronic coronary artery disease, and percutaneous transluminal coronary angioplasty. METHODS: Hemorheological variables (plasma and whole blood viscosities, hematocrit, red blood cell aggregation), hemostaseological parameters (plasma fibrinogen and von Willebrand factor (vWf)), and platelet aggregation were detected in more recent studies in cardio- and cerebrovascular diseases, and diabetes mellitus. Common risk factors (lipid profile, smoking, glucose level, previous diseases) and medication were also recorded. RESULTS: High portion of vascular patients were demonstrated to have poor ex vivo platelet inhibition. Effective antiplatelet treatment detected by aggregometry was related to lower plasma fibrinogen concentration and red blood cell aggregation and was also associated with less recurrent vascular events during the follow-up (p < 0.001). Beside the impaired hemorheological characteristics, the diabetic patients showed elevated vWf activity, which turned to correlate with hemoglobin A1c concentration (p < 0.01) rather than the fasting glucose. SUMMARY: Our studies indicate the active role and interaction of hemorheological and hemostaseological factors in atherosclerotic heart diseases.

Aged↗

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↗

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

Short-term effect of low-dose atorvastatin on haemorrheological parameters, platelet aggregation and endothelial function in patients with cerebrovascular disease and hyperlipidaemia.

INTRODUCTION AND OBJECTIVE: Haemorrheological parameters and endothelial function are known to be altered in vascular diseases, including stroke. Treatment with HMG-CoA reductase inhibitors ('statins') improves cerebrovascular (and cardiovascular) morbidity and mortality in patients with atherosclerosis; the beneficial effects may involve lipid-independent mechanisms. The aim of this study was to assess the short-term effect of low-dose atorvastatin on haemorrheological parameters, platelet aggregation and endothelial dysfunction in patients with chronic cerebrovascular disease and hyperlipidaemia. PATIENTS AND METHODS: Twenty-seven patients (mean age 61 +/- 8 years) with chronic cerebrovascular disease and hyperlipidaemia were included in the study. Serum lipid levels, haemorrheological parameters (haematocrit, plasma fibrinogen levels, plasma and whole blood viscosity [WBV] and red blood cell [RBC] aggregation and deformability) and platelet aggregation were assessed at baseline and after 1 and 3 months of treatment with atorvastatin (Sortis) 10 mg/day. von Willebrand factor (vWF) activity (a measure of endothelial function) was measured at baseline and after 1 month of treatment. Adverse events were recorded at each visit. Physical examinations, haematological assessments and serum and urine chemistry assays were performed during the study. RESULTS: Plasma total cholesterol levels were reduced by a mean of 27% compared with baseline after both 1 and 3 months of treatment (p < 0.001). Low density lipoprotein-cholesterol levels were reduced by a mean of 40% and 38% (p < 0.001), respectively, after 1 and 3 months of treatment, compared with baseline values. Triglyceride levels decreased by 20% at 1 month and by 10% after 3 months (p < 0.001). Atorvastatin significantly improved WBV after 3 months of treatment and RBC deformability after 1 month and 3 months of treatment (p < 0.05). Collagen-induced platelet aggregation was significantly decreased at 1 (p < 0.05) and 3 months (p < 0.001) compared with baseline values, despite unaltered antiplatelet therapy. vWF activity was also improved significantly (p < 0.05) after 1 month of treatment. CONCLUSIONS: Our findings show that the beneficial effects of atorvastatin are complex. Besides lipid lowering, atorvastatin can improve haemorrheological parameters, platelet aggregation and endothelial dysfunction after short-term and low-dose therapy. Whether such early laboratory changes translate into clinical utility for secondary stroke prevention awaits the results of endpoint trials.

Aged↗

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↗

PubMed2003

[Investigation of von Willebrand-factor as a marker of endothelial dysfunction in atherosclerotic patients].

OBJECTIVE: To determine von Willebrand-factor activity as the marker of endothelium dysfunction in vascular diseases and to compare it to healthy controls. METHODS: von Willebrand-factor activity was determined by enzyme-linked immunosorbant assay (ELISA) in patients with acute coronary syndromes (29 patients, 67 +/- 13 years), acute stroke (15 pts, 67 +/- 12 years) on admission, 2nd and 6th day; and chronic vascular diseases (56 pts, 67 +/- 10 years) and was compared to the values of healthy controls (23 persons, 36 +/- 12 years). RESULTS: von Willebrand-factor activity was significantly (p < 0.001) higher in all the measured vascular patients than in the control group. The values of acute patients were significantly (p < 0.05-0.001) higher than those of patients with chronic vascular diseases. In the hospital phase von Willebrand-factor activity in acute patients increased continuously and on day 6 was significantly (p < 0.05-0.01) higher than on admission. von Willebrand-factor activity was significantly (p < 0.05) higher in troponin positive patients with acute coronary syndromes compared to the troponin negative subjects. CONCLUSIONS: von Willebrand-factor was found to be a suitable marker of endothelial dysfunction. The higher von Willebrand-factor activity in patients with vascular diseases compared to the control group can be caused by the endothelial dysfunction and extensive atherosclerosis. The significantly higher von Willebrand-factor activity in acute disorders suggests the more severe endothelium dysfunction and could be related to the development of acute event through increased platelet adhesion and aggregation.

Aged↗

PubMed2003

[Chromium (III)-ion enhances the utilization of glucose in type-2 diabetes mellitus].

INTRODUCTION: The prevalence of the type 2 diabetes mellitus is still growing. Although the occurrence of insulin resistance is quite frequent in the whole population, diabetes not always develops because for a time the compensating mechanism avoids it. In a frequent variation of type-2 diabetes the disease is not the result of an alteration in the insulin receptor or the glucose transporter, but a genetically determined defect of the postreceptorial intracellular signaling mechanism plays a role in its occurrence. There have been investigations for decades to find out more about the role of chromium (III) ions in glucose metabolism and in the prevention of type-2 diabetes. It has also been investigated if chromium substitution can prevent or treat those forms of diabetes where chromium deficiency is suspected to be in the background of the disorder. AIM: The aim of our present investigation is to test the role of chromium (III) compounds in glucose metabolism that are known from literature. The authors examined the effect of oral chromium supplementation on antidiabetic treatment. Chromium supplementation was applied for 6 months. METHODS: Before, through and after the investigation changes in the patient's carbohydrate and lipid metabolism were followed by laboratory tests. RESULTS: At the end of our examination the cholesterin level significantly, the HbA1c level close to the significant value decreased. Due to their results the authors presume that chromium (III) compounds may be effective in the treatment of patients' with decreased glucose tolerance or type-2 diabetes mellitus as a supplement to their therapy.

Adult↗

PubMed2003

[Effects of cardiovascular risk factors on hemorheologic parameters in cerebrovascular patients].

INTRODUCTION: Hemorheological factors are of significance in the determination of flow characteristics of blood and play an important role in the pathogenesis of cerebrovascular diseases. AIMS AND METHODS: In this study the changes of rheological factors--hematocrit (Hct), plasma fibrinogen concentration (PFC), whole blood (WBV) and plasma viscosity (PV), red blood cell aggregation (AI) and deformability and the association between these parameters and cardiovascular risk factors were investigated in 297 patients (173 males, 124 females, mean age: 60 11 years) with chronic phase (3 months after onset) ischemic cerebrovascular diseases, and in 68 healthy volunteers (30 males, 38 females, mean age: 36 6 years). RESULTS: All investigated hemorheological factors were significantly (p < 0.05-0.0001) elevated in cerebrovascular patients compared to normal controls, the rise in Hct, WBV and PV are some of the most prominent findings. In the group of hypertensive, hyperlipidemic patients, smokers and alcoholics Hct, PFC, WBV, PV and AI were significantly (p < 0.05-0.0001) higher compared to healthy controls, the same factors except plasma fibrinogen concentration showed association with diabetic history. Comparing cerebrovascular patients with or without risk factors, the most severe hemorheological deficit was observed in patients with hyperlipidemia and smoking habits. CONCLUSIONS: In this study the authors proved in chronic ischemic cerebrovascular patients that hemorheological abnormalities persist in most cases for a long time after an acute stroke, significant correlation could be seen between blood rheology and cardiovascular risk factors. Examination of rheological parameters can support to choose the optimal medical treatment in the secondary prevention of stroke, correction of hemorheological disturbances can reduce the risk of recurrent stroke.

Adult↗