Oscillometric measurement of the ankle-brachial index and the estimated carotid-femoral pulse wave velocity improves the sensitivity of an automated device in screening peripheral artery disease.

Background and aims: To overcome the time and personnel constraints of the Doppler method, automated, four-limb blood pressure monitors were recently developed. Their additional functions, such as measuring the estimated carotid-femoral pulse wave velocity (ecfPWV), have been, thus far, less studied. We aimed to compare the sensitivity and specificity of different ankle-brachial index (ABI), toe-brachial index (TBI), and ecfPWV measurement methodologies to evaluate their contribution to peripheral artery disease (PAD) screening. Methods: Among 230 patients (mean age 64 ± 14 years), ABI measurements were performed using a Doppler device and a manual sphygmomanometer. The Doppler ABI was calculated by taking the higher, while the modified Doppler ABI by taking the lower systolic blood pressure of the two ankle arteries as the numerator, and the higher systolic blood pressure of both brachial arteries as the denominator. The automated ABI measurement was carried out using an automatic BOSO ABI-system 100 PWV device, which also measured ecfPWV. TBI was obtained using a laser Doppler fluxmeter (Periflux 5000) and a photoplethysmographic device (SysToe). To assess atherosclerotic and definitive PAD lesions, vascular imaging techniques were used, including ultrasound in 160, digital subtraction angiography in 66, and CT angiography in four cases. Results: ROC analysis exhibited a sensitivity/specificity of 70.6%/98.1% for the Doppler ABI (area under the curve, AUC = 0.873), 84.0%/94.4% for the modified Doppler ABI (AUC = 0.923), and 61.5%/97.8% for the BOSO ABI (AUC = 0.882) at a cutoff of 0.9. Raising the cutoff to 1.0 increased the sensitivity of BOSO to 80.7%, with the specificity decreasing to 79.1%. The ecfPWV measurement (AUC = 0.896) demonstrated a 63.2%/100% sensitivity/specificity in predicting atherosclerotic lesions at a cutoff of 10 m/s. Combining BOSO ABI and ecfPWV measurements recognized 89.5% of all PAD limbs. Conclusion: The combined BOSO ABI and ecfPWV measurements may help select patients requiring further non-invasive diagnostic evaluation for PAD. The user-friendly feasibility may make it suitable for screening large populations.

Screening for Peripheral Artery Disease Using an Automated Four-Limb Blood Pressure Monitor Equipped with Toe-Brachial Index Measurement.

Toe-brachial index (TBI) measurement helps to detect peripheral artery disease (PAD) in patients with incompressible ankle arteries due to medial arterial calcification, which is most frequently associated with diabetes. We aimed to evaluate how an automated four-limb blood pressure monitor equipped with TBI measurement could contribute to PAD screening. In 117 patients (mean age 63.2 ± 12.8 years), ankle-brachial index (ABI) measurement was performed using the Doppler-method and the MESI mTablet. TBI was obtained via photoplethysmography (MESI mTablet, SysToe) and a laser Doppler fluxmeter (PeriFlux 5000). Lower limb PAD lesions were evaluated based on vascular imaging. A significant correlation was found between Doppler and MESI ankle-brachial index values (r = 0.672), which was stronger in non-diabetic (r = 0.744) than in diabetic (r = 0.562) patients. At an ABI cut-off of 0.9, Doppler (AUC = 0.888) showed a sensitivity/specificity of 67.1%/97.4%, MESI (AUC 0.891) exhibited a sensitivity/specificity of 57.0%/100%; at a cut-off of 1.0, MESI demonstrated a sensitivity/specificity of 74.7%/94.8%. The TBI values measured using the three devices did not differ significantly (p = 0.33). At a TBI cut-off of 0.7, MESI (AUC = 0.909) revealed a sensitivity/specificity of 92.1%/67.5%. Combining MESI ABI and TBI measurements recognised 92.4% of PAD limbs. Using an ABI cut-off level of 1.0 and sequential TBI measurement increases the sensitivity of the device in detecting PAD. The precise interpretation of the obtained results requires some expertise.

Examination of Lower Limb Microcirculation in Diabetic Patients with and without Intermittent Claudication.

Intermittent claudication is a frequent complaint in lower extremity artery disease, but approximately two thirds of patients are asymptomatic, most of which are diabetic patients. Non-invasive angiological and microrheological tests on diabetic subjects with and without intermittent claudication were performed in the present study. In total, 98 diabetic patients were included and divided into two groups: 20 patients (63.5 ± 8.8 years, 55% men, 45% women) had intermittent claudication, 78 patients (65.5 ± 9.3 years, 61.5% men, 38.5% women) were asymptomatic. Hand-held Doppler ultrasound examination, transcutaneous tissue partial oxygen pressure (tcpO2) measurement, Rydel-Seiffer tuning fork tests, and 6-min walk tests were performed, and erythrocyte aggregation was investigated. Ankle-brachial index (p < 0.02) and tcpO2, measured during provocation tests (p < 0.003) and the 6-min walk test (p < 0.0001), significantly deteriorated in the symptomatic group. A higher erythrocyte aggregation index and faster aggregate formation was observed in claudication patients (p < 0.02). Despite the statistically better results of the asymptomatic group, 13% of these patients had severe limb ischemia based on the results of tcpO2 measurement. Claudication can be associated with worse hemodynamic and hemorheological conditions in diabetic patients; however, severe ischemia can also develop in asymptomatic subjects. Non-invasive vascular tests can detect ischemia, which highlights the importance of early instrumental screening of the lower limbs.

Disease-Specific Quality of Life among Patients with Peripheral Artery Disease in Hungary.

Peripheral artery disease (PAD) is a progressive atherosclerotic disease significantly impacting functional status and health-related quality of life (HRQoL). This study aimed to investigate HRQoL among PAD patients in Hungary using the validated Hungarian version of the PADQoL questionnaire. Patients with symptomatic PAD were consecutively recruited from the Department of Angiology, Clinical Center, University of Pécs, Hungary. Demographics, risk factors, and comorbidities were registered. Disease severity was measured by Fontaine and WIFI stages. Descriptive statistical analysis, Chi-square test, and non-parametric tests were performed (p < 0.05). Overall, 129 patients (mean age 67.6 ± 11.9 years, men 51.9%) participated in our study. The Hungarian PADQoL demonstrated good internal consistency (α range: 0.745-0.910). Factors on intimate and social relationships gave the best (89.15 ± 20.91; 63.17 ± 26.05) and sexual function (28.64 ± 27.42), and limitations in physical functioning (24.68 ± 11.40) the worst scores. PAD had a significant negative impact on the social relationships of patients aged 21-54 years (51.6 ± 25.4). Fontaine stage IV patients experienced significantly lower HRQoL due to fear and uncertainty (46.3 ± 20.9) and limited physical functioning (33.2 ± 24.8). The Hungarian PADQoL identified central aspects of HRQoL. Advanced PAD was found to impact several areas of HRQoL, primarily physical functioning and psycho-social well-being, drawing attention to the importance of early diagnosis and management.

Hemizygous nonsense variant in the moesin gene (MSN) leads to a new autoimmune phenotype of Immunodeficiency 50.

Here, we present the findings of an investigation involving two male siblings with juvenile total tooth loss, early-onset chronic leg ulcers, and autoimmune thyroiditis, as well as focal segmental glomerulosclerosis with associated pulmonary emphysema in one and diabetes mellitus in the other. The clinical picture and lupus anticoagulant, cryoglobulin, and cold agglutinin positivity suggested the diagnosis of antiphospholipid syndrome. Flow cytometry analysis showed immunophenotypes consistent with immune dysregulation: a low number of naive T cells, elevated CD4+ T cell counts, and decreased CD8+ T-cell counts were detected, and more than half of the T-helper population was activated. Considering the siblings' almost identical clinical phenotype, the genetic alteration was suspected in the background of the immunodeficiency. Whole exome sequencing identified a previously not described hemizygous nonsense variant (c.650G>A, p.W217X) within exon 6 of the moesin (MSN) gene localized on chromosome X, resulting in significantly decreased MSN mRNA expression compared to healthy controls. We present a putative new autoimmune phenotype of Immunodeficiency 50 (MIM300988) characterized by antiphospholipid syndrome, Hashimoto's thyroiditis, leg ulcers, and juvenile tooth loss, associated with W217X mutation of the MSN gene.

Hungarian adaptation of the Peripheral Artery Disease Quality of Life questionnaire / A perifériás veroérbetegek életminoségét vizsgáló angol nyelvu kérdoív magyar adaptálása.

Összefoglaló. Bevezetés: A perifériás veroérbetegség napjaink egyik világméretu népegészségügyi problémája, több mint 200 millió embert érint világszerte. A Peripheral Artery Disease Quality of Life (PADQOL) kérdoívet azzal a céllal fejlesztették ki, hogy a betegség fizikai tünetein kívül annak szubjektív betegségterhét, pszichoszociális és emocionális hatásait is vizsgálja. Célkituzés: Az eredeti, angol nyelvu PADQOL betegségspecifikus, önkitöltos kérdoív magyar nyelvu, érvényes változatának kifejlesztése, annak fordítása, kultúrközi adaptációja és magyar nyelvi validálása. Módszerek: Az életminoség-kérdoív lingvisztikai validálása nemzetközi protokoll alapján történt: két szakfordító külön-külön lefordította a kérdoívet angol forrásnyelvrol magyarra; egy harmadik szakfordító bevonásával elkészült a két verzió szintézise, majd azt két, angol anyanyelvu fordító visszafordította angol forrásnyelvre, amit konszenzusmegbeszélés követett. A "pre-final" magyar verzió érthetoségét 30, angiológiai járó és fekvo beteg bevonásával, kognitív interjúk lefolytatásával, pilotvizsgálat során teszteltük. A PADQOL kérdoív faktorstruktúrájának feltárásához faktoranalízist végeztünk, az alskálák megbízhatóságát, a tételek belso konzisztenciáját a Cronbach-alfa-együttható kiszámításával vizsgáltuk. Az elemzésekhez IBM SPSS 23.0 programcsomagot használtunk. Eredmények: A PADQOL nyelvi validálása jelentéstani, tapasztalati és idiomatikus ekvivalencia tekintetében nem jelentett nehézséget. A kognitív interjúk során egy kérdés esetén tapasztaltunk értelmezési nehézséget. A kérdoív "pre-final" verziója tartalmilag és nyelvileg könnyen értheto, kitöltése nem okoz nehézséget. Az egyes dimenziók Cronbach-α-értéke 0,624 és 0,887 között volt. A legrosszabb értéket a Félelem és bizonytalanság (score-átlag: 14,07) életminoség-dimenzió mutatta. Következtetés: Létrehoztuk a PADQOL kérdoív végso magyar verzióját, mely méroeszköz alkalmas a nyelvi és kultúrközi adaptáció következo lépésének elvégzésére, nagyobb betegpopuláción történo pszichometriai és klinikometriai vizsgálat által a perifériás veroérbetegek életminoségének, szubjektív betegségterhének felmérését célzó validálásra. Orv Hetil. 2020; 161(51): 2153-2161. INTRODUCTION: Peripheral artery disease is one of the greatest, global public health concerns affecting more than 200 million people worldwide. The Peripheral Artery Disease Quality of Life questionnaire was developed to assess the subjective disease burden of peripheral artery disease, by focusing on psychosocial and emotional effects besides physical symptoms and functional limitations. OBJECTIVE: To develop the valid Hungarian version of the original PADQOL via the standard linguistic validation and cross-cultural adaptation procedure. METHODS: The linguistic validation was conducted according to an international protocol: two independent forward translations, a synthesis of the translations, back translations and consensus team review. The pilot-testing of the 'pre-final' Hungarian version was conducted via cognitive interviews with 30 in- and outpatients attending the Department of Angiology. Factor analysis was performed, Cronbach-alpha values were calculated to establish the reliability of subscales and to determine the internal consistency if items. IBM SPSS 23.0 was used. RESULTS: The linguistic validation of PADQOL into Hungarian posed no difficulties in terms of semantic, experiential and idiomatic equivalence. One item was found difficult to interpret during cognitive interviewing. The 'pre-final' version of the questionnaire was easy to understand and complete. Cronbach-alpha values of factors ranged between 0.624 and 0.887. The lowest value was that of factor 4: Fear and Uncertainty (mean score: 14.07). CONCLUSION: The linguistic validation of PADQOL into Hungarian was successful, the final Hungarian version is a tool that should reveal valuable insights with regard to subjective disease burden of patients living with peripheral artery disease subsequent to psychometric and clinicometric validation on a larger patient population. Orv Hetil. 2020; 161(51): 2153-2161.

Lower limb ischemia and microrheological alterations in patients with diabetic retinopathy.

BACKGROUND: Diabetes mellitus is frequently associated with vascular pathologies and hemorheological disorders. METHODS: 105 patients with diabetic retinopathy (DRP) (mean age 64.64±9.01 years, 56 males, 49 females), 35 age-matched non-diabetic (mean age 61.65±7.6 years, 14 males and 21 females) and 42 young healthy volunteers (mean age 25.52±3.32 years, 22 males, 20 females) were recruited. Lower extremity artery disease (LEAD) and microcirculatory alterations were screened by hand-held Doppler, transcutaneous partial tissue oxygen tension (tcpO2), tuning fork test, 6-minute walk test, erythrocyte aggregation and deformability. RESULTS: High prevalence of LEAD was detected in diabetic population: 55.3% fulfilled the criteria of LEAD based on ankle-brachial index; severely impaired tcpO2 was measured in 18.6%. The results of non-invasive measurements of the diabetic patients were significantly worse than those of the control groups (p < 0.05). Hemorheological disturbances could be characterized by the significantly higher erythrocyte aggregation (p < 0.05) and lower erythrocyte deformability (p < 0.05) in the diabetic population. CONCLUSION: Macro- and microcirculatory lower limb disorders could be revealed at high prevalence in diabetic patients with retinopathy. Measurement of tcpO2 and hemorheological variables could be useful to discover patients at higher risk for diabetic foot complications.

Viscometer validation studies for routine and experimental hemorheological measurements.

BACKGROUND: Viscosity measurement is challenging due to the internal properties of blood and the artifacts deriving from the various viscometer systems. OBJECTIVE: We aimed to determine the pitfalls of a cone-plate viscometer (Brookfield DV-III Ultra LV) before starting measurements and compare it to our capillary type model (Hemorex Hevimet 40). Effects of sample storage and thermal calibration were assessed as well. METHODS AND RESULTS: Intra-observer variability was studied by 10 replicate measurements of 7 blood samples, mean coefficients of variation were less than 5%. Instruments were compared by measuring 26 blood samples, an average difference of 7% in WBV and 10% in PV was observed. 9 blood samples were stored at 4°C, 22°C and 37°C up to 48 hours to study the effect of storage on viscosity values. WBV at 50 and 100 s-1 became significantly lower after 3 hours at 37°C (p < 0.05). WBV at higher shear rates and PV remained constant at all temperatures. To evaluate the possibility of measuring one sample at different temperatures, 8 blood samples were measured at 40°C with the device calibrated both at 20°C and 40°C; no significant difference was observed. CONCLUSIONS: Thorough validation studies are required before starting experimental and routine viscosity measurements.

Toe-brachial index and exercise test can improve the exploration of peripheral artery disease.

BACKGROUND AND AIMS: We assumed that hand-held Doppler ultrasound (DUS) at rest was insufficient to assess the severity of peripheral artery disease (PAD). Toe pressure and transcutaneous tissue oxygen pressure were studied to prove whether these could identify more patients with severe lower limb ischemia; exercise was applied to provoke ischemia. METHODS: 120 patients with PAD and 30 volunteers without PAD were recruited. DUS, transcutaneous tissue oxygen pressure (tcpO2) and toe pressure measurements were performed at rest and after exercise. The differential power of these examinations for severe limb ischemia (SLI) was determined by receiver-operating curves (ROCs) and pattern recognition by independent multicategory analysis (PRIMA). RESULTS: There was an obvious significant difference between the patient and control groups at rest; after exercise; the ratio of severely impaired values (ankle-brachial index - ABI, toe-brachial index - TBI, tcpO2 measured on index forefoot) increased significantly in the patient group (p < 0.05). TBI, tcpO2, ABI measured after exercise could differentiate SLI better than the values of these tests at rest (p < 0.001). In ROC analysis, the largest area under the curve (AUC) was covered by post- (AUC: 0.860) and pre-exercise TBI (AUC: 0.785), and post-exercise tcpO2 (AUC: 0.720) (p < 0.001). Post-exercise TBI gained the best discriminant score in PRIMA. CONCLUSIONS: Pre- and post-exercise non-invasive vascular tests could reveal severe limb ischemia. Toe pressure measurement and TBI should become a basic part of the vascular workup.

Platelet Aggregometry Testing: Molecular Mechanisms, Techniques and Clinical Implications.

Platelets play a fundamental role in normal hemostasis, while their inherited or acquired dysfunctions are involved in a variety of bleeding disorders or thrombotic events. Several laboratory methodologies or point-of-care testing methods are currently available for clinical and experimental settings. These methods describe different aspects of platelet function based on platelet aggregation, platelet adhesion, the viscoelastic properties during clot formation, the evaluation of thromboxane metabolism or certain flow cytometry techniques. Platelet aggregometry is applied in different clinical settings as monitoring response to antiplatelet therapies, the assessment of perioperative bleeding risk, the diagnosis of inherited bleeding disorders or in transfusion medicine. The rationale for platelet function-driven antiplatelet therapy was based on the result of several studies on patients undergoing percutaneous coronary intervention (PCI), where an association between high platelet reactivity despite P2Y12 inhibition and ischemic events as stent thrombosis or cardiovascular death was found. However, recent large scale randomized, controlled trials have consistently failed to demonstrate a benefit of personalised antiplatelet therapy based on platelet function testing.

Altered microrheological parameters in Raynaud's phenomenon.

Raynaud's phenomenon is an episodic, painful attack of the acral parts caused by local diminished blood supply. The aim of our study was to examine hemorheological parameters, cold agglutinins, cryoglobulins and their relationship in patients suffering from Raynaud's phenomenon.Blood was taken from 74 patients (mean age: 48 years, female/male: 56/18). Cold agglutinins and cryoglobulins were determined. Hemorheological parameters were also measured such as hematocrit, plasma and whole blood viscosity, red blood cell aggregation and deformability. Results were compared to a group of 58 healthy controls (mean age: 31.5 years, female/male: 24/34).Cold agglutinins were positive in 70%, cryoglobulins in 43% of patients. When compared to healthy controls, increased red blood cell aggregation (64.54  ±  8.93 vs. 61.11  ±  7.05) and decreased red blood cell deformability (0.669  ±  0.002 vs. 0.681  ±  0.001) was observed in Raynaud's patients (p < 0.05), but there were no differences in hematocrit (43.27% ± 3.85 vs. 44.10% ± 3.70), plasma (1.27 mPas ± 0.08 vs. 1.24 mPas ± 0.09) and whole blood viscosity (4.12 mPas ± 0.52 vs. 4.26 mPas ± 0.46). No differences were found between the hemorheological profile of cold agglutinin/cryoglobulin positive and negative patients. Also primary and secondary Raynaud's patients had similar rheological profile.Erythrocyte aggregation and deformability seems to be unfavorable in Raynaud's patients that can play a role in the disturbance of the microcirculation.

Comparison of hemorheological changes in patients after acute coronary events, intervention and ambulatory rehabilitation.

During the past decades, our group have investigated the hemorheological parameters (HPs) of more than 1,000 patients with various forms of ischemic heart disease (IHD). Our data indicate that HPs are altered in patients with IHD and the extent of the alterations is in good correlation with the clinical severity of the disease. Our findings have also proven that HPs play a critical role in the pathogenesis of myocardial ischemia.The lack of regular exercise is an important cardiovascular risk factor. Regular physical activity - as part of the cardiovascular rehabilitation training program (CRP) - is recommended for the treatment of IHD and the prevention of first or further cardiovascular events. To estimate the beneficial hemorheological effects of CRP, compared to patients after a coronary event or intervention and not participating in CRP, the data of four of our prospective studies (three non-CRP and one CRP-participating) were evaluated.Hematocrit (Hct), plasma and whole blood viscosity (WBV), Hct/WBV ratio significantly (p < 0.05) increased in the non-CRP groups during the 6-12 months follow-up, while in the CRP group they significantly decreased (p < 0.05). Red blood cell aggregation decreased in a much greater manner in the CRP group.Our results indicate that CRP has beneficial hemorheological effects and is able to reverse the deterioration of HPs after coronary events or intervention.

Gender differences in hemorheological parameters and in in vitro platelet aggregation in acetylsalicylic acid and clopidogrel treated vascular patients.

BACKGROUND: Sex-specific response to antiplatelet medications have been reported in several previous studies. OBJECTIVE: We investigated a possible connection between gender differences in hemorheological parameters and in vitro platelet aggregation in vascular patients treated with widely used antiplatelet agents. METHODS: In vitro platelet aggregation was assessed in 2687 patients treated with 100 mg acetylsalicylic acid (ASA), 1047 patients treated with 75 mg clopidogrel and 311 patients on dual antiplatelet therapy (100 mg aspirin and 75 mg clopidogrel) according to the method of Born. In subgroups of patients fibrinogen concentration, whole blood and plasma viscosity, red blood cell aggregation and hematocrit were simultaneously measured. The subjects were divided into groups according to their gender. RESULTS: ADP induced platelet aggregation was significantly higher in women in the case of ASA treatment (p<0.001). No gender differences could be observed in platelet function in patients treated with clopidogrel or on dual antiplatelet therapy. Hematocrit and whole blood viscosity were significantly higher in men in all groups (p<0.001), while no significant gender differences were observed in red blood cell aggregation indices in either group. Fibrinogen concentration was significantly higher in women than in men among patients treated with 100 mg ASA (p<0.05), but not in the other groups. CONCLUSIONS: Significantly higher fibrinogen concentration found in aspirin treated women than men may play a role in higher ADP induced platelet aggregation. Gender differences in response to monotherapy suggest that benefits from combination therapy may be greater in females. The clinical relevance of higher ADP induced platelet aggregation in women treated with ASA needs further investigation.

[Vinpocetin in neurological diseases]. / Vinpocetin alkalmazása neurológiai kórképekben.

INTRODUCTION: Stroke is the third leading cause of death worldwide (following cardiovascular and cancer mortality) and associated with serious disability for the vast majority of patients. There is no salvage therapy for irreversibly damaged brain areas, improving the circulation of the surrounding hypoperfused areas may be associated with beneficial clinical effects. Cerebral hypoperfusion may play a role in the pathogenesis of other kind of neurological diseases, improvement of global circulation may have a preventive effect on these conditions. AIMS: The aim of our study was to review the experimental and clinical articles focusing on the role of vinpocetin in different neurological conditions. RESULTS: Vinpocetin appears to have several different mechanisms of action that allow for its antiinflammatory, antioxidant, vasodilating, antiepileptic and neuroprotective activities in experimental conditions. On the other hand, several meta-analysis of the existing studies in acute stroke examining short and long term fatality rates with vinpocetin was unable to assess efficacy. In chronic cerebrovascular patients, vinpocetin improves impaired hemorheologic variables, has significant vasodilating properties, improves endothelial dysfunction, neuroimaging studies showed selective increase in cerebral blood flow and cerebral metabolic rate, all of which are potentially beneficial in cerebrovascular disease and may improve cognitive functions. SUMMARY: Based on the above mentioned results, vinpocetin plays an important role both in basic research and in clinical management of different neurological diseases.

Thrombosis preventive potential of chicory coffee consumption: a clinical study.

The protective effects of plant polyphenol intake on cardiovascular morbidity and mortality are widely acknowledged. Caffeine-free chicory coffee is a rich source of plant phenolics, including caffeic acid, which inhibits in vitro platelet aggregation, and also phenylpyruvate tautomerase enzymatic activity of the proinflammatory cytokine, macrophage migration inhibitory factor (MIF). To assess whether chicory coffee consumption might confer cardiovascular benefits a clinical intervention study was performed with 27 healthy volunteers, who consumed 300 mL chicory coffee every day for 1 week. The dietary intervention produced variable effects on platelet aggregation, depending on the inducer used for the aggregation test. Whole blood and plasma viscosity were both significantly decreased, along with serum MIF levels, after 1 week of chicory coffee consumption. Moreover, significant improvements were seen in red blood cell deformability. No changes in hematocrit, fibrinogen level or red blood cell counts were detected. The full spectrum of these effects is unlikely to be attributable to a single compound present in chicory coffee, nevertheless, the phenolics, including caffeic acid, are expected to play a substantial role. In conclusion, our study offers an encouraging starting-point to delineate the antithrombotic and antiinflammatory effects of phenolic compounds found in chicory coffee.

Clinical importance of aspirin and clopidogrel resistance.

Aspirin and clopidogrel are important components of medical therapy for patients with acute coronary syndromes, for those who received coronary artery stents and in the secondary prevention of ischaemic stroke. Despite their use, a significant number of patients experience recurrent adverse ischaemic events. Interindividual variability of platelet aggregation in response to these antiplatelet agents may be an explanation for some of these recurrent events, and small trials have linked "aspirin and/or clopidogrel resistance", as measured by platelet function tests, to adverse events. We systematically reviewed all available evidence on the prevalence of aspirin/clopidogrel resistance, their possible risk factors and their association with clinical outcomes. We also identified articles showing possible treatments. After analyzing the data on different laboratory methods, we found that aspirin/clopidogrel resistance seems to be associated with poor clinical outcomes and there is currently no standardized or widely accepted definition of clopidogrel resistance. Therefore, we conclude that specific treatment recommendations are not established for patients who exhibit high platelet reactivity during aspirin/clopidogrel therapy or who have poor platelet inhibition by clopidogrel.

Effect of parenteral or oral vinpocetine on the hemorheological parameters of patients with chronic cerebrovascular diseases.

INTRODUCTION: Hemorheological factors play an important role in the pathomechanism of ischemic cerebrovascular disorders. Abnormal rheological conditions in patients with chronic cerebrovascular disease predispose for recurrent strokes. Vinpocetine (VP), a synthetic ethyl esther of apovincamine, has successfully been used in the treatment of cerebrovascular diseases, in part because of its favourable rheological effects. PATIENTS AND METHODS: The study investigates the hemorheological changes in 40 patients in the chronic stage of ischemic cardiovascular disease after administration of vinpocetine. All patients received a high dose of intravenous VP in doses gradually increased to l mg/kg/day. In addition, 20 patients (mean age: 61+/-8 years) received 30 mg VP orally for 3 months. The other 20 patients (mean age: 59+/-6 years), who received placebo tablets, served as controls. Hemorheological parameters (hematocrit, plasma fibrinogen, whole blood viscosity, red blood cell aggregation and deformability) were evaluated at 1 and 3 months. RESULTS: The high-dose parenteral VP significantly decreased red blood cell aggregation, plasma and whole blood viscosity (p < 0.05) compared to the initial values. In patients with additional oral treatment, plasma and whole blood viscosities were significantly lower compared to the placebo patients at 3 months (p < 0.05). CONCLUSION: Our results confirmed the beneficial rheological effects of high-dose parenteral VP (partially caused by hemodilution) observed previously, and also warrant its long-term oral admission to maintain the beneficial rheological changes.

Plasma viscosity: a forgotten variable.

Evaluation of plasma viscosity has been underutilized in the clinical practice. Plasma viscosity is determined by water-content and macromolecular components. Plasma is a highly concentrated protein solution, therefore weak protein-protein interactions can play a role that is not characterized by electrophoresis. The effect of a protein on plasma viscosity depends on its molecular weight and structure. The less spheroid shape, the higher molecular weight, the higher aggregating capacity, and the higher temperature or pH sensitivity a protein has, the higher plasma viscosity results. Plasma is a Newtonian fluid, its viscosity does not depend on flow characteristics, therefore it is simple to measure, especially in capillary viscosimeters. Its normal value is 1.10-1.30 mPa s at 37 degrees C and independent of age and gender. The measurement has high stability and accuracy, thus little alterations may be pathologically important. Inflammations, tissue injuries resulting in plasma protein changes can increase its value with high sensitivity, though low specificity. It can increase in parallel with erythrocyte sedimentation rate (ESR), but it is not influenced by hematocrit (anemia, polycytemia), or time to analysis. Based on these favorable features, in 1942 plasma viscosity was recommended to substitute ESR. In hyperviscosity syndromes plasma viscosity is better in follow-up than ESR. In rheumatoid arthritis, its sensitivity and specificity are better than that of ESR or C-reactive protein. Plasma fibrinogen concentration and plasma viscosity are elevated in unstable angina pectoris and stroke and their higher values are associated with higher rate of major adverse clinical events. Elevation of plasma viscosity correlates to the progression of coronary and peripheral artery diseases. In conclusion, plasma viscosity should be measured routinely in medical practice.