Peter Kenyeres

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.

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

Background and objectiveRecent 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.Methods599 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.ResultsCompared 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 β-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 reducíase 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).ConclusionsThe 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 β-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.

Erythrocyte transport efficacy of human blood: a rheological point of view

Background  Large‐scale epidemiological studies have demonstrated that both anaemia and polycytaemia are independent cardiovascular risk factors. This was substantiated by the Framingham study, which demonstrated a U‐shaped relation between haemoglobin concentration and mortality. It was previously noted that delineating the corresponding haematocrit/blood viscosity ratios in the function of haematocrit provided a distribution of an inverted U‐shaped curve. The peak appeared physiologically important because it denotes a healthy balance between a relatively high oxygen binding capacity and a moderately low blood viscosity. It was the aim of this study to examine the mathematical relationship between the haematocrit and haematocrit/blood viscosity ratio.

Clinical importance of antiplatelet drugs in cardiovascular diseases

Platelets play an important role both in normal hemostasis and in pathological thrombus formation. Several large-scale clinical studies have proved that the inhibition of platelet aggregation results in a significant decrease in mortality and morbidity of ischemic atherothrombotic events, thus antiplatelet therapy became a key pharmacological method in prevention and treatment of such cardiovascular, cerebrovascular and peripheral arterial diseases. The present paper aims to give a brief overview of the most important antiplatelet drugs, their mechanism of action and their recommended usage in cardiovascular diseases. We also discuss possible methods to monitor the effectiveness of therapy and possible causes of therapeutic failure.

Sedimentation characteristics of leucocytes can predict bacteraemia in critical care patients

Background: Early detection of blood stream infection can be lifesaving, but the results of blood cultures are not usually available before 24 hours after blood sampling. An earlier indication would lead to the initiation of immediate and adequate antibiotic treatment with obvious advantages for the patient. Objective: To evaluate the ability of leucocyte count, serum procalcitonin (PCT) concentration, erythrocyte sedimentation rate (ESR), and leucocyte antisedimentation rate (LAR) in predicting the blood culture results in critical care patients. Methods: 39 consecutive patients with their first febrile episode were investigated prospectively. LAR was determined as the percentage of leucocytes crossing the midline of a blood column upward during one hour of gravity sedimentation. The relevance of the different variables was estimated by likelihood ratio tests and area under receiver operating characteristic curves (AUC). Results: 23 patients had positive blood culture results and 16 negative. LAR was significantly higher in bacteraemic patients than in non-bacteraemic patients (p = 0.001), but leucocyte count, ESR and PCT level failed to show significant differences. Leucocyte count, PCT, and ESR yielded low discriminative values with the AUCs of 0.66, 0.64, and 0.52, respectively. LAR provided a likelihood ratio of 3.6 and an AUC of 0.80 (95% confidence interval, 0.64 to 0.95) (p = 0.002). Conclusions: The simple LAR test can predict blood culture results and support urgent treatment decisions in critical care patients in their first febrile episode.

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. Copyright

Serum procalcitonin level and leukocyte antisedimentation rate as early predictors of respiratory dysfunction after oesophageal tumour resection.

IntroductionPostoperative care after oesophageal tumour resection holds a high risk of respiratory complications. We therefore aimed to determine the value of systemic inflammatory markers in predicting arterial hypoxaemia as the earliest sign of developing lung injury after oesophageal tumour resection.MethodsIn a prospective observational study, 33 consecutive patients were observed for three days (T1–T3) after admission (T0) to an intensive care unit following oesophageal tumour resection. The daily highest values of the heart rate, axillary temperature, leukocyte count and PaCO2 were recorded. Serum C-reactive protein and procalcitonin concentrations and the leukocyte antisedimentation rate (LAR) were determined at T1 and T2. Respiratory function was monitored 6-hourly measurement of the PaO2/FIO2 ratio, and the lowest value was recorded at T3. Patients were categorised as normoxaemic or hypoxaemic using the cutoff value of 300 mmHg for PaO2/FIO2.ResultsSeventeen out of 33 patients were classified as hypoxaemic and 16 patients as normoxaemic at T3. Increases of temperature at T0 and of the procalcitonin and LAR values at T2 were predictive of hypoxaemia at T3 (P < 0.05, P < 0.01 and P < 0.001, respectively). The area under the receiver-operating characteristic curve was 0.65 for the temperature at T0, which was significantly lower than that for the procalcitonin level at T2 (0.83; 95% confidence interval, 0.69–0.97; P < 0.01) and that for LAR at T2 (0.89; 95% confidence interval, 0.77–1.00; P < 0.001).ConclusionThese results suggest that an elevated LAR (>15%) and an elevated procalcitonin concentration (>2.5 ng/ml) measured on the second postoperative day can predict next-day arterial hypoxaemia (PaO2/FIO2 < 300 mmHg) after oesophageal tumour resection.

Moderate red wine consumption improves hemorheological parameters in healthy volunteers

Pieces of epidemiological evidence have supported that moderate red wine consumption reduces the risk of cardiovascular diseases (French-paradox). Our previous in vitro experiment has demonstrated favourable hemorheological effects of red wine, alcohol-free red wine extract and ethanol. Thirty-nine healthy, non-smoking male volunteers between 18-40 years were assigned into two groups: control group had drunk water, while red wine group had consumed 2 dl of red wine each day at dinner for 3 weeks. No alcohol had been drunk for one week prior to the study. Blood was obtained in the morning of the first and last day. Hematocrit (Hct), plasma (PV) and whole blood viscosity (WBV) (Hevimet 40 capillary viscometer), red blood cell (RBC) aggregation (Myrenne and LORCA aggregometer) and deformability (LORCA ektacytometer) were measured and Hct/WBV ratio was calculated to determine oxygen carrying capacity. Hct was adjusted to 40%. Hct and PV were not affected. WBV remained unchanged in controls, but it considerably decreased in the red wine group compared to the 3-week control group, while Hct/WBV ratio became significantly higher in the red wine group compared to the control (p < 0.05). RBC aggregation significantly decreased in the red wine group and became significantly lower compared to the 3-week controls (p < 0.05). Red wine significantly increased RBC deformability (p < 0.05) at high shear stress. Our results show that moderate red wine consumption has beneficial effects on hemorheological parameters which may contribute to the French-paradox.

The role of hemorheological factors in cardiovascular medicine

Cardiovascular diseases (CVD) are the most frequent cause of death throughout the world. The coronary vessel system is a special part of the circulation since there is a continuous change in blood flow, perfusion pressure and shear rate during each cardiac cycle. It is also the place of the narrowest capillaries in the human body, therefore the role of rheological alterations may be of greater importance than in the other parts of the circulatory system. During the past decades, our group has investigated hemorheological parameters (HP) in over 1,000 patients diagnosed with various forms of ischemic heart disease (IHD). In one prospective study, we measured the HP of patients with acute coronary syndrome (ACS). On admission, all examined variables were significantly worse than those of control subjects. During the hospital phase, some of the HP showed further deterioration, and HP remained in the pathologic range during the follow-up period. In another study, we showed that HP are in close correlation with the severity of coronary artery disease. In patients treated with percutaneous coronary intervention, changes in HP were very similar to those observed in subjects with ACS. In a recent study, we analyzed HP in patients undergoing CABG surgery. Our data suggest a hemorheological advantage of off-pump surgery. In another study low Hct/WBV ratio can be regarded as a risk factor of cardiac death in IHD. Our data indicate that rheological parameters are significantly altered in patients with IHD: the extent of the alterations is in excellent correlation with the clinical severity of the disease. Our findings prove that HP play a critical role in the pathogenesis of myocardial ischemia. In recent in vitro and in vivo studies we have investigated the effects of red wine on hemorheological parameters. Our results show that moderate red wine consumption has beneficial effects on hemorheological parameters which may contribute to the French paradox.

In vitro hemorheological effects of red wine and alcohol-free red wine extract.

The French paradox is based on epidemiological evidence which supports that moderate red wine consumption reduces the risk of cardiovascular diseases. A number of experimental animal studies reported favourable cardiovascular effects of alcohol-free red wine extract (AFRW). Our study was designed to determine red wine and AFRW induced changes in various hemorheological parameters. These effects may play a role in the pathophysiology of the French paradox regarding the cardiovascular protective impacts of red wine. Blood samples of healthy volunteers were mixed with red wine to achieve alcohol concentrations of 1 per thousand, 3 per thousand and 10 per thousand, respectively, with equivalent amount of AFRW or physiological saline. Blood samples were pretreated with red wine or AFRW in order to prove the protective effects on erythrocytes from impairment of deformability caused by the free radical generator phenazine methosulfate (PMS). Erythrocyte aggregation (Myrenne and LORCA), deformability (LORCA) and platelet aggregation (Carat TX4) were measured. Erythrocyte aggregation using Myrenne aggregometer was inhibited by red wine and AFRW compared to the saline treated samples. The difference reached already significance at 1 per thousand concentration at the AFRW samples (p < 0.05). Furthermore, red wine caused stronger inhibition than AFRW. The difference between the two agents became significant at 10 per thousand concentration (p < 0.05). LORCA aggregation index and threshold shear rate supported these results at the highest concentration. Erythrocyte deformability of healthy volunteers did not change significantly for any concentrations of red wine and AFRW. On the other hand AFRW at 3 per thousand concentration significantly prevented erythrocytes from impairment of deformability caused by PMS (p < 0.05). Platelet aggregation was significantly inhibited by the highest concentration of AFRW (p < 0.05). Our results show that red wine and AFRW have some beneficial effects on hemorheological parameters that may contribute to the French paradox.