Fibrinogen and silent atherosclerosis in subjects with cardiovascular risk factors.

Fibrinogen may play an active role in the development and progression of atherosclerotic plaques. We assessed the association between fibrinogen levels and atherosclerotic plaques over three different arterial sites in an asymptomatic never-treated male population with increased cardiovascular risk. We included 652 men aged 40 to 60 years old with at least one of the following cardiovascular risk factors: cholesterol > 6.2 mmol/L and/or systolic blood pressure > or = 160 mm Hg and/or diastolic blood pressure > or = 95 mm Hg, and/or because they smoked. Carotid and femoral arteries and the abdominal aorta were assessed by using ultrasonographic methods for the presence of plaque, and subjects were categorized according to the presence (or absence) and extent (one versus two or three sites) of plaque. Plasma fibrinogen was measured according to the thrombin-time method of Clauss. While the presence of atherosclerosis was significantly related to age, current smoking, systolic pressure, LDL cholesterol, and fibrinogen levels, the extent of atherosclerosis was related to age and triglyceride and fibrinogen levels. Multiple regression analysis indicated independent associations between fibrinogen and the presence and extent of atherosclerosis. Plaque prevalence was significantly more pronounced with increasing tertile of fibrinogen levels. The odds ratio of the upper to lower fibrinogen tertiles for the presence of plaque was 1.6 (95% confidence interval, 1.4 to 1.8) and 1.4 (95% confidence interval, 1.2 to 1.7) for its extent. Adjustment for other risk factors slightly reduced the association between fibrinogen and atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Increasing erythrocyte aggregability with the progressive grades of chronic venous insufficiency: importance and mechanisms.

Erythrocyte aggregation (EA) has appeared as the most interesting parameter among rheological measurements in chronic venous insufficiency (CVI). We therefore conducted two different kinds of studies to provide further information about the distribution and mechanisms of EA in CVI. We first analysed EA values in 67 patients, classified according to 3 evolutive groups: 27 patients suffering only from subjective symptoms of venous disease (grade 1), 19 patients with varicosis and sapheno-femoral incompetence (grade 2), 21 patients with varicosis and trophic skin changes (grade 3). EA values were also measured in 22 healthy controls. Analysis of EA was performed for equal concentrations of fibrinogen and adjusted for age. EA was significantly higher in CVI. The aggregation index, related to the kinetics of aggregates formation, rose significantly even from grade 1 while compared to controls and rose further with the evolutive grades. The same trend was found with the partial dissociation threshold (i.e. red cells aggregates cohesion). As the measurements were performed at standardized hematocrit and the results expressed after fibrinogen levels adjustment, this suggests the involvement of other factors. We subsequently investigated whether red cells from CVI patients aggregate more than those of controls when suspended in the same medium. The results showed that a cellular factor is unlikely to be involved, and that an interaction between red cells and plasma proteins other than fibrinogen could also explain the increased EA in CVI.

Role of blood pressure, uric acid, and hemorheological parameters on plasma homocyst(e)ine concentration.

Elevated concentration of plasma homocyst(e)ine is an independent risk factor for clinical atherosclerosis. In this study, the concentration of plasma homocyst(e)ine in men who lacked a history of atherosclerotic disease was correlated with hemodynamic, rheological and biochemical parameters. Hypertensive subjects had higher concentrations of plasma homocyst(e)ine than normotensive subjects. Positive correlations were found between concentrations of plasma homocyst(e)ine and several risk factors, but some of these correlations disappeared when they were adjusted for other variables. However, multivariate analyses demonstrated that systolic blood pressure, plasma uric acid, and hematocrit were predictors of concentrations of plasma homocyst(e)ine, after adjusting for certain risk factors. The possible significance of these interrelationships in atherogenesis require further study.

[Functional capacity of fibrinogen and erythrocyte aggregation in the diabetic]. / Capacité fonctionnelle du fibrinogène et agrégation érythrocytaire chez le diabétique.

The aim of this work is to study the possible influence of a qualitative modification of fibrinogen on its capacity of erythrocyte aggregation. Fibrinogens were isolated and then purified from blood sample of 15 insulin-dependent diabetics and of 7 healthy subjects. The erythrocyte aggregative effect of the purified fibrinogens was measured for various concentrations (0 g/1-5 g/l). The erythrocyte aggregation was determined by the ECHO CELL whose functioning principle is based upon ultrasonic interferometry. Results allow one to distinguish three kinds of fibrinogen: the first kind inducing a similar erythrocyte aggregation as that obtained by the fibrinogens from healthy subjects, the second kind inducing an erythrocyte hyperaggregation, the third kind inducing an erythrocyte hypoaggregation. Thus the possibility of a qualitative abnormality of fibrinogen, affecting its erythrocyte aggregative capacity in diabetic patients, could be suggested. This qualitative abnormality of fibrinogen might be due to a modification of its molecular structure because of an abnormal elevated glycation during diabetes.

[Measurement of immunologic agglutination of erythrocytes by ultrasonic interferometry]. / Mesure de l'agglutination immunologique des globules rouges par interférométrie ultrasonore.

Ultrasound interferometry is a new methodology which has been developed in our laboratories in order to measure precisely and quickly the size of particles sedimenting in liquid on horizontal surface, upon gravity. Applied to red blood cells, this method evaluates the sedimentation of erythrocytes, their aggregation induced by proteins or aggregating compounds as well as their agglutination upon immune reactions. The quantitative assessment of red cell agglutination was applied to the study of blood groups and to the search for red cell antibodies. Preliminary results show that ultrasound interferometry is 1) quantitative, measuring the size of agglutinates; 2) sensitive; 3) specific; 4) fast; 5) able to detect irregular antibodies.

[Quality control in clinical hemorheology: preliminary study by three centers]. / Contrôle de qualité en hémorhéologie clinique: étude préliminaire sur trois centres.

Clinical or pharmacological trials require reproducible laboratory tests. The aim of this work was to investigate the conditions of quality control of two laboratory tests, blood viscosity and red cell aggregation used for hemorheology trials in three centers. The results showed that viscosity measurements require 2 standards. For red cell aggregation, the control suspension standardized media (normal an pathological aggregation) showed a good intercentre reproducibility of the dissociation thresholds but a wide variability of aggregation times. Complementary studies in 5 or 6 centres are planned in order to define national standards of quality control.

Improvement of microcirculation abnormalities in sickle cell patients upon buflomedil treatment.

The efficacy of the vasoactive compound buflomedil on previously described microcirculation abnormalities observed in sickle cell disease (SCD) was investigated using bulbar conjunctival angioscopy (BCA) and laser doppler flux metering. Eleven sickle cell disease patients at steady state were studied in a double-blind randomized parallel-versus-placebo study (5 patients were given placebo and 6 patients received 600 mg buflomedil per day for 21 days after a washout period of 15 days). The blood flux score measured by BCA improved, indicating reduced entrapment of sickle red blood cells. There was a striking improvement of reactive alterations of vasomotion in the buflomedil group, particularly in postocclusive reactive hyperemia; the half return time was also significantly reduced. These results encourage further studies with buflomedil to investigate long-term effects of this compound in SCD, potential prevention of acute vaso-occlusive events, and degenerative complications.

Hypercholesterolaemia alters arterial and blood factors related to atherosclerosis in hypertension.

To evaluate the influence of hypercholesterolaemia on arterial and blood factors related to cardiovascular disease in hypertension, 20 normocholesterolaemic and 31 hypercholesterolaemic hypertensive patients underwent determinations of whole blood filterability (WBF), plasma fibrinogen concentration (PF) and aortic pulse wave velocity (PWV). Both of the groups had similar age, body mass index, cumulative smoking dose and blood pressure. Hypercholesterolaemics had lower WBF (P less than 0.02), higher PF (P less than 0.02) and higher PWV (P less than 0.01) than normocholesterolaemics. In the whole population WBF correlated with age (P less than 0.005), mean blood pressure (P less than 0.01), total cholesterol (P less than 0.05) and plasma fibrinogen (P less than 0.01). However, in a multivariate analysis where age and pressure were controlled as variables, only the association between WBF and PF remained significant (P less than 0.001). Thus, the higher fibrinogen affects whole blood filterability in hypercholesterolaemic hypertensive patients. In the whole population PWV correlated positively with HDL cholesterol (P less than 0.01) and age (P less than 0.001) and the association with HDL cholesterol remained significant in a multivariate analysis (P less than 0.001) where age was controlled. The effect of ageing on arterial rigidity seems to be similar in both hypertensive groups as deduced from the identical regression slopes relating pulse wave velocity to age. So in hypertension with high cholesterol, arterial rigidity was increased without changes in arterial stiffening with age.