Human decay accelerating factor expressed on endothelial cells of transgenic pigs affects complement activation in an ex vivo liver perfusion model.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to W Koenig.
Explore the source record for details and available documents.
During the last decade, a variety of experimental, clinical and epidemiological data have been published, documenting an association between fibrinogen and atherosclerosis as well as with its most frequent clinical complications, myocardial infarction and stroke. Although the design of epidemiological studies was not strictly comparable, and studies were carried out in very different populations, with various methods of fibrinogen measurement, the results are remarkable consistent. Together with clinical and experimental data, they strongly suggest a causal role for fibrinogen in atherogenesis and in the pathophysiology of acute ischemic syndromes. Hence, fibrinogen should be determined in patients at high risk for cardiovascular complications. The clinical benefit of lowering fibrinogen in certain patient groups or alternatively, the inhibition of specific fibrinogen induced effects, should be studied in randomised trials.
This article provides an overview of recently accumulated evidence on the pathogenetic role of fibrinogen in various vascular beds; and tries to elucidate determinants for patients' susceptibility so that subgroups at particular risk of severe clinical complications can be characterized more accurately. Based on the considerably elevated risk of cardiovascular complications associated with increased levels of plasma fibrinogen, the potential value of lowering fibrinogen in the primary or secondary prevention of atherosclerotic disease is now recognized as an important topic for consideration. Recent progress in this field will also be reviewed.
Plasma viscosity is reported to be predictive of coronary heart disease (CHD) and stroke. To find out whether regional differences in CHD event rates correlate with differences in plasma viscosity, we compared plasma viscosity in a high-risk area for CHD (Glasgow Multinational Monitoring of Trends and Determinants in Cardiovascular Disease [MONICA] and Scottish Heart Health Study population surveys, 1985/86; n = 1166) and in a lower-risk area (MONICA Augsburg survey, 1984/85; n = 3258) in men and women aged 25-64 years. Mean plasma viscosity (37 degrees C) was 1.261 (SD 0.067) mPa s in Augsburg and 1.327 (0.093) mPa s in the west of Scotland for men, and 1.248 (0.066) mPa s and 1.318 (0.087) mPa s, respectively, for women. The unadjusted difference of the means between the west of Scotland and Augsburg was 0.066 (95% CI from weighted regression 0.058-0.073) mPa s for men and 0.070 (0.062-0.078) mPa s for women. Adjustment for age, smoking behaviour, total and high-density-lipoprotein cholesterol, systolic and diastolic blood pressure, and body-mass index had no effect on these differences. Age-standardised coronary event rates in 1985-87 were at least two times higher among men, and four times higher among women, in MONICA Glasgow than in MONICA Augsburg. This large geographical difference in plasma viscosity might partly explain the differences in CHD event rates between these populations. Further studies are needed on the determinants of plasma viscosity, and on its potential roles in atherosclerosis, thrombosis, and ischaemia.
The authors investigated 244 consecutive patients with suspected coronary artery disease by coronary angiography and quantitative left ventriculography to compare the Minnesota Q/QS code (MC) with clinical electrocardiographic (ECG) interpretation. Patients who were suspected to have wall motion abnormalities for reasons other than coronary artery disease for possible regional wall motion abnormalities were excluded. Out of 244 patients, 159 (65%) had wall motion abnormalities. The sensitivity for detecting wall motion abnormalities was 21% for MC 1.1 and 51% for MC 1.1-3, whereas clinical ECG interpretation showed a sensitivity of 73%. Specificity for MC 1.1 was 93% and for MC 1.1-3 it was 84%. Specificity of clinical ECG interpretation (84%) was comparable. Compared to the MC, clinical ECG interpretation showed a stronger association with left ventricular ejection fraction, number of segments with abnormal wall motion, and severity of wall motion abnormality. Anterior myocardial infarction presented more often with clinical ECG changes (71%) and with a Q/QS code (50%) than inferior myocardial infarction (61% and 41%, respectively). In summary, in contrast to clinical ECG criteria, the MC has high specificity at the expense of a low sensitivity.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Conventional risk factors predict only about 30-50% of incidental cases in cardiovascular diseases, which are still the leading cause of death in western societies. During the last decade, the importance of thrombosis as an essential mechanism in acute myocardial infarction (AMI) and stroke has been established. The introduction of thrombolysis has led to an impressive reduction in AMI case fatality and possibly also to a substantial amelioration of its prognosis. Evidence from experimental, clinical and epidemiological studies suggest, that several hemostatic and hemorheological factors (e.g., fibrinogen, Factor VII, plasma viscosity, hematocrit, red blood cell aggregation, total white cell count) might not only play an important role in the evolution of acute thrombotic events, but may also take part in the pathophysiology of atherosclerosis. An increasing number of studies reports altered hemostatic and hemorheological parameters to be associated with smoking, hyperlipoproteinemia, and high blood pressure, as well as with adverse dietary habits and other life-style factors. To date, their way of interaction with the atherosclerotic process is poorly understood. Hemorheological or hemostatic mechanisms that might promote thromboatherogenesis include the predisposition to thrombosis via a hypercoagulable state, the enhancement of atherosclerosis by fibrinogen and its metabolites, and finally the reduction of blood flow through various rheological effects (e.g., increase in plasma viscosity and red cell aggregation, or leukocyte activation). Future research should focus in more detail on the interrelationship between accepted risk factors and the hemostatic system as well as hemorheological parameters. Deeper insight into the mechanisms involved might lead to new preventive strategies as well as to therapeutic procedures in the management of atherosclerosis and associated thrombotic events.
BACKGROUND: Recent studies have suggested that several hemostatic factors, leukocyte count, and plasma viscosity are predictive of coronary heart disease. Detailed analyses on lifestyle correlates, in particular plasma lipids and lipoproteins, of determinants of blood rheology have not been reported from epidemiological studies. METHODS AND RESULTS: We studied the relation between determinants of blood rheology and components of lipoproteins in a large sample of a population aged 25-64 years. The rheological parameters investigated were plasma viscosity, hemoglobin, and total serum protein; the lipoprotein variables included total cholesterol, high density lipoprotein (HDL) cholesterol, and the apoproteins A-I, A-II, and B. Covariables considered for possible confounding effects were age, body mass index, smoking behavior, alcohol consumption, and hypertension. Plasma viscosity was found to have a positive linear association with total cholesterol and apoprotein B (partial correlations after adjustment for all covariables including total serum protein for men and women were r = 0.23/0.19 and 0.24/0.25, respectively) and a small negative linear association with HDL cholesterol (r = -0.14/-0.10) and with apoprotein A-I (r = -0.08/-0.06). Polynomial regression showed a strong quadratic relation with HDL cholesterol in men, whereas no other variable revealed an appreciable deviation from linearity. The covariables had only a small, if any, confounding effect. Total serum protein, after control for the covariables, appeared to be associated only with total cholesterol. No association was found with hemoglobin. CONCLUSIONS: We conclude that rheological mechanisms may be involved in the pathogenesis of ischemic syndromes in hyperlipidemias. However, the finding that in particular men with very low HDL cholesterol exhibit increased plasma viscosity cannot be explained in pure rheological terms but may be, at least in part, the result of concomitant hypertriglyceridemia. This was not assessed in this study.
Explore the source record for details and available documents.
The authors describe a thirty-eight-year-old woman with familial hypercholesterolemia treated by dextran sulfate cellulose adsorption apheresis. This technique and the selective extracorporeal LDL cholesterol elimination by immunoabsorption or heparin-induced precipitation not only dramatically decrease blood lipids but also result in a marked improvement in the rheologic profile. It is suggested that the amelioration of blood rheology by LDL apheresis may represent the cause for the early clinical improvement felt by most patients with severe coronary heart disease and hypercholesterolemia.
As part of a randomized, single-blind, comparative study evaluating the efficacy of lovastatin and bezafibrate retard in the treatment of primary hypercholesterolemia, hemorheologic parameters (whole blood viscosity, hematocrit, plasma viscosity, red blood cell aggregation and deformability, and fibrinogen) were studied in 35 patients. Whole blood viscosity and plasma viscosity improved significantly after 3 months of treatment with lovastatin, whereas other hemorheologic variables remained unchanged. Stratifying 24 patients by their lipoprotein Lp(a) levels showed that in those with low Lp(a) (less than or equal to 25 mg/dL) high-density lipoprotein cholesterol increased and red blood cell aggregation as well as deformability decreased considerably, whereas in the group with high Lp(a) levels (greater than 25 mg/dL), the opposite behavior was observed. Treatment of primary hypercholesterolemia with lovastatin may not only reduce the risk for atherosclerotic complications by its pronounced decrease of low-density lipoprotein cholesterol, but also may favorably alter blood rheology, and may decrease insudation of plasmatic components into the arterial wall and improve tissue perfusion, in particular on the microcirculatory level. The possible relevance of Lp(a) levels for the hemorheologic effects of lovastatin remains to be elucidated.
The efficacy of extended release felodipine 10 mg (ER) o.d., a new dihydropyridine calcium antagonist, and 25 mg hydrochlorothiazide (HCTZ) o.d. have been compared in a randomized, double-blind, crossover trial in 28 mildly to moderately hypertensive subjects (supine diastolic blood pressure, BP, greater than or equal to 95 mm Hg and less than or equal to 110 mm Hg on three separate occasions). Both drugs significantly reduced systolic and diastolic BP in the sitting position felodipine from 157.1/93.8 mm Hg at baseline to 133/78.9 mm Hg 2.5 h after medication and to 138/82.7 mm Hg after 2 weeks of treatment, and HCTZ from 156/95.6 mm Hg to 147/88.4 mm Hg 2.5 h after medication and to 149/89.5 mm Hg also after 2 weeks. A decrease of the same magnitude in standing systolic and diastolic BP was observed after both treatment regimens with the exception of diastolic BP 2.5 h after dosing with HCTZ, which was not significantly lower. At all times (2.5 h and 2 weeks), the reduction in systolic and diastolic BP was greater after felodipine compared to HCTZ. Heart rate was significantly increased after felodipine in both the sitting and standing positions, and both 2.5 h following medication and after 2 weeks of treatment. The difference between the regimens was significant only 2.5 h after dosing. Overall, felodipine 10 mg ER o.d. was superior to 25 mg HCTZ o.d. in lowering BP.
The relationship between determinants of blood viscosity and blood pressure (BP) variables was studied in a large sample of a population aged 25 to 64 years. Plasma viscosity, hemoglobin, and total serum protein were examined. Systolic and diastolic BP and the prevalence of hypertension showed a crude positive association with plasma viscosity levels in both sexes. Age, body mass index, and total serum protein appeared to have a confounding effect on this relationship, whereas hemoglobin, smoking behavior, and alcohol consumption did not. A crude positive association was also found between total serum protein levels and the prevalence of hypertension in men and women; however, since total serum protein was treated as a covariable, no further analyses were carried out. In contrast to findings reported in the literature, hemoglobin levels were not correlated with BP variables in either sex. After adjusting for all confounders, a significant main effect of plasma viscosity still was found. However, the magnitude of the effect was not as large as for body mass index, a well-established risk variable for hypertension. These results indicate that BP is positively associated with plasma viscosity. Whether increased plasma viscosity in hypertension constitutes a primary or a secondary phenomenon remains to be answered. Since plasma viscosity is significantly associated with hypertension but any BP variable, increased levels of plasma proteins (particularly fibrinogen as the main determinant of plasma viscosity) may represent the cause for elevated plasma viscosity. This might contribute to persistently increased resistance to blood flow on the microcirculatory level in arterial hypertension.
The neurohumoral responses after 10 mg of felodipine extended release (ER), a new dihydropyridine calcium antagonist, and 25 mg of hydrochlorothiazide (HCTZ) were compared in a randomized, double-blind, crossover trial in 28 mild to moderate hypertensives. Antihypertensive drugs were gradually discontinued. Felodipine ER, 10 mg was given once daily for 2 weeks; after another washout period of 1 week, patients were switched to 25 mg of HCTZ once daily and vice versa. Blood pressure (BP) was measured at baseline, 2.5 h after medication, and after 2 weeks of treatment (24 h postdosing) using an oscillometric device. Felodipine ER and HCTZ both lowered BP effectively. However, felodipine ER was superior in reducing systolic and diastolic BP during the short term and medium term. Treatment with felodipine ER over 2 weeks increased sympathetic outflow as indicated by elevated plasma norepinephrine levels, whereas plasma epinephrine was mainly unaffected, as were plasma renin and aldosterone levels. On the other hand, 25 mg of HCTZ increased plasma renin and aldosterone, but left catecholamines unchanged. Despite persistent increased sympathetic activity, the reduction in BP in this study was more pronounced after felodipine ER as compared to HCTZ. The lack of a difference between heart rates under both medications after 2 weeks of treatment suggests a resetting of the baroreflex by felodipine ER and furthermore that the increased norepinephrine levels may not be clinically relevant, but demonstrate the maintained baroreflex activity. HCTZ, in doses as low as 25 mg, is still capable of stimulating the renin-angiotensin-aldosterone system.
Left ventricular function and wall thickness were evaluated in 111 type I diabetic subjects (mean age 25.5 +/- 9 years, mean duration of diabetes 13.4 +/- 6.2 years), using 2-D-derived M-mode echocardiography. Patients were carefully selected for the absence of major coronary risk factors or manifest cardiac disorders, and compared with 91 age- and sex-matched control subjects. Fractional shortening and the maximal velocity of cirumferential fibre shortening did not differ significantly between the two groups. Furthermore, no differences were found in the diastolic functional parameter of velocity of circumferential fibre extension. Posterior wall thickness was significantly increased in the diabetic patients compared to the controls (9.5 +/- 1.8 mm vs. 8.4 +/- 1.3 mm. P less than 0.01). As the thickness of the interventricular septum was also moderately increased (9.2 +/- 2.2 mm vs. 8.9 +/- 1.7 mm, NS), these findings provide evidence for an early structural change of the myocardium in young diabetic patients without clinically relevant functional consequences.
The haemorheological effects of felodipine extended release (ER), a new dihydropyridine calcium antagonist, were compared with hydrochlorothiazide (HCTZ) in 28 mild to moderate hypertensives (18 men and 10 women, aged 30-70 years) in a randomized, double-blind, crossover trial. Antihypertensive drugs were gradually discontinued. Felodipine Er, 10 mg, was given once daily for 2 weeks, and after another wash-out period of 1 week, patients were switched to 25 mg HCTZ, once daily, and vice versa. Whole blood viscosity (BV) at three different shear stresses, haematocrit (Hct), plasma viscosity (PV), red blood cell (RBC) aggregation, RBC deformability, and fibrinogen were measured under standardized conditions 2.5 h after medication, and after 2 week of treatment (24 h post-dosing). Felodipine ER improved BV acutely, but not during treatment over a 2-week period. By contrast, HCTZ did not affect BV, but decreased RBC deformability 2.5 h after medication intake. After 2 weeks of treatment, the negative effect on RBC deformability had increased slightly. Furthermore, fibrinogen and PV were significantly elevated at this stage. In summary, felodipine ER did not improve blood rheology over a 2-week treatment period in this study. HCTZ exhibited marginal but significant negative effects on fibrinogen, PV and indices of RBC deformability, but not on RBC aggregation.