Influence of lipids and obesity on haemorheological parameters in patients with deep vein thrombosis

It is not well established whether haemorheological alterations constitute independent risk factors for deep vein thrombosis (DVT). We have determined in 149 DVT patients and in 185 control subjects the body mass index (BMI), the haemorheological profile: blood viscosity (BV), plasma viscosity (PV), fibrinogen (Fg), erythrocyte aggregation (EA), erythrocyte deformability (ED) and plasma lipids. In the crude analysis BMI, Fg, PV, EA, triglycerides (TG) and ApoB were statistically higher and HDL cholesterol (HDL-Chol) statistically lower in DVT patients than in controls. No differences in BV and ED were observed. After BMI adjustment, Fg, PV and EA remained statistically higher in DVT cases than in controls (P = 0.013; P = 0.012; P = 0.013; P = 0.028, respectively). When the risk of DVT associated with these variables (using cut-offs that corresponded to the mean plus one SD of the control group) was estimated, EA > 8.2 and PV > 1.28 mPa . s were significantly associated with DVT even further adjustment for lipids and obesity (OR = 2.78, P = 0.004; OR = 1.91, P = 0.024, respectively). However, PV did not remain statistically significant after additional adjustment for Fg. When we consider together all the analyzed variables in order to control every variable for each other, TG > 175 mg/dl (OR = 3,2, P = 0.004) and BMI > 30 kg/m(2) (OR = 3.5, P = 0.003), were also independently associated with a greater risk of DVT. Our results suggest that increased EA constitute an independent risk factor for DVT. However, when associated to hyperlipidaemia and obesity it further increases thrombotic risk.     

Which factors affect high D-dimer levels in the elderly?

To study the age-related changes in plasma D-dimer levels and the effect of atherosclerotic disease and long-term immobilization on haemostasis the elderly, we measured plasma D-dimer levels in 148 subjects aged from 60 to 94 years using an ELISA. We also measured plasma fibrinogen, serum uric acid, total cholesterol, triglycerides, HDL cholesterol, beta-lipoprotein fractions, and apolipoproteins (A-I, A-II, B, E). Plasma D-dimer levels (326 +/- 148 ng/ml) were significantly higher in the healthy elderly subjects than in younger controls (180 +/- 58 ng/ml, p less than 0.01) and increased further with age (r = 0.344, p less than 0.01). D-dimer levels were significantly higher in elderly women than in elderly men (p less than 0.05). The D-dimer level correlated significantly with both the fibrinogen antigen level (r = 0.286, p less than 0.001) and the clotting activity (r = 0.275, p less than 0.01), and also correlated with apolipoprotein E levels. There were no correlations with the other parameters assessed. The D-dimer levels were significantly higher in the elderly subjects with atherosclerotic disease (516 +/- 285 ng/ml) than in healthy elderly subjects (p less than 0.001). Moreover, the levels were even higher in elderly subjects with long-term immobilization (866 +/- 408 ng/ml) than in subjects with atherosclerosis, even after age, sex and underlying diseases were taken into consideration. These results indicate that coagulation and fibrinolysis activity are increased in the elderly, especially those with atherosclerotic disease and that moreover long-term immobilization further accelerates their haemostatic hyperactivity.     

Sialic acid is an inflammation marker associated with a history of deep vein thrombosis

INTRODUCTION: Deep vein thrombosis (DVT) induces a systemic chronic inflammation and it has been associated with atherosclerosis. Increased levels of total sialic acid (TSA) have been shown to correlate with inflammation and atherosclerotic processes. The aim of this study was to investigate whether or not increased levels of TSA are associated with a history of DVT and with inflammation and coagulation markers, as well as with the lipid profile. MATERIALS AND METHODS: TSA, fibrinogen, C-reactive protein (CRP), fibrin D-dimer (D-dimer), prothrombin fragment 1+2 (F1+2), endogenous thrombin generation, cholesterol and triglycerides were measured in 68 patients who had suffered, in the previous 6-12 months, a first episode of idiopathic DVT, and in 68 age- and sex-matched healthy subjects. RESULTS: Levels of TSA, fibrinogen, CRP and D-dimer observed in patients were significantly higher than those detected in healthy subjects. TSA positively correlated with fibrinogen (R=0.47, p<0.01), cholesterol (R=0.46, p<0.01), triglycerides (R=0.38, p<0.01) and CRP (R=0.28, p<0.05). The logistic regression analysis confirmed that both high fibrinogen (> or =340 mg/dl) and cholesterol (> or =267 mg/dl) levels significantly and independently influence the TSA concentration. TSA levels above the 95th percentile of controls (>72 mg/dl) were detected in 33% of patients (OR=8.9; p<0.0001; 95% CI 2.4 to 31.7). CONCLUSIONS: Patients with a history of DVT had associated high levels of TSA. In these patients, TSA correlated to markers of inflammation activity and lipid profile. Thus, TSA appears to be a useful vascular inflammatory marker in idiopathic DVT.     

Predictive value of coagulation markers concerning clinical outcome 90 days after anterior myocardial infarction.

To study the predictive value of coagulation markers concerning clinical outcome, prothrombin fragment F1.2 (F1.2), fibrin monomer antigen (FM), D-Dimer (DD), and fibrinogen were measured in plasma samples drawn 2 and 7 days after acute myocardial infarction (AMI) in 314 consecutive patients randomized in a clinical trial of low molecular weight heparin (Dalteparin) (the FRAMI trial). Placebo-treated patients suffering death or new AMI within 90 days had significantly higher levels at day 2 of FM (Enzymun-Test FM), and DD (TINAquant D-dimer) (p = 0.001 and 0.02, respectively), but not F1.2 (Enzygnost F1.2 micro), relative to those without serious clinical events. At day 7 all three coagulation activation markers were significantly higher in patients with subsequent adverse clinical outcome. The Dalteparin group had significantly lower levels of these markers as compared to the placebo group. Left ventricular (LV) thrombus formation was not associated with changes in coagulation activation. However, patients with thrombus had significantly higher fibrinogen levels than those without thrombus (p = 0.004 day 2), independent of treatment group. Thus, markers of coagulation activation may be useful in stratification of patients when estimating risk for adverse clinical outcome after AMI. Furthermore, elevated fibrinogen levels are associated with increased risk of LV thrombus formation.     

"Ex vivo" influence of fatty acids from plasma cholesterol and triglycerides on the fatty acid pattern of platelets

We have studied "ex vivo", in 92 normal subjects, the influence of fatty acids (FA) that esterify plasma cholesterol and triglycerides on the fatty acid composition of phospholipids, triglycerides and free fatty acid fractions in platelets. High and significant correlations (p less than 0.001) were found for some of the platelet phospholipid FA and the same FA that esterify plasma cholesterol [18:1 (r = 0.56); 18:2 (r = 0.71) and 20:5 (r = 0.42)] and plasma triglycerides [18:1 (r = 0.57) and 18:2 (r = 0.66)]. Some significant correlations were also found between some of the platelet triglyceride FA and the same FA that esterify plasma phospholipids [18:1 (r = 0.58)], triglycerides [18:1 (r = 0.51), 18:2 (r = 0.52)] cholesterol [18:1 (r = 0.44)] and plasma free fatty acids [18:1 (r = 0.39); 18:2 (r = 0.40)]. By evaluating these results in conjunction with those of an earlier study, it can be concluded that "in vivo" the FA from different plasma lipid fractions and especially those esterifying the plasma cholesterol and phospholipid fractions, can influence the FA composition of platelet phospholipids in normal subjects. In trying to interpret the role played by plasma lipids in platelet lipids, it may be of interest to take into account the interrelationships found in this study.     

Expression of fibrinogen receptors in platelets of migraine patients--correlation with platelet GPIIb content and plasma cholesterol

Binding of fibrinogen to platelets washed from blood of migraine patients (n = 30) and control donors (n = 24) was compared. In addition, contents of platelet glycoprotein IIb and platelet fibrinogen were determined in both groups by radioimmunoassay. The receptor capacity for fibrinogen in platelets activated by ADP was significantly higher (p less than 0.01) in migraine patients (52,505 +/- 4,925) than in controls (33,881 +/- 3,965). The mean contents of GPIIb (3.51 +/- 0.34 micrograms/10(8) platelets) and fibrinogen (37.26 +/- 4.05 micrograms/10(8) platelets) in migraine platelets were also markedly increased (p less than 0.01 and p less than 0.001, respectively) when compared to controls (2.21 +/- 0.18 micrograms of GPIIb and 18.75 +/- 2.29 micrograms of fibrinogen per 10(8) platelets, respectively). There was a high correlation between the number of fibrinogen receptors exposed by ADP and the total amount of platelet GPIIb both in migraine patients (R = 0.69, p less than 0.01) and controls (R = 0.62 p less than 0.01), as well as plasma cholesterol in the case of migraine patients (R = 0.82, p less than 0.001).     

Independent association of fibrinogen with carotid intima-media thickness in asymptomatic subjects

BACKGROUND: Fibrinogen has been found to be an independent risk factor for cardiovascular disease. Both genetic and environmental factors contribute to its variability in plasma. However, whether the relation between fibrinogen and carotid intima-media thickness (IMT) is independent of those factors has not been established. Therefore, the aim of this study was to investigate the relations of plasma fibrinogens and the -455 G/A Bbeta-fibrinogen polymorphism with the carotid IMT in a series of asymptomatic subjects. METHODS: Markers of inflammation, C-reactive protein (CRP) and leukocytes, and endothelial perturbation (von Willebrand factor, vWF) were measured in 135 subjects. All individuals underwent a complete clinical examination and lipid measurements (cholesterol and its fractions HDL and LDL and triglycerides). The carotid IMT was measured by B-mode ultrasound in the common carotid artery. RESULTS: Patients in the highest fibrinogen tertile had a significantly higher BMI (p < 0.01), LDL-cholesterol (p < 0.01), leukocyte count, CRP and vWF (p < 0.001). In the univariate model a strong positive relationship was found between plasma fibrinogen and carotid IMT (p < 0.01). Fibrinogen also correlated positively with age, BMI, arterial systolic pressure, cholesterol, cholesterol-LDL, smoking, CRP and vWF (p < 0.01). In the multivariate analysis, the association of fibrinogen with carotid IMT remained significant (p < 0.01) after adjustment for all the parameters analyzed. CONCLUSION: In a population sample of adults without clinically overt atherosclerotic disease, elevated fibrinogen was related to carotid IMT independent of a wide range of important confounding variables.     

Elevated high molecular weight fibrinogen in plasma is predictive of coronary ischemic events after acute myocardial infarction

This study investigates the association between the concentration and function of plasma fibrinogen molecules measured at the time of hospital admission in patients with acute myocardial infarction (AMI), with reference to the risk of new coronary ischemic events during a three-day follow-up period of. Before starting fibrinolytic and anticoagulant treatment plasma fibrinogen, high molecular weight fibrinogen (HMW-fibrinogen), fibrin formation rate (FbFR) and phosphorous content in fibrinogen were determined in 90 AMI patients. During a three-day follow-up period 12 patients suffered new ischemic events. The 12 patients with coronary ischemia had higher concentrations of plasma fibrinogen (312+/-23 vs. 270+/-73 mg/dl, p<0.05) and HMW-fibrinogen (246+/-35 vs. 189+/-23 mg/dl, p<0.001) and a higher FbFR (65+/-30 vs. 40+/-25, p<0.001) than patients without these events. No association was found between the phosphorous content in fibrinogen and new coronary ischemic events. We conclude that after myocardial infarction an elevated plasma level of HMW-fibrinogen and a high FbFR value at the time of hospital admission are associated with new coronary ischemic events during a three-day follow-up period.     

Evidence of redox unbalance in post-acute ischemic stroke patients

Measurements of the redox balance after the ischemic stroke occurrence might be useful to monitor the outcome of patients who suffered an ischemic stroke in terms of stroke recurrence and other vascular events. For this purpose, fifteen patients (mean age 71.40±2.50 years) with a first-ever ischemic stroke were included in the study within 30 days of stroke onset. Stroke severity was evaluated according to the National Institutes of Health Stroke Scale (NIHSS). Redox balance was assessed by measuring plasma amount of total peroxidative by-products, nitrite/nitrate metabolites (NOx), as expression of nitric oxide (NO) plasma bioavailability, total plasma antioxidant capacity (TEAC), Cu/Zn Superoxide Dismutase (Cu/Zn SOD) activity, serum urate concentration and autoantibodies against ox-LDL (OLAB) serum level. Total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were also measured. Fifteen apparently healthy controls (mean age 70.28±2.03 years) were investigated to compare redox markers. Stroke patients had higher plasma values of total peroxidative by-products, NOx stable metabolites and of total cholesterol, triglycerides, and LDL-C than controls (P < 0.05). No differences in OLAB levels, Cu/Zn-SOD activity, serum urate concentration, and plasma HDL-C amount were found in stroke patients when compared to controls. Total plasma antioxidant capacity was lower in stroke patients than in controls. NOx values correlated positively with the NIHSS score in stroke patients (r=0.668; P=0.0065). The observed presence of redox unbalance in stroke patients could represent an early indicator of diffuse endothelial activation during which patients may be at increased risk of stroke recurrence and other vascular events.     

Evidence of prolonged disturbances in the haemostatic,hemorheologic and inflammatory profiles in transmural myocardial infarction survivors

Haemostatic, hemorheologic and inflammatory disturbances have been associated with acute coronary syndromes. Most knowledge is reported in cross sectional studies and are without time dependent evolution of these profiles. The aim of this study was to evaluate, during the first year, the evolution of the haemostatic, hemorheologic and inflammatory profiles determined at hospital discharge in survivors with transmural myocardial infarction (MI). Eighty eight (79 male; 9 female) mean age of 58 +/- 11 years, survivors of a transmural MI were prospectively studied at discharge, 6 months and one year after the event. Haemostatic (protein C, antithrombin III and plasminogen activator inhibitor 1), hemorheologic (blood fluidity and components) and inflammatory profiles (polymorphonuclear elastase and leukocyte count) were determined using standard methodology. The results of the study can be summarized as follows: (1) Protein C decreased (p < 0.05) over time while PAI-1 only varied significantly until 6(th) month. (2) Plasma viscosity and fibrinogen (p < 0.001) decrease over time, while erythrocyte aggregation (p < 0.001) and haematocrit increased. Whole blood viscosity did not vary. (3) Leukocyte decreased (p < 0.001) and elastase did not (4). Those patients with cardiovascular events (n = 7) had higher PAI-1 concentration (p < 0.05) and leukocyte count (p < 0.01), at discharge (5) Left ventricle ejection fraction correlated significantly with plasma viscosity (r = 0.35 p < 0.05). The results of this longitudinal study show dynamic modifications of the haemostatic, hemorheologic and inflammatory profiles during the first year of a transmural myocardial infarction. In addition, there are interrelations between them and the clinical profile that could help to explain the clinical evolution of this group of patients.     

Factor VII hyperactivity in acute myocardial thrombosis. A relation to the coagulation activation

It has been shown that coagulation factor VII (FVII) has an increased coagulant activity (FVIIc) in cardiovascular high risk patients and that it is a important risk factor for the development of ischaemic heart disease (IHD) and cardiovascular death. In this study, we measured FVII coagulant (FVIIc) and immunological (FVIIag) activities during the acute phase of unstable angina (UA) and acute uncomplicated and complicated myocardial infarction (AMI). We have also studied its changes in relation to thrombin formation and coagulation activation, as assessed by determination of thrombin-antithrombin circulating complexes (T-AT) at the same time. Our results show a marked increase in FVIIc in all patients, with highest significant levels in complicated AMI. In fact, this increase was also different between groups, complicated AMI showing a significant degree of increase in FVIIc in relation to UA and uncomplicated AMI. FVIIag did not vary between groups and controls, implicating a progressive activation of FVII. As expected, we found comparable levels of T-AT in UA and in AMI patients, suggesting that a common thrombotic process is involved in both situations. FVIIc was strongly correlated to T-AT in all patients (r = 0. 750; p less than 0.001) and also within groups. This study underlines the important positive contribution of FVIIc to IHD and to the prognosis of its thrombotic acute events, and shows that the increase in FVII activity is associated with an increase of a thrombotic marker (thrombin-antithrombin). Further studies are needed to evaluate if FVII activation is the cause or the consequence of the thrombotic processes.     

Gender differences in the expression of erythrocyte aggregation in relation to B beta-fibrinogen gene polymorphisms in apparently healthy individuals

An increased erythrocyte aggregation (EA) is associated with capillary slow flow, tissue hypoxemia and endothelial dysfunction. Fibrinogen is a major determinant in the formation of aggregated red blood cells. It has been suggested that the B beta-fibrinogen -455 G/A polymorphism is associated with erythrocyte hyperaggregability in men with coronary artery disease. The purpose of this study was to investigate the influence of the beta-fibrinogen -455 G/A polymorphism on erythrocyte aggregation in apparently healthy individuals. Plasma fibrinogen, red blood cell count, serum lipids, erythrocyte sedimentation rate, and the genotype of the B beta-fibrinogen -455 G/A polymorphism were examined in a cohort of 545 apparently healthy individuals and those with atherothrombotic risk factors. A whole blood erythrocyte aggregation test was performed by using a simple slide test and image analysis. In men, EA levels and plasma fibrinogen levels were significantly higher in subjects carrying the -455 A allele compared to subjects with the -455 GG genotype. This association did not exist in women carrying the fibrinogen -455 A allele. The -455 GA/AA men presented significantly higher correlation between the plasma fibrinogen concentrations and EA. This observation raises the prospect of possible change in the functional properties of the -455 GA/AA fibrinogen, enhancing its ability to induce EH. This study suggests that the B beta-fibrinogen -455 A allele is related to EH in men only. Putative mechanism could be hyperfibrinogenemia and a functional change in the fibrinogen molecule that alters its ability to interact with red blood cells and supports the aggregability of these cells.     

Hemo-rheologic disorders as risk factors of ischemic cerebral infarction]

The problem of blood rheological abnormalities as risk factors for ischaemic stroke is only incompletely known. The blood rhreological++ parameters were measured in 35 patients with ischaemic stroke (groups: CS--completed stroke, TIA/RIND--transient brain ischaemia or reversible ischaemic neurological deficit) in the first 48 hours after the onset of the disease and then, for control, after 2-3 weeks. Persistence of abnormal rheological parameters of blood was observed, with increased plasma viscosity, reduced plasticity of erythrocytes, higher fibrinogen level, and increased erythrocyte aggregation 2-3 weeks after the onset of acute ischaemic stroke, which suggests their role as possible risk factors. In the group with completed stroke a significant increase of erythrocyte aggregation was noted 2-3 weeks after disease onset which may be connected with increased absorption of fibrinogen molecules on erythrocyte cell membrane.     

γ'/total fibrinogen ratio is associated with short-term outcome in ischaemic stroke

Fibrinogen γ' (γ') is a natural isoform of fibrinogen, and alters the rate of formation and the properties of clots. It could therefore affect outcome after ischaemic stroke. The prognostic significance of γ' fibrinogen levels is, however, still unclear. It was the objective of this study to assess levels of γ' in ischaemic stroke, and its association with short-term outcome. We included 200 ischaemic stroke patients and 156 control persons. Total fibrinogen and γ' levels were measured; outcome at discharge was assessed by means of the modified Rankin Scale score (defined as unfavourable when >2). We compared levels between patients and controls using multiple linear regression analysis, and logistic regression analysis was used to assess the relationship between levels and outcome. All analyses were adjusted for age and sex. Mean γ' levels were significantly higher in patients with ischaemic stroke than in controls (0.37 vs. 0.32 g/l, p<0.001), and patients also had a higher γ'/total fibrinogen ratio (0.102 vs. 0.096, p=0.19). The γ'/total fibrinogen ratio is associated with unfavourable outcome in patients with ischaemic stroke (odds ratio per unit increase of γ'/total fibrinogen ratio 1.27, 95% confidence interval 1.09-1.47). Our study shows that patients with ischaemic stroke have increased levels of fibrinogen γ' and suggests a trend towards an increased γ'/total fibrinogen ratio in ischaemic stroke. Increased fibrinogen γ' relative to total fibrinogen levels are associated with unfavourable outcome in the early phase after stroke.     

Increased erythrocyte adhesiveness and aggregation in obstructive sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea (OSA) is associated with an increased incidence of stroke and myocardial infarction as well as increased prothrombotic and inflammatory processes. Although erythrocyte adhesiveness/aggregation is known to be elevated in cardiovascular diseases, it has never been evaluated in OSA. The aim of this study was to examine the possible association of OSA and erythrocyte adhesiveness/aggregation. METHODS: The study was conducted in the Sleep Laboratory of a tertiary university-affiliated medical center in 79 patients (age 57.1+/-12.9 years) with a diagnosis of OSA (apnea hypopnea index 41.2+/-25.9). Findings were compared with data on 1079 controls without clinical symptoms of OSA, matched for sex, age, and body mass index. Overnight polysomnography and blood sampling for erythrocyte sedimentation rate, levels of fibrinogen, high-sensitivity C-reactive protein, and erythrocyte adhesion/aggregation test consisting of measures of erythrocyte percentage and vacuum range on image analysis. RESULTS: The study group had significantly higher values than controls of all three markers of inflammation (p<0.001 for erythrocyte sedimentation rate and fibrinogen; p=0.037 for C-reactive protein). Erythrocyte percentage was significantly lower in the sleep apnea group (84.05+/-15.97 vs. 90.79+/-11.23%, p<0.001), and vacuum range was significantly higher (8.22+/-7.98 vs. 4.63+/-4.05 microm, p<0.001), indicating stronger erythrocyte adhesion/aggregation. Both these factors were significantly correlated with erythrocyte sedimentation rate and to hs-CRP (percentage: r=-0.630; 0.258, p=0.005; 0.031; vacuum range: r=0.494; -0.328, p=0.001; 0.005 respectively). CONCLUSION: OSA is associated with increased erythrocyte aggregation/adhesion, which is correlated with an increase in inflammation markers. These findings might help explain the increased cardiovascular morbidity in OSA.     

β-纤维蛋白原基因启动子区Hae Ⅲ多态性与缺血性脑血管病患者血浆纤维蛋白原浓度关系的研究

目的 研究中国汉族人群中β-纤维蛋白原基因启动子区HaeⅢ-455G／A多态性与血浆纤维蛋白原浓度和缺血性脑血管病的关系。方法 随机选取134名缺血性脑血管病患和166名对照人群，用PCR(聚合酶链式反应)和RFLP(限制性片段长度多态性)方法，分析受检的基因型，用Follin酚法测定血浆纤维蛋白原的浓度。结果 对照组中AA纯合子的血浆纤维蛋白原浓度(34lmg/dL)高于GA杂合子(298mg/dL)和GG纯合子(298mg／dL）的血浆纤维蛋白原浓度，缺血性脑血管病患组中AA纯合子的血浆纤维蛋白原浓度(353mg/dL)高于GA杂合子(287mg/dL)和GG纯合子(302mg/dL)的血浆纤维蛋白原浓度。然而，β-纤维蛋白原基因启动子区HaeⅢ-455G／A多态性与缺血性脑血管病无相关性。结论 β-纤维蛋白原基因启动子区HaeⅢ-455G／A多态性虽可影响血浆纤维蛋白原浓度，但并非是缺血性脑血管病的一个重要遗传决定因子。     

Genetic variation in estrogen receptor, C-reactive protein and fibrinogen does not predict the plasma levels of inflammation markers after longterm hormone replacement therapy

Markers of inflammation, such as C-reactive protein (CRP) and fibrinogen, are associated with the risk of atherothrombosis. Plasma levels of these markers of inflammation are affected by hormone replacement therapy (HRT) and modulated by smoking. We studied whether genetic variation in the estrogen receptor- 1 (ESR1), CRP and fibrinogen-beta genes influences the plasma levels of inflammation markers after HRT. Plasma CRP and fibrinogen were measured after five years follow-up in healthy postmenopausal women (per-protocol group) who were randomised to hormone therapy (n=187) or no treatment (n=249). The effect of HRT, smoking and genetic variations in ESR1 (PvuII and XbaI), CRP (1444C/T) and fibrinogen-beta (FGB, -455G/A) were determined. The plasma concentration of CRP was higher in the HRT group than in the control group (2.03 mg/l and 1.41 mg/l, respectively; p < 0.001), while the concentration of fibrinogen was lower in the HRT group than in the control group (3.02 g/l and 3.20 g/l, respectively; p < 0.001), indicating that it is unlikely that inflammation is the common underlying pathway. There was a significant interaction between smoking and HRT on the fibrinogen (p=0.02), but not on the CRP concentration (n.s.). Genetic polymorphisms in ESR1, CRP and fibrinogen were not associated with an effect of HRT on the CRP and fibrinogen plasma levels, and no significant interaction with smoking was observed. In conclusion, higher plasma levels of CRP and lower plasma levels of fibrinogen were observed in women using HRT; however, genetic polymorphisms in ESR1, CRP and FGB were not associated with these effects of HRT.     

Fibrin gel network characteristics and coronary heart disease: relations to plasma fibrinogen concentration, acute phase protein, serum lipoproteins and coronary atherosclerosis.

The native fibrin gel structure formed in vitro from plasma samples was examined by liquid permeation of the hydrated fibrin gel networks in 18 men who had suffered a myocardial infarction before the age of 45 years and in 20 control subjects. Patients with an elevated plasma fibrinogen concentration had a considerably lower fibrin gel porosity (permeability coefficient, Ks) compared with patients with a normal plasma fibrinogen level and with controls. The calculated fiber mass-length ratio of the fibrin gel networks was decreased in both patient groups. Gel porosity differed markedly between individuals at a given plasma fibrinogen concentration. Fairly strong inverse correlations were found between plasma orosomucoid level on the one hand and Ks (r = -0.617, p less than 0.01) or fiber mass-length ratio (r = -0.499, p less than 0.05) on the other. The low density lipoprotein (LDL) cholesterol concentration also correlated inversely with Ks (r = -0.471, p less than 0.05) and fiber mass-length ratio (r = -0.522, p less than 0.05). Significant inverse relations, which were independent of plasma fibrinogen and lipoprotein concentrations, were detected between Ks (r = -0.519, p less than 0.05) and calculated fiber mass-length ratio (r = -0.723, p less than 0.001) and number and severity of coronary artery stenoses determined by angiography. A proneness to formation of tight, rigid and space-filling fibrin network structures with small pores thus appears to be associated with premature coronary artery disease.     

Tissue factor and homocysteine levels in ischemic heart disease are associated with angiographically documented clinical recurrences after coronary angioplasty

BACKGROUND: In ischemic heart disease (IHD) patients high plasma levels of Tissue Factor (TF), the trigger of coagulation cascade, are present. Homocysteine (Hcy) is a risk factor for coronary artery disease, and several different pathophysiological mechanisms by which Hcy may play a role in thrombus formation have been postulated in "in vitro" studies. We investigated the "in vivo" role of Hcy in affecting plasma levels of TF, its inhibitor Tissue Factor Pathway Inhibitor (TFPI) and hypercoagulability. METHODS AND RESULTS: We investigated 119 IHD patients who underwent PTCA and compared them with 103 healthy subjects. TF, TFPI, Thrombin-Antithrombin complexes (TAT) and Hcy levels were significantly higher in the patients than in the controls. A positive correlation was found between Hcy and TF (r = 0.54; p < 0.0001), Hcy and TFPI (r = 0.26; p <0.05) as well as Hcy and TAT (r = 0.33; p <0.0001) levels. An inverse correlation existed between folate intake and Hcy levels (r = -0.28; p = 0.001). Hcy levels within the first quartile and in the highest quartile were associated with a lower (p < 0.001) and higher (p <0.0001) rate of clinical recurrences, respectively. Patients with TF values in the first quartile had a lower rate of angiographically documented clinical recurrences as compared to those in the fourth quartile (p <0.01); those in the highest quartile of TF showed a higher rate of recurrences (p = 0.001). Multivariate analysis confirmed these results (first quartile of Hcy: OR 0.02, C1 0.002-0.27; fourth quartile of Hcy: OR 36.5, C1 3.6-365/first quartile of TF: OR 0.006, C1 0.001-0.44; fourth quartile of TF: OR 16.4, C1 3.0 - 90.0), also after adjustment for risk factors and Hcy and TF respectively. CONCLUSIONS: In this study we show that TF, TFPI and TAT levels are correlated with Hcy plasma levels in IHD patients, providing evidence of an "in vivo" pathophysiological mechanism of hyperhomocysteinemia. The observed association between angiographically documented clinical recurrences and TF and Hcy values awaits confirmation in studies designated to evaluate this issue on a larger number of patients.