Gilia Raneli

Coagulation, fibrinolysis and haemorheology in premenopausal obese women with different body fat distribution.

Recently waist/hip ratio (WHR), a marker of body fat distribution, has been described as a risk factor for cardiovascular disease (CVD). The aim of the present study was to evaluate the influence of body fat distribution on metabolic, haemostatic and haemorheological pattern in premenopausal obese women with different WHR. Fourty premenopausal obese women were subdivided into two groups, matched for age and body mass index (BMI): 20 women with abdominal obesity (WHR = 0.94 +/- 0.02) and 20 women with peripheral obesity (WHR = 0.77 +/- 0.03). Twenty nonobese women were recruited as control group. The abdominal obesity group had significantly higher blood glucose, triglycerides, total cholesterol, Apolipoprotein B and plasma insulin levels and lower high density lipoprotein (HDL) cholesterol and Apolipoprotein A1 levels than the control group. All the haemostatic (figrinogen, Factor VII, plasminogen activator inhibitor (PAI) activity and tissue plasminogen activator (t-PA) antigen (Ag) pre venous occlusion (VO)) and haemorheological parameters (haematocrit, whole blood filterability, blood and plasma viscosity) were significantly higher in the abdominal obesity group as compared to the control group. In contrast, mean values of t-PA (Ag) post VO were significantly lower in abdominal obese women. Moreover positive correlations between WHR and plasma insulin (r = 0.68, p < 0.05), between WHR and fibrinogen (r = 0.63, p < 0.05) and between WHR and PAI pre VO (r = 0.71, p < 0.05) and a negative correlation between WHR and t-PA (Ag) post VO (r = -0.55, p < 0.05) were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Non lipid, dose-dependent effects of pravastatin treatment on hemostatic system and inflammatory response

AbstractObjectives: The aim of the present study was to evaluate the effects of pravastatin treatment on lipid, inflammation, and coagulation parameters in patients suffering from myocardial infarction with or without carotid atherosclerotic lesions (groups 1 and 2, respectively). Methods: In the first phase of the study, a cross-sectional comparison of lipid, inflammation, and coagulation parameters was performed between the patients and the control group (group 3). Highly significant differences in these parameters were observed, especially in group 1. In the second phase of the study, we assessed the effects of a persistent reduction in cholesterol synthesis induced by increasing doses of pravastatin (20 mg daily for 8 weeks and 40 mg daily for a further 8 weeks). In addition to the well-established lipid-lowering effect, significant changes in inflammation and coagulation parameters were observed. In particular, pravastatin at a dosage of 20 mg/day significantly reduced only fibrinogen levels, while at a dosage of 40 mg/day significantly reduced factor VII, fibrinogen, prothrombin fragments 1 and 2, thrombin–antithrombin complexes, tissue plasminogen activator antigen (tPA:Ag) before venous occlusion (b.o.), inhibitor of plasminogen activator activity (PAI) b.o., PAI activity after occlusion (a.o.), the human autoantibodies against oxidized low-density lipoprotein (LDL), and the c fraction of the third component system levels, and significantly increased tPA:Ag a.o. levels. Results: Our results show that in patients suffering from myocardial infarction the risk of thrombotic complications can be decreased with pravastatin, especially by larger doses. However, the relationship must be further investigated because the observed reductions in the hemostatic system and inflammatory response seemed to be dose dependent, while the effects of pravastatin treatment were not significantly correlated with total and LDL cholesterol changes.

Changes induced by pravastatin treatment on hemostatic and fibrinolytic patterns in patients with type IIb hyperlipoproteinemia

Abstract A randomized, double-blind, parallel-group study of pravastatin versus placebo was carried out for 24 weeks in 20 patients with type IIb primary hyperlipoproteinemia. Total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, blood glucose, apolipoproteins (apo) A1 and B, and lipoprotein (a) (Lp[a]) levels were determined. A venous occlusion test was also performed in all patients. Pre- and postvenous occlusion tests were determined: tissue plasminogen activator antigen (t-PA[Ag]), plasminogen activator inhibitor (PAI) activity, factor VII, fibrinogen, plasminogen, and hematocrit. Compared with placebo, pravastatin significantly reduced total cholesterol, LDL cholesterol, apo B, and triglyceride levels, as well as significantly increased HDL cholesterol and apo A1 levels. A mild, statistically nonsignificant reduction in Lp(a) was observed in the patients treated with pravastatin. Compared with placebo, pravastatin significantly reduced factor VII, fibrinogen, plasminogen, and PAI activity levels before and after venous occlusion. A significant reduction of t-PA(Ag) at rest was found in patients treated with pravastatin, whereas there was no significant difference in t-PA(Ag) levels after venous occlusion. Our data confirm the well-known lipid-regulating effect of pravastatin and suggest a positive effect of pravastatin on the regulation of hemostatic and fibrinolytic systems in patients with type IIb hyperlipoproteinemia.

Fibrinolysis in hypertriglyceridaemic subjects in response to venous occlusion.

We have measured various fibrinolytic and coagulation parameters (t-PA antigen, PAI, fibrinogen, plasminogen and factor VII) before and after 10 min of venous occlusion in 20 hypertryglyceridaemic subjects (twelve males and eight females, age 38 ± 4 years, body mass index 23 ± 1.5) and 20 healthy normal subjects, matched for sex (twelve males and eight females), age (37 ± 3.5 years) and body mass index (22.8 ± 1.4). At rest, t-PA:Ag, PAI, fibrinogen, plasminogen and factor VII were significantly (P < 0.005) higher in hypertriglyceridaemic subjects than in normal controls. After venous occlusion, the increase in all parameters except t-PA:Ag was more marked in the patient group than in the controls. Only the percentage increase in t-PA:Ag was higher in normal controls (358.8%) than in hypertriglyceridaemic subjects (91.9%). There was a positive correlation between serum triglycerides levels and PAI at rest (r = 0.72, P < 0.01) and a negative correlation between serum triglycerides levels and t-PA antigen after venous occlusion (r = −0.45, P < 0.05) suggesting an impairment of fibrinolysis in hypertriglyceridaemia.

Improvement of fibrinolysis and plasma lipoprotein levels induced by gemfibrozil in hypertriglyceridemia

A randomized double-blind study was carried out with gemfibrozil (600 mg b.i.d.) vs placebo in 20 patients (twelve males and eight females, age 52 +/- 3 years, BMI 24.2 +/- 0.4) suffering from primary hypertriglyceridemia (Fredricksons type IV). Each group was treated for a 12 week period with gemfibrozil (n = 10) or placebo (n = 10) patients) in a double-blind fashion. Total cholesterol, HDL-cholesterol (HDL-C) and its subfractions (HDL2-C and HDL3-C), blood glucose, Apolipoproteins A1 and B, fibrinogen, plasminogen, factor VII, t-PA:Ag and PAI activity pre- and post-venous occlusion (VO) were determined. In the gemfibrozil-treated group a significant decrease of total cholesterol and triglycerides and a significant increase of HDL-C and HDL2-C were found. During gemfibrozil treatment a significant reduction of factor VII, fibrinogen and plasminogen levels was also observed. After 12 weeks of treatment in the gemfibrozil group the release of t-PA:Ag in response to venous occlusion was significantly higher and plasma PAI activity was significantly lower than in placebo group. Moreover positive correlations between HDL cholesterol and t-PA:Ag post-VO (r = 0.56, P < 0.01) and between HDL2-C cholesterol and t-PA:Ag post-VO (r = 0.59, P < 0.01) and a negative correlation between triglycerides and t-PA:Ag post-VO (r = -0.65, P < 0.01) were found. The data obtained suggest that gemfibrozil, in addition to the well established lipid-regulating effect, appears to have a positive role in the regulation of reverse cholesterol transport and fibrinolytic system.

Fibrinolytic effect of gemfibrozil versus placebo administration in response to venous occlusion

Abstract Impact of hypertriglyceridemia on atherosclerotic vascular disease and thromboembolic events is recently emphasized by primary prevention studies on the development of coronary artery disease. A randomized double-blind study was carried out with gemfibrozil (600 mg b.i.d.) versus placebo in 20 patients (12 males and 8 females, age 52±3 years, BMI 24.2±0.4) suffering from primary hypertriglyceridemia (Fredricksons type IV). After a 4-week stabilization period in which administration of lipid-lowering drugs was stopped and an isocaloric diet was prescribed, patients were randomized into two groups. Each group was treated for a 12 week period with gemfibrozil (10 patients) or placebo (10 patients) in a double-blind fashion. Every 4 weeks triglycerides, total cholesterol, HDL-cholesterol, blood glucose and Apolipoproteins A1 and B were determined. At baseline and at the end of the treatment period a venous occlusion test was performed in all subjects. Before and after 10 min venous stasis were measured: t-PA antigen, PAI activity, fibrinogen, plasminogen, Factor VII and haematocrit. In the gemfibrozil-treated group a significant decrease of triglycerides and a significant increase of HDL-C was found. During gemfibrozil treatment a significant reduction of Factor VII, fibrinogen and plasminogen levels either before or after venous occlusion was also observed. After 12 weeks of treatment in the gemfibrozil group the release of t-PA in response to venous occlusion was significantly higher and plasma PAI activity was significantly lower than in placebo group, suggesting a profibrinolytic effect of the drug.

Cross-over study on effects of Mediterranean diet in two randomly selected population samples

Two randomly selected population samples in Western Sicily, one rural (n 40) and one urban (n 40), were studied to evaluate the impact of dietary intervention on lipid, coagulative and fibrinolytic parameters. The two groups received the diets in a cross-over design with the following sequences: (a) baseline period; (b) 8-week dietary intervention period; (c) 8-week return to the original diet. During (a) and (c) all subjects consumed their usual diet. During the dietary intervention period (b), the rural sample consumed the urban sample’s diet, while the urban sample consumed the rural sample’s diet (the so-called “Mediterranean diet”). At baseline, after 8 weeks’ dietary intervention period and after 8 weeks’ return to the original diet, the following parameters were measured: blood glucose, total cholesterol, HDL-cholesterol, triglycerides, apolipoproteins A1 and B100, fibrinogen, factors VII and VIII, tissue plasminogen activator and plasminogen activator inhibitor Our results show a positive effect of the Mediterranean diet on lipid, coagulative and fibrinolytic parameters which play a key role in the pathogenesis of atherosclerosis and indicate that this dietary pattern may help in the primary prevention of CHD.

Effects of heparin treatment on hemostatic abnormalities in obese non—insulin-dependent diabetic patients

This study was conducted to identify the mechanisms responsible for coagulative and fibrinolytic alterations and to study the effects of a short-term treatment with low-dose heparin on hemostatic abnormalities in obese non-insulin-dependent diabetes mellitus (NIDDM) patients. Four groups of age- and sex-matched patients were studied: (1) lean nondiabetic subjects (n = 30) with a body mass index (BMI) less than 25 kg/m2 (lean control subjects), (2) obese nondiabetic subjects (n = 30) with a BMI greater than 30 kg/m2 (obese control subjects), (3) lean NIDDM patients (n = 30), and (4) obese NIDDM patients (n = 30). All subjects were tested on the following parameters: fibrinogen, factor VII, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), tissue plasminogen activator (t-PA) antigen (Ag) before and after venous occlusion (VO), and plasminogen activator inhibitor type-1 (PAI-1) activity pre- and post-VO. In addition, all these parameters were evaluated in obese NIDDM patients after 10 days of treatment with a single dose of 12,500-U/d subcutaneous calcium heparin and after a 10-day washout period. At baseline, obese nondiabetic subjects, lean NIDDM patients, and especially obese NIDDM patients displayed significantly (P < .01) higher levels of fibrinogen, factor VII, F1 + 2, TAT, t-PA(Ag) pre-VO, and PAI-1 pre- and post-VO and significantly (P < .01) lower levels of t-PA(Ag) post-VO. In obese NIDDM patients treated with heparin fibrinogen, factor VII, F1 + 2, TAT, t-PA(Ag) pre-VO, and PAI-1 pre- and post-VO levels significantly (P < .01) decreased and t-PA(Ag) post-VO levels significantly (P < .01) increased at the end of treatment. Our findings demonstrate in obese nondiabetic subjects, lean NIDDM patients, and especially obese NIDDM patients the hemostatic abnormalities contributing to an enhanced risk of thrombotic complications. We conclude that in obese NIDDM patients, short-term treatment with heparin may reduce this thrombophilic state and have a potential benefit in the progression of diabetic microvascular and macrovascular disease and needs further investigation.

Activation of coagulation but normal fibrinolysis in patients with type IIa hyperlipoproteinemia

Abstract Disturbances in lipid metabolism such as hypercholesterolemia or hypertriglyceridemia are widely accepted risk factor for atherosclerosis (1). Recent studies have suggested that a hypercoagulable state and a reduced fibrinolytic activity may also be independent risk factors for atherosclerotic vascular disease and thrombo-embolic complications (2–3). Moreover these studies should be considered with the significant evidence that shows several complex interactions which occur between the lipid and hemostatic system. In fact a positive correlation was found between Factor VII coagulant activity and dietary fat intake and between platelet thromboxane production and serum total cholesterol levels (4–6). Finally, several authors suggest a positive correlation between impaired fibrinolysis and serum triglyceride levels, whereas studies on fibrinolytic system in hypercholesterolemic patients are very few (7–9). The aim of this study was to verify the existence of a thrombophilic state in patients with type IIa hyperlipoproteinemia without signs of atherosclerotic vascular disease in order to suggest an appropriate primary prevention.

Elevated levels of lipoprotein (a) in patients suffering from myocardial infarction with carotid atherosclerotic lesions.

The aim of the present study was to evaluate metabolic, coagulation and fibrinolytic parameters in 45 patients [31 men, 14 women, aged 56.5 +/- 3.5 years (mean +/- SD)] who had suffered myocardial infarction more than 6 months earlier, with or without carotid atherosclerotic lesions. After the extracranial carotid arteries had been evaluated using a B-mode Duplex scanning system, patients were subdivided into two groups: group 1 (n = 20) with carotid plaques or measurable intima-media thickness; and group 2 (n = 25) without carotid plaques or measurable intima-media thickness. Twenty-two age- and sex-matched subjects were recruited as controls (group 3). Groups 1 and 2 displayed significantly higher levels of total cholesterol, apolipoprotein B, human autoantibodies against oxidised low-density lipoprotein and the c fraction of the third component system, and significantly lower levels of high-density lipoprotein cholesterol and apolipoprotein A1 than group 3. However, serum levels of triglyceride and lipoprotein (a) were significantly higher in group 1 than in the control group. Moreover, groups 1 and 2 displayed significantly higher levels of factor VII, fibrinogen, fragment 1+2, thrombin-antithrombin complex and plasminogen activator inhibitor after venous occlusion, and significantly lower levels of tissue-type plasminogen activator after venous occlusion than group 3. Significantly higher levels of tissue-type plasminogen activator and plasminogen activator inhibitor before venous occlusion were observed in groups 1 and 2 and significantly lower levels of antithrombin III, protein C and protein S were observed in group 1 compared with the controls. Patients were also analysed according to levels of lipoprotein (a). The lowest levels of tissue-type plasminogen activator after venous occlusion and the highest levels fragment 1 + 2, the c fraction of the third component system, and plasminogen activator inhibitor after venous occlusion were observed in patients with the highest levels of lipoprotein (a). Our data demonstrate an activation of coagulation and deficient fibrinolysis in survivors of myocardial infarction, particularly in those with associated carotid atherosclerotic lesions. We speculate that this thrombophilic state may play a key role in the pathogenesis of atherosclerotic vascular disease and thromboembolic complications.