Rosamaria Cordova

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)

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.

Effect of gemfibrozil treatment on fibrinolysis system in patients with hypertriglyceridemia

Abstract The effect of gemfibrozil on lipidic, coagulative, and fibrinolytic pattern was studied in 20 patients with primary type IV hyperlipoproteinemia. After a 4-week stabilization period during which administration of lipid-lowering drugs was stopped and an isocaloric diet (20% protein, 30% fat, and 50% carbohydrates) was prescribed, 20 patients (12 men and 8 women; mean age, 38 ± 4 years; body mass index, 23.4 ± 1.5) suffering from primary hypertriglyceridemia were included in this study and treated for a 12-week period with gemfibrozil (600 mg BID). Every 4 weeks the following parameters were checked: glycemia, triglycerides, total cholesterol, high density lipoprotein-cholesterol, total cholesterol/HDL-cholesterol ratio, apolipoproteins A–I and B, tissue plasminogen activator antigen, plasminogen activator inhibitor activity, fibrinogen, plasminogen, antithrombin III, protein C, factor VII, and inopeptide A. 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 hemostasis 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.

INCREASED THROMBIN GENERATION AND COMPLEMENT ACTIVATION IN PATIENTS WITH TYPE IIA HYPERLIPOPROTEINEMIA: EFFECTS OF SIMVASTATIN TREATMENT

Abstract The aim of this study was to demonstrate the existence of increased thrombin generation and complement activation in patients with type IIa primary hyperlipoproteinemia, but no signs of atherosclerotic vascular disease and to assess the effects of simvastatin treatment in these patients. We studied 40 patients with type IIa primary hyperlipoproteinemia and 40 healthy subjects matched for sex, age, body mass index, and smoking status. The study was divided into two phases. In the first phase, a cross-sectional comparison of lipid and hemostatic patterns was performed between patients and controls. In the second phase, we assessed the effect of a persistent reduction in cholesterol synthesis induced by simvastatin in patients with hypercholesterolemia. The lipid pattern in patients with hypercholesterolemia was consistent with the characteristic features of this form of hyperlipoproteinemia. Moreover, factor VII, fibrinogen, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complexes (TAT), fibronectin, and the c fraction of the third component of the complement system (C3c) levels were significantly higher, and antithrombin III was significantly lower in patients than in controls. Regarding the fibrinolytic pattern, in patients there were no significant differences in tissue plasminogen activator antigen before and after venous occlusion (VO), plasminogen activator inhibitor type 1 activity before and after VO, plasminogen, and alpha 2 -antiplasmin plasma levels compared with control subjects. Factor VII, fibrinogen, F1+2, TAT, fibronectin, and C3c were significantly correlated with total and low-density lipoprotein (LDL) cholesterol levels, whereas no significant correlation with high-density lipoprotein (HDL) cholesterol and triglyceride levels was found. In addition to the well-established lipid-lowering effect, simvastatin (20 mg/d for 8 weeks) significantly reduced factor VII, fibrinogen, F1+2, TAT, fibronectin, and C3c levels in patients with hypercholesterolemia, but the observed reductions were not significantly correlated with total and LDL cholesterol levels. Our results show that type IIa hyperlipoproteinemia is characterized by increased in vivo thrombin generation and complement activation with no abnormalities of fibrinolysis. This thrombophilic state, which is associated with a high incidence of atherosclerosis and thrombotic complications, can be decreased with simvastatin via cholesterol lowering, but the relationship between these events remains to be investigated.

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.