One-year atorvastatin treatment in hypercholesterolemic patients with or without carotid artery disease.

AIM: Statins are the drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of premature cardiovascular events including myocardial infarction, stroke, and surgical revascularization. METHODS: A 1-year open-label study was conducted to test the efficacy and tolerability of Atorvastatin titrated to the target, in proven FH patients and to evaluate certain inflammatory parameters. One hundred and two FH patients (44 men and 58 women; mean age 58.7+/-3.6 years) were included in the study. After evaluation using the B-mode duplex scanning system of extracranial carotid arteries, the patients were divided into two groups: Group 1 (15 men, 25 women) with carotid plaques or intima-media thickness (IMT) greater than 0.95 mm and Group 2 (30 men, 32 women) without carotid plaques or IMT less than 0.95 mm. After a 6-week hypolipemic diet phase all the patients were treated with atorvastatin titrated to achieve a low density lipoprotein (LDL-C) <100 mg/dL. Patients with carotid lesions were also submitted to an oral fixed dose of aspirin 100 mg/day. RESULTS: In patients without and with carotid lesions, atorvastatin treatment (mean dosage: 23.5 mg/day) reduced triglycerides by 8.7% (P<0.005) and 10.6% (P<0.005), total cholesterol by 41.5% (P<0.005) and 42.6% (P<0.005), LDL-C by 55.8% (P<0.005) and 57.3% (P<0.005) and apolipoprotein B by 38.3% (P<0.005) and 37.2% (P<0.005) respectively, and increased the mean levels of high density lipoprotein cholesterol (HDL-C) by 8.7% (P<0.005) and 11% (P<0.005), and apolipoprotein A-I by 3.2% (P<0.05) and 3.3%, respectively. In both groups of patients the mean decrease (52 weeks) of fibrinogen was 19.8% (P<0.005) and 10.4% (P<0.005), respectively and of high sensitivity C-reactive protein (hs-CRP), 36.2% (P<0.005) and 38.2% (P<0.005), respectively. No variation of the parameters of safety and clinical tolerability of the drugs administered was observed. No variation in hematocrit in the patients taking ASA treatment was observed. CONCLUSIONS: In FH patients, 1-year atorvastatin treatment titrated to the target (LDL-C <100 mg/dL) was well tolerated and improved serum lipid levels and inflammatory parameters.

Effects of moderate Sicilian red wine consumption on inflammatory biomarkers of atherosclerosis.

OBJECTIVE: The aim of the study is to evaluate the effect of moderate Sicilian red wine consumption on cardiovascular risk factors and, in particular, on some inflammatory biomarkers. METHODS: A total of 48 subjects of both sexes who were nondrinkers or rare drinkers of moderate red wine were selected and randomly subdivided into two groups assigned to receive with a crossover design a Sicilian red wine (Nero d'Avola or Etna Torrepalino) during meals: Group A (n = 24), in whom the diet was supplemented for 4 weeks with 250 ml/day of red wine, followed by 4 weeks when they returned to their usual wine intake; and Group B (n = 24), in whom the usual wine intake was maintained for 4 weeks, followed by 4 weeks when the diet was supplemented with 250 ml/day of red wine. The following were values measured in all tests: blood glucose, total and HDL-cholesterol and triglycerides, LDL-cholesterol, LDL/HDL ratio, apolipoproteins A1 and B, Lp(a), plasma C-reactive protein, TGFbeta1, D-Dimer, Factor VII , PAl Ag, t-PA Ag, fibrinogen, oxidized LDL Ab, total plasma antioxidant capacity. RESULTS: At the end of the red wine intake period, LDL/HDL, fibrinogen, factor VII, plasma C-reactive protein and oxidized LDL Ab were significantly decreased, while HDL-C, Apo A1,TGFbeta1, t-PA, PAI and total plasma antioxidant capacity were significantly increased. CONCLUSIONS: Our results show a positive effect of two Sicilian red wines on many risk factors and on some inflammatory biomarkers, suggesting that a moderate consumption of red wine in the adult population is a positive component of the Mediterranean diet.

[Evaluation of resistance to activated protein C in myocardial infarction patients]. / Valutazione della resistenza alla proteina C attivata in soggetti con pregresso IMA.

BACKGROUND: It is known that resistance to activated protein C (APCR), often associated with a single point mutation (Arg506-->Gln) in the coagulation factor V gene (factor V Leiden), is the most frequent inherited abnormality of blood coagulation. It plays a key role as pathogenetic factor of venous thromboembolism, but its association with an increased risk of arterial thrombosis is uncertain. Aim of the present study was to evaluate the prevalence of APCR in men, who suffered myocardial infarction more than 6 months earlier and without cardiovascular risk factors (hypercholesterolemia, smoking, diabetes, obesity and hypertension). METHODS: The study was carried on 20 men aged <65 years who have suffered myocardial infarction. Twenty healthy subjetcs matched for sex and age were recruited as controls. We determined: PTT, PTT-PCA (Activated Protein C), PTT-PCA/PTT, AntiThrombin III, Protein C, Protein S, Fibrinogen, Glucose, Triglycerides, Cholesterol, HDL-C, LDL-C, APO A1, APO B100, Lp(a), oxizided LDL antibody and some components of the complement system (C3c, C4). RESULTS: In the group of patients there were six subjects (30%) with APCR, while there were no subjects in the control group (0%) with APCR. Patients were subdivided into two groups: with and without APCR. Patients with APCR displayed significantly higher levels of fibrinogen (367.5+/-48.4 vs 268.3+/-37.7), LDL-C (147.0 +/-20.7 vs 125.8+/-25,6), APO B100 (133.8+/-29.8 vs 121.8+/-31.5), oxizide LDL antibody (596.8+/-357 vs 315.3+/-179.6) and C4 (45.6+/-10 vs 37.85+/-11,3). Significant positive correlations (p<0.05) were observed between PTT-PCA/PTT ratio and fibrinogen (r=0.68) and between PTT-PCA/PTT ratio and oxidized LDL antibody (r=0.61). CONCLUSIONS: In conclusion, the high prevalence of APCR (30%) in our patients seems to be important in order to carry out a primary prevention of arterial thrombosis and a secondary prevention of new thromboembolic complications.

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

OBJECTIVES: 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.

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.

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.

[Thrombophilic state inpatients suffering from myocardial infarction with or without carotid atherosclerotic lesions]. / Sindrome trombofilica in pazienti affetti da pregresso infarto del miocardio con o senza lesioni aterosclerotiche carotidee.

The aim of the present study was to evaluate some metabolic, coagulation and fibrinolytic parameters in 35 patients (24 males and 11 females, mean age 57 +/- 4 years) suffering from myocardial infarction more than 6 months before with or without carotid atherosclerotic lesions. After evaluation by B-mode duplex scanning system of extracranial carotid arteries, the patients were subdivided into two groups: Group 1 (n = 16, with carotid plaques or intima-media thickening) and Group 2 (n = 19, without carotid plaques or intima-media thickening). Eighteen age- and sex-matched subjects were recruited as controls (Group 3). Groups 1 and 2 displayed significantly higher levels of total cholesterol and apolipoprotein B and significantly lower levels of HDL-cholesterol and apolipoprotein A1 than Group 3, while serum triglyceride and lipoprotein (a)-Lp (a) levels were significantly higher in Group 1 as compared to the control group. Moreover, Group 1 and 2 displayed significantly higher levels of factor VII, fibrinogen, F1+2, thrombin-antithrombin complex and plasminogen activator inhibitor (PAI) post venous occlusion and significantly lower levels of tissue plasminogen activator (t-PA) post venous occlusion than Group 3. Significantly higher levels of t-PA and PAI pre venous occlusion and significantly lower levels of antithrombin III, C-protein and S-protein were observed in Group 1 as compared to controls. In patients with highest Lp(a) level, the lowest t-PA level post venous occlusion and the highest PAI level post venous occlusion were observed. Our data show an activation of coagulation and a 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.

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 (Fredrickson's 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.

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)

Cardiovascular risk factors and dietary habits in secondary school children in southern Italy.

Interest in research on atherosclerosis involving children has been the consequence of confluent evidence that atherogenic process begins in early life and grows silently until the occurrence of clinical events in middle-age or later. We carried out a cross-study in the Mediterranean area on a random sample of a secondary school of Casteldaccia (a farming and fishing village located on the Northern coast of Sicily, East of Palermo), consisting of 186 teen-agers (103 males and 83 females) aged between 10 and 13 years (average age: 11.3 +/- 0.2 years). We determined: total cholesterol, triglycerides, HDL-cholesterol, LDL-Cholesterol, apolipoproteins A1 and B, glycaemia, body mass index (BMI), systolic and diastolic blood pressure. Dietary habits were recorded on two occasions by a weekly diary (of the 7 days food record type) with the collaboration of dieticians. The prevalence of plasma cholesterol levels between 170-200 mg% and exceeding 200 mg% was 24.2% and 12.4% respectively, of overweight (BMI > 25) was 9.7% and of hypertension (SBP > 125 and/or DBP > 85 mmHg) was 8.6%. In comparison with Mediterranean diet according to Euratom study (1969), the following are the most impressive findings: an increase of cholesterol (+54%) and fat intake (+2% of total calories), a reduction of fibre intake (-32%) and an increase of 2S-P difference (+27%) and of total fats/fibre ratio (+53%).

Evaluation of cardiovascular risk factors in overweight and obese subjects.

Twenty obese subjects (Males = 8, Females = 12; average age = 39.5 +/- 2.5 years; B.M.I. = 36.2 +/- 2.5), 20 overweight subjects (Males = 8, Females = 12; average age = 38.5 +/- 2 years; B.M.I. = 28.8 +/- 0.4) and 20 non obese healthy subjects as controls, matched for sex and age (Males = 8, Females = 12; average age = 37.5 +/- 2 years; B.M.I. = 22.4 +/- 0.8) were selected. We determined: blood glucose, triglycerides, total cholesterol, HDL-cholesterol, Apolipoproteins A1 and B, Factor VII, fibrinogen and plasminogen. Before and after a venous occlusion test were also measured: t-PA Antigen, PAI activity and haematocrit. Metabolic, coagulative and fibrinolytic pathological changes were observed in overweight and obese subjects and the interaction of these risk factors may contribute to the pathogenesis of atherosclerosis vascular disease and to the high rate of thromboembolic events reported in obesity.

Blood coagulation and fibrinolysis in obese NIDDM patients.

Four group of age- and sex-matched patients were studied: 1. nondiabetic subjects (n = 20) with a body mass index (BMI) < 25 Kg/m2 (lean control subjects); 2. obese non diabetic subjects (n = 22) with a BMI > 30 Kg/m2 (obese control subjects); 3. lean NIDDM subjects (n = 22); and 4. obese NIDDM subjects (n = 24). We determined: total cholesterol, triglycerides, HDL-cholesterol, blood glucose, Apolipoproteins A1 and B, insulin, Lp(a), Factor VII, fibrinogen, plasminogen, t-PA(Ag) pre and post venous occlusion (VO) and PAI activity pre and post VO. In addition to metabolic abnormalities obese non diabetic subjects and lean and obese NIDDM patients displayed significantly higher levels of fibrinogen, Factor VII, plasminogen, PAI pre and post VO and tPA(Ag) pre VO and significantly lower levels of t-PA(Ag) post VO. Our findings demonstrate an impairment of the haemostatic and fibrinolytic mechanisms which may be a key role in the pathogenesis of atherosclerotic vascular complications in obesity and in NIDDM.

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.

Prevalence of diabetes mellitus and of associated risk factors for atherosclerosis in a randomized population sample of western Sicily. Casteldaccia study.

Within the Targeted Programme of the Italian National Research Council "Preventive and Rehabilitative Medicine" subproject: Risk Factors, organized in nine centers on a national scale, the Operative Unit of Palermo carried out a transverse epidemiological study on a randomized population sample of western Sicily: Casteldaccia, 1984. 1.200 subjects subdivided by age in four decades (20-29; 30-39; 40-49; 50-59 years) and by sex (600 males and 600 females) were enlisted; the participation was 60.25% (No. 723; M = 364; F = 359). Following standardized procedures main cardiovascular risk factors were measured: glycaemia (GOD-PAP), triglycerides (enzymatic), total cholesterol (CHOD-PAP), HDL-cholesterol (MgCl2 dextran sulphate), apolipoproteins A1 and B (R.I.D.), B.M.I. (kg/m2), smoking habits and systolic and diastolic blood pressure (according to WHO manual on Cardiovascular Survey Methods). A questionnaire was used to record the familiar anamnesis, medical history of subjects, term of possible hyperglycaemia, current therapy (use of insulin, oral hypoglycaemic agent, dietetic treatment). The prevalence of diabetes mellitus was 8.16% (59/723): 4.67% (17/364) in males and 11.69% (42/359) in females. The most frequent risk factors associated with diabetes mellitus were; overweight (81%), hypercholesterolemia (49%), hypertriglyceridemia (45%), hypertension (37%) and cigarette smoking (15%).

[Behavior of various blood coagulation and hemorrheological parameters in arteriosclerotic vascular disease of the lower legs]. / Comportamento di alcuni parametri emocoagulativi ed emoreologici nelle vasculopatie arteriosclerotiche degli arti inferiori.

Red blood cell filterability was compared with some blood coagulation parameters in 50 patients suffering from atherosclerosis obliterans of lower limbs at stages II, III and IV. The reduced red blood cell filterability correlated positively with the stage of the arterial disease (r = 0.8185), with levels of plasma fibrinogen (r = 0.8366) and with the euglobulin lysis time (r = 0.8124), while negative correlations with platelet reactivity threshold (r = 0.6928) and with antithrombin III activity (r = 0.6557) were found. The authors believe that in the therapy of these vascular diseases it is necessary to modify the reduced red blood cell filterability together with the blood coagulation order.