Fluvastatin and tissue factor pathway inhibitor in type IIA and IIB hyperlipidemia and in acute myocardial infarction.

Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor that regulates tissue factor-induced blood coagulation. In an open-label 8-week study, 20 hypercholesterolemic patients (10 type IIa and 10 type IIb) were enrolled and given fluvastatin 40 mg once daily at bedtime. At baseline (after a 4-week controlled diet) and at week 8, total cholesterol, total triglycerides and lipoprotein subfractions were assessed. TFPI antigen levels were measured at the same time by ELISA. We also measured TFPI concentrations in 10 control subjects and in 10 patients at the time of and ten days after acute myocardial infarction. In type IIa patients fluvastatin reduced total cholesterol levels by 26% and LDL-cholesterol by 30% (P < 0.001); in type IIb, fluvastatin significantly reduced total cholesterol levels by 24% (P < 0.001). In both dyslipidemic groups the baseline total TFPI levels were significantly higher than in the control group (P < 0.002). The therapeutic lipid-lowering effect was paralleled by a significantly reduction of total TFPI antigen concentrations from 132 +/- 23 to 71 +/- 37 ng/mL (P < 0.001) in type IIa and from 120 +/- 30 to 91 +/- 29 ng/mL (P < 0.05) in type IIb patients; in control subjects total TFPI levels were 81 +/- 22 ng/mL; however the lipoprotein-bound TFPI antigen subfractions did not differ significantly in the treated and control groups. In patients with recent myocardial infarction there was a significant reduction from day 0 to day 10 in total TFPI antigen levels, from 120 +/- 48 ng/mL to 80 +/- 16 ng/mL (P < 0.05). The reported reduction of TFPI antigen levels after fluvastatin treatment could be a sign of normalization of an up-regulated clotting system rather than an unfavourable reduction of a natural anticoagulant.

Fibrinolytic response in subjects with hypertriglyceridemia and low HDL cholesterol.

The combination of hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) appears to be an excessively high risk factor for coronary artery disease (CAD). In the Helsinki study, both coronary events and mortality were decreased by gemfibrozil, especially in subjects with low HDL-C and high triglycerides (TG). On the other hand, it is known that high levels of TG can be associated with high levels of circulating plasminogen activator inhibitor (PAI), which is also a possible risk factor for CAD. The aim of the present study was to see: 1) whether the combination of low HDL-C and high TG is associated with a more impaired fibrinolytic response than in either isolated condition, and 2) whether gemfibrozil administration can improve fibrinolysis in patients with both high TG and low HDL-C. Twelve non-obese, non-diabetic subjects (eight men, four women; mean age 55 +/- 13 yrs) with low HDL-C (< 35 mg/dL men; < 45 mg/dL women) and high TG (mean 253.6 +/- 42.6 mg/dL) entered the study (Group A). Additionally fourteen comparable subjects with normal HDL-C were also investigated (Group B), plus 12 comparable subjects with isolated low HDL-C (Group C). Ten healthy people served as the control group. The following plasma fibrinolytic parameters were measured: tissue plasminogen activator antigen, PAI antigen and activity, euglobulin fibrinolytic activity (EFA) on fibrin plates, plasminogen and alpha-2-antiplasmin activities. All except the latter two values were also measured after venous occlusion (vo). In baseline conditions, patients in Groups A and B had higher EFA values before vo and higher PAI-1 antigen and alpha-2-antiplasmin levels after vo than those of controls or the subjects in Group C. The relationship between PAI antigen and PAI activity and TG was not confirmed in our population (n = 48). We also saw no interference due to HDL-C, while there was a significant relationship between EFA before vo and both TG and cholesterol. After gemfibrozil treatment (600 mg bid for 12 weeks), the lipid profiles of subjects with high TG and low HDL-C were significantly improved. There was also a slight reduction of PAI activity after vo, while the PAI-1 antigen had decreased significantly from baseline after vo (56.3 +/- 13 ng/mL before vo; 48.4 +/- 21 ng/mL after vo; P = 0.04). The higher risk of CAD in patients with low HDL-C and high TG might be in part related to impairment of fibrinolysis, which occurs in patients with isolated high TG. The close relationship existing between both TG and cholesterol levels and fibrinolytic activity confirm the key role of this latter process in the development of CAD.

Effect of vegetarian soy diet on hyperlipidaemia in nephrotic syndrome.

Nephrotic patients with persistent proteinuria also have various lipid abnormalities that may promote atherosclerosis and more rapid progression of renal disease. We aimed to find out whether dietary manipulation can correct the hyperlipidaemia found in these patients. After a baseline control period of 8 weeks on their usual diets, 20 untreated patients with chronic glomerular diseases, stable long-lasting severe proteinuria (5.9 [SD 3.4] g/24 h) and hyperlipidaemia (mean serum cholesterol 8.69 [3.34] mmol/l) ate a vegetarian soy diet for 8 weeks. The diet was low in fat (28% of total calories) and protein (0.71 [0.36] g/kg ideal body weight daily), cholesterol free, and rich in monounsaturated and polyunsaturated fatty acids (polyunsaturated/saturated ratio 2.5) and in fibre (40 g/day). After the diet period the patients resumed their usual diets for 8 weeks (washout period). During the soy-diet period there were significant falls in serum cholesterol (total, low-density lipoprotein, and high-density lipoprotein) and apolipoproteins A and B, but serum triglyceride concentrations did not change. Urinary protein excretion fell significantly. The concentrations of all lipid fractions and the amount of proteinuria tended to return towards baseline values during the washout period. We do not know whether the favourable effect of this dietary manipulation on proteinuria was due to the qualitative or quantitative modifications of dietary protein intake or was a direct consequence of the manipulation of dietary lipid intake.

Procollagen-type III peptide serum concentrations in alcoholic and non-alcoholic liver disease.

The type III procollagen aminopeptide (sPIIIP) serum levels were measured in 197 patients with liver disease and were correlated with morphological and serological alterations and with alcohol drinking habits. The sPIIIP levels resulted significantly increased in 51% of 43 patients with untreated chronic active hepatitis (CAH), in 61% of 36 patients with CAH plus cirrhosis, in 69% of 26 patients with inactive cirrhosis, in 4 out of 8 patients with alcoholic steatosis and fibrillogenesis, but remained unchanged in 38 cases of alcoholic steatosis plus siderosis and in 13 cases of chronic persistent hepatitis. A correlation between sPIIIP levels and the histological pattern of fibrosis could not be demonstrated in a single type of fibrotic liver disease and no differences were found between alcoholic and non-alcoholic patients. We agree upon the opinion that high sPIIIP levels may identify liver fibrogenic activity, but this test needs further technical improvements before it could be widely used in the clinical practice.