Hyperlipoproteinemic Patients Research Articles

Lipoprotein apheresis reduces biomarkers of plaque destabilization and cardiovascular risk

Lipoprotein apheresis (LA) is believed to exert anti-atherosclerotic effects beyond LDL-cholesterol reduction. We investigated 22 patients undergoing regular LA on a weekly basis (group A) before (AP) and after LA procedure (EP), 15 healthy individuals (group B), and 22 hyperlipoproteinemic patients with concomitant cardiovascular end organ damage treated without LA therapy (group C). Biomarkers of endothelial inflammation (hsCRP), plaque destabilization, and rupture (sVCAM, MMP-9, PAPP-A, ADMA) were quantified. Intergroup comparison revealed a statistically significant lower MMP-9 level in group A (AP and EP) compared with group C (P < 0.01), whereas PAPP-A levels were lower in group B compared with group A and C (P = 0.04). EP ADMA-levels and EP sVCAM levels in group A were statistically lower compared with group B and C. AP and EP values comparison revealed a significant reduction for hsCRP (mean 41.0 ± 16.7%, P < 0.01), sVCAM (mean 69.6 ± 14.0%, P < 0.01), PAPP-A (mean 88.7 ± 20.4%, P < 0.01), ADMA (mean 69.7 ± 18.4% P < 0.01). In conclusion, we observed a transient decrease in the plasma concentrations of several biomarkers expressed during plaque destabilization and elevated cardiovascular risk after a single LA treatment.

Rheologic, haemostatic, and coagulative variables in type II hyperlipoproteinemic subjects

The aim of the study was to evaluate the direct influence of cholesterol and triglycerides on the rheologic-coagulative pattern. Blood rheologic properties (blood plasmatic and seric viscosity, whole blood and red cell filterability), some coagulative factors (fibrinogen, levels of clotting factors VII and VIII activity), and beta-thromboglobulin and platelet factor 4 were studied in 156 men aged 40–54 years, 87 with type II hyperlipoproteinemia (46 type IIa and 41 type IIb) and 69 normolipemic controls. Smokers and patients with arterial hypertension, diabetes mellitus, or cardiovascular clinical manifestations were excluded. Increased blood viscosity (shear rate 225 sec-1,p<0.01) and higher value of beta-thromboglobulin and platelet factor 4 (p<0.001 both) were observed in type IIb hyperlipoproteinemic patients. Levels of fibrinogen and factor VII and VIII activity did not differ in hyperlipemic patients and controls. After multiple regression analysis, levels of platelet factor 4, plasma viscosity, and fibrinogenemia were positively related with triglycerides concentration; total cholesterol concentration was positively related to fVII activity and inversely with red cell filterability. We conclude that the rheologic-coagulative pattern is more severely altered in type IIb than in type IIa hyperlipoproteinemia, and that these alterations are strictly related to the severity of the increase in trigly cerides and cholesterol levels.

Macrophage-granulocyte colony-stimulating factor and fibroblast growth factor in the blood of patients with hyperlipoproteinemia.

Solid-phase ELISA revealed increased content of macrophage-granulocyte colony-stimulating factor and basic fibroblast growth factor in the serum of hyperlipoproteinemic patients.

Severe hyperlipidemia-associated pregnancy: prevention in subsequent pregnancy by diet.

Severe hyperlipidemia-associated pregnancy: prevention in subsequent pregnancy by diet.

Short-term effects of statin therapy in patients with hyperlipoproteinemia after liver transplantation: results of a randomized cross-over trial

Background/Aims : Hyperlipoproteinemia is frequent following liver transplantation and may lead to atherosclerosis. Lipid-lowering agents may be useful, but could interfere with the function of the transplanted organ and with immunosuppression. We therefore evaluated in a prospective, randomized, open-labeled cross-over trial the effect of two frequently used 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (pravastatin 10 mg d −1 and cerivastatin 0.1 mg d −1) in hyperlipoproteinemic patients after liver transplantation. Methods : Sixteen patients (6.3±2.0 years post-transplantation, cyclosporine n =11, tacrolimus n =5) with hyperlipoproteinemia (cholesterol 246±42, triglycerides 191±87, low-density lipoprotein (LDL)-cholesterol 161±35, high-density lipoprotein (HDL)-cholesterol 44±11 mg dl −1) were included. Treatment periods of 6 weeks were separated by a 4-week washout period. Results : Both medications were tolerated well, no effects on serum concentrations of liver enzymes or immunosuppressive agents were observed. Cerivastatin and pravastatin decreased ( P <0.001) cholesterol by 21±10% and 15±10%, LDL-cholesterol by 27±14% and 17±15%, respectively, while triglyceride and HDL-cholesterol concentrations did not change significantly. LDL/HDL-cholesterol markedly improved ( P <0.001) by 29±16% (cerivastatin) and 16±16% (pravastatin). Cerivastatin was more potent than pravastatin in patients receiving cyclosporine A, while there was no significant difference in patients receiving tacrolimus. Conclusions : Low-dose cerivastatin and pravastatin significantly improve lipid profiles following liver transplantation without affecting liver function or immunosuppression.

Effects of Simvastatin on Serum Paraoxonase Activity

High density lipoprotein (HDL)-associated paraoxonase activity may play an important role in the inhibition of low density lipoprotein (LDL) oxidation. Previous studies have demonstrated that serum paraoxonase activity is decreased in patients with hyperlipoproteinaemia and coronary heart disease, and a few investigators have suggested that the lipid-lowering statins may increase paraoxonase levels. To examine the effect of short-term treatment with simvastatin on lipids and paraoxonase activity in patients with hyperlipoproteinaemia. Prospective nonblind single-group sequential study. 112 (52 male and 60 female) hyperlipoproteinaemic patients with Fredrickson type IIa and IIb hyperlipoproteinaemia (mean age 52.15 ± 7.99 years, mean body mass index 27.53 ± 4.30 kg/m2). Serum cholesterol, lipoproteins, triglycerides, apolipoproteins and liver function were measured, and serum paraoxonase activity was determined spectrophotometrically using paraoxon as substrate. Simvastatin 20 mg/day was administered for 1 month, and measurements were repeated. Simvastatin significantly decreased serum cholesterol [from 10.25 ± 2.73 (SD) to 8.85 ± 2.02 mmol/L], triglyceride (from 3.95 ± 2.51 to 3.15 ± 1.47 mmol/L), LDL (from 6.36 ± 1.70 to 4.94 ± 1.48 mmol/L) and apolipoprotein B100 (from 1.93 ± 0.41 to 1.56 ± 0.35 g/L) levels, whereas HDL and apo A1 levels did not change significantly (from 1.19 ± 0.34 to 1.22 ± 0.39 mmol/L, and from 1.56 ± 1.99 to 1.64 ± 0.24 g/L, respectively). HDL-associated paraoxonase activity did not change significantly (from 182.25 ± 37.21 to 166.49 ± 35.01 U/L) after simvastatin therapy. Short-term administration of simvastatin did not increase the activity of the HDL-associated antioxidant enzyme paraoxonase.

Low density lipoprotein (LDL) binding affinity for the LDL receptor in hyperlipoproteinemia

We measured the binding affinity of low density lipoprotein (LDL) for the LDL receptor in patients with various types of hyperlipoproteinemia and investigated the effects of LDL lipid composition and particle size on receptor affinity. LDL (1.019< d<1.063) was isolated by sequential ultracentrifugation from the serum of normolipidemic controls and patients with hyperlipoproteinemia. Patients with type IIa hyperlipoproteinemia had LDL with a similar receptor affinity to that of normal LDL. However, patients with hypertriglyceridemia (type IIb and type IV hyperlipoproteinemia) had LDL with a low receptor affinity, and the degree of the reduction in affinity paralleled the severity of the hypertriglyceridemia. The LDL of hypertriglyceridemic patients was rich in protein and triglycerides, had a low content of cholesterol and phospholipids, and was smaller than normal, thus resembling the atherogenic lipoprotein known as small, dense LDL. These abnormalities were observed even in patients with mild hypertriglyceridemia regardless of their serum cholesterol levels. The degree of alteration in LDL lipid composition and particle size was strongly associated with the reduction of LDL receptor affinity. We also examined the effects of two lipid-lowering agents (bezafibrate and probucol) on the characteristics of LDL. LDL receptor affinity was only improved when the lipid composition and particle size were normalized by drug therapy. Although it has been reported that decreased cholesteryl ester transfer protein (CETP) activity results in the formation of small LDL, plasma CETP activity was normal in the hyperlipoproteinemic patients and the normalization of LDL characteristics by drug therapy was not accompanied by an increase of CETP activity. Our results suggested that an abnormal lipid composition and/or small particle size might cause a decrease in the receptor affinity of LDL. These structural and functional abnormalities were reversed by drug therapy, underlining the importance of treating hypertriglyceridemia for the prevention of atherosclerosis.

Paraoxonase and arylesterase activities in the serum of two hyperlipoproteinaemic patients after repeated extracorporal lipid precipitation

The effect of heparin-induced extracorporal lipid precipitation (HELP) on the activities of paraoxonase (EC 3.1.8.1) and arylesterase (EC 3.1.1.2) was studied in serum of a patient with hyperlipoproteinaemia (A) and of a patient with non-insulin dependent diabetes mellitus and hyperlipoproteinaemia (B). The enzyme activities were measured spectrophotometrically (Tris–HCl buffer, pH 7.4, 37°C) with paraoxon and phenylacetate as substrates of paraoxonase and arylesterase, respectively. Both patients underwent HELP applications once a week over a period of 7 weeks. Over that period no overall change was observed either in enzyme activities or in the lipid and protein content of the sera. However, each HELP session caused an immediate decrease of EDTA-insensitive arylesterase activity (on average 56% in A and 42% in B), while EDTA-sensitive arylesterase remained almost unaltered. Paraoxonase remained unchanged in A, but decreased in B (∼60%). Of the atherogenic lipoprotein parameters, the most pronounced decrease was found in VLDL-cholesterol and in triglycerides (on average 45% in A and 32% in B), while the anti-atherogenic HDL-cholesterol decreased <10%. Possible implications of the effect of HELP on the enzyme activities studied remain to be explained.

Low density lipoprotein apolipoprotein B metabolism: comparison of two methods to establish kinetic parameters

Elevated plasma cholesterol concentrations represent a major risk factor for coronary artery disease (CAD). Low density lipoprotein (LDL)-apolipoprotein (apo) B plays a key role in this process. Metabolic parameters of LDL-apoB such as fractional catabolic rate (FCR) and production rate help to understand the underlying pathomechanisms of elevated LDL-apoB and are usually determined with tracer studies (gold-standard). However, these parameters can also be calculated from the rebound of plasma LDL-apoB concentration following a perturbation such as apheresis, if it is assumed that the perturbation itself does not affect metabolic parameters. LDL-apoB metabolism was determined using two methods in eight hyperlipoproteinemic patients (47±15 years, body mass index (BMI) 27.5±4.1 kg/m): (a) by endogenous labeling using D 3-leucine (bolus 5 mg/kg) as tracer and multicompartmental modeling; and (b) by fitting a monoexponential equation to LDL-apoB rebound concentration data following apheresis. LDL-apoB metabolic parameters determined using the two methods (mean±S.D.; FCR-tracer: 0.18±0.07 per day, FCR-rebound: 0.27±0.25 per day; production-tracer: 12.0±3.9 mg/kg per day; production-rebound: 15.2±8.0 mg/kg per day) were not correlated, were not concordant (intraclass correlation coefficient), and were not significantly different. Furthermore, only in five of the eight patients the rebound analysis predicted LDL-apoB steady-state concentrations that were within 20% of observed steady-state concentrations. These results indicate that parameters derived from LDL-apoB mass rebound following apheresis cannot be used as a surrogate for parameters established with tracer methodology probably because the assumption that apheresis does not affect metabolic parameters of LDL-apoB may not be true in all patients.

Characterization of remnant-like particles isolated by immunoaffinity gel from the plasma of type III and type IV hyperlipoproteinemic patients

Previous studies have investigated the potential atherogenicity and thrombogenicity of triglyceride-rich lipoprotein (TRL) remnants by isolating them from plasma within a remnant-like particle (RLP) fraction, using an immunoaffinity gel containing specific anti-apoB-100 and anti-apoA-I antibodies. In order to characterize lipoproteins in this RLP fraction and to determine to what extent their composition varies from one individual to another, we have used automated gel filtration chromatography to determine the size heterogeneity of RLP isolated from normolipidemic control subjects (n = 8), and from type III (n = 6) and type IV (n = 9) hyperlipoproteinemic patients, who by selection had similarly elevated levels of plasma triglyceride (406 ± 43 and 397 ± 35 mg/dl, respectively). Plasma RLP triglyceride, cholesterol, apoB, apoC-III, and apoE concentrations were elevated 2- to 6-fold (P < 0.05) in hyperlipoproteinemic patients compared to controls. RLP fractions of type III patients were enriched in cholesterol and apoE compared to those of type IV patients, and RLP of type IV patients were enriched in triglyceride and apoC-III relative to those of normolipidemic subjects. In normolipidemic subjects, the majority of RLP had a size similar to LDL or HDL. The RLP of hyperlipoproteinemic patients were, however, larger and were similar in size to TRL, or were intermediate in size (i.e., ISL) between that of TRL and LDL. Compared to controls, ISL in the RLP fraction of type III patients were enriched in apoE relative to apoC-III, whereas in type IV patients they were enriched in apoC-III relative to apoE. These results demonstrate that: 1) RLP are heterogeneous in size and composition in both normolipidemic and hypertriglyceridemic subjects, and 2) the apoE and apoC-III composition of RLP is different in type III compared to type IV hyperlipoproteinemic patients.—Marcoux, C., M. Tremblay, K. Nakajima, J. Davignon, and J. S. Cohn. Characterization of remnant-like particles isolated by immunoaffinity gel from the plasma of type III and type IV hyperlipoproteinemic patients. J. Lipid Res. 1999. 40: 636–647.

The Serum Paraoxonase Activity in Patients with Chronic Renal Failure and Hyperlipidemia

Human serum paraoxonase is physically associated with an apolipoprotein (Apo-A₁) and clusterin-containing high-density lipoprotein (HDL) and prevents low-density lipoprotein from lipid peroxidation. The aim of our study was to determine whether paraoxonase activity or phenotype is altered in patients with chronic renal failure and in hyperlipidemic subjects without renal insufficiency and to compare the values with those of healthy controls. We investigated the serum paraoxonase activity and polymorphism in 119 hemodialyzed uremic patients, 107 patients with primary hyperlipoproteinemia, and in 110 healthy control subjects. The serum paraoxonase activity was significantly decreased both in hyperlipidemic (p < 0.01) and uremic patients (p < 0.001) as compared with controls. On comparison, the serum paraoxonase activity was significantly lower (p < 0.001) in uremic than in hyperlipoproteinemic patients. The HDL and Apo-A₁ levels were as follows: uremic < hyperlipidemic < control. To assess whether the observed reduction in paraoxonase activity was due to HDL and Apo-A₁ level decreases, we standardized the enzyme activity for HDL and Apo-A₁ concentrations. We found that the standardized paraoxonase activity (paraoxonase/HDL ratio) was also lower in the uremic patients (103.3 ± 69.5) as compared with hyperlipidemic patients (137.64 ± 81.0) and controls (194.45 ± 94.45). The standardized values for Apo-A₁ showed a similar tendency: paraoxonase/Apo-A₁ ratio in uremic patients 89.64 ± 47.8, in hyperlipidemic patients 128.12 ± 69.83, and in controls 161.40 ± 47.35. The phenotypic distribution of paraoxonase (AA, AB, BB) did not change significantly in the patient groups. These results suggest that HDL concentration and phenotypic distribution of paraoxonase may not be the only determining factors, but that other as yet undetermined factors could be involved in the enzyme activity changes.

A competitive reverse transcription–PCR to study apolipoprotein ε gene expression

We developed a rapid and simple competitive reverse transcription-polymerase chain reaction for the quantification of apo epsilon mRNA in human monocyte-derived macrophages. The method was applied, and its reliability was shown in patients with the familial lipoprotein disorder, type III hyperlipoproteinemia. Type III hyperlipoproteinemic patients express markedly higher concentrations of apo epsilon mRNA when compared with healthy controls. Patients with this disease are usually (>90%) homozygous for a receptor binding-defective isoform of apolipoprotein apo E (apo E2). The higher expression of apo epsilon mRNA in the patients could, therefore, be a physiological mechanism to compensate for functionally defective apo E. The developed procedure might be valuable in assessment of apo epsilon gene expression in human disease.

Human β-migrating very low density lipoprotein induces foam cell formation in human mesangial cells

To elucidate the mechanism of foam cell formation in the mesangial region of a kidney observed in a familial type III hyperlipoproteinemic patient presenting with diabetes mellitus and nephrotic syndrome, we have examined, in the present study, the effect of human β-VLDL (apo E2/E2) on foam cell formation in human mesangial cells, since an increase in β-VLDL is a characteristic feature of this patient. Human β-VLDL (apo E2/E2) induced foam cell formation in human mesangial cells. The binding of [ 125I]LDL to human mesangial cells was inhibited completely by both LDL and β-VLDL. On the other hand, the binding of [ 125I] β-VLDL was completely inhibited by β-VLDL, but partially by LDL. The LDL receptor, but not the VLDL receptor was down-regulated by accumulation of cholesteryl esters. These results suggest that human β-VLDL (apo E2/E2)-induced foam cell formation in mesangial cells is mediated through both the LDL receptor pathway and the β-VLDL specific pathway, in which the VLDL receptor is one of the candidates.

4.P.108 Glucose tolerance and fatty acid composition of the major plasma lipid classes in hyperlipoproteinemic patients

4.P.108 Glucose tolerance and fatty acid composition of the major plasma lipid classes in hyperlipoproteinemic patients

2.P.52 Comparison of type II hyperlipoproteinemic patients with apoprotein E2, E3, and E4 phenotypes with respect to the response of plasma levels of lipids and apoproteins to simvastatin

2.P.52 Comparison of type II hyperlipoproteinemic patients with apoprotein E2, E3, and E4 phenotypes with respect to the response of plasma levels of lipids and apoproteins to simvastatin

Disturbances in dietary fat metabolism and their role in the development of atherosclerosis

It was suggested that postprandial lipoproteins (PPLp) may play an important role in atherogenesis. To examine this hypothesis, we studied PPLp metabolism in normolipidemic individuals and hyperlipoproteinemic (HLP) patients on various diets, physical activity programs and hypolipidemic drugs as well as in patients with coronary artery disease (CAD). We used the vitamin A-fat loading test, which labels intestinally derived lipoproteins with retinyl palmitate. Type IV HLP patients demonstrated a severe defect in chylomicron clearance. Type III HLP patients showed severely disordered clearance of chylomicron remnants. Compared to the saturated fatty acid enriched diet, the omega 6 polyunsaturated acid enriched diet reduced chylomicrons and their remnant levels by 56% and 38%, respectively. The diet enriched in omega 3 polyunsaturated acid decreased chylomicrons and their remnant levels by 67% and 53%, respectively. Physical conditioning reduced chylomicron levels by 37%. Gemfibrozil decreased chylomicron levels in type IV HLP patients. Cholestyramine increased chylomicron levels by 88%. Bezafibrate reduced chylomicrons and their remnants levels and increased fasting HDL-C in patients with isolated low HDL-C levels. Continuous prolonged intravenous heparin administration inhibited chylomicron clearance. Normolipidemic patients with CAD had significantly higher plasma levels of chylomicron remnants than matched controls with normal coronary arteries. The studies reported here demonstrate that both chylomicrons and their remnants are present in the plasma of normolipidemic people and more so for hyper- or dyslipidemic patients for a prolonged period of time after fat ingestion. The duration and magnitude of this postprandial lipemia can be regulated or altered by such interventions as diet, physical activity, and drugs. Our case control studies strongly support the hypothesis that PPLp may play a crucial part in atherogenesis, and therefore justify measuring their levels in high risk patients. We believe that in selected patient groups the use of one or more of the interventions mentioned here is warranted.

Plasma lipoprotein distribution of apoC-III in normolipidemic and hypertriglyceridemic subjects: comparison of the apoC-III to apoE ratio in different lipoprotein fractions

In order to assess the relationship between plasma accumulation of triglyceride-rich lipoproteins (TRL) and lipoprotein levels of apoC-III and apoE, we have measured apoC-III and apoE in lipoproteins separated according to size (by automated gel filtration chromatography) from plasma of normolipidemic subjects (plasma triglyceride (TG): 0.84 +/- 0.10 mmol/l; mean +/- SE, n = 8), and from type III (n = 8) and type IV (n = 8) hyperlipoproteinemic patients, matched for plasma TG (5.76 +/- 0.62 v 5.55 +/- 0.45 mmol/l, resp.). Total plasma apoC-III concentration was similar in type III and type IV patients (33.1 +/- 3.4 v 37.6 +/- 4.4 mg/dl, respectively), but was significantly increased compared to normolipidemic controls (10.0 +/- 1.0 mg/dl, P < 0.001). TRL apoC-III was lower and high density lipoprotein (HDL) apoC-III was significantly higher in type III versus type IV subjects (14.8 +/- 3.2 vs. 22.8 +/- 3.0 mg/dl, P < 0.05; 8.3 +/- 1.0 vs. 5.2 +/- 0.5 mg/dl, P < 0.05). Plasma concentration of apoC-III in lipoproteins that eluted between TRL and HDL (intermediate-sized lipoproteins, ISL) was similar in the two hypertriglyceridemic groups (10.1 +/- 1.3 vs. 9.7 +/- 1.6 mg/dl), but was significantly higher (P< 0.05) than controls (2.2 +/- 0.3 mg/dl). TRL, ISL, and HDL apoE concentrations were significantly higher in type III versus type IV subjects (P < 0.05). All lipoprotein fractions in type III patients were characterized by lower apoC-III to apoE ratios. In contrast, the TRL apoC-III to apoE ratio of type IV patients was similar and the ISL apoC-III to apoE ratio was significantly higher, compared to normolipidemic individuals. These results indicate that compared to normolipidemic individuals, remnant-like lipoproteins in the ISL fraction of type IV patients are enriched in apoC-III relative to apoE, whereas those of type III patients are enriched in apoE relative to apoC-III.

Uptake of chylomicrons by the liver, but not by the bone marrow, is modulated by lipoprotein lipase activity.

We have shown that chylomicrons are catabolized by the liver and bone marrow in rabbits and marmosets. In the present investigation, we studied the role of various apolipoproteins and lipoprotein lipase in the clearance of these particles by the liver and bone marrow in rabbits. Incubation of chylomicrons with purified apolipoprotein (apo) E or C-II resulted in more rapid clearance of these particles from the plasma, whereas incubation of chylomicrons with apoA-I, apoC-I, apoC-III1, or apoC-III2, did not affect their clearance rates. Analysis of tissue uptake revealed that the increased plasma clearance rate of chylomicrons enriched with apoE or apoC-II was primarily due to enhanced uptake by the liver. The uptake of chylomicrons by the bone marrow increased after their enrichment with apoA-I but decreased after their enrichment with apoC-II. Because apoC-II is a cofactor for lipoprotein lipase, we hypothesized that the increased clearance rates were due to faster hydrolysis of chylomicrons and rapid generation of chylomicron remnants. To test this hypothesis, lipoprotein lipase activity was inhibited by injection of an antilipoprotein lipase monoclonal antibody. Inhibition of lipoprotein lipase retarded clearance of chylomicrons from the plasma and decreased their uptake by the liver but did not affect their uptake by the bone marrow. These studies suggest that bone marrow can take up chylomicrons in the absence of lipoprotein lipase activity and provide an explanation for the presence of foam cells in the bone marrow of type I hyperlipoproteinemic patients.

High resolution lh nmr spectra of human apolipoprotein C-iii2 using DPC to model the lipoprotein environment

Abstract: While the apolipoproteins play a central biochemical role in lipid transportation and cardiovascular diseases, structural studies of the apolipoproteins have been primarily confined to optical spectroscopies (circular dichroism and fluorescence). Using deuterated dodecylphosphocholine (DPC) to model the lipoprotein environment, we report the acquisition of high resolution lH NMR spectra for human apolipoprotein C-III2 isolated from the plasma of a type V hyperlipoproteinemic patient. At a peptide:DPC ratio of 1:60 the pK8 of His1s was determined to be 6.15 suggesting the residue is solvent accessible.

Effects of pravastatin sodium and simvastatin on plasma fibrinogen level and blood rheology in type II hyperlipoproteinemia

Elevated plasma fibrinogen level is known to progress atherosclerosis and to be one of the risk factors for the occurrence of cardiovascular diseases. The objective of this study is to evaluate the changes in plasma fibrinogen level and blood rheology in patients with type II hyperlipoproteinemia before and after random administrations of HMG-CoA (3-hydroxy-3-methylglutaryl-cocarboxylase-A) reductase inhibitors, pravastatin sodium and simvastatin, and compare with results in normal subjects. Of a total of 28 patients with type II primary hyperlipoproteinemia with >230 mg/dl fasting total plasma cholesterol, 16 patients (mean, 59.7 years old) were administered 10–15 mg/day of pravastatin sodium for an average of 10.2 weeks, and 12 patients (mean, 62.0 years old) were administered 5–10 mg/day of simvastatin for an average of 13.9 weeks. Patients were evaluated before and after drug administration and results were compared with those of 16 normal subjects of similar age (mean, 56.9 years old). Blood viscosities were measured using a cone-plate viscometer (Biorheolizer, BRL-1000, Japan). The following were measured before and after drug administration: whole blood viscosity at shear rates of 75–375 s −1, corrected blood viscosity at low (112.5 s −1) and high (225.0 s −1) shear rates for the standard hematocrit of 45%, plasma viscosity, hematocrit, total protein, serum albumin, and plasma fibrinogen. Total cholesterol level was significantly decreased (from 270 to 225, mg/dl, mean values; P < 0.0007) an average of 10.2 weeks after start of pravastatin sodium administration. In addition to the reductions of whole blood viscosity, at every shear rate examined, corrected blood viscosity, and plasma viscosity, plasma fibrinogen levels were significantly decreased (from 354 to 309 mg/dl, mean values; P < 0.0007) after start of pravastatin sodium administration. Fibrinogen level and blood rheology were not significantly changed after start of simvastatin administration despite similar significant reductions in total cholesterol level (from 260 to 207 mg/dl, mean values; P < 0.0001) to those in the case of pravastatin sodium. From the results, we conclude that administration of pravastatin sodium, but not simvastatin, reduced the plasma fibrinogen level and blood viscosities to normal levels in type II hyperlipoproteinemic patients while both drugs reduced total cholesterol level. The hydrophilicity and a small binding capacity with plasma protein of pravastatin sodium may be responsible in part for the beneficial hemorheologic effects observed in the patients with type II hyperlipoproteinemia. Further investigations should be conducted to confirm the findings observed.