Tsuda Y, Satoh K, Kitadai M, Takahashi T, Izumi Y, Hosomi N
Second Department of Internal Medicine, Kagawa Medical School, Japan.
Atherosclerosis. 1996 May;122(2):225-33. doi: 10.1016/0021-9150(95)05757-9.
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-e-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.
众所周知，血浆纤维蛋白原水平升高会促进动脉粥样硬化发展，是心血管疾病发生的危险因素之一。本研究的目的是评估II型高脂蛋白血症患者在随机服用HMG-CoA（3-羟基-3-甲基戊二酰辅酶A）还原酶抑制剂普伐他汀钠和辛伐他汀前后血浆纤维蛋白原水平和血液流变学的变化，并与正常受试者的结果进行比较。在总共28例空腹总血浆胆固醇>230mg/dl的II型原发性高脂蛋白血症患者中，16例患者（平均59.7岁）每天服用10 - 15mg普伐他汀钠，平均服用10.2周，12例患者（平均62.0岁）每天服用5 - 10mg辛伐他汀，平均服用13.9周。在给药前后对患者进行评估，并将结果与16例年龄相仿的正常受试者（平均56.9岁）的结果进行比较。使用锥板粘度计（日本Biorheolizer，BRL - 1000）测量血液粘度。在给药前后测量以下指标：剪切速率为75 - 375s⁻¹时的全血粘度、标准血细胞比容为45%时低（112.5s⁻¹）剪切速率和高（225.0s⁻¹）剪切速率下的校正血液粘度、血浆粘度、血细胞比容、总蛋白、血清白蛋白和血浆纤维蛋白原。开始服用普伐他汀钠平均10.2周后，总胆固醇水平显著降低（从270降至225mg/dl，平均值；P < 0.0007）。除了全血粘度、在所检测的每个剪切速率下的校正血液粘度和血浆粘度降低外，开始服用普伐他汀钠后血浆纤维蛋白原水平也显著降低（从354降至309mg/dl，平均值；P < 0.0007）。开始服用辛伐他汀后，尽管总胆固醇水平与普伐他汀钠组有相似的显著降低（从260降至207mg/dl，平均值；P < 0.0001），但纤维蛋白原水平和血液流变学没有显著变化。从结果来看，我们得出结论，在II型高脂蛋白血症患者中，服用普伐他汀钠而非辛伐他汀可将血浆纤维蛋白原水平和血液粘度降低至正常水平，而两种药物均可降低总胆固醇水平
