Tonolo G, Melis M G, Formato M, Angius M F, Carboni A, Brizzi P, Ciccarese M, Cherchi G M, Maioli M
Chair of Metabolic Diseases, Institute of Clinica Medica, Department of Physiological, Biochemical and Cellular Sciences, University of Sassari, Italy.
Eur J Clin Invest. 2000 Nov;30(11):980-7. doi: 10.1046/j.1365-2362.2000.00735.x.
Experimental evidence indicates that statins might have direct vascular effects independently from low-density lipoprotein (LDL) cholesterol reduction and we reported that the reduction in urinary albumin excretion rate during Simvastatin treatment in type 2 diabetic patients was not correlated with LDL-cholesterol decrease. However in humans there are no data regarding possible additional effects of Simvastatin on blood pressure and urinary albumin excretion beyond its capacity to lower serum cholesterol.
Twenty-six microalbuminuric hypertensive type 2 diabetic patients (diastolic blood pressure - after four months wash-out from the previous antihypertensive therapy - consistently > 90 and < 100 mmHg; plasma LDL-cholesterol > 3.9 and < 6.5 mmol L-1) were enrolled in the study. In random order, these patients received Simvastatin (20 mg day-1) or Cholestyramine (6 g three times a day) for a period of 10 months and after three months of wash-out (cross-over) the sequence was reversed for an additional 10 months. Blood pressure, lipid parameters, glycated haemoglobin and urinary albumin excretion were measured during the study. Additionally, in eight patients, urinary glycosaminoglycan excretion (GAG) was also measured during the study.
Simvastatin and Cholestyramine were equally effective in reducing total and LDL cholesterol. Only during Simvastatin treatment a significant reduction in diastolic blood pressure and both 24 h urinary albumin and GAG excretion rates were observed, while no significant changes were seen with Cholestyramine treatment.
Our results clearly show for the first time that the reduction of blood pressure, together with 24 h urinary albumin excretion rate - two established cardiovascular risk factors, obtained during Simvastatin therapy in hypertensive type 2 diabetic patients - is in large part independent from the reduction of LDL Cholesterol.
实验证据表明，他汀类药物可能具有独立于降低低密度脂蛋白（LDL）胆固醇之外的直接血管效应，并且我们报道过，2型糖尿病患者在辛伐他汀治疗期间尿白蛋白排泄率的降低与LDL胆固醇的降低无关。然而，在人类中，尚无关于辛伐他汀除降低血清胆固醇能力之外对血压和尿白蛋白排泄可能存在的其他影响的数据。
26例微量白蛋白尿性高血压2型糖尿病患者（在前一次抗高血压治疗洗脱4个月后，舒张压持续＞90且＜100 mmHg；血浆LDL胆固醇＞3.9且＜6.5 mmol/L）被纳入研究。这些患者随机顺序接受辛伐他汀（20 mg/天）或考来烯胺（6 g，每日3次）治疗10个月，在3个月洗脱期（交叉）后，顺序颠倒再进行10个月治疗。研究期间测量血压、血脂参数、糖化血红蛋白和尿白蛋白排泄。此外，在8例患者中，研究期间还测量了尿糖胺聚糖排泄（GAG）。
辛伐他汀和考来烯胺在降低总胆固醇和LDL胆固醇方面同样有效。仅在辛伐他汀治疗期间观察到舒张压以及24小时尿白蛋白和GAG排泄率显著降低，而考来烯胺治疗未见显著变化。
我们的结果首次清楚地表明，在高血压2型糖尿病患者的辛伐他汀治疗期间获得的血压降低以及24小时尿白蛋白排泄率降低（两种已确定的心血管危险因素）在很大程度上独立于LDL胆固醇的降低。
