Department of Medicine, Division of General Internal Medicine 541, University Medical Center Nijmegen, University Hospital Nijmegen, PO Box 9101, 6500 HB, Nijmegen, The Netherlands,
Clin Drug Investig. 2000;20(2):67-79. doi: 10.2165/00044011-200020020-00001.
Hypercholesterolaemia is strongly associated with increased vessel wall thickness as measured by ultrasound. The question is whether aggressive cholesterol lowering with high-dose atorvastatin can alter intima media thickening to a greater extent than conventional therapy in patients with familial hypercholesterolaemia (FH). The baseline characteristics of a double-blind, randomised trial are described to determine whether two active treatments (high-dose atorvastatin 80mg versus conventional dose simvastatin 40mg), administered over a period of 2 years, may retard the process of intima media thickening in the carotid and femoral arteries of patients with FH.
325 patients with FH were randomised. Patients entered an 8-week placebo period in which all lipid-lowering medication was discontinued. Thereafter, baseline measurements of lipoprotein parameters and intima media thickness (IMT) of carotid and femoral artery were performed.
Baseline low density lipoprotein (LDL) cholesterol (±SD) levels were 8.11 ± 1.92 mmol/L (312 ± 73 mg/dl) in men and 8.22 ± 1.91 mmol/L (316 ± 73 mg/dl) in women, respectively. Mean posterior wall IMT in the left common carotid artery (CCA) was significantly greater in men (0.94 ± 0.29mm) compared with women (0.85 ± 0.20) [p < 0.05]. A similar difference was found for the internal carotid artery (ICA). In the carotid bifurcation, IMT was 1.20 ± 0.50mm in men and 1.1 ± 0.54mm in women. The IMT of the common femoral artery (CFA) was 2.03 ± 0.88mm in men with cardiovascular disease (CVD) and 1.63 ± 0.70mm in men without CVD (p < 0.05). Strikingly, plaques were present in all men and 95% of the women with CVD. The cholesterol-year score and HDL cholesterol levels partially explained the variation in IMT in the carotid bifurcation, whereas gender and smoking contributed to the variation in IMT in the CFA in this group of patients.
The patients participating in the Atorvastatin and Simvastatin on Atherosclerosis Progression (ASAP) trial constitute the largest well-documented FH population exhibiting marked increases in IMT of both carotid and femoral arteries and a very high prevalence of plaques, indicating extreme CVD risk. Since lipid-lowering therapy provides the highest benefit in precisely such patients, the ASAP trial will help assess whether aggressive LDL cholesterol intervention leads to retardation of subclinical atherosclerosis progression, as estimated with ultrasonographically assessed IMT.
超声检查显示，高胆固醇血症与血管壁增厚密切相关。问题是，与常规治疗相比，高剂量阿托伐他汀的强化降脂治疗是否能更大程度地改变家族性高胆固醇血症（FH）患者的内膜中层增厚。本文描述了一项双盲、随机试验的基线特征，以确定两种积极的治疗方法（高剂量阿托伐他汀 80mg 与常规剂量辛伐他汀 40mg），在 2 年的时间内，是否能延缓 FH 患者颈动脉和股动脉的内膜中层增厚过程。
325 例 FH 患者被随机分组。患者先进入为期 8 周的安慰剂期，在此期间停用所有降脂药物。然后，对脂蛋白参数和颈动脉及股动脉内膜中层厚度（IMT）进行基线测量。
男性和女性的基线低密度脂蛋白（LDL）胆固醇（±SD）水平分别为 8.11 ± 1.92mmol/L（312 ± 73mg/dl）和 8.22 ± 1.91mmol/L（316 ± 73mg/dl）。左颈总动脉（CCA）后壁 IMT 在男性中明显大于女性（0.94 ± 0.29mm 比 0.85 ± 0.20mm）[p<0.05]。颈内动脉（ICA）也存在类似的差异。在颈动脉分叉处，男性 IMT 为 1.20 ± 0.50mm，女性为 1.1 ± 0.54mm。男性股总动脉（CFA）的 IMT 为 2.03 ± 0.88mm，伴有心血管疾病（CVD）的男性为 1.63 ± 0.70mm（p<0.05）。值得注意的是，所有患有 CVD 的男性和 95%的女性均存在斑块。胆固醇年积分和高密度脂蛋白胆固醇水平部分解释了颈动脉分叉处 IMT 的变化，而性别和吸烟则导致了该组患者股动脉 IMT 的变化。
参加阿托伐他汀和辛伐他汀对动脉粥样硬化进展（ASAP）试验的患者构成了最大的、有充分记录的 FH 人群，他们的颈动脉和股动脉 IMT 明显增加，斑块的发生率非常高，表明存在极高的 CVD 风险。由于降脂治疗在这些患者中提供了最大的益处，因此 ASAP 试验将有助于评估强化 LDL 胆固醇干预是否会导致亚临床动脉粥样硬化进展的减缓，如超声评估 IMT 所估计的那样。
