Stein E A, Lane M, Laskarzewski P
Medical Research Laboratories, Highland Heights, Kentucky 41076, USA.
Am J Cardiol. 1998 Feb 26;81(4A):66B-69B. doi: 10.1016/s0002-9149(98)00041-1.
In 1996, the first 2 studies using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor ("statin") therapy in hypertriglyceridemic subjects were published. In subjects with isolated triglyceride elevations who were treated with atorvastatin 5, 20, and 80 mg/day, large and dose-related reductions were noted. In subjects with combined hyperlipidemia treated with 10 mg simvastatin, triglyceride reduction similar to that reported for the 5 mg atorvastatin dose was seen. In response to these findings, we conducted comparative assessments to determine whether all statins are effective in lowering triglyceride levels and whether their effect on triglycerides is related to factors such as drug, dose, and baseline triglyceride levels. To standardize these assessments, we devised a ratio that related changes in triglyceride levels to the known predictable response of low-density lipoprotein (LDL) cholesterol to statins. This triglyceride/LDL cholesterol ratio was obtained by dividing the percent change from baseline in the triglyceride level by the percent change from baseline in the LDL cholesterol level. The triglyceride/LDL cholesterol ratio was initially applied to several published studies, and found to be approximately 1.0 and 0.5 in hypertriglyceridemic and nonhypertriglyceridemic populations, respectively. We then assessed the effect of various statins on triglycerides using a pooled laboratory database of 2,689 subjects who had participated in 7 separate studies with similar designs. All of the studies had a placebo run-in followed by a randomized, double-blind, active treatment phase of at least 4 weeks with a statin. Entry into these studies required a triglyceride level of <400 mg/dL. In subjects with baseline triglyceride >250 mg/dL, significant and dose-dependent reductions in triglyceride of 22-45% were seen with all statins. When baseline triglyceride was <150 mg/dL, no significant or dose-dependent effect on triglyceride was seen. The triglyceride/LDL cholesterol ratio was evaluated using a linear model that included baseline triglyceride level, drug, and dose. Only the baseline triglyceride level was significantly (p <0.001) related to this ratio. Moreover, the triglyceride/LDL cholesterol ratio was fairly constant across all statins and doses for patients with baseline triglyceride levels of <150 mg/dL, 150-250 mg/dL, and >250 mg/dL, at 0.0+/-0.3, 0.5+/-0.2, and 1.2+/-0.3, respectively. We conclude that all statins are effective in decreasing triglyceride levels, but only in hypertriglyceridemic patients. Due to the relatively constant triglyceride/LDL cholesterol ratio, our analysis indicates that the more effective the statin is in decreasing LDL cholesterol, the more effective it will also be in decreasing triglyceride levels in patients with hypertriglyceridemia.
1996年，发表了首批两项在高甘油三酯血症患者中使用3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂（“他汀类药物”）治疗的研究。在接受每日5毫克、20毫克和80毫克阿托伐他汀治疗的单纯甘油三酯升高患者中，观察到甘油三酯有大幅度且与剂量相关的降低。在接受10毫克辛伐他汀治疗的混合性高脂血症患者中，甘油三酯降低情况与报道的5毫克阿托伐他汀剂量相似。针对这些研究结果，我们进行了比较评估，以确定所有他汀类药物在降低甘油三酯水平方面是否有效，以及它们对甘油三酯的影响是否与药物、剂量和基线甘油三酯水平等因素有关。为了使这些评估标准化，我们设计了一个比率，将甘油三酯水平的变化与低密度脂蛋白（LDL）胆固醇对他汀类药物的已知可预测反应联系起来。这个甘油三酯/LDL胆固醇比率是通过将甘油三酯水平相对于基线的百分比变化除以LDL胆固醇水平相对于基线的百分比变化得出的。该甘油三酯/LDL胆固醇比率最初应用于几项已发表的研究，发现在高甘油三酯血症人群和非高甘油三酯血症人群中分别约为1.0和0.5。然后，我们使用一个汇集的实验室数据库评估了各种他汀类药物对甘油三酯的影响，该数据库包含2689名参与了7项设计相似的独立研究的受试者。所有研究都有一个安慰剂导入期，随后是至少4周的他汀类药物随机、双盲、积极治疗阶段。参与这些研究要求甘油三酯水平<400毫克/分升。在基线甘油三酯>250毫克/分升的受试者中，所有他汀类药物均使甘油三酯显著且呈剂量依赖性降低22% - 45%。当基线甘油三酯<150毫克/分升时，未观察到对甘油三酯有显著或剂量依赖性影响。使用包含基线甘油三酯水平、药物和剂量的线性模型评估甘油三酯/LDL胆固醇比率。只有基线甘油三酯水平与该比率显著相关（p<0.001）。此外，对于基线甘油三酯水平<150毫克/分升、150 - 250毫克/分升和>250毫克/分升的患者，所有他汀类药物和剂量的甘油三酯/LDL胆固醇比率相当恒定，分别为0.0±0.3、0.5±0.2和1.2±0.3。我们得出结论，所有他汀类药物在降低甘油三酯水平方面均有效，但仅对高甘油三酯血症患者有效。由于甘油三酯/LDL胆固醇比率相对恒定，我们的分析表明，他汀类药物降低LDL胆固醇越有效，其降低高甘油三酯血症患者甘油三酯水平的效果也越显著。
