Rouffy J, Chanu B, Bakir R, Sauvanet J P
J Pharmacol. 1983;14 Suppl 2:183-99.
It is certain that atherosclerosis is multi-factorial. Amongst the numerous risk factors two are particularly important: hypertension and primary or secondary abnormalities of plasma lipids and lipoproteins (high levels of total cholesterol, LDL and VLDL cholesterol, triglycerides or VLDL triglycerides, apoprotein B, low levels of HDL cholesterol, apoprotein A1 and probably HDL2). On the basis of a general review of the literature, the authors evaluate the changes in lipids, lipoproteins and apoproteins induced by different beta-blockers. Overall, the most constant and most obvious (particularly in hyperlipidaemic patients) disturbances combine an increase in total triglycerides or VLDL triglycerides and a fall in HDL cholesterol. There is little change in total cholesterol or LDL cholesterol. Side effects seen with most beta-blockers, cardioselective or not, differ in degree from one drug to another. They are particularly marked with some (propranolol) while they are virtually absent with others (pindolol). The mechanism of action is discussed (essentially inhibition of extra-hepatic lipoprotein lipase activity). These findings would seem to lead to the following practical conclusions: 1) Before starting antihypertensive treatment it is important to confirm lipid and lipoprotein levels, particularly bearing in mind the epidemiological links between moderate essential hypertension and lipoprotein abnormalities, especially those with a component of hypertriglyceridaemia. 2) Lipid profile including estimation by precipitation of HDL cholesterol must be studied during antihypertensive therapy and if there is a marked and confirmed deterioration towards an "increased atherogenicity", it is reasonable to envision a change of the antihypertensive agent. With the some efficacy on blood pressure levels and general tolerance, the choice should favour drugs having the least unfavourable effects on lipoprotein metabolism.
动脉粥样硬化是多因素导致的,这一点是确定无疑的。在众多风险因素中,有两个因素尤为重要:高血压以及血浆脂质和脂蛋白的原发性或继发性异常(总胆固醇、低密度脂蛋白和极低密度脂蛋白胆固醇、甘油三酯或极低密度脂蛋白甘油三酯、载脂蛋白B水平升高,高密度脂蛋白胆固醇、载脂蛋白A1以及可能还有高密度脂蛋白2水平降低)。基于对文献的全面综述,作者评估了不同β受体阻滞剂引起的脂质、脂蛋白和载脂蛋白变化。总体而言,最持续且最明显的紊乱(尤其是在高脂血症患者中)是总甘油三酯或极低密度脂蛋白甘油三酯升高以及高密度脂蛋白胆固醇降低。总胆固醇或低密度脂蛋白胆固醇变化不大。大多数β受体阻滞剂(无论是否具有心脏选择性)的副作用在程度上因药物而异。某些药物(普萘洛尔)的副作用尤为明显,而其他一些药物(吲哚洛尔)几乎没有副作用。文中讨论了其作用机制(主要是抑制肝外脂蛋白脂肪酶活性)。这些发现似乎可得出以下实际结论:1)在开始抗高血压治疗前,重要的是确认脂质和脂蛋白水平,尤其要考虑到中度原发性高血压与脂蛋白异常之间的流行病学联系,特别是那些伴有高甘油三酯血症成分的情况。2)在抗高血压治疗期间必须研究包括通过沉淀法估算高密度脂蛋白胆固醇在内的血脂谱,如果出现明显且经确认的向“致动脉粥样硬化性增加”的恶化情况,则有理由考虑更换抗高血压药物。在对血压水平和总体耐受性有相同疗效的情况下,选择应倾向于对脂蛋白代谢不利影响最小的药物。