Boquist S, Ruotolo G, Hellénius M L, Danell-Toverud K, Karpe F, Hamsten A
Department of Emergency and Cardiovascular Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Atherosclerosis. 1998 Apr;137(2):391-400. doi: 10.1016/s0021-9150(97)00278-5.
Beta-adrenergic receptor-blocking agents are commonly used for treatment of hypertension, angina pectoris and arrhythmias and as secondary prevention after myocardial infarction. The modest protection against myocardial infarction conferred by these compounds in primary-preventive studies has suggested that beneficial effects of beta-blockade are counteracted by known adverse influences on lipid and glucose metabolism. As most beta-blockers increase plasma triglycerides and decrease the high density lipoprotein (HDL) cholesterol concentration, a randomized, double-blind, cross-over study was conducted to evaluate whether a 12-week treatment with metoprolol (100 mg o.d.) or placebo affected the metabolism of postprandial triglyceride-rich lipoproteins in 15 middle-aged men with a modestly increased cardiovascular risk. Metoprolol treatment significantly increased the postprandial responses of very low density lipoprotein (VLDL) and VLDL remnants to a mixed meal-type of oral fat tolerance test. The effect was particularly prominent for larger (Svedberg flotation rate (Sf) > 400 and Sf 60-400) particle species (P < 0.001 in repeated measures ANOVA), whereas the smaller (Sf 20-60) particles were less affected (P < 0.05). The changes in the postprandial responses of the different VLDL species were mainly related to an effect on the fasting plasma concentrations, with limited or no influences on VLDL catabolism during the postprandial state. In contrast, metoprolol treatment did not significantly influence the postprandial responses of chylomicrons and chylomicron remnants. Notably, the enhanced fasting and postprandial triglyceridaemia during metoprolol treatment was neither accompanied by a rise in fasting or postprandial free fatty acid concentrations, nor by alterations of the glucose and insulin responses to a standard oral glucose challenge. The ensuing shift in the LDL particle size distribution towards smaller particles was limited (fraction small LDL: metoprolol 22.8 +/- 15.7% versus placebo 19.3 +/- 15.0%, P < 0.05). In conclusion, metoprolol treatment primarily enhances fasting and postprandial triglyceridaemia in middle-aged men by increasing the basal hepatic production of VLDL.
β-肾上腺素能受体阻滞剂常用于治疗高血压、心绞痛和心律失常，并作为心肌梗死后的二级预防用药。这些化合物在一级预防研究中对心肌梗死的保护作用有限，这表明β受体阻滞剂的有益作用被其对脂质和葡萄糖代谢的已知不良影响所抵消。由于大多数β受体阻滞剂会增加血浆甘油三酯并降低高密度脂蛋白（HDL）胆固醇浓度，因此进行了一项随机、双盲、交叉研究，以评估美托洛尔（每日100 mg）或安慰剂治疗12周是否会影响15名心血管风险略有增加的中年男性餐后富含甘油三酯脂蛋白的代谢。美托洛尔治疗显著增加了极低密度脂蛋白（VLDL）和VLDL残粒对混合餐型口服脂肪耐量试验的餐后反应。对于较大（斯维德伯格漂浮率（Sf）>400和Sf 60 - 400）的颗粒种类，这种影响尤为显著（重复测量方差分析中P<0.001），而较小（Sf 20 - 60）的颗粒受影响较小（P<0.05）。不同VLDL种类餐后反应的变化主要与对空腹血浆浓度的影响有关，对餐后状态下VLDL分解代谢的影响有限或无影响。相比之下，美托洛尔治疗对乳糜微粒和乳糜微粒残粒的餐后反应没有显著影响。值得注意的是，美托洛尔治疗期间空腹和餐后甘油三酯血症的增强既没有伴随着空腹或餐后游离脂肪酸浓度的升高，也没有伴随着对标准口服葡萄糖刺激的葡萄糖和胰岛素反应的改变。随后低密度脂蛋白颗粒大小分布向较小颗粒的转变有限（小LDL比例：美托洛尔22.8±15.7%，安慰剂19.3±15.0%，P<0.05）。总之，美托洛尔治疗主要通过增加肝脏基础VLDL生成来增强中年男性的空腹和餐后甘油三酯血症。
