孟鲁司特和小剂量氨茶碱对哮喘患者心血管疾病危险因素的影响
2007/11/02
近年研究发现5脂氧化酶/白三烯代谢通路在心血管疾病的预防中可能发挥重要作用。作者观察了半胱胺酰白三烯受体拮抗剂－孟鲁司特和小剂量氨茶碱对哮喘患者脂质代谢和炎性标记物等心血管疾病危险因素的影响。
结果显示：与安慰剂组比较，服用孟鲁司特（10mg/d）的哮喘患者血清C反应蛋白水平显著降低，服用孟鲁司特或小剂量氨茶碱 (300mg/d) 的哮喘患者与心血管疾病相关的危险因素－血清总胆固醇、甘油三脂、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇水平显著下降。
由此可见，服用孟鲁司特或小剂量氨茶碱的哮喘患者与心血管疾病相关的危险因素－炎症指标和脂质水平显著下降，提示这些平喘药物能降低哮喘患者发生心血管疾病的风险。
（蔡闯 广州医学院第一附属医院 广州呼吸病研究所 510120 摘译）
（Chest. 2007;132:868-874）
The Effect of Montelukast and Low-Dose Theophylline on Cardiovascular Disease Risk Factors in Asthmatics.
Allayee H, Ph.D, Hartiala J, M.S, Lee W, M.P.H, Mehrabian M, Ph.D, Irvin CG, Ph.D, Conti DV, Lima JJ, Pharm.D.
Background . Recent studies have implicated the 5-lipoxygenase/leukotriene (5-LO/LT) pathway in cardiovascular disease (CVD), which may have important implications for asthmatics since several drugs that target this pathway are currently used to treat asthma. We sought to determine whether montelukast, a cysteinyl LT antagonist, and low-dose theophylline, affected serum inflammatory and lipid CVD risk factors in a recently completed clinical trial of asthmatics.
Methods. Patients were randomized to receive either montelukast (10mg/d), theophylline (300mg/d), or placebo. A baseline run-in period of 7-14 days was followed by treatment for 6 months. Serum levels of C-reactive protein (CRP), interleukin-6, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density cholesterol (HDL-C) were measured 1 and 6 months after treatment.
Results. Patients with moderate to severe asthma on montelukast (n=60) had significantly lower serum CRP compared to placebo (n=73) after 1 month (1.7mg/L vs. 3.2mg/L, respectively; P < 0.006) and 6 months of treatment (2.3mg/L vs. 3.5mg/L, respectively; P < 0.04). At both time points, serum levels of all lipids were also significantly lower in the montelukast and theophylline groups compared to placebo but these effects were primarily observed in individuals who were also using inhaled corticosteroids as monotherapy for asthma.
Conclusions. Asthmatics on montelukast and, to some extent, low-dose theophylline have lower levels of CVD-associated inflammatory biomarkers and lipid levels. These observations suggest these asthma medications may have some beneficial value in asthmatics with respect to CVD risk, although the effects on HDL-C levels should also be taken into consideration.
Keywords 5-Lipoxygenase, cardiovascular disease, inflammation, leukotriene inhibitors, lipids
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