【www.zhangdahai.com--党风廉正工作总结】
【摘要】 心房颤动是临床上最常见的心律失常之一,近年许多研究表明他汀类药物可以减少心房颤动的发生、发展和复发,但机制尚不清楚,可能与其抗炎和抗氧化,减少心肌纤维化,影响心房肌的结构重构与电重构,抑制肾素-血管紧张素系统的活性,抗动脉粥样硬化,降低心脏自主神经功能等作用有关。
【关键词】 他汀类药物;心房颤动;机制
心房颤动(Atrial fibrillation, Af)是临床上最常见的心律失常之一,其发生率在一般人群为0.4% ～1.0% ,在心血管病患者为4% ～40%[1]。房颤时,心房的辅助泵作用丧失,心输出量下降15% ～35%。老年患者的脑卒中约1/3是由房颤引起的。与窦性心律者相比,房颤患者远期心力衰竭、全因死亡的风险均增加。传统对房颤的治疗最主要的是节律和心室率控制两大方面, 同时进行合理的抗血栓治疗。关于其一级预防,除了从根本上治疗基础疾病和控制危险因素以外,目前还有较多证据支持一些非传统的抗心律失常药物如血管紧张素转化酶抑制剂 (ACEI)、血管紧张素ll受体阻断剂(ARB),他汀类药物等可用于房颤预防。
他汀类药物,即羟甲基戊二酸单酰辅酶A(3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors,HMG-CoA)还原酶抑制剂,随着临床的广泛应用及基础研究的的深入,发现其除了最早调脂作用外,还具有抑制炎症、改善内皮功能、抗血小板聚集、稳定动脉粥样斑块与抗心律失常等作用,从而也扩大了该类药物的应用范围,使其在心血管病防治方面的地位也日益受到重视。近年来对其在心房颤动的预防方面的研究较多,故就其在房颤中的作用及可能机制作一综述。
1 临床研究
1.1 预防房颤的发生 许多心血管病变,例如:瓣膜性心脏病、高血压、心肌梗死、心力衰竭等,都是与Af有关的独立危险因素。近年来不少研究表明他汀类药物对心血管病所致的房颤有预防作用。Young-Xu[2]等最早发现他汀类药物对稳定型冠心病患者有独立于调脂作用以外的预防Af发生的作用,并且存在明确的正性疗效/剂量反应关系。Hanna等[3]的一项前瞻性、纵向、多中心的研究显示他汀类药物治疗可显著降低左心室收缩功能减退患者的Af发病率(P3个月)进行电复律,转复后随访44个月,经多因素回归分析显示,服用他汀类药物组能显著降低Af复发率。0zaydin等[11]的前瞻性随机研究表明:对Af持续时间48 h以上的患者,阿托伐他汀能明显降低其Af复发的风险。Dernellis等[12]随访80例患有阵发性Af的患者6个月,发现阿托伐他汀治疗组的房颤发生率显著低于安慰剂组(P 2.1 抗炎和抗氧化机制作用 炎症改变心房组织心肌细胞的电生理,使心房肌的非均一性增加及传导速度减慢,有利于折返的形成,从而促进Af的发生和持续。C反应蛋白(CRP)是组织炎症反应敏感的标志物之一,可以间接反映局部炎症的程度。Kumagai K等[18]以无菌性心包炎致房颤的狗模型来研究他汀类药物抗房颤作用,结果发现,阿托伐他汀组的CRP水平明显降低(P [4] Adabag AS.Nelson DB,Bloomfield HE. Effects of statin therapy on preventing atrial fibrillation in coronary disease and heart failure. Am Heart J,2007,154(6):1140-1145.
[5] Dotani MI,Elnicki DM ,Jain AC,et al.Effect of preoperative statin therapy and cardiac outcomes after coronary artery bypass grafting.Am J Cardiol,2000,86(10):1128 -1130,A6.
[6] Ozaydin M,Dogan A,Varol E,et al.Statin use before by-pass surgery decreases the incidence and shortens the duration of postoperative atrial fibrillation .Cardiology,2007,107(2):117-121.
[7] Arribas-Leal JM,Pascual-Figal DA,Tomel-Osorio PL,et al.Epidemiology and new predictors of atrial fibrillation after coronary surgery.Rev Esp Cardiol,2007,60(8):841-847.
[8] Patti G,Chello M.Candura D,et al.Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery:results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After cardiac surgery) study.Circulation,2006,114(14):1455-1461.
[9] Virani SS, Nambi V,Razavi M,et al.Preoperative statin therapy is not associated with a decrease in the incidence of postoperative atrial fibrillation in patients undergoing cardiac surgery.Am Heart J,2008,155(3):541-546.
[10] Siu CW,Lau CP, Tse HF.Prevention of atria1 fibrillation recurrence by statin therapy in patients with lone atrial fibrillation after successful cardioversion.Am J Cardiol,2003,92(11):1343-1345.
[11] Ozaydin M,Varol E,Asian SM,et al.Effect of atorvastatin on the recurrence rates of atria1 fibrillation after electrical cardioversion. Am J Cardiol,2006,97(10):1490-1493.
[12] Dernellis J,Panaretou M.Effect of C-reactive protein reduction on paroxysmal atrial fibrillation.Am Heart J,2005,150(5):1064.e7-e12.
[13] 石 伟,刘增长,苏 立,殷跃辉。他汀类药物治疗心房颤动随机对照试验的Meta分析.中国�证医学杂志,2009,9(5):570-573.
[14] Tveit A,Grundtviq M,Gundersen T,et al.Analysis of pravastatin to prevent recurrence of atrial fibrilation after electrical cardioversion.Am J Cardio1.2004,93(6):780-782.
[15] Amit G,Katz A,Bar-On S,et al. Association of statin therapy and the risk of atrial fibrillation in patients with a permanent pacemaker.Clin Cardiol,2006,29(6):249-252.
[16] Chung MK,Martin DO,Sprecher D .et al.C-reactive protein elevation in patients
with atrial arrhythmias:inflammatory mechanisms and persistence of atrial fibrillation.Circulation,2001,104(24):2886-2991.
[17] Aviles RJ,Martin DO,Appenson-Hansen C.et al.1nflammation as a risk for atrial fibrillation.Circulation,2003,108(24):3006-3010.
[18] Kumagai K,Nakashima H,Saku K.The HMG-CoA reductase inhibitor atorvastatin prevents atrial fibrillation by inhibiting inflammation in a canine sterile pericarditis model.Cadiovasc Res,2004,62(1):105-111.
[19] Adam O ,Frost G,Custodis F,et al.Role of Racl GTPase activation in atrial fibrillation.J Am Coil Cardiol,2007,50(4):359-367.
[20] Landmesser U,Bahlmann F,Mueller M,et al.Simvastatin versus ezetimibe:pleiotropic and lipid-lowering effects on endothelial function in humans.Circulation,2005,111(18):2356-2363.
[21] 商丽华,胡大一 ,赵秀丽,等.普伐他汀对快速起搏心房肌结构重构的影响 .中华心律失常学杂志,2004,8(3):172-176.
[22] Marín F,Pascual DA,Roldán V,et al.Statins and postoperative risk of atrial fibrillation following coronary artery bypass grafting.Am J Cardiol,2006,97(1):55-60.
[23] Hayashidani S,Tsutsui H ,Shiomi T,et al.Fluvastatin,a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction.Circulation,2002,105(7):868-873.
[24] Porter KA,Turner NA,O’Regan DJ,et al.Simvastatin reduces human atrial myofibroblast proliferation independently of cholesterol lowering via inhibition of RhoA.Cardiovasc Res,2004,61(4):745-755.
[25] Botto GL,Luzi M,Sagone A.Atrial fibrillation:The remodelling phenomenon.Eur Heart J Suppl,2003,5(H):H1-H7.
[26] Tuininga YS,Wiesfeld AC,van Veldhuisen DJ,et al.Electrophysiological changes of angiotensin-converting enzyme inhibition after myocardial infarction.J Card Fail,2000,6(2):77-79.
[27] Gensini F,Padeletti L,Fatini C,et al.Angiotensin-converting enzyme and endothelial nitric oxide synthase polymorphisms in patients with atrial fibrillation.Pacing Clin Electrophysiol,2003,26(1pt2):295-298.
[28] Luo JD,Zhang WW ,Zhang GP,et al.Simvastatin inhibits cardiac hypertrophy and angiotensin-converting enzyme activity in rats with aortic stenosis.Clin Exp Pharmaco1 Physiol,1999,26(11):903-908.
[29] Tsai CT,Lai LP,Kuo KT,et al. Angiotensin II activates signal transducer and activators of transcription 3 via Racl in atrial myocytes and fibroblasts:implication for the therapeutic effect of statin in atrial structural remodeling.Circulation,2008,117(3):344-355.
[30] 王健,张学臻,黄文波,等.辛伐他汀对慢性心房重构犬心房肌细胞内游离钙的影响.山东医药,2006,46(28):25-26.
[31] Vaquero M,Caballero R,Gómez R,et al.Effects of atorvastatin and simvastatin on atrial plateau currents.J Mol Cell Cardiol,2007,42(5):931-945.
[32] 王耀辉,杨成明.他汀类药物对血管平滑肌细胞增殖的抑制机制.医学综述,2003,9(9):567-568.
[33] Pliquett RU,Cornish KG,Peuler JD,et al.Simvastatin normalizes autonomic neural control in experimental heart failure.Circulation,2003,107(19):2493-2498.
