急性ST段抬高型心肌梗死患者经皮冠状动脉介入治疗术前血清醛固酮水平与冠脉病变及近期预后的相关性研究
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摘要
目的探讨在急性ST段抬高型心肌梗死(STEMI)患者中发病初期的血清醛固酮(A1d)水平是否可以预测血管病变的范围,是否与近期预后有关。
方法入选天津医科大学第二医院心脏科2008年3月-10月于CCU连续收入院的67例急性ST段抬高型心肌梗死患者,行经皮冠状动脉介入治疗术(PCI),术前股动脉穿刺后留取血清,采用放射免疫法(RIA)测定血清醛固酮水平。采集患者的病史,记录冠脉造影术中前降支病变比率、起始0级TIMI血流数量、病变长度、血栓分级等,并观察住院期间及发病后30 d包括死亡、再梗死、脑卒中、心衰加重、急诊搭桥或再次PCI等心血管事件情况。按血清醛固酮水平分成2组：A组(醛固酮<150μg/L)和B组(醛固酮≥150μg/L),比较两组患者的冠脉病变支数,采用多变量Logistic回归分析判断醛固酮是否可以预测急性心肌梗死患者的近期预后。
结果与低血清醛固酮水平组(A组)患者比较,高醛固酮水平组(B组)发病-介入时间长(P<0.05),累及平均病变冠脉血管支数增加(P<0.05),并有不良心脏事件增加之势。此外经多变量Logistic回归分析中,除糖尿病(HR 2.934,95%CI 1.314 to 6.548,p=0.0086)外,血清醛固酮水平(HR 0.705,95%CI0.573 to0.868,p=0.0010)也是病变血管范围的独立预测因子。
结论急性ST段抬高型心肌梗死患者早期血清醛固酮水平增高预示累及病变血管多,可能增加不良心脏事件的发生。提示急性心肌梗死早期药物降低血清醛固酮水平,可能改善患者的近期预后。
Objective To assess the value of serum aldosterone levels measure before percutaneous coronary intervention(PCI) in predicting multiple diseased coronary vessels and short-term clinical prognosis in patients with acute ST segment elevation myocardial infarction(STEMI).
METHODS The study included 67 consecutive patients with acute STEMI undergoing PCI in CCU in the Second Hospital of Tianjin Medical University from March 2008 to October 2008. Blood samples were drawn through the femoral arterial sheath before cardiac catheterization with the patients in the supine position. Serum aldosterone levels were measured with a commercially available radioimmunoassay (RIA)kit. The patients history were collected the morbid change ratio of anterior descending branch, the length of morbid change and thrombus classification were noted down. All patients were tracked for subsequent cardiovascular events including cardiac death, myocardial infarction, heart failure,second PCI, coronary artery bypass and stroke during in-hospital and 30-day follow-ups. According to the serum aldosterone levels, the patients were divided into 2 groups, group A:serum aldosterone levels< 150μg/L, group B:serum aldosterone levels≥150μg/L. Quantity of diseased coronary vessels in the two groups of acute STEMI patients was compared, and multivariate Logistic regression analysis was used to judge whether the serum aldostrone levels can predict the short-term clinical prognosis in the patients with acute STEMI.
RESULTS The patients with higher levels of serum aldosterone spent longer time of occurrence to PCI, and more multiple diseased coronary vessels compared than that with/lower aldosterone levels. And it had been found that there was an a increasing trend of cardiovascular serum events in the patients with higher serum aldosterone levels during follow ups. Logistic analysis showed that the diagnosis of diabetes (HR 2.934,95%CI 1.314 to 6.548, p=0.0086) and serum aldosterone level (HR 0.705,95%CI 0.573 to 0.868, p=0.0010) were independent prognostic factors after adjustment of all entered baseline variables.
CONCLUSION The higher serum aldosterone level was associated with the increase of diseased coronary vessels and may be responsible for subsequent short-term cardiovascular events following PCI.
方法入选天津医科大学第二医院心脏科2008年3月-10月于CCU连续收入院的67例急性ST段抬高型心肌梗死患者,行经皮冠状动脉介入治疗术(PCI),术前股动脉穿刺后留取血清,采用放射免疫法(RIA)测定血清醛固酮水平。采集患者的病史,记录冠脉造影术中前降支病变比率、起始0级TIMI血流数量、病变长度、血栓分级等,并观察住院期间及发病后30 d包括死亡、再梗死、脑卒中、心衰加重、急诊搭桥或再次PCI等心血管事件情况。按血清醛固酮水平分成2组：A组(醛固酮<150μg/L)和B组(醛固酮≥150μg/L),比较两组患者的冠脉病变支数,采用多变量Logistic回归分析判断醛固酮是否可以预测急性心肌梗死患者的近期预后。
结果与低血清醛固酮水平组(A组)患者比较,高醛固酮水平组(B组)发病-介入时间长(P<0.05),累及平均病变冠脉血管支数增加(P<0.05),并有不良心脏事件增加之势。此外经多变量Logistic回归分析中,除糖尿病(HR 2.934,95%CI 1.314 to 6.548,p=0.0086)外,血清醛固酮水平(HR 0.705,95%CI0.573 to0.868,p=0.0010)也是病变血管范围的独立预测因子。
结论急性ST段抬高型心肌梗死患者早期血清醛固酮水平增高预示累及病变血管多,可能增加不良心脏事件的发生。提示急性心肌梗死早期药物降低血清醛固酮水平,可能改善患者的近期预后。
Objective To assess the value of serum aldosterone levels measure before percutaneous coronary intervention(PCI) in predicting multiple diseased coronary vessels and short-term clinical prognosis in patients with acute ST segment elevation myocardial infarction(STEMI).
METHODS The study included 67 consecutive patients with acute STEMI undergoing PCI in CCU in the Second Hospital of Tianjin Medical University from March 2008 to October 2008. Blood samples were drawn through the femoral arterial sheath before cardiac catheterization with the patients in the supine position. Serum aldosterone levels were measured with a commercially available radioimmunoassay (RIA)kit. The patients history were collected the morbid change ratio of anterior descending branch, the length of morbid change and thrombus classification were noted down. All patients were tracked for subsequent cardiovascular events including cardiac death, myocardial infarction, heart failure,second PCI, coronary artery bypass and stroke during in-hospital and 30-day follow-ups. According to the serum aldosterone levels, the patients were divided into 2 groups, group A:serum aldosterone levels< 150μg/L, group B:serum aldosterone levels≥150μg/L. Quantity of diseased coronary vessels in the two groups of acute STEMI patients was compared, and multivariate Logistic regression analysis was used to judge whether the serum aldostrone levels can predict the short-term clinical prognosis in the patients with acute STEMI.
RESULTS The patients with higher levels of serum aldosterone spent longer time of occurrence to PCI, and more multiple diseased coronary vessels compared than that with/lower aldosterone levels. And it had been found that there was an a increasing trend of cardiovascular serum events in the patients with higher serum aldosterone levels during follow ups. Logistic analysis showed that the diagnosis of diabetes (HR 2.934,95%CI 1.314 to 6.548, p=0.0086) and serum aldosterone level (HR 0.705,95%CI 0.573 to 0.868, p=0.0010) were independent prognostic factors after adjustment of all entered baseline variables.
CONCLUSION The higher serum aldosterone level was associated with the increase of diseased coronary vessels and may be responsible for subsequent short-term cardiovascular events following PCI.
引文
[1]孙晓明,罗南萍,刘恒国等,缺血性脑血管病和冠心病患者Ald与ET-1相关性研究[J],放射免疫学杂志.2008,21(6)488-490.
[2]常以芳,胡淑芳,葛志明.卡维地洛对慢性心衰患者心功能、神经内分泌激素激活及血管内皮功能影响的临床研究[J].实用诊断与治疗杂志,2005,19(6)：413-415.
[3]韦汐,贺平.血压昼夜规律特征及高血压患者肾素-血管紧张素-醛固酮系统靶器官损伤的关系.中国临床康复杂志.2005,9(39)：68.
[4]Connell JM, Davies E. The new biology of aldosterone. J Endocrinol.2005,186 (1):1114.
[5]Dinh DT, Frauman AG, Johnston CI, et al. Angiotensin receptors: distribution signalling and function [J]. Clinical Science,2001,100(5): 481-492.
[6]Krug AW, Allenhofer L, Monticone R, et al.Elevated Mineralocorticoid Receptor Activity in Aged Rat Vascular Smooth Muscle Cells Promotes a Proinflammatory Phenotype via Extracellular Signal-Regulated Kinase 1/2 Mitogen-Activated Protein Kinase and Epidermal Growth Factor Receptor-Dependent Pathways[J]. Hypertension.2010 Apr 26.
[7]Kobayashi N, Fukushima H, Takeshima H, et al.Effect of Eplerenone on Endothelial Progenitor Cells and Oxidative Stress in Ischemic Hindlimb[J].Am J Hypertens.2010 Apr 29.
[8]孙晓明,罗南萍,刘恒国等,缺血性脑血管病和冠心病患者Ald与ET-1相关性研究[J],放射免疫学杂志.2008,21(6)488-490.
[9]常以芳,胡淑芳,葛志明.卡维地洛对慢性心衰患者心功能、神经内分泌激素激活及血管内皮功能影响的临床研究[J].实用诊断与治疗杂志,2005,19(6)：413-415.
[10]Mit suhide Naruse, Akiyo Tanabe, At suhisa Sato, et al.Aldosterone break through during angiotensin Ⅱ receptor antagonist t herapy in storke-porne spontaneously hypertensive rats[J]. Hypertension,2002,40 (1):28-33.
[11]Shi H, Ma C, Liu Y,et al.Inhibitory effect on activated renin-angiotensin system by astragaloside Ⅳ in rats with pressure-overload induced cardiac hypertrophy[J]. Zhongguo Zhong Yao Za Zhi.2009 Dec; 34(24):3242-6.
[12]Horky K.Direct renin inhibitor aliskiren in the treatment of cardiovascular and renal diseases[J]. Vnitr Lek.2010 Feb; 56(2):120-6.
[13]Anand K, Mooss A N, Mohiuddin S M. Aldosterone inhibition reduces the risk of sudden cardiac death in patients with heart faihre[J]. J RAAS,2006,7(1):15-19.
[14]Ovaert P, Elliott J, Bernay F, et al. Aldosterone receptor antagonists--how cardiovascular actions may explain their beneficial effects in heart failure.J Vet Pharmacol Ther[J].2010 Apr; 33(2):109-17.
[15]Eric Van Belle, Sophie Susen, Frederic Mouquet, et al. Aldosterone, A major determinant of long-term mortality in elective PCI[J]. Circulation,2007,116(5):701-703.
[16]Anand K, Mooss A N, Mohiuddin S M. Aldosterone inhibition reduces t he risk of sudden cardiac deat h in patient s wit h heart faihre[J]. J RAAS,2006,7 (1):15-19.
[17]Chaudhary K, Nistala R, Whaley-Connell A.Is there a future for direct renin inhibitors?Expert Opin Investig Drugs.2010 May;19(5):653-61.
[18]Schrier RW, Masoumi A, Elhassan E.Aldosterone:Role in Edematous Disorders, Hypertension, Chronic Renal Failure, and Metabolic Syndrome[J].Clin J Am Soc Nephrol.2010 May 6.
[19]Ismail H, Mitchell R, McFarlane SI, et al.Pleiotropic effects of inhibitors of the RAAS in the diabetic population:above and beyond blood pressure lowering[J].Curr Diab Rep.2010 Feb;10(1):32-6.
[20]Pfeffer MA, Braunwald E, Moye LA, et al. for the SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction and myocardial infarction:results of the Survival and Ventricular Enlargement Trial[J]. N Engl J Med.1992;327:69-77.
[21]Delyani J A, Robison E L, Rudolph A E. Effect of as elective aldosterone receptor antagonistin myocardial infarction[J]. Am J Physiol Heart Circ Physiol,2001,281 (2):H647-654.
[22]Farzin Beygui, Jean-Philippe Collet, Jean-Jacques Benoliel, et al. High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST2elevation myocardial infarction [J]. Circulation,2006,114 (24): 2604-2610.
[23]Eric Van Belle, Sophie Susen, Frederic Mouquet, et al.Aldosterone, A major determinant of long-term mortality in elective PCI[J]. Circulation,2007,116 (5):Ⅱ-703.
[24]Vinson GP, Coghlan JP.Expanding view of aldosterone action, with an emphasis on rapid action[J].Clin Exp Pharmacol Physiol.2010 Apr;37(4):410-6.
[25]Eric Van Belle, Sophie Susen, Frederic Mouquet, et al. Aldosterone, A major determinant of long-term mortality in elective PCI[J]. Circulation,2007,116(5):701-703.
[26]Whaley-Connell A, Johnson MS, Sowers JR.Aldosterone:role in the cardiome tabolic syndrome and resistant hypertension[J].Prog Cardiovasc Dis.2010 Mar-Apr;52(5):401-9.
[27]Sun Y, Zhang J, LU L, et al. Aldosterone-induced inflammationin rat heart:role of oxidative stress[J]. Am J Pathol,2002,161(5):1773-1781.
[28]Briet M, Schiffrin EL.Aldosterone:effects on the kidney and cardiovascular system.Nat Rev Nephrol[J].2010 May;6(5):261-73.
[29]Oguz A.Renin-angiotensin-aldosterone system inhibition and cardiovascular protection[J].Turk Kardiyol Dern Ars.2009 Oct;37 Suppl 6:4-12.
[30]Lopez B, Gonzalez A, Diez J.Circulating biomarkers of collagen metabolism in cardiac diseases[J].Circulation.2010 Apr 13;121(14):1645-54.
[31]Cannier A, Bendall J K, Fuchs S, et al. Cardiac-specific increase in aldosterone production induced coronary dysfunction in aldosterone synthase-transgenic mice[J]. Circulation,2004,110(24):1819-1825.
[32]Abate E, Sartor R, Ceconi C, et al. Pharmacological treatment of chronic systolic heart failure:are we scraping the bottom of the barrel[J]? J Cardiovasc Med 2010 Apr 21. Expert Opin Investig Drugs.2010 May;19(5):653-61.
[33]Fejes-Toth G, Naray-Fejes-Toth A. Early Aldosterone-regulated genes in cardiomyocytes:clues to cardiac remodeling? [J].Endocrinology,2007,148(4): 1502-1510.
[34]Verma A,Solomon SD.Optimizing care of heart failure after acute MI with an aldosterone receptor antagonist.Curr Heart Fail Rep,2007,4(4):183-189.
此外,螺内酯还可以降低急性心肌梗死患者血浆透明质酸含量,而透明质酸主要做为结缔组织基质发挥作用,是反映组织活动性胶原代谢的指标,这进一步说明了螺内酯对心室重构的抑制作用]。前胶原蛋白水解酶C-1对于胶原沉积是一种正调节蛋白,在胶原沉积中起着关键性的作用。有研究对心肌梗死5周大鼠心肌瘢痕局部以及血管周围成纤维细胞中的前胶原蛋白水解酶C-1以及Ⅰ型胶原mRNA进行原位杂交,发现这两种转录物的水平明显升高,而给予螺内酯干预后这种效应明显减弱。与给药组及假手术组相比,未予干预的心肌梗死大鼠前胶原蛋白水解酶C-1以及Ⅰ型胶原的升高是前述两组的2-5倍。充分说明螺内酯可以有效抑制梗死后心肌中前胶原蛋白水解酶C-1以及Ⅰ型胶原的表达,抑制心室重构。
[1]Tsikouris JP, Cox DC. Pharmacologic blockade of the renin angiotensin system: vascular benefits beyond commonly understood pharmacologic actions[J]. Pharmacotherapy.2003; 23:1141-52.
[2]Kon V, Jabs K. Angiotensin in atherosclerosis. Curr Opin Nephrol Hypertens[J]. 2004;13:291-7.
[3]The SOLVD Investigators. Effects of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions[J]. N Engl J Med.1992; 327:85-91.
[4 Pfeffer MA, Braunwald E, Moye LA, et al. for the SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction and myocardial infarction:results of the Survival and Ventricular Enlargement Trial[J]. N Engl J Med.1992;327:69-77.
[5][HOPE] The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients[J]. N Engl J Med.2000; 342:145-53.
[6]Fox KM. European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease Investigators. Efficacy on perindopril in reduction of cardiovascular events among patients with stable coronary artery disease randomized, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet.2003; 362:782-8.
[7][PEACE] The PEACE Trial Investigators. Angiotensin-converting-enzyme inhibition in stable coronary artery disease[J]. N Engl J Med.2004; 35: 2058-68.
[8]Carstens J; Pedersen EB. Renal effects of urodilatin in healthy subjects are independent of blockade of the cyclooxygenase and angiotensin Ⅱ receptor. Scand J Clin Lab Invest[J].2008; 68:2-10.
[9]Patel D; Bohlke M; Phattanarudee S. Cardiovascular responses and neurotransmitter changes during blockade of angiotensin Ⅱ receptors within the ventrolateral medulla[J].Neurosci Res.2008; 60:340-348.
[10]Mufti S; Wenzel S; Euler G. Angiotensin Ⅱ-dependent loss of cardiac function: mechanisms and pharmacological targets attenuating this effect[J].J Cell Physiol. 2008;217:242-249.
[11]Choudhary R; Baker KM; Pan J. All-trans retinoic acid prevents angiotensin Ⅱ-and mechanical stretch-induced reactive oxygen species generation and cardiomyocyte apoptosis[J].J Cell Physiol.2008; 215:172-181.
[12]Duncker DJ; Bache RJ.Regulation of coronary blood flow during exercise. Physiol Rev.2008; 88:1009-1086.
[13]Wright CE; Angus JA; Korner PI.Structural factors increase blood pressure through the interaction of resistance vessel geometry with neurohumoral and local factors:estimates in rabbits with renal cellophane-wrap hypertension with intact effectors and during neurohumoral blockade[J]. J Hypertens.2002; 20: 471-483.
[14]Xu X; Wan W; Powers AS.Effects of exercise training on cardiac function and myocardial remodeling in post myocardial infarction rats.J Mol Cell Cardiol[J]. 2008; 44:114-122.
[15]Xu Z; Okamoto H; Akino M.Pravastatin attenuates left ventricular remodeling and diastolic dysfunction in angiotensin Ⅱ-induced hypertensive mice[J]. J Cardiovasc Pharmacol [J].2008; 51:62-70.
[16]Ellmers LJ; Scott NJ; Medicherla S. Transforming growth factor-beta blockade down-regulates the renin-angiotensin system and modifies cardiac remodeling after myocardial infarction. Endocrinology[J].2008; 149:5828-5834.
[17]Fraccarollo D; Galuppo P; Schmidt Ⅰ. Additive amelioration of left ventricular remodeling and molecular alterations by combined aldosterone and angiotensin receptor blockade after myocardial infarction[J]. Cardiovasc Res. 2005V67N1:97-105.
[18]Choudhary R; Baker KM; Pan J.All-trans retinoic acid prevents angiotensin Ⅱ-and mechanical stretch-induced reactive oxygen species generation and cardiomyocyte apoptosis. J Cell Physiol.2008; 215:172-181.
[19]Ismail H, Mitchell R, McFarlane SI, et al.Pleiotropic effects of inhibitors of the RAAS in the diabetic population:above and beyond blood pressure lowering[J].Curr Diab Rep.2010 Feb;10(1):32-6.
[20]Pfeffer MA, Braunwald E, Moye LA, et al. for the SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction and myocardial infarction:results of the Survival and Ventricular Enlargement Trial[J]. N Engl J Med.1992;327:69-77.
[21]Ikeda K; Tojo K; Udagawa T.Cellular physiology of rat cardiac myocytes in cardiac fibrosis:in vitro simulation using the cardiac myocyte/cardiac non-myocyte co-culture system[J]. Hypertens Res.2008; 31:693-706.
[22]Helske S; Lindstedt KA; Laine M.Induction of local angiotensin Ⅱ-producing systems in stenotic aortic valves[J]. J Am Coll Cardiol.2004;44:1859-1866.
[23]Fraga Silva RA; Pinheiro SV; Goncalves AC.The antithrombotic effect of angiotensin-(1-7) involves mas-mediated NO release from platelets[J]. Mol Med. 2008;14:28-35.
[24]Rastelli VM; Oliveira MA; dos Santos R.Lack of potentiation of bradykinin by angiotensin-(1-7) in a type 2 diabetes model:role of insulin[J].Peptides.2007; 28: 1040-1049.
[25]Marangoni RA; Carmona AK; Passaglia RC.Role of the kallikrein-kinin system in Ang-(1-7)-induced vasodilation in mesenteric arterioles of Wistar rats studied in vivo-in situ.Peptides.2006; 27:1770-1775.
[26]Ocaranza MP; Palomera C; Roman M.Effect of hypertension on angiotensin-(1-7) levels in rats with different angiotensin-I converting enzyme polymorphism[J].Life Sci.2006;78:1535-1542.
[27]Sun Y, Zhang J, LU L, et al. Aldosterone-induced inflammationin rat heart:role of oxidative stress[J]. Am J Pathol,2002,161(5):1773-1781.
[28]Cannier A, Bendall J K, Fuchs S, et al. Cardiac-specific increase in aldosterone production induced coronary dysfunction in aldosterone synthase-transgenic mice[J]. Circulation,2004,110(24):1819-1825.
[29]Iwashima Y, Horio T, Kuorda S, et al. Influence of plasma aldosteorne on left ventricular geometry and diastolic function in treated essential hypertension[J]. Hypertens Res,2002,25(1):49-56.
[30]Anand K, Mooss A N, Mohiuddin S M. Aldosterone inhibition reduces the risk of sudden cardiac death in patients with heart faihre[J]. JRAAS,2006,7(1):15-19.
[31]Eric Van Belle, Sophie Susen, Frederic Mouquet, et al. Aldosterone, A major determinant of long-term mortality in elective PCI[J]. Circulation,2007,116 (5): 701-703.
[32]Amano T, Matsubara H, Izawa M, et al. Impact of plasma aldosterone levels for prediction of in-stent restenosis[J]. Am J Cardiol,2006,97(6):785-788.
[33]Davila D F, Nunez T J, Odrenman R, et al. Mechanism of neurohormonal activation in chronic congestive heart failure:pathophysiology and therapeutic implication[J].Int J Cardiol,2005,101(3):343-346.
[34]Pitt B, Reichek N, Willenbrock R, et al. Effects of eplerenone/enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy:the left ventricular hypertrophy study[J]. Circulation,2003,108(15): 1831-1838.
[35]Struthers A D. Aldosterone blockade in cardiovascular disease [J]. Heart,2004, 90 (10):1229-1234.
[36]Hayashi M, Tutamoto T, Wada A, et al. Immediate administration of miner locoticoid receptor antagonists pironolactone prevents post-infarct left ventricular remodeling associated with suppression of acute myocardial collagen synthesis in patients with first anterior acute myocardial infarction[J]. Circulation,2003, 107(20):2559-2565.
[37]Collins R, Peto R, MacMahon S, et al. Blood pressure stroke and coronary heart disease. Short-term reductions in blood pressure:overview of randomized drug trials in their epidemiological context[J]. Lancet.1990; 335:827-38.
[38]Guay DR. Trandolapril:a newer angiotensin-converting enzyme inhibitor[J]. Clin Ther.2003; 25:713-75.
[39]Al-Mallah M, Tleyjeh I, Abdel-Latif A, et al. Angiotensin-converting enzyme inhibitors in coronary artery disease and preserved left ventricular systolic function[J]. J Am Coll Cardiol.2006; 47:1576-83.
[40]Khan BV, Sola S, Lauten W, et al. Quinapril, an ACE inhibitor, reduces markers of oxidative stress in the metabolic syndrome[J]. Diabetes Care[J].2004; 27: 1712-15.
[41]Al-Mallah M, Tleyjeh I, Abdel-Latif A, et al. Angiotensin-converting enzyme inhibitors in coronary artery disease and preserved left ventricular systolic function. J Am Coll Cardiol[J].2006; 47:1576-83.
[42]Pitt B, O'Neill B, Feldman R, et al.The Quinapril Ischemic Event Trial (QUIET) evaluation of chronic ACE inhibitor therapy in patients with ischemic heart disease and preserved left ventricular function[J]. Am J Cardiol.2001; 87: 1058-63.
[43]Pfeffer M, McMurray J, Velazquez E, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both[J]. N Engl J Med.2003; 349:1893-906.
[44]Pfeffer M, McMurray J, Velazquez E, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med.2003;349:1893-906.
[45]Kondo J, Sone T, Suboi H, et al. Effects of low-dose angiotensin Ⅱ receptor blocker candesartan on cardiovascular events in patients with coronary artery disease. Am Heart J.2003; 146:1022-7.
[46]Prasad A, Koh KK, Schenke WH, et al. Role of angiotensin Ⅱ type 1 receptor in the regulation of cellular adhesion molecules in atherosclerosis. Am Heart J. 2001;142:248-53.
[47]Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the losartan intervention for endpoint reduction in hypertension study (LIFE):a randomized trial against atenolol. Lancet.2002;359:995-1003.
[48]Tsikouris JP, Cox DC. Pharmacologic blockade of the renin angiotensin system: vascular benefits beyond commonly understood pharmacologic actions. Pharmacotherapy.2003;23:(11)41-52.
[49]Hayashi M, Tsutamoto T, Wada A, et al.Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of acute myocardial collagen synthesis in patients with first anterior acute myocardial infarction. Circulation,2003,107 (20):2559-2565.
[50]Delcayre C,Silvestre JS,Garnier A, et al. Cardiac aldosterone production and ventricular remodeling. Kidney International,2000,57:1346-1351.
[51]Pittm B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with sever heart failure:Randomized aldactone evaluation study investigators. [J] N Engl J Med,1999,341(10):709-717.
[52]Modena MQ Molinari R, Rossi R, et al. Modification in setum concentrations of aminoterminal propeptide of typelll procollagen in patient with previous transmural myocardial infarction[J]. Am Heart J,1998,135:287-292.
[53]Matsumoto R, Yoshiyama M, Omura T, et al. Effects of aldosterone receptor antagonist and angiotensinⅡ type I receptor blocker on cardiac transcriptional factors and mRNA expression in rats with myocardial infarction[J]. Circ J, 2004,68(4):376-382.
[54]Tsutamoto T. Mineralocorticoid receptor antagonist spironolactone improves left ventricular remodeling in patients with congestive heart failure and acute myocardial infarction[J]. Nippon Yakurigaku Zasshi.2004,124(2):90-100.
[55]Takeda M, Tatsumi T, Matsunaga S, et al. Spironolactone modulates expressions of cardiac mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase2 and prevents ventricular remodeling in post-infarct rat hearts[J]. Hypertens Res,2007,30(5):427-437.
[2]常以芳,胡淑芳,葛志明.卡维地洛对慢性心衰患者心功能、神经内分泌激素激活及血管内皮功能影响的临床研究[J].实用诊断与治疗杂志,2005,19(6)：413-415.
[3]韦汐,贺平.血压昼夜规律特征及高血压患者肾素-血管紧张素-醛固酮系统靶器官损伤的关系.中国临床康复杂志.2005,9(39)：68.
[4]Connell JM, Davies E. The new biology of aldosterone. J Endocrinol.2005,186 (1):1114.
[5]Dinh DT, Frauman AG, Johnston CI, et al. Angiotensin receptors: distribution signalling and function [J]. Clinical Science,2001,100(5): 481-492.
[6]Krug AW, Allenhofer L, Monticone R, et al.Elevated Mineralocorticoid Receptor Activity in Aged Rat Vascular Smooth Muscle Cells Promotes a Proinflammatory Phenotype via Extracellular Signal-Regulated Kinase 1/2 Mitogen-Activated Protein Kinase and Epidermal Growth Factor Receptor-Dependent Pathways[J]. Hypertension.2010 Apr 26.
[7]Kobayashi N, Fukushima H, Takeshima H, et al.Effect of Eplerenone on Endothelial Progenitor Cells and Oxidative Stress in Ischemic Hindlimb[J].Am J Hypertens.2010 Apr 29.
[8]孙晓明,罗南萍,刘恒国等,缺血性脑血管病和冠心病患者Ald与ET-1相关性研究[J],放射免疫学杂志.2008,21(6)488-490.
[9]常以芳,胡淑芳,葛志明.卡维地洛对慢性心衰患者心功能、神经内分泌激素激活及血管内皮功能影响的临床研究[J].实用诊断与治疗杂志,2005,19(6)：413-415.
[10]Mit suhide Naruse, Akiyo Tanabe, At suhisa Sato, et al.Aldosterone break through during angiotensin Ⅱ receptor antagonist t herapy in storke-porne spontaneously hypertensive rats[J]. Hypertension,2002,40 (1):28-33.
[11]Shi H, Ma C, Liu Y,et al.Inhibitory effect on activated renin-angiotensin system by astragaloside Ⅳ in rats with pressure-overload induced cardiac hypertrophy[J]. Zhongguo Zhong Yao Za Zhi.2009 Dec; 34(24):3242-6.
[12]Horky K.Direct renin inhibitor aliskiren in the treatment of cardiovascular and renal diseases[J]. Vnitr Lek.2010 Feb; 56(2):120-6.
[13]Anand K, Mooss A N, Mohiuddin S M. Aldosterone inhibition reduces the risk of sudden cardiac death in patients with heart faihre[J]. J RAAS,2006,7(1):15-19.
[14]Ovaert P, Elliott J, Bernay F, et al. Aldosterone receptor antagonists--how cardiovascular actions may explain their beneficial effects in heart failure.J Vet Pharmacol Ther[J].2010 Apr; 33(2):109-17.
[15]Eric Van Belle, Sophie Susen, Frederic Mouquet, et al. Aldosterone, A major determinant of long-term mortality in elective PCI[J]. Circulation,2007,116(5):701-703.
[16]Anand K, Mooss A N, Mohiuddin S M. Aldosterone inhibition reduces t he risk of sudden cardiac deat h in patient s wit h heart faihre[J]. J RAAS,2006,7 (1):15-19.
[17]Chaudhary K, Nistala R, Whaley-Connell A.Is there a future for direct renin inhibitors?Expert Opin Investig Drugs.2010 May;19(5):653-61.
[18]Schrier RW, Masoumi A, Elhassan E.Aldosterone:Role in Edematous Disorders, Hypertension, Chronic Renal Failure, and Metabolic Syndrome[J].Clin J Am Soc Nephrol.2010 May 6.
[19]Ismail H, Mitchell R, McFarlane SI, et al.Pleiotropic effects of inhibitors of the RAAS in the diabetic population:above and beyond blood pressure lowering[J].Curr Diab Rep.2010 Feb;10(1):32-6.
[20]Pfeffer MA, Braunwald E, Moye LA, et al. for the SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction and myocardial infarction:results of the Survival and Ventricular Enlargement Trial[J]. N Engl J Med.1992;327:69-77.
[21]Delyani J A, Robison E L, Rudolph A E. Effect of as elective aldosterone receptor antagonistin myocardial infarction[J]. Am J Physiol Heart Circ Physiol,2001,281 (2):H647-654.
[22]Farzin Beygui, Jean-Philippe Collet, Jean-Jacques Benoliel, et al. High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST2elevation myocardial infarction [J]. Circulation,2006,114 (24): 2604-2610.
[23]Eric Van Belle, Sophie Susen, Frederic Mouquet, et al.Aldosterone, A major determinant of long-term mortality in elective PCI[J]. Circulation,2007,116 (5):Ⅱ-703.
[24]Vinson GP, Coghlan JP.Expanding view of aldosterone action, with an emphasis on rapid action[J].Clin Exp Pharmacol Physiol.2010 Apr;37(4):410-6.
[25]Eric Van Belle, Sophie Susen, Frederic Mouquet, et al. Aldosterone, A major determinant of long-term mortality in elective PCI[J]. Circulation,2007,116(5):701-703.
[26]Whaley-Connell A, Johnson MS, Sowers JR.Aldosterone:role in the cardiome tabolic syndrome and resistant hypertension[J].Prog Cardiovasc Dis.2010 Mar-Apr;52(5):401-9.
[27]Sun Y, Zhang J, LU L, et al. Aldosterone-induced inflammationin rat heart:role of oxidative stress[J]. Am J Pathol,2002,161(5):1773-1781.
[28]Briet M, Schiffrin EL.Aldosterone:effects on the kidney and cardiovascular system.Nat Rev Nephrol[J].2010 May;6(5):261-73.
[29]Oguz A.Renin-angiotensin-aldosterone system inhibition and cardiovascular protection[J].Turk Kardiyol Dern Ars.2009 Oct;37 Suppl 6:4-12.
[30]Lopez B, Gonzalez A, Diez J.Circulating biomarkers of collagen metabolism in cardiac diseases[J].Circulation.2010 Apr 13;121(14):1645-54.
[31]Cannier A, Bendall J K, Fuchs S, et al. Cardiac-specific increase in aldosterone production induced coronary dysfunction in aldosterone synthase-transgenic mice[J]. Circulation,2004,110(24):1819-1825.
[32]Abate E, Sartor R, Ceconi C, et al. Pharmacological treatment of chronic systolic heart failure:are we scraping the bottom of the barrel[J]? J Cardiovasc Med 2010 Apr 21. Expert Opin Investig Drugs.2010 May;19(5):653-61.
[33]Fejes-Toth G, Naray-Fejes-Toth A. Early Aldosterone-regulated genes in cardiomyocytes:clues to cardiac remodeling? [J].Endocrinology,2007,148(4): 1502-1510.
[34]Verma A,Solomon SD.Optimizing care of heart failure after acute MI with an aldosterone receptor antagonist.Curr Heart Fail Rep,2007,4(4):183-189.
此外,螺内酯还可以降低急性心肌梗死患者血浆透明质酸含量,而透明质酸主要做为结缔组织基质发挥作用,是反映组织活动性胶原代谢的指标,这进一步说明了螺内酯对心室重构的抑制作用]。前胶原蛋白水解酶C-1对于胶原沉积是一种正调节蛋白,在胶原沉积中起着关键性的作用。有研究对心肌梗死5周大鼠心肌瘢痕局部以及血管周围成纤维细胞中的前胶原蛋白水解酶C-1以及Ⅰ型胶原mRNA进行原位杂交,发现这两种转录物的水平明显升高,而给予螺内酯干预后这种效应明显减弱。与给药组及假手术组相比,未予干预的心肌梗死大鼠前胶原蛋白水解酶C-1以及Ⅰ型胶原的升高是前述两组的2-5倍。充分说明螺内酯可以有效抑制梗死后心肌中前胶原蛋白水解酶C-1以及Ⅰ型胶原的表达,抑制心室重构。
[1]Tsikouris JP, Cox DC. Pharmacologic blockade of the renin angiotensin system: vascular benefits beyond commonly understood pharmacologic actions[J]. Pharmacotherapy.2003; 23:1141-52.
[2]Kon V, Jabs K. Angiotensin in atherosclerosis. Curr Opin Nephrol Hypertens[J]. 2004;13:291-7.
[3]The SOLVD Investigators. Effects of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions[J]. N Engl J Med.1992; 327:85-91.
[4 Pfeffer MA, Braunwald E, Moye LA, et al. for the SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction and myocardial infarction:results of the Survival and Ventricular Enlargement Trial[J]. N Engl J Med.1992;327:69-77.
[5][HOPE] The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients[J]. N Engl J Med.2000; 342:145-53.
[6]Fox KM. European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease Investigators. Efficacy on perindopril in reduction of cardiovascular events among patients with stable coronary artery disease randomized, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet.2003; 362:782-8.
[7][PEACE] The PEACE Trial Investigators. Angiotensin-converting-enzyme inhibition in stable coronary artery disease[J]. N Engl J Med.2004; 35: 2058-68.
[8]Carstens J; Pedersen EB. Renal effects of urodilatin in healthy subjects are independent of blockade of the cyclooxygenase and angiotensin Ⅱ receptor. Scand J Clin Lab Invest[J].2008; 68:2-10.
[9]Patel D; Bohlke M; Phattanarudee S. Cardiovascular responses and neurotransmitter changes during blockade of angiotensin Ⅱ receptors within the ventrolateral medulla[J].Neurosci Res.2008; 60:340-348.
[10]Mufti S; Wenzel S; Euler G. Angiotensin Ⅱ-dependent loss of cardiac function: mechanisms and pharmacological targets attenuating this effect[J].J Cell Physiol. 2008;217:242-249.
[11]Choudhary R; Baker KM; Pan J. All-trans retinoic acid prevents angiotensin Ⅱ-and mechanical stretch-induced reactive oxygen species generation and cardiomyocyte apoptosis[J].J Cell Physiol.2008; 215:172-181.
[12]Duncker DJ; Bache RJ.Regulation of coronary blood flow during exercise. Physiol Rev.2008; 88:1009-1086.
[13]Wright CE; Angus JA; Korner PI.Structural factors increase blood pressure through the interaction of resistance vessel geometry with neurohumoral and local factors:estimates in rabbits with renal cellophane-wrap hypertension with intact effectors and during neurohumoral blockade[J]. J Hypertens.2002; 20: 471-483.
[14]Xu X; Wan W; Powers AS.Effects of exercise training on cardiac function and myocardial remodeling in post myocardial infarction rats.J Mol Cell Cardiol[J]. 2008; 44:114-122.
[15]Xu Z; Okamoto H; Akino M.Pravastatin attenuates left ventricular remodeling and diastolic dysfunction in angiotensin Ⅱ-induced hypertensive mice[J]. J Cardiovasc Pharmacol [J].2008; 51:62-70.
[16]Ellmers LJ; Scott NJ; Medicherla S. Transforming growth factor-beta blockade down-regulates the renin-angiotensin system and modifies cardiac remodeling after myocardial infarction. Endocrinology[J].2008; 149:5828-5834.
[17]Fraccarollo D; Galuppo P; Schmidt Ⅰ. Additive amelioration of left ventricular remodeling and molecular alterations by combined aldosterone and angiotensin receptor blockade after myocardial infarction[J]. Cardiovasc Res. 2005V67N1:97-105.
[18]Choudhary R; Baker KM; Pan J.All-trans retinoic acid prevents angiotensin Ⅱ-and mechanical stretch-induced reactive oxygen species generation and cardiomyocyte apoptosis. J Cell Physiol.2008; 215:172-181.
[19]Ismail H, Mitchell R, McFarlane SI, et al.Pleiotropic effects of inhibitors of the RAAS in the diabetic population:above and beyond blood pressure lowering[J].Curr Diab Rep.2010 Feb;10(1):32-6.
[20]Pfeffer MA, Braunwald E, Moye LA, et al. for the SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction and myocardial infarction:results of the Survival and Ventricular Enlargement Trial[J]. N Engl J Med.1992;327:69-77.
[21]Ikeda K; Tojo K; Udagawa T.Cellular physiology of rat cardiac myocytes in cardiac fibrosis:in vitro simulation using the cardiac myocyte/cardiac non-myocyte co-culture system[J]. Hypertens Res.2008; 31:693-706.
[22]Helske S; Lindstedt KA; Laine M.Induction of local angiotensin Ⅱ-producing systems in stenotic aortic valves[J]. J Am Coll Cardiol.2004;44:1859-1866.
[23]Fraga Silva RA; Pinheiro SV; Goncalves AC.The antithrombotic effect of angiotensin-(1-7) involves mas-mediated NO release from platelets[J]. Mol Med. 2008;14:28-35.
[24]Rastelli VM; Oliveira MA; dos Santos R.Lack of potentiation of bradykinin by angiotensin-(1-7) in a type 2 diabetes model:role of insulin[J].Peptides.2007; 28: 1040-1049.
[25]Marangoni RA; Carmona AK; Passaglia RC.Role of the kallikrein-kinin system in Ang-(1-7)-induced vasodilation in mesenteric arterioles of Wistar rats studied in vivo-in situ.Peptides.2006; 27:1770-1775.
[26]Ocaranza MP; Palomera C; Roman M.Effect of hypertension on angiotensin-(1-7) levels in rats with different angiotensin-I converting enzyme polymorphism[J].Life Sci.2006;78:1535-1542.
[27]Sun Y, Zhang J, LU L, et al. Aldosterone-induced inflammationin rat heart:role of oxidative stress[J]. Am J Pathol,2002,161(5):1773-1781.
[28]Cannier A, Bendall J K, Fuchs S, et al. Cardiac-specific increase in aldosterone production induced coronary dysfunction in aldosterone synthase-transgenic mice[J]. Circulation,2004,110(24):1819-1825.
[29]Iwashima Y, Horio T, Kuorda S, et al. Influence of plasma aldosteorne on left ventricular geometry and diastolic function in treated essential hypertension[J]. Hypertens Res,2002,25(1):49-56.
[30]Anand K, Mooss A N, Mohiuddin S M. Aldosterone inhibition reduces the risk of sudden cardiac death in patients with heart faihre[J]. JRAAS,2006,7(1):15-19.
[31]Eric Van Belle, Sophie Susen, Frederic Mouquet, et al. Aldosterone, A major determinant of long-term mortality in elective PCI[J]. Circulation,2007,116 (5): 701-703.
[32]Amano T, Matsubara H, Izawa M, et al. Impact of plasma aldosterone levels for prediction of in-stent restenosis[J]. Am J Cardiol,2006,97(6):785-788.
[33]Davila D F, Nunez T J, Odrenman R, et al. Mechanism of neurohormonal activation in chronic congestive heart failure:pathophysiology and therapeutic implication[J].Int J Cardiol,2005,101(3):343-346.
[34]Pitt B, Reichek N, Willenbrock R, et al. Effects of eplerenone/enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy:the left ventricular hypertrophy study[J]. Circulation,2003,108(15): 1831-1838.
[35]Struthers A D. Aldosterone blockade in cardiovascular disease [J]. Heart,2004, 90 (10):1229-1234.
[36]Hayashi M, Tutamoto T, Wada A, et al. Immediate administration of miner locoticoid receptor antagonists pironolactone prevents post-infarct left ventricular remodeling associated with suppression of acute myocardial collagen synthesis in patients with first anterior acute myocardial infarction[J]. Circulation,2003, 107(20):2559-2565.
[37]Collins R, Peto R, MacMahon S, et al. Blood pressure stroke and coronary heart disease. Short-term reductions in blood pressure:overview of randomized drug trials in their epidemiological context[J]. Lancet.1990; 335:827-38.
[38]Guay DR. Trandolapril:a newer angiotensin-converting enzyme inhibitor[J]. Clin Ther.2003; 25:713-75.
[39]Al-Mallah M, Tleyjeh I, Abdel-Latif A, et al. Angiotensin-converting enzyme inhibitors in coronary artery disease and preserved left ventricular systolic function[J]. J Am Coll Cardiol.2006; 47:1576-83.
[40]Khan BV, Sola S, Lauten W, et al. Quinapril, an ACE inhibitor, reduces markers of oxidative stress in the metabolic syndrome[J]. Diabetes Care[J].2004; 27: 1712-15.
[41]Al-Mallah M, Tleyjeh I, Abdel-Latif A, et al. Angiotensin-converting enzyme inhibitors in coronary artery disease and preserved left ventricular systolic function. J Am Coll Cardiol[J].2006; 47:1576-83.
[42]Pitt B, O'Neill B, Feldman R, et al.The Quinapril Ischemic Event Trial (QUIET) evaluation of chronic ACE inhibitor therapy in patients with ischemic heart disease and preserved left ventricular function[J]. Am J Cardiol.2001; 87: 1058-63.
[43]Pfeffer M, McMurray J, Velazquez E, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both[J]. N Engl J Med.2003; 349:1893-906.
[44]Pfeffer M, McMurray J, Velazquez E, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med.2003;349:1893-906.
[45]Kondo J, Sone T, Suboi H, et al. Effects of low-dose angiotensin Ⅱ receptor blocker candesartan on cardiovascular events in patients with coronary artery disease. Am Heart J.2003; 146:1022-7.
[46]Prasad A, Koh KK, Schenke WH, et al. Role of angiotensin Ⅱ type 1 receptor in the regulation of cellular adhesion molecules in atherosclerosis. Am Heart J. 2001;142:248-53.
[47]Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the losartan intervention for endpoint reduction in hypertension study (LIFE):a randomized trial against atenolol. Lancet.2002;359:995-1003.
[48]Tsikouris JP, Cox DC. Pharmacologic blockade of the renin angiotensin system: vascular benefits beyond commonly understood pharmacologic actions. Pharmacotherapy.2003;23:(11)41-52.
[49]Hayashi M, Tsutamoto T, Wada A, et al.Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of acute myocardial collagen synthesis in patients with first anterior acute myocardial infarction. Circulation,2003,107 (20):2559-2565.
[50]Delcayre C,Silvestre JS,Garnier A, et al. Cardiac aldosterone production and ventricular remodeling. Kidney International,2000,57:1346-1351.
[51]Pittm B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with sever heart failure:Randomized aldactone evaluation study investigators. [J] N Engl J Med,1999,341(10):709-717.
[52]Modena MQ Molinari R, Rossi R, et al. Modification in setum concentrations of aminoterminal propeptide of typelll procollagen in patient with previous transmural myocardial infarction[J]. Am Heart J,1998,135:287-292.
[53]Matsumoto R, Yoshiyama M, Omura T, et al. Effects of aldosterone receptor antagonist and angiotensinⅡ type I receptor blocker on cardiac transcriptional factors and mRNA expression in rats with myocardial infarction[J]. Circ J, 2004,68(4):376-382.
[54]Tsutamoto T. Mineralocorticoid receptor antagonist spironolactone improves left ventricular remodeling in patients with congestive heart failure and acute myocardial infarction[J]. Nippon Yakurigaku Zasshi.2004,124(2):90-100.
[55]Takeda M, Tatsumi T, Matsunaga S, et al. Spironolactone modulates expressions of cardiac mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase2 and prevents ventricular remodeling in post-infarct rat hearts[J]. Hypertens Res,2007,30(5):427-437.