卡维地洛对老年舒张性心力衰竭患者心功能及糖脂代谢的影响
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摘要
为了明确卡维地洛对老年舒张性心力衰竭(Diastolic heart failure,DHF)患者心功能及糖脂代谢的影响,本文对2006年2月-2007年1月在我科就诊并诊断为舒张性心力衰竭的老年患者(年龄在60岁以上)76例,随机分成治疗组和对照组进行了回顾性研究。观察两组治疗前后患者临床症状、反映舒张功能的指标的改变及血糖、血脂代谢的改变。结果发现:治疗组患者在治疗后临床症状获得改善(P<0.05),左室舒张功能指标亦优于治疗前,对照组亦有一定改善,而治疗组与对照组相比差异有显著性。治疗组用药前后血糖、血脂变化无显著性差异,与对照组相比差异具有显著性。治疗过程中,两组均未发生明显不良反应,无一例停药。本研究结果表明:应用卡维地洛可改善老年舒张性心力衰竭患者的左室功能,且对糖脂代谢无不良影响。
Accompany to the population aging, the morbidity of elder heart failure increased gradually. But diastole dysfunction is the first symptom in the early stage of heart failure, it appeared as diastolic heart failure. There is one percent three of diastolic heart failure in the chronic heart failure. There are many reports ofβ-adrenal receptor blocker be used in congestive cardiac failure before, but there less reports of nonselectiveβ-adrenal receptor blocker be used in diastolic heart failure. So our study is to treat diastolic heart failure with Carvedilol which is nonselectiveβ-adrenal receptor blocker, then observe the change of heart function and glucolipometabolic of the patients. We chose 76 patients (all older than 60) who visit our department from Feb 2006 to Jar 2007, diagnosed as diastolic heart failure which depended on the denominator revised by Chinese heart failure institution. To divide the patients into two parts stochastic,one part contains 34 patients is treated group , the other contains 42 patients is control group, they all be given routine treatment of diastolic heart failure , include diuretic agent, vasodilator agent, angiotensin-converting enzyme inhibitor, digitalis of small dosage, the treated group give carvediol in addition( from little dose to more ), first give 3.125mg twice a day for 7 to 14 days, then observe the blood pressure and heart rate , if the blood pressure and heart rate didn’t lower then normal, and there is no atrioventricular conduction blocker increase the dosage to 6.25mg twice a day, and then to increase gradually per 7 to 14 days until get 25mg as the target dosage , the course of treatment is 3-6 month. During the course observe the change of symptom, test the blood pressure, take electrocardiogram, and also observe the adverse reaction. To determine the parameter of the diastolic function of heart , such as early diastolic filling time, atrial contraction time , E/A, isovolumic relaxation time (IVRT), left atrial dimension (LAD), stroke volume (SV), acceleration index (ACI), systemic vascular resistance (SVR), thoracic fluid content (TFC), left ventricular ejection fraction (LVEF), before and after treatment of two groups by ultrasonic cardiogram and uninjured cardio dynamic machine , then compare the results . And also compare the change of glucolipometabolic. The study is a retrospective study.
Result: 1、There is significance difficult in therapeutic effect between the treated group and the control group (p<0.05); 2、After treatment the clinical symptom of the treated group has been improved ( p<0.05),the control group also has been improved , there has significance difficult between the two groups; 3、There has no significance difficult of glucose and lipid between before and after treatment in treated group. But there has significance difficult between the two groups. During the treatment there has no significance adverse effect in the two groups, non stop treatment.
Conclusion: 1、Carvedilol could improve the function of left ventricular of elder diastolic heart failure . The mechanism is:①It could depress the left ventricular end-diastolic volume, depress the myocardial volume of oxygen by its negative isotropic effect, so it could improve heart muscle ischemia and ventricular diastole function. In addition, the function of it such as negative chronotropic effect could prolong the diastolic time, improve engorge of left ventricular and increase the volume of end-diastole;②It could active suppression the activity of sympathetic, block the increase of tension of adrenaline in heart, block the toxic effect to heart by catecholamine, inhibit the apoptosis of cadiocyte, block and reverse the reconstitution of ventricles by the blockage ofβ1、β2-recepter;③It could depress peripheral resistance by block theα1-recepter; it also could dilate the coronary artery, increase the blood supply. In addition it could neutralize myocardium inhibitory action induced by the block ofβ-receptor;④It has the effect of antioxidation, and it could eliminate oxygen free radical in body and the distinct protection of blood vessel;⑤It has the function of anti-tachyarrhythmia, so it could depress the tachyarrhythmia. In addition, there is no significant difference in LAD and ACI, it may related to the short obverse time. 2、It has no significance effect on the metabolic of glucose and lipid which is similar with the study by Jacob. 3、The patients of treatment group had no obviously complaint during the course. Most of the patients could tolerance the target dosage. There is two patient got lower heart rate (lower than 55) before get the target dosage, but they all tolerate the therapy dosage maintained. So to use Carvedilol is safe. 4、The mechanism of uninjured cardiodynamics machine is dependent on impedance measurement of electrobiology of the thorax. It could calculus the stroke volume, cardiac output and other haemodynamics parameters, so the condition of haemodynamics and the ventricular function could be evaluated. This method is safe and easy. There are some studies in abroad confirm that the results are accurate and reliability now.
In short, Carvedilol could improve the function of left ventricular of elder diastolic heart failure , and has no significance effect on the metabolic of glucose and lipid. But the study only observe the short effect, is lack of large-scale clinical trial, is waiting for further study.
Accompany to the population aging, the morbidity of elder heart failure increased gradually. But diastole dysfunction is the first symptom in the early stage of heart failure, it appeared as diastolic heart failure. There is one percent three of diastolic heart failure in the chronic heart failure. There are many reports ofβ-adrenal receptor blocker be used in congestive cardiac failure before, but there less reports of nonselectiveβ-adrenal receptor blocker be used in diastolic heart failure. So our study is to treat diastolic heart failure with Carvedilol which is nonselectiveβ-adrenal receptor blocker, then observe the change of heart function and glucolipometabolic of the patients. We chose 76 patients (all older than 60) who visit our department from Feb 2006 to Jar 2007, diagnosed as diastolic heart failure which depended on the denominator revised by Chinese heart failure institution. To divide the patients into two parts stochastic,one part contains 34 patients is treated group , the other contains 42 patients is control group, they all be given routine treatment of diastolic heart failure , include diuretic agent, vasodilator agent, angiotensin-converting enzyme inhibitor, digitalis of small dosage, the treated group give carvediol in addition( from little dose to more ), first give 3.125mg twice a day for 7 to 14 days, then observe the blood pressure and heart rate , if the blood pressure and heart rate didn’t lower then normal, and there is no atrioventricular conduction blocker increase the dosage to 6.25mg twice a day, and then to increase gradually per 7 to 14 days until get 25mg as the target dosage , the course of treatment is 3-6 month. During the course observe the change of symptom, test the blood pressure, take electrocardiogram, and also observe the adverse reaction. To determine the parameter of the diastolic function of heart , such as early diastolic filling time, atrial contraction time , E/A, isovolumic relaxation time (IVRT), left atrial dimension (LAD), stroke volume (SV), acceleration index (ACI), systemic vascular resistance (SVR), thoracic fluid content (TFC), left ventricular ejection fraction (LVEF), before and after treatment of two groups by ultrasonic cardiogram and uninjured cardio dynamic machine , then compare the results . And also compare the change of glucolipometabolic. The study is a retrospective study.
Result: 1、There is significance difficult in therapeutic effect between the treated group and the control group (p<0.05); 2、After treatment the clinical symptom of the treated group has been improved ( p<0.05),the control group also has been improved , there has significance difficult between the two groups; 3、There has no significance difficult of glucose and lipid between before and after treatment in treated group. But there has significance difficult between the two groups. During the treatment there has no significance adverse effect in the two groups, non stop treatment.
Conclusion: 1、Carvedilol could improve the function of left ventricular of elder diastolic heart failure . The mechanism is:①It could depress the left ventricular end-diastolic volume, depress the myocardial volume of oxygen by its negative isotropic effect, so it could improve heart muscle ischemia and ventricular diastole function. In addition, the function of it such as negative chronotropic effect could prolong the diastolic time, improve engorge of left ventricular and increase the volume of end-diastole;②It could active suppression the activity of sympathetic, block the increase of tension of adrenaline in heart, block the toxic effect to heart by catecholamine, inhibit the apoptosis of cadiocyte, block and reverse the reconstitution of ventricles by the blockage ofβ1、β2-recepter;③It could depress peripheral resistance by block theα1-recepter; it also could dilate the coronary artery, increase the blood supply. In addition it could neutralize myocardium inhibitory action induced by the block ofβ-receptor;④It has the effect of antioxidation, and it could eliminate oxygen free radical in body and the distinct protection of blood vessel;⑤It has the function of anti-tachyarrhythmia, so it could depress the tachyarrhythmia. In addition, there is no significant difference in LAD and ACI, it may related to the short obverse time. 2、It has no significance effect on the metabolic of glucose and lipid which is similar with the study by Jacob. 3、The patients of treatment group had no obviously complaint during the course. Most of the patients could tolerance the target dosage. There is two patient got lower heart rate (lower than 55) before get the target dosage, but they all tolerate the therapy dosage maintained. So to use Carvedilol is safe. 4、The mechanism of uninjured cardiodynamics machine is dependent on impedance measurement of electrobiology of the thorax. It could calculus the stroke volume, cardiac output and other haemodynamics parameters, so the condition of haemodynamics and the ventricular function could be evaluated. This method is safe and easy. There are some studies in abroad confirm that the results are accurate and reliability now.
In short, Carvedilol could improve the function of left ventricular of elder diastolic heart failure , and has no significance effect on the metabolic of glucose and lipid. But the study only observe the short effect, is lack of large-scale clinical trial, is waiting for further study.
引文
[1]Cecilia Gutierrez, and Daniel G, Blanchard, Diastolic Heart Failure: Challenges of Diagnosis and Treatment,Am Fam Physician 2004;69:2609-16.
[2] Hokk, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol 1993; 22:6A-13A.
[3] Berry C, Murdoch DR, McMurray JJ. The economics of chronic heart failure. Heart Fail 2001; 3:283-91.
[4] O’Connell JB, Bristow MR. Economic impact of heart failure in the United States: time for a different approach. Heart Lung Transplant 1994; 3:S107-12.
[5] Bristow MR. Mechanism of action of beta-blocking agents in heart failure. A m J Cardiol, 1997, 80(11A): 15L-25L.
[6] Bristow MR. Path physiologic and pharmacologic rationales for clinical management of chronic heart failure with beat-blocking agents [J].AmJ Cardiol, 1993, 71:12c-22c.
[7]Benjamin EJ, Levy D, Vasari SM, D’Agostino RB , Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort . The FraminghamHeart Study . JAMA 1994; 271:840-4.
[8] Wei JY. Age and the cardiovascular system . N Engl J Med 1992; 327:1735-9.
[9] Gaasch WH. Diagnosis and treatment of heart failure based on left ventricular systolic or diastolic dysfunction .JAMA 1994; 271:1276-80.
[10] Mandinov L , Eberli FR , Seiler C , et al. Diastolic heart failure . Cardiovascular Res , 2000, 45:813 - 825.
[11]周裔忠,祝善俊,于林君,舒张性心力衰竭诊断与治疗的进展,中华心血管病杂志,2004,32(5):478-480.
[12] Lit win S, Grossman W. Diastolic dysfunction as a cause of heart failure. J Am Coll Cardiol 1993; 22: 49A-55A.
[13] Zile M, Brutsaert D. New concepts in diastolic dysfunction and diastolic heart failure: part II: causal mechanism and treatment. Circulation 2002; 105: 1503-8.
[14] Apstein CS, Morgan JP. Cellular mechanism underlying left ventricular diastolic failure . In: Gaasch WH, LeWinter MM, editors. Left ventricular diastolic dysfunction and heart failure; 1994:3,24.
[15] Redfield MM, Jacobsen SJ, Burnett JC Jr, Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failureepidemic. JAMA, 2003, 289:194-202.
[16]Goyal D, Choudhary A, Lip GYH, Diastolic heart failure: Recognition, diagnosis and management .Expert in Pharmacotherapy, 2004, 5:1745-1754.
[17] Banerjee P, Clark AL, Nikitin N, et al. Diastolic heart failure, paroxysmal or chronic ? European Heart Journal, 2004,6:427-431.
[18]Cleland J, Dargie H, Drexler H, Guidelines for the diagnosis and treatment of chronic heart failure: executive summary. European Heart Journal,2005,26; 1115-1140.
[19] How to diagnose diastolic heart failure. European Study Group on Diastolic Heart Failure . European Heart Journal 1998; 19: 990 1003.
[20]Bristow MR. Mechanism of action of beta-blocking agents in heart failure. Am J Cardiol, 1997, 80(11A):26-40.
[21] Bristow M R. Why does the myocardium fail? In sights from basic science. Lancet, 1998 , 352(1) :8 - 14.
[22]Pepper GS , Lee RW, Sympathetic activation in heart failure and its treatment with β-blockade. Arch Intern Med, 1999, 159(8):225 - 234.
[23]Squire IB, Barnett DB. The rational use of β-adrenoceptor blockers in the treatment of heart failure,The changing face of an old therapy, Br J Clinical Pharmacol,2000 ,49 :1 - 9.
[24]Eichhorn EJ , Bristow MR. Medical therapy can improve the biological properties of the chronically failing heart ,A new area in the treatment of heart failure, Circulation ,1996 ,94 (9) :2285 - 2296.
[25]Constant J . A review of why and how we may use β-blockers in congestive heart failure, Chest , 1998 , 113 :800- 808.
[26]戴闺柱,慢性心力衰竭治疗的现代概念,中华心血管病杂志,2000 ,28 (1):75 - 78.
[27]戴闺柱,心力衰竭生物学治疗的新认识,中华心血管病杂志,2000 ,28 (4) :314-316.
[28]Andersson B, Caidahl K, di Lenarda A, Changes in early and late diastolic filling patterns induced by long-term adrenergicβ-blockade in patients with idiopathic dilated cardiomyopathy. Circulation 1996; 94: 673 82.
[29] Shibata MC, Flather MD, Bohm M, Borbola J, Cohen-Solal A, Dumitrascu D, et al. Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure. Rationale and design . Int J Cardiol 2002;86 :77-85.
[30]Ruffolo RR Jr , Feuerstein GZ, Ohlstein EH, Recent observations with adrenoceptor blockade. Am J Hyper, 1998, 11:9- 14.
[31]李拥军,周秀娟,程蕴琳,卡维地洛与充血性心力衰竭,医学综述,2004,10:608- 611.
[32]Ehsan Khan, Beta blockers: Types and clinical implications, British Journal of Cardiac Nursing 2006:132 -138.
[33]Bristow MR,β-adrenergic receptor blockade in chronic heart failure. Circulation 2000; 101:558-569.
[34]Bristow MR, What type ofβ-blocker should be used to treat chronic heart failure? Circulation, 2000, 102:484-486.
[35]戴闺柱 , β受体阻滞剂治疗心力衰竭:选择性β1 受体阻滞或全受体阻滞? 中华心血管病杂志,2001 ,29(11): 696-698.
[36]张妍 周旭晨,β受体阻滞剂治疗心力衰竭新进展,中国医师进修杂志,2006 ,29(4):9-12 .
[37]CIBIS - II investigators and committees1 The cardiac insufficiency bisoprolol Study II : a randomized trial ,Lancet 1999 ,353 :9-13.
[38]Weber MA, The role of the new beta-blockers in treating cardiovascular disease,Am J Hypertension ,2005,12,18(12 Pt 2):169S-176S.
[1]Hisashi Kai, Fumitaka Kuwahara, Keisuke Tokuda, and Tsutomu Imaizumi, Diastolic Dysfunction in Hypertensive Hearts: Roles of Perivascular Inflammation and Reactive Myocardial Fibrosis, Hypertensions Res 2005;28:483-490.
[2] Vasan RS, Larson MG, Benjamin EJ, Evans JC, Reiss CK, Levy D: Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: prevalence and mortality in a population-based cohort. J Am Coll Cardiol,1999;33:1948-1955.
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[21]李拥军,周秀娟,程蕴琳.卡维地洛与充血性心力衰竭.医学综述,2004,10:608-61
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[23]余仲林, 刘叔文, 吴曙光,卡维地洛对脂质的影响,解放军药学学报 2001,17(1):28.
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[2] Hokk, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol 1993; 22:6A-13A.
[3] Berry C, Murdoch DR, McMurray JJ. The economics of chronic heart failure. Heart Fail 2001; 3:283-91.
[4] O’Connell JB, Bristow MR. Economic impact of heart failure in the United States: time for a different approach. Heart Lung Transplant 1994; 3:S107-12.
[5] Bristow MR. Mechanism of action of beta-blocking agents in heart failure. A m J Cardiol, 1997, 80(11A): 15L-25L.
[6] Bristow MR. Path physiologic and pharmacologic rationales for clinical management of chronic heart failure with beat-blocking agents [J].AmJ Cardiol, 1993, 71:12c-22c.
[7]Benjamin EJ, Levy D, Vasari SM, D’Agostino RB , Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort . The FraminghamHeart Study . JAMA 1994; 271:840-4.
[8] Wei JY. Age and the cardiovascular system . N Engl J Med 1992; 327:1735-9.
[9] Gaasch WH. Diagnosis and treatment of heart failure based on left ventricular systolic or diastolic dysfunction .JAMA 1994; 271:1276-80.
[10] Mandinov L , Eberli FR , Seiler C , et al. Diastolic heart failure . Cardiovascular Res , 2000, 45:813 - 825.
[11]周裔忠,祝善俊,于林君,舒张性心力衰竭诊断与治疗的进展,中华心血管病杂志,2004,32(5):478-480.
[12] Lit win S, Grossman W. Diastolic dysfunction as a cause of heart failure. J Am Coll Cardiol 1993; 22: 49A-55A.
[13] Zile M, Brutsaert D. New concepts in diastolic dysfunction and diastolic heart failure: part II: causal mechanism and treatment. Circulation 2002; 105: 1503-8.
[14] Apstein CS, Morgan JP. Cellular mechanism underlying left ventricular diastolic failure . In: Gaasch WH, LeWinter MM, editors. Left ventricular diastolic dysfunction and heart failure; 1994:3,24.
[15] Redfield MM, Jacobsen SJ, Burnett JC Jr, Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failureepidemic. JAMA, 2003, 289:194-202.
[16]Goyal D, Choudhary A, Lip GYH, Diastolic heart failure: Recognition, diagnosis and management .Expert in Pharmacotherapy, 2004, 5:1745-1754.
[17] Banerjee P, Clark AL, Nikitin N, et al. Diastolic heart failure, paroxysmal or chronic ? European Heart Journal, 2004,6:427-431.
[18]Cleland J, Dargie H, Drexler H, Guidelines for the diagnosis and treatment of chronic heart failure: executive summary. European Heart Journal,2005,26; 1115-1140.
[19] How to diagnose diastolic heart failure. European Study Group on Diastolic Heart Failure . European Heart Journal 1998; 19: 990 1003.
[20]Bristow MR. Mechanism of action of beta-blocking agents in heart failure. Am J Cardiol, 1997, 80(11A):26-40.
[21] Bristow M R. Why does the myocardium fail? In sights from basic science. Lancet, 1998 , 352(1) :8 - 14.
[22]Pepper GS , Lee RW, Sympathetic activation in heart failure and its treatment with β-blockade. Arch Intern Med, 1999, 159(8):225 - 234.
[23]Squire IB, Barnett DB. The rational use of β-adrenoceptor blockers in the treatment of heart failure,The changing face of an old therapy, Br J Clinical Pharmacol,2000 ,49 :1 - 9.
[24]Eichhorn EJ , Bristow MR. Medical therapy can improve the biological properties of the chronically failing heart ,A new area in the treatment of heart failure, Circulation ,1996 ,94 (9) :2285 - 2296.
[25]Constant J . A review of why and how we may use β-blockers in congestive heart failure, Chest , 1998 , 113 :800- 808.
[26]戴闺柱,慢性心力衰竭治疗的现代概念,中华心血管病杂志,2000 ,28 (1):75 - 78.
[27]戴闺柱,心力衰竭生物学治疗的新认识,中华心血管病杂志,2000 ,28 (4) :314-316.
[28]Andersson B, Caidahl K, di Lenarda A, Changes in early and late diastolic filling patterns induced by long-term adrenergicβ-blockade in patients with idiopathic dilated cardiomyopathy. Circulation 1996; 94: 673 82.
[29] Shibata MC, Flather MD, Bohm M, Borbola J, Cohen-Solal A, Dumitrascu D, et al. Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure. Rationale and design . Int J Cardiol 2002;86 :77-85.
[30]Ruffolo RR Jr , Feuerstein GZ, Ohlstein EH, Recent observations with adrenoceptor blockade. Am J Hyper, 1998, 11:9- 14.
[31]李拥军,周秀娟,程蕴琳,卡维地洛与充血性心力衰竭,医学综述,2004,10:608- 611.
[32]Ehsan Khan, Beta blockers: Types and clinical implications, British Journal of Cardiac Nursing 2006:132 -138.
[33]Bristow MR,β-adrenergic receptor blockade in chronic heart failure. Circulation 2000; 101:558-569.
[34]Bristow MR, What type ofβ-blocker should be used to treat chronic heart failure? Circulation, 2000, 102:484-486.
[35]戴闺柱 , β受体阻滞剂治疗心力衰竭:选择性β1 受体阻滞或全受体阻滞? 中华心血管病杂志,2001 ,29(11): 696-698.
[36]张妍 周旭晨,β受体阻滞剂治疗心力衰竭新进展,中国医师进修杂志,2006 ,29(4):9-12 .
[37]CIBIS - II investigators and committees1 The cardiac insufficiency bisoprolol Study II : a randomized trial ,Lancet 1999 ,353 :9-13.
[38]Weber MA, The role of the new beta-blockers in treating cardiovascular disease,Am J Hypertension ,2005,12,18(12 Pt 2):169S-176S.
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