《糖尿病与心衰发生机制及诊疗现状.ppt》由会员分享，可在线阅读，更多相关《糖尿病与心衰发生机制及诊疗现状.ppt（34页珍藏版）》请在三一文库上搜索。
1、糖尿病与心力衰竭 发生机制和诊疗进展,南方医院心血管内科 许 顶 立,美国心血管疾病发病率和 死亡原因百分比,发病率,心血管死因构成比,AHA 2001,0.5%,0.5%,50M,12.4M,4.5M,1M,4.7M,1 in 5 males and females has some form of cardiovascular disease,心力衰竭的死亡率,Framingham的研究（1948年1988年）： 有症状的心力衰竭患者，男性患者平均存活时间为3.2年，女性为5.4年。,心力衰竭的年发病率,病生机制和诊断重要进展,心室重塑和心肌细胞凋亡是心力衰竭的重要病理生理机制，抑制心力衰
2、竭时神经内分泌的过度激活是降低心力衰竭患者死亡率的重要方法。 心导管检查和放射性核素心血管造影可以准确检测心脏收缩舒张功能，多谱勒超声心动图也是临床判断心脏收缩舒张功能简便和准确的方法，有床旁诊断价值。 舒张性心力衰竭（Diastolic Heart Failure） 为心力衰竭的一种特殊类型，是指各种疾病导致心室的舒张功能障碍但心室收缩功能尚正常而引发的临床综合征。目前的资料表明，充血性心力衰竭病人中约20-40%为单纯舒张性心力衰竭。,Coronary artery disease is the cause of HF in about two thirds of patients wit
3、h left ventricular systolic dysfunction. The remainder have a nonischemic cardiomyopathy, which may have an identifiable cause (e.g., hypertension, thyroid disease, valvular disease, alcohol use, or myocarditis) or may have no known cause (e.g., idiopathic dilated cardiomyopathy).,Diabetes is the le
4、ading cause of blindness in patients aged 20-74 years. Diabetes is also the leading cause of end-stage renal disease. Approximately 60-70% of patients with diabetes develop some degree of neuropathy, including erectile dysfunction. 60-70% of all diabetes-related deaths are attributable to the macrov
5、ascular manifestations of the disease. Diabetic vascular disease is responsible for a 2- to 4-fold increase in the incidence of coronary heart disease (CHD) and stroke and a 2- to 8-fold increase in the risk for heart failure. Diabetes have a 15- to 40-fold increased risk for lower extremity amputat
6、ions.,Pharmacotherapy 2002, 22(4):436-444.,During 13,811 person-years of follow-up, 173 subjects developed incident heart failure, as confirmed by chart review. Five factors were independent predictors of heart failure: male sex (RR = 1.7; CI, 1.3 to 2.4), older age (RR = 1.9; CI, 1.3 to 2.7 for age
7、 75 to 84 years, RR = 3.0; CI, 1.7 to 5.5 for age 85 years and older, compared with or = 70 mm Hg (RR = 2.3; CI, 1.3 to 4.3, compared with or = 28 kg/m2 (RR = 1.6; CI, 1.0 to 2.4, compared with 24 kg/ m2). Myocardial infarction occurred during follow-up in 8% of the cohort and was also an important
8、predictor of heart failure (RR = 21; CI, 15 to 31).,The development of heart failure in the elderly,Am J Med 1999 Jun;106(6):605-12,Diabetic cardiomyopathy Spector KS,Prior to 1972, the increased cardiovascular morbidity and mortality that diabetics endure had been attributed to vascular disease. In
9、 1972, Rubler et al. proposed the existence of a diabetic cardiomyopathy based on their expereince with four adult diabetic patients who suffered from congestive heart failure (CHF) in the absence of discernable coronary artery disease, valvular or congenital heart disease, hypertension, or alcoholi
10、sm. Alternative explanations for CHF, such as anemia and vascular and renal disease in these four patients, gave rise to criticisms, but a wave of subsequent studies in the 1970s and 1980s provided credence to this new disease entity. Diabetic cardiomyopathy is independent of atherosclerotic cardiov
11、ascular disease. The exact mechanism is still questionable, and several mechanisms have been proposed including small and microvascular disease, autonomic dysfunction, metabolic derangements, and interstitial fibrosis.,Clin Cardiol 1998 Dec;21(12):885-7,糖尿病性心肌病,The diabetic cardiomyopathy is a disea
12、se caused by diabetes and is characterised by the presence of diastolic and/or systolic left ventricular dysfunction. Diabetes may produce metabolic alterations, interstitial fibrosis, myocellular hypertrophy, microvascular disease and autonomic dysfunction. It is thought that all of them may cause
13、cardiomyopathy. Other abnormalities that are usually associated with diabetes such as hypertension, coronary artery disease and nephropathy should be excluded before diagnosing diabetic cardiomyopathy. There is no evidence that diabetic cardiomyopathy alone can produce heart failure. However, subcli
14、nical ventricular dysfunction has been described in young asymptomatic diabetic patients without other diseases that could affect the cardiac muscle. In these cases we should consider that diabetes is the only cause of the myocardial disease. More studies are needed to know the natural history of di
15、abetic cardiomyopathy.,An Med Interna 2002, 19(6):313-20,Patients with diabetes mellitus have an increased morbidity and mortality from cardiovascular disease, which both coronary artery disease and congestive heart failure (CHF) are largely responsible for. Diabetes with and without hypertension is
16、 an important cause of LV dysfunction and CHF. Diabetes may be responsible for the metabolic and ultrastructural causes of LV dysfunction, while hypertension may be responsible for the marked fibrotic changes that are found. The role of insulin to reverse both metabolic and structural changes is rev
17、iewed both from experimental data and with the limited amount of clinical data available. The therapy of CHF in patients with diabetes is similar to that of patients without diabetes. A significant opportunity exists to reduce morbidity and mortality with beta-blockers and ACE inhibitors when ischae
18、mia and CHF are both present. However, studies in patients diabetes have been limited to post hoc subgroup analyses and rarely as predefined subgroups. Clinical trials involving patients with diabetes with and without hypertension and LV dysfunction are clearly needed in the future to adequately add
19、ress the needs of this high risk subgroup.,Drugs 2002;62(2):285-307,In the UKPDS, tight control of blood pressure with either a b-blocker or an angiotensin-converting enzyme (ACE) inhibitor reduced the risks for diabetes-related death (32%), heart failure (56%), stroke (44%), and microvascular disea
20、se (37%).25,Mechanisms of Action of Oral Glucose-Lowering Drugs by Class,Metformin (immediate or extended release) Decreased insulin resistance, decreased hepatic glucose output, increased peripheral glucose utilization Sulfonylureas, meglitinides, nateglinide Increased insulin secretion a-Glucosida
21、se inhibitors Delayed digestion of complex carbohydrates Glitazones Decreased insulin resistance, decreased hepatic glucose output, increased peripheral glucose utilization,In a posthoc analysis of data from the ill-fated Sibrafiban vs Aspirin to Yield Maximum Protection from Ischemic Heart Events P
22、ost Acute Coronary Syndromes I and II (SYMPHONY I and II) their analysis, the Duke researchers noted that mortality risk appears to correlate directly with choice of therapy for diabetes. They found that there was a 2.6-fold increased risk of death for patients taking injected insulin and sulfonylur
23、ea drugs, compared with insulin-sensitizing therapies, such as metformin. In addition, they found that at 90 days into the trials, 12% of diabetic patients on insulin-providing therapy had a major adverse event, compared with 5% of diabetic patients on insulin-sensitizing therapy. The researchers sa
24、id such findings suggest that lowering glucose does not translate into lowering cardiovascular risk and that elevated blood sugar levels may be a marker for, rather than a causative factor in, cardiovascular disease.,Potential Downside to Diabetes Treatment,Medscape Cardiology 2002, 6(2).,Potential
25、Downside to Diabetes Treatment,In the final twist of fate, some diabetes treatments have been linked with exacerbation of cardiovascular disease. Glitazone therapy, commonly prescribed for treatment of diabetic patients, has been associated with fluid retention as well as plasma volume expansion. A
26、retrospective analysis of insurance claims from 35 health insurers covering 1.7 million Americans examined the association between glitazones and an increased risk for heart failure. Thomas Delea, PhD, and colleagues at Policy Analysis Inc. (Brookline, Massachusetts) used the insurance records to id
27、entify 8288 people with diabetes taking glitazones and 41,440 who did not take the drugs. Delea then compared claims over a 36-month period from the time of the first prescription for a glitazone. At a mean of 8.5 months follow-up, risk of developing heart failure was 4.5% in glitazone patients, com
28、pared with 2.6% in controls. After controlling for obesity, high blood pressure, and smoking, glitazone use remained an independent predictor for heart failure, and compared with nonusers, there was still a 50% increase in risk of heart failure.,Medscape Cardiology 2002, 6(2).,Patients with insulin
29、resistance or type 2 diabetes have a particularly high risk for heart failure and a poor prognosis once they develop heart failure. The choice of drugs for the management of heart failure in these patients should be directed at changing the natural history of the disease. The various drugs available
30、 for the treatment of heart failure, including ACE inhibitors and beta-adrenergic blockers, are known to be beneficial and should be given as first-line agents. Aggressive risk-factor modification and tight blood pressure and glycemic control are crucial. Much work is needed to establish the safety
31、and efficacy of various oral antidiabetic agents, especially the TZDs, for which the theoretic benefits are substantial and overall morbidity and mortality impact remain ill-defined.,Endocrinol Metab Clin North Am 2001,30(4):1031-46,四、慢性收缩性心力衰竭的药物治疗策略,1999年，Heart Failure Consensus Recommendations Co
32、mmittee 制定了心力衰竭的推荐治疗方案，发表在The American Journal of Cardiology。 2001年，ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult。发表在Circulation。 2002年，中华医学会心血管病分会制定了收缩性心力衰竭的治疗建议，发表在中华心血管病杂志。现将其主要观点介绍如下：,1心力衰竭的预防：,控制冠状动脉的危险因素，包括高血压、高血脂、肥胖和吸烟。 在新近发生的心肌梗死患者中，再灌注治疗以及ACEI和受体
33、阻滞剂的神经内分泌拮抗作用，能够减少心肌损害和后继事件发生的危险性。 在无症状性左室功能不全的患者中，ACEI和受体阻滞剂能够相互补益，产生良好效果。,2心力衰竭的一般处理：,通过限制盐的摄入和监控每日体重来维持体液平衡。 通过鼓励患者进行适量运动来改善身体状况，应避免过多的卧床休息。 控制房颤，在高危患者中使用抗凝剂，对适宜的患者行血管再通术。 避免应用抗心律失常的药物，非甾体类抗炎药和大多数钙通道阻滞剂。 不提倡心力衰竭患者过多的床上休息；鼓励患者进行适量运动，这可带来很多益处，包括减轻神经内分泌的激活。,3 利尿剂的应用原则：,对于所有有症状的心力衰竭患者都应使用利尿剂，因为他们有液体潴
34、留的倾向。虽然利尿剂能有效地控制症状，但不应单独应用。 利尿剂治疗的目的是减轻液体潴留所致的症状和体征，如颈静脉怒张和或水肿。 初用和或调整利尿剂使用时，测量体重是最好的监控方法。 利尿剂可能会改变其他治疗心力衰竭的药物（如ACEI和受体阻滞剂）的疗效和毒性。 适当剂量的利尿剂对心力衰竭患者非常重要。利尿剂的剂量不足可能减弱ACEI的疗效，并可能增加受体阻滞剂的危险性。,4血管紧张素转换酶抑制剂（ACEI）的应用原则：,所有（不是一些或大部分而是所有）的由左室收缩功能不全所致的心力衰竭患者都应接受ACEI的治疗，除非不能耐受或存在禁忌症。采用ACEI治疗要尽早，不应在病情加重或出现对其他药耐受
35、时才应用。 ACEI可能延缓症状的改善。但即使没有出现临床症状的改善，ACEI可以延缓疾病的进程。 早期出现的副反应不能阻止ACEI的长期应用。 常用药物：卡托普利（开搏通），依那普利（悦宁定），雷米普利（瑞泰），培哚普利（雅施达），福辛普利（蒙诺），贝那普利（洛汀新），赖诺普利（捷赐瑞），西拉普利（一平苏）。,5受体阻滞剂的应用原则：,所有由左室收缩功能不全所致的稳定的心功能II、III级的心力衰竭患者都应接受受体阻滞剂的治疗，除非不能耐受或存在禁忌症。采用受体阻滞剂治疗不应在病情加重或其他药出现耐受时才应用。但要从极小量开始。 有证据显示由左室收缩功能不全所致的心功能I、IV级的心力衰竭患
36、者可应用卡维地洛治疗。 受体阻滞剂可能延缓症状的改善。但即使没有出现临床症状的改善，受体阻滞剂可以延缓疾病的进程。 早期出现的副反应不能阻止受体阻滞剂的长期应用。 有效药物：卡维地洛（达利全、络德，3.125mg/d），美托洛尔（倍他乐克,6.25mg/d），比索洛尔（康可、博苏,2.5mg/d）。关于受体阻滞剂的用量是否应加至靶剂量的问题存在许多争议，推荐的治疗方案赞成大剂量的治疗，但仍存在争议。,6地高辛的应用原则：,地高辛能够改善由左室收缩功能不全所致的心力衰竭患者的临床症状，地高辛应当与利尿剂、ACEI和受体阻滞剂联合应用。 地高辛的剂量问题仍存在着争议，是否应当监测血浆地高辛水平来指
37、导治疗仍不清楚。 地高辛有很好的耐受性，但有些学者担心此药物可能在治疗范围内就已存在毒性。 方案认为ACEI、受体阻滞剂是必须要用的，而地高辛不是必须要用的药物，但使用地高辛毕竟可以使患者症状改善。但不能单独只使用地高辛。,7肼苯哒嗪硝酸酯的应用原则：,不能在未使用ACEI前使用肼苯哒嗪硝酸酯联合治疗；患者可以耐受ACEI时，不能用肼苯哒嗪硝酸酯联合治疗替代ACEI。 患者因低血压或氮质血症而不能耐受ACEI治疗时，应当考虑使用肼苯哒嗪硝酸酯联合治疗。 几乎没有证据支持硝酸酯类或肼苯哒嗪可以单独用于心力衰竭的治疗。但有证据表明两者在血液动力学方面和生理方面有协同作用，肼苯哒嗪可延缓硝酸酯类耐药
38、性的发生。,8血管紧张素拮抗剂和醛固酮拮抗剂的应用原则：,在心力衰竭的治疗中，不能认为血管紧张素受体拮抗剂等同于或优于ACEI。 不能在未使用ACEI前使用血管紧张素受体拮抗剂；患者可以耐受ACEI时，不能用血管紧张素受体拮抗剂替代ACEI。 只有当患者因咳嗽或血管性水肿而不能耐受ACEI治疗时才考虑使用血管紧张素受体拮抗剂。 严重心力衰竭患者，应考虑使用安体舒通。 没有资料表明安体舒通在非严重心力衰竭中有作用。在RALES研究基础上的亚组分析表明：在除了用ACEI治疗外，还用受体阻滞剂治疗的患者中，安体舒通的作用更显著。这支持如下观点：使用多种神经内分泌阻滞剂治疗心力衰竭是最佳策略。,9钙通
39、道阻滞剂的应用：,钙通道阻滞剂不能应用于心力衰竭的治疗。 在心力衰竭时应避免应用大多数钙通道阻滞剂，甚至伴有心绞痛或高血压时，也要避免应用。但氨氯地平（络活喜）对生存率无不利影响。 现阶段，氨氯地平不应用来作为延长非缺血性心肌病患者的生存率的治疗。,10抗心律失常药物的应用：,I 类抗心律失常药物不能用于心力衰竭患者，除非出现紧急的威胁生命的室性心律失常。 某些III类抗心律失常药物，如胺碘酮，似乎不增加死亡的危险性，它是优于I类的抗心律失常药物。 在已使用ACEI和受体阻滞剂的心力衰竭患者中，不建议常规用胺碘酮来预防猝死。 电解质紊乱可致心律失常，并影响抗心律失常药物的作用和安全性。,11静
40、脉正性肌力药物的应用：,因为门诊心力衰竭病人静脉输注磷酸二酯酶抑制剂和受体激动剂的增多，所以推荐的治疗方案里提及此治疗： 不推荐在家、在医生的诊所或在临时病房里，间歇性地静脉给予正性肌力药，甚至对严重的心力衰竭患者也不推荐。 对于极少数不能脱离正性肌力药物治疗以维持生活质量的患者，可以考虑门诊连续静脉给药。尽管在症状改善时有可能增加患者死亡的危险性。,心力衰竭的治疗,一线治疗药物为：血管紧张素转换酶抑制剂（ACEI）、 受体阻滞剂、利尿剂和洋地黄。,心力衰竭的死亡率 （已用ACEI治疗）,NYHA IV,NYHA IV,LVEF35%,LVEF35%,LVEF40%,NYHA IIIIV,五、器官移植技术和替代技术,双心室起搏除颤器治疗心衰,五、器官移植技术和替代技术,人工心脏辅助装置 心脏移植（异体心脏，异种心脏，人工心脏） 细胞移植（心肌干细胞，骨髓干细胞，骨骼肌细胞）,21世纪心血管病领域面临的两大挑战： 心力衰竭 心房纤颤,