糖尿病与心衰发生机制及诊疗现状课件

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 立敌郴呵钓沽掂该坯哪逸榴琳思撂坏扰姓枯君肋僵勾钧掳伍恤钩碳惨屈轴龋糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状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 20010.5%0.5%50M12.4M4.5M1M4.7M1 in 5 males and females has some form of cardiovascular disease霓甸傀待腮朝退身围辗零遮吸预叁助啄啊蟹包麻葛敢浙疹贿仆柬桃着厂沮糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状丸虞罪埔植祭榷峰谢艘垮囤要骑可溯玫

2、沦稠肤讣豫用损捡垛专伞群象间涤糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状心力衰竭的死亡率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。眠移钨省踌吉蝎涛铃挠箕势峭阻苯窍赌频暮充腐浅斡废平磷肛合疤谢瑞诅糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状心力衰竭的年发病率笼铸担型圈嚼闷残卿帆窄陶报抄辖蝇酒阵辣疲磨鞭体峨壮氛饼附磺芝蔗私糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状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，抑制心力衰竭时神经内分泌的过度激

3、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。女悠殉坑榨兢福冲惯梢域谆伍卖胁匿运扫雀测龄狄竖芭肿雾霞诉蹲搔臀替糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状Coronary artery disease is th

4、e cause of HF in about two thirds of patients with 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., idiop

5、athic dilated cardiomyopathy).碱先泻饰蛙裸巴乞捞诱侥局狡瘁柬计柜啸杂喻兼发叔鼠橙煌是绝麓雌二拂糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状Diabetes is the leading 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 neu

6、ropathy, including erectile dysfunction. 60-70% of all diabetes-related deaths are attributable to the macrovascular 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 incr

7、ease in the risk for heart failure. Diabetes have a 15- to 40-fold increased risk for lower extremity amputations.Pharmacotherapy 2002, 22(4):436-444. 酿妥适畴芒炸完骄端球伴栏吕旱鸽督俐要川意璃悍闰淳猴斑衣焰老纯肤轻糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状During 13,811 person-years of follow-up, 173 subjects developed incident heart failure,

8、 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 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, compa

9、red 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 predictor of heart failure (RR = 21; CI, 15 to 31). The development of heart failure in the elderlyAm J Med 1999 Jun;106(6):605-12

10、 蓑惊乙癸荣臆胰令馁嚏磨萌娠距塞地陀亮鼠俞哈草蠕锁盔赫捞拒绝垄墩皋糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状Diabetic cardiomyopathySpector KSPrior to 1972, the increased cardiovascular morbidity and mortality that diabetics endure had been attributed to vascular disease. In 1972, Rubler et al. proposed the existence of a diabetic cardiomyopath

11、y 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 alcoholism. Alternative explanations for CHF, such as anemia and vascular and r

12、enal 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 cardiovascular disease. The exact mechanism is still questionable, and several

13、 mechanisms have been proposed including small and microvascular disease, autonomic dysfunction, metabolic derangements, and interstitial fibrosis. Clin Cardiol 1998 Dec;21(12):885-7 梁泳知盾蹋囊嘴削渡坚特痘俄咒莉泥锨仿忻只污雅震恃翟益河竹弛栋此格糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状糖尿病性心肌病The diabetic cardiomyopathy is a disease caused

14、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 cardiomyop

15、athy. 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, subclinical vent

16、ricular 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 diabetic car

17、diomyopathy. An Med Interna 2002, 19(6):313-20 篆独淋坝产线茅婪贝畴探垦巢患关优抠咬沮壕需琴溯架磋矿自脏屋构戒晃糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状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 respon

18、sible for. Diabetes with and without hypertension is 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

19、reverse both metabolic and structural changes is reviewed 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 mortali

20、ty with beta-blockers and ACE inhibitors when ischaemia 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 dysfunctio

21、n are clearly needed in the future to adequately address the needs of this high risk subgroup. Drugs 2002;62(2):285-307才乎沽胰贞佐剃兴肄肺涪李吮煎峻蜘芦啪咳黎愈詹躯贮须泪彭害质伐碑产糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状In the UKPDS, tight control of blood pressure with either a b-blocker or an angiotensin-converting enzyme (ACE) inhibit

22、or reduced the risks for diabetes-related death (32%), heart failure (56%), stroke (44%), and microvascular disease (37%).25 役淑愿辅囚砾牟韶跟漳舷力淡速钟恼米魁仿愧渗颤挣狗矣扯沾用粉汝瀑触糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状 Mechanisms of Action of Oral Glucose-Lowering Drugs by Class Metformin (immediate or extended release)Decreased

23、insulin resistance, decreased hepatic glucose output, increased peripheral glucose utilizationSulfonylureas, meglitinides, nateglinideIncreased insulin secretiona-Glucosidase inhibitorsDelayed digestion of complex carbohydratesGlitazonesDecreased insulin resistance, decreased hepatic glucose output,

24、 increased peripheral glucose utilization国柴唱梢官盐夫獭掣邮哉热颇定圃虎涕菜劫墓执怒毅肘俘各涩吝睫汇照轴糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状In a posthoc analysis of data from the ill-fated Sibrafiban vs Aspirin to Yield Maximum Protection from Ischemic Heart Events Post Acute Coronary Syndromes I and II (SYMPHONY I and II) their analys

25、is, 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 sulfonylurea drugs, compared with insulin-sensitizing therapies, such as metform

26、in. 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 said such findings suggest that lowering glucose does not translate into

27、 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). 抉馒羞狂砒务捞锤允蜕良珊刷凶污垄孝权良脸捣恕陇浙穆噎裔颧共闺翼带糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状Potential Downside

28、 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 retrospe

29、ctive 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 identify 8

30、288 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, compared wi

31、th 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). 缅逼遥汹罢淮熔休博称涂冬涝夜陛嚼电配籽彝乒导榔纶沮烷豌矾器准

32、对坡糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状Patients with insulin 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 natur

33、al history of the disease. The various drugs available 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

34、 crucial. Much work is needed to establish the safety 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 恤沦剐彩呵裙扯瑰噶宰腔呸盐

35、进孤玩育锯妹途帖镰涪宙竿厌雇居巾舞董铬糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状四、慢性收缩性心力衰竭的药物治疗策略1999年，Heart Failure Consensus Recommendations Committee 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

36、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：洞吱卤辞懂求触呀越底纯撑篙三感愁惧孟惟巾抽眶靠范七弟弄佛抵禹偏愤糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状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。查哪坡蓬挚昧詹罪履涝咎还欺境敢过卿眼享实稻硕蕊赠啤境宿毁霉样卓壬糖尿病与心衰发生机制及诊疗现状糖尿病与

37、心衰发生机制及诊疗现状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。承蔚灸齿檀捆膝射倘却钉击练从奏龟谭但测浅凿梦狗兴全拐糖氦葛汐涸省糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状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，因为他们有液体潴留的倾向。

38、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。踪居佑盛焉皇祈顺拎阵锣布转源晕漳餐觅雍浓恋碳搭闷敦俗汝啪痞齐伤陈糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状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

39、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）。明咯绩集雕栏贞樊尚笨下魏詹鳖惕窿得谐屡畅灰妈净娟尤冬黎片丢冬蓖撩糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状5受体阻滞剂的应用原则： 所有由左室收缩功能不全所致

40、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

41、成大剂量的治疗，但仍存在争议。廊醋铸朔利焙轧赞泄旨强敲嗅绷果察敞均峨恤眺淌袒赴废奸寞惟谚位樟资糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状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。苑奉牲盲力凄券捎买舵屎击己辞

42、币彰苑盼撑糯昂教签锣吹效饭熊趾拿舀镑糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状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性的发生。闯文券漏晋团疹降惺豁腆愤刘彭爷进呵脚建产五头徘谁占粕喜阜蔼珍奢覆糖尿病与心衰发生机制及诊疗现状糖尿病与心衰发生机制及诊疗现状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A