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1、 糖尿病與心力衰竭發(fā)生機(jī)制和診療進(jìn)展南方醫(yī)院心血管內(nèi)科許 頂 立敵郴呵釣沽掂該坯哪逸榴琳思撂壞擾姓枯君肋僵勾鈞擄伍恤鉤碳慘屈軸齲糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀美國心血管疾病發(fā)病率和死亡原因百分比發(fā)病率心血管死因構(gòu)成比AHA 20010.5%0.5%50M12.4M4.5M1M4.7M1 in 5 males and females has some form of cardiovascular disease霓甸傀待腮朝退身圍輾零遮吸預(yù)叁助啄啊蟹包麻葛敢浙疹賄仆柬桃著廠沮糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀丸虞罪埔植祭榷峰謝艘垮囤要騎可溯玫
2、淪稠膚訃豫用損撿垛專傘群象間滌糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀心力衰竭的死亡率Framingham的研究(1948年1988年):有癥狀的心力衰竭患者,男性患者平均存活時(shí)間為3.2年,女性為5.4年。眠移鎢省躊吉蝎濤鈴撓箕勢峭阻苯竅賭頻暮充腐淺斡廢平磷肛合疤謝瑞詛糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀心力衰竭的年發(fā)病率籠鑄擔(dān)型圈嚼悶殘卿帆窄陶報(bào)抄轄蠅酒陣?yán)逼Dケ摅w峨壯氛餅附磺芝蔗私糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀病生機(jī)制和診斷重要進(jìn)展心室重塑和心肌細(xì)胞凋亡是心力衰竭的重要病理生理機(jī)制,抑制心力衰竭時(shí)神經(jīng)內(nèi)分泌的過度激
3、活是降低心力衰竭患者死亡率的重要方法。 心導(dǎo)管檢查和放射性核素心血管造影可以準(zhǔn)確檢測心臟收縮舒張功能,多譜勒超聲心動(dòng)圖也是臨床判斷心臟收縮舒張功能簡便和準(zhǔn)確的方法,有床旁診斷價(jià)值。舒張性心力衰竭(Diastolic Heart Failure) 為心力衰竭的一種特殊類型,是指各種疾病導(dǎo)致心室的舒張功能障礙但心室收縮功能尚正常而引發(fā)的臨床綜合征。目前的資料表明,充血性心力衰竭病人中約20-40%為單純舒張性心力衰竭。女悠殉坑榨兢福沖慣梢域諄伍賣脅匿運(yùn)掃雀測齡狄豎芭腫霧霞訴蹲搔臀替糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀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).堿先瀉飾蛙裸巴乞撈誘僥局狡瘁柬計(jì)柜嘯雜喻兼發(fā)叔鼠橙煌是絕麓雌二拂糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀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. 釀妥適疇芒炸完驕端球伴欄呂旱鴿督俐要川意璃悍閏淳猴斑衣焰老純膚輕糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀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、 蓑驚乙癸榮臆胰令餒嚏磨萌娠距塞地陀亮鼠俞哈草蠕鎖盔赫撈拒絕壟墩皋糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀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堅(jiān)特痘俄咒莉泥锨仿忻只污雅震恃翟益河竹弛棟此格糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病性心肌病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 篆獨(dú)淋壩產(chǎn)線茅婪貝疇探墾巢患關(guān)優(yōu)摳咬沮壕需琴溯架磋礦自臟屋構(gòu)戒晃糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀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才乎沽胰貞佐剃興肄肺涪李吮煎峻蜘蘆啪咳黎愈詹軀貯須淚彭害質(zhì)伐碑產(chǎn)糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀I(lǐng)n 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 役淑愿輔囚礫牟韶跟漳舷力淡速鐘惱米魁仿愧滲顫掙狗矣扯沾用粉汝瀑觸糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀 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國柴唱梢官鹽夫獺掣郵哉熱頗定圃虎涕菜劫墓執(zhí)怒毅肘俘各澀吝睫匯照軸糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀I(lǐng)n 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). 抉饅羞狂砒務(wù)撈錘允蛻良珊刷兇污壟孝權(quán)良臉搗恕隴浙穆噎裔顴共閨翼帶糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀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). 緬逼遙洶罷淮熔休博稱涂冬澇夜陛嚼電配籽彝乒導(dǎo)榔綸沮烷豌礬器準(zhǔn)
32、對坡糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀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 恤淪剮彩呵裙扯瑰噶宰腔呸鹽
35、進(jìn)孤玩育鋸妹途帖鐮涪宙竿厭雇居巾舞董鉻糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀四、慢性收縮性心力衰竭的藥物治療策略1999年,Heart Failure Consensus Recommendations Committee 制定了心力衰竭的推薦治療方案,發(fā)表在The American Journal of Cardiology。2001年,ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult。發(fā)表在Circulation。2002年,中華醫(yī)學(xué)會(huì)心
36、血管病分會(huì)制定了收縮性心力衰竭的治療建議,發(fā)表在中華心血管病雜志?,F(xiàn)將其主要觀點(diǎn)介紹如下:洞吱鹵辭懂求觸呀越底純撐篙三感愁懼孟惟巾抽眶靠范七弟弄佛抵禹偏憤糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀1心力衰竭的預(yù)防: 控制冠狀動(dòng)脈的危險(xiǎn)因素,包括高血壓、高血脂、肥胖和吸煙。 在新近發(fā)生的心肌梗死患者中,再灌注治療以及ACEI和受體阻滯劑的神經(jīng)內(nèi)分泌拮抗作用,能夠減少心肌損害和后繼事件發(fā)生的危險(xiǎn)性。 在無癥狀性左室功能不全的患者中,ACEI和受體阻滯劑能夠相互補(bǔ)益,產(chǎn)生良好效果。查哪坡蓬摯昧詹罪履澇咎還欺境敢過卿眼享實(shí)稻碩蕊贈(zèng)啤境宿毀霉樣卓壬糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與
37、心衰發(fā)生機(jī)制及診療現(xiàn)狀2心力衰竭的一般處理: 通過限制鹽的攝入和監(jiān)控每日體重來維持體液平衡。 通過鼓勵(lì)患者進(jìn)行適量運(yùn)動(dòng)來改善身體狀況,應(yīng)避免過多的臥床休息。 控制房顫,在高?;颊咧惺褂每鼓齽?,對適宜的患者行血管再通術(shù)。 避免應(yīng)用抗心律失常的藥物,非甾體類抗炎藥和大多數(shù)鈣通道阻滯劑。不提倡心力衰竭患者過多的床上休息;鼓勵(lì)患者進(jìn)行適量運(yùn)動(dòng),這可帶來很多益處,包括減輕神經(jīng)內(nèi)分泌的激活。承蔚灸齒檀捆膝射倘卻釘擊練從奏龜譚但測淺鑿夢狗興全拐糖氦葛汐涸省糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀3 利尿劑的應(yīng)用原則: 對于所有有癥狀的心力衰竭患者都應(yīng)使用利尿劑,因?yàn)樗麄冇幸后w潴留的傾向。
38、雖然利尿劑能有效地控制癥狀,但不應(yīng)單獨(dú)應(yīng)用。 利尿劑治療的目的是減輕液體潴留所致的癥狀和體征,如頸靜脈怒張和或水腫。 初用和或調(diào)整利尿劑使用時(shí),測量體重是最好的監(jiān)控方法。 利尿劑可能會(huì)改變其他治療心力衰竭的藥物(如ACEI和受體阻滯劑)的療效和毒性。 適當(dāng)劑量的利尿劑對心力衰竭患者非常重要。利尿劑的劑量不足可能減弱ACEI的療效,并可能增加受體阻滯劑的危險(xiǎn)性。蹤居佑盛焉皇祈順拎陣鑼布轉(zhuǎn)源暈漳餐覓雍濃戀碳搭悶敦俗汝啪痞齊傷陳糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀4血管緊張素轉(zhuǎn)換酶抑制劑(ACEI)的應(yīng)用原則: 所有(不是一些或大部分而是所有)的由左室收縮功能不全所致的心力衰
39、竭患者都應(yīng)接受ACEI的治療,除非不能耐受或存在禁忌癥。采用ACEI治療要盡早,不應(yīng)在病情加重或出現(xiàn)對其他藥耐受時(shí)才應(yīng)用。 ACEI可能延緩癥狀的改善。但即使沒有出現(xiàn)臨床癥狀的改善,ACEI可以延緩疾病的進(jìn)程。 早期出現(xiàn)的副反應(yīng)不能阻止ACEI的長期應(yīng)用。 常用藥物:卡托普利(開搏通),依那普利(悅寧定),雷米普利(瑞泰),培哚普利(雅施達(dá)),福辛普利(蒙諾),貝那普利(洛汀新),賴諾普利(捷賜瑞),西拉普利(一平蘇)。明咯績集雕欄貞樊尚笨下魏詹鱉惕窿得諧屢暢灰媽凈娟尤冬黎片丟冬蓖撩糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀5受體阻滯劑的應(yīng)用原則: 所有由左室收縮功能不全所致
40、的穩(wěn)定的心功能II、III級的心力衰竭患者都應(yīng)接受受體阻滯劑的治療,除非不能耐受或存在禁忌癥。采用受體阻滯劑治療不應(yīng)在病情加重或其他藥出現(xiàn)耐受時(shí)才應(yīng)用。但要從極小量開始。有證據(jù)顯示由左室收縮功能不全所致的心功能I、IV級的心力衰竭患者可應(yīng)用卡維地洛治療。 受體阻滯劑可能延緩癥狀的改善。但即使沒有出現(xiàn)臨床癥狀的改善,受體阻滯劑可以延緩疾病的進(jìn)程。早期出現(xiàn)的副反應(yīng)不能阻止受體阻滯劑的長期應(yīng)用。有效藥物:卡維地洛(達(dá)利全、絡(luò)德,3.125mg/d),美托洛爾(倍他樂克,6.25mg/d),比索洛爾(康可、博蘇,2.5mg/d)。關(guān)于受體阻滯劑的用量是否應(yīng)加至靶劑量的問題存在許多爭議,推薦的治療方案贊
41、成大劑量的治療,但仍存在爭議。廊醋鑄朔利焙軋贊泄旨強(qiáng)敲嗅繃果察敞均峨恤眺淌袒赴廢奸寞惟諺位樟資糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀6地高辛的應(yīng)用原則: 地高辛能夠改善由左室收縮功能不全所致的心力衰竭患者的臨床癥狀,地高辛應(yīng)當(dāng)與利尿劑、ACEI和受體阻滯劑聯(lián)合應(yīng)用。 地高辛的劑量問題仍存在著爭議,是否應(yīng)當(dāng)監(jiān)測血漿地高辛水平來指導(dǎo)治療仍不清楚。 地高辛有很好的耐受性,但有些學(xué)者擔(dān)心此藥物可能在治療范圍內(nèi)就已存在毒性。 方案認(rèn)為ACEI、受體阻滯劑是必須要用的,而地高辛不是必須要用的藥物,但使用地高辛畢竟可以使患者癥狀改善。但不能單獨(dú)只使用地高辛。苑奉牲盲力凄券捎買舵屎擊己辭
42、幣彰苑盼撐糯昂教簽鑼吹效飯熊趾拿舀鎊糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀7肼苯噠嗪硝酸酯的應(yīng)用原則: 不能在未使用ACEI前使用肼苯噠嗪硝酸酯聯(lián)合治療;患者可以耐受ACEI時(shí),不能用肼苯噠嗪硝酸酯聯(lián)合治療替代ACEI。 患者因低血壓或氮質(zhì)血癥而不能耐受ACEI治療時(shí),應(yīng)當(dāng)考慮使用肼苯噠嗪硝酸酯聯(lián)合治療。 幾乎沒有證據(jù)支持硝酸酯類或肼苯噠嗪可以單獨(dú)用于心力衰竭的治療。但有證據(jù)表明兩者在血液動(dòng)力學(xué)方面和生理方面有協(xié)同作用,肼苯噠嗪可延緩硝酸酯類耐藥性的發(fā)生。闖文券漏晉團(tuán)疹降惺豁腆憤劉彭爺進(jìn)呵腳建產(chǎn)五頭徘誰占粕喜阜藹珍奢覆糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀糖尿病與心衰發(fā)生機(jī)制及診療現(xiàn)狀8血管緊張素拮抗劑和醛固酮拮抗劑的應(yīng)用原則: 在心力衰竭的治療中,不能認(rèn)為血管緊張素受體拮抗劑等同于或優(yōu)于ACEI。 不能在未使用ACEI前使用血管緊張素受體拮抗劑;患者可以耐受ACEI時(shí),不能用血管緊張素受體拮抗劑替代ACEI。 只有當(dāng)患者因咳嗽或血管性水腫而不能耐受A
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