1、心力衰竭的診斷與治療面臨的選擇與挑戰(zhàn) 內(nèi) 容腦鈉肽、N端腦鈉肽前體在心力衰竭診斷和處理中的地位他汀類藥物治療心力衰竭 力不從心？在初級(jí)保健中被誤診為心力衰竭的比例： - Framingham: 40% (McKee 1971) - Boston:42% (Carlson 1985) - Kuopio: 50% (Remes 1991)急診室中25-50%的失代償心力衰竭病人被誤診 充血性心力衰竭: 在臨床上是否易于診斷?三大癥狀非特異性（氣促、踝腫和疲勞）,特別 對(duì)于肥胖、老年和婦女。心衰體征僅提示心衰存在，但仍需有心功能評(píng) 價(jià)的客觀證據(jù)。BNP 100 but 500 HF likely N

2、T-proBNP年齡分層降低了假陽性和假陰性，提高了陽性預(yù)測(cè)值 ICON 的三重界值無需根據(jù)腎功能對(duì)NT-proBNP界值進(jìn)一步調(diào)整83%55%92%73%85%1800 pg/ml所有 75 歲 (n=519)86%66%88%84%90%總計(jì)85%88%82%82%90%900 pg/ml所有 50-75 歲 (n=554)95%99%76%93%97%450 pg/ml所有 50 歲 (n=183)精確度陰性預(yù)測(cè)值陽性預(yù)測(cè)值特異性敏感性合適界值年齡分層Januzzi, et al, Eur Heart J 2005Anwaruddin, et al, JACC, 2006診斷急性心力衰竭

3、國際氨基末端腦鈉肽原協(xié)助數(shù)據(jù)根據(jù)年齡分層的NT-proBNP“診斷”界值 診斷心衰的三大常規(guī) 胸片是心衰初步診斷的重要部分 心臟超聲是現(xiàn)在的“金標(biāo)準(zhǔn)” （仍不能完全解決急性呼吸困難的鑒別問題）到目前為止，由美國和歐洲心臟病協(xié)會(huì)推薦使用的BNP或NT-proBNP是唯一用于診斷心力衰竭的實(shí)驗(yàn)室檢測(cè)指標(biāo)胸片、心臟超聲和BNP/NT-proBNP檢測(cè)是診斷心衰的三大常規(guī) Richards et al. J Am Coll Cardiol 2006;47:5260 BNP 和 NT-proBNP的檢測(cè)分析NT-proBNP 半衰期相對(duì)較長，濃度相對(duì)較穩(wěn)定，含量相對(duì)較高（比 BNP 約高 1620倍），

4、檢測(cè)相對(duì)較容易，是較理想的預(yù)測(cè)標(biāo)志物BNP 半衰期相對(duì)較短，（18分鐘），檢測(cè)血液時(shí)間要求高；在了解病人即刻情況時(shí)較有價(jià)值BNP或NT-proBNP的臨床應(yīng)用價(jià)值基本相同每天或隔天檢測(cè)BNP并無臨床價(jià)值，治療1W后BNP才出現(xiàn)明顯變化Am J Cardiol 2004;93:1562-1563Am J Cardiol 2008;101:3A病人因急性呼吸困難來急診病史采集, 體格檢查, ECG, 胸片 + NTproBNP充血性心力衰竭 高度不可能充血性心力衰竭 高度可能充血性心力衰竭不可能？可能？其他檢查NTproBNP450pg/mL - 病人 900pg/mL - 病人 50-75 歲1

5、800pg/mL 病人 75歲Bayes-Genis A. Rev Esp Cardiol 2005體征OR95% CIp-value咳嗽0.180.06-0.520.001利用袢利尿劑3.991.58-10.10.003夜間陣發(fā)性呼吸困難4.501.32-15.40.02頸靜脈怒張3.051.06-8.790.04心力衰竭前2.631.02-6.800.05下肢水腫2.960.94-9.310.06第三心音奔馬律10.40.82-130.70.07COPD/哮喘前0.480.20-1.190.11端坐呼吸2.060.73-5.830.17喘鳴0.810.29-2.220.17 灰色區(qū)域中心力

6、衰竭的獨(dú)立預(yù)測(cè)因子van Kimmenade, et al, AJC, 2006Acute Heart Failure-BNP levels and risk stratification from the ED to dischargeUNDER 100 HEART FAILURE UNLIKELY CAUSE OF SOBUNDER 250 PATIENT IS AT LOW RISK AND MAY BE DISCHARGED SAFELYCONSIDER BNP IN THE CONTEXT OF CLINICAL SYMPTOMSABOVE 600 pg/ml PATIENT IS

7、CONSIDERED STILL AT HIGH RISK ED ADMISSIONINPATIENTDISCHARGEARRIVAL(Tiime)1,500 600 250 100 BNPValues(pg/ml)600 pg/ml400/pg/ml 急性心力衰竭, 5000 pg/ml 是短期預(yù)后的界值 判斷急性心力衰竭短期（60天）預(yù)后Januzzi et al. Arch Intern Med 2006 判斷急性心力衰竭長期（1年）預(yù)后對(duì)于1年危險(xiǎn)度的分層，最佳界值是1000 pg/mlVan Kimmenade et al. JACC 2006 多種標(biāo)志物檢測(cè): + GFR聯(lián)合傳統(tǒng)標(biāo)

8、志物， NT-proBNP預(yù)后價(jià)值加強(qiáng)BNP藥理作用：治療急性失代償性心衰擴(kuò)血管（vasodilator）利 鈉 （natriuretic）利 尿 （diuretic）抗纖維化（antifibrotic）Nesiritide（natrecor）Fitzgerald, ACC 2004 BNP: - 治療過程中明顯升高，不能反應(yīng)體內(nèi)分泌BNP濃度 - 治療結(jié)束后2小時(shí)才低于基線 NT-proBNP - 治療中12小時(shí)即可以明顯低于基線水平，反映治療效果 - 治療結(jié)束24小時(shí)可以達(dá)到最大程度的降低 在接受奈西立肽治療的心衰患者中 對(duì)BNP和NT-proBNP 變化的監(jiān)測(cè)12 hrs24 hrs I

9、nfusionJourdain P et al et al. JACC 2007;49:1733-9BNP的監(jiān)測(cè)指導(dǎo)治療:STARS-BNP 多中心研究BNP/NT-proBNP可以指導(dǎo)治療嗎? 內(nèi) 容腦鈉肽、N端腦鈉肽前體在心力衰竭診斷和處理中的地位他汀類藥物治療心力衰竭 力不從心？ Beneficial Effects of StatinsAnti-Inflammatory EffectsAntioxidant EffectsEndothelial FunctionEffects on AngiogenesisCardiac Hypertrophy and LV RemodelingNeu

10、rohormonal ActivationJ Am Coll Cardiol. 2008;51(4) Statins and Risks for Death and Heart Failure Hospitalisation in 25,000 heart failure patientsGo A et al. JAMA 2006;296:2105211105101520253035Rate per 100 person-yearsBaselineCHDNo BaselineCHDOverallRate of DeathNo.2459819705489305101520253035Baseli

11、neCHDNo BaselineCHDOverallRate of HospitalizationNo.24598197054893No StatinStatinAdjusted mortality among patients with ischemic etiology (n = 62,273) Mortality among patients with heart failure of nonischemic etiology (n = 31,551)AB既往的研究結(jié)果使人們對(duì)他汀治療心衰充滿希望然而，這些試驗(yàn)只是產(chǎn)生假說的初步研究他汀類能否進(jìn)一步用于臨床的心衰治療,尚需要開展大規(guī)模的前

12、瞻性研究 率先完成的是CORNOA試驗(yàn) Patients (n=5011) Chronic ischaemic systolic heart failure receiving optimal HF treatment (diuretics, ACE inhibitors, ARBs, beta-blocker therapy)Ejection fraction0.40 (NYHA class III/IV)or 0.35 (NYHA class II)60 yearsrosuvastatin 10 mg (n=2514)placebo (n=2497)End points:Time to c

13、ardiovascular death, non-fatal MI, non-fatal strokeTotal mortalityVisit:Week:18 to 224 to 230465213 monthlyFinal3 yA Randomized, Double-Blind, Placebo-Controlled Study with Rosuvastatin in Patients with Chronic Symptomatic Systolic Heart Failure CORONA - Study DesignEligibility Optimal HF treatment

14、institutedMedian follow-up 2.7 yearsPlaceborun-in Kjekshus J et al. Eur J Heart Fail 2005;7:1059-1069Mean age (years)73 73 75 years (%)4141Female sex (%) 2424NYHA class (%)II3737III6261IV1.61.4Ejection Fraction0.310.31Myocardial infarction (%) 60 60Angina pectoris (%) 7273CABG or PCI (%) 2626Hyperte

15、nsion (%) 6363PlaceboRosuvastatinn=2497n=2514 CORONA - Baseline characteristicsKjekshus J et al. N Eng J Med 2007; 357 doi 10.1056/NEJMoa0706201Total cholesterol (mmol/L) 5.35 5.36 LDL cholesterol (mmol/L) 3.563.54hsCRP, median (mg/L) 3.53.5Loop or thiazide diuretic (%) 8889 Aldosterone antagonist (

16、%) 3939ACE inhibitor (%) 8080Beta-blocker (%) 7575Antiplatelet or anticoagulant (%) 90 90 PlaceboRosuvastatin n=2497n=2514 CORONA - Medical History Kjekshus J et al. N Eng J Med 2007; 357 doi 10.1056/NEJMoa0706201-50-40-30-20-10010LDL-CHDL-CTGCRPCORONAEffects on LDL-C, HDL-C, TG and CRP at 3 months;

17、Absolute difference between rosuvastatin and placebo Between group difference from baseline (%)45%5.0%20.5%37.1%p0.001p0.001p0.001p0.001Kjekshus J et al. N Eng J Med 2007; 357 doi 10.1056/NEJMoa0706201CORONA - Primary Endpoint The combined endpoint of cardiovascular death or non-fatal MI or non-fata

18、l stroke (time to first event)Hazard ratio = 0.9295% CI 0.83 to 1.02p=0.12Months of follow-up0363024181260102030PlaceboRosuvastatin 10 mgNo. at riskPlacebo249723152156200318511431811Rosuvastatin251423452207206819321484855Percent of patients with primary endpointKjekshus J et al. N Eng J Med 2007; 35

19、7 doi 10.1056/NEJMoa0706201Months of follow-up036302418126PlaceboRosuvastatin 10 mg03612915Hazard ratio = 0.8495% CI 0.70 to 1.00p = 0.05No. at riskPlacebo249723152156200318511431811Rosuvastatin251423452207206819321484855Data on FileCORONA Post hoc analysis of the number fatal/non-fatal MI or stroke

20、 in the primary endpoint Percent of patients with eventp=0.01p=0.007p0.0014,0742,4641,2991,5103,6942,1931,1091,50101,0002,0003,0004,000Heart failureAll causeCV causeNon-CV causePlacebo (n=2,497)Rosuvastatin 10 mg (n=2,514)CORONA - Secondary EndpointsTotal number of hospitalizationsNo. hospitalisationsKjekshus J et al. N Eng J Med 2007; 357 doi 10.1056/NEJMoa0706201 對(duì)CORONA試驗(yàn)的解釋 入選患者平均年齡達(dá)73歲， 63%患者的NYHA心功能為 和級(jí) 。試圖通過改變粥樣硬化自然史，影響心血管罹患率和死亡率的作用可能有限 在CORONA試驗(yàn)的亞組分析中，發(fā)現(xiàn)對(duì)于那些心衰程度輕，一般狀況良好的年輕患者，他汀更能凸顯其優(yōu)勢(shì)?；蛩≡谀挲g相對(duì)較年輕的輕度心衰患者中可能會(huì)得到不同的結(jié)