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1、冠状动脉粥样硬化性心脏病(coronary atherosclerotic heart disease) 大连医科大学附属二院心内科 牛 楠动脉粥样硬化atherosclerosisIntroductionArteriosclerosis Thickening and loss of elasticity of arterial walls Hardening of the arteries Greatest morbidity and mortality of all human diseases via Narrowing Weakening Plaque That Has Been Su
2、rgically Removed from Coronary ArteryCourtesy Ronald D. Gregory and John Riley, MD.Non Modifiable Risk FactorsAge A dominant influence Atherosclerosis begins in the young, but does not precipitate organ injury until later in lifeGender Men more prone than women, but by age 60-70 about equal frequenc
3、yFamily History Familial cluster of risk factors Genetic differencesModifiable Risk Factors (potentially controllable) Hyperlipidemia Hypertension Cigarette smoking Diabetes Mellitus Elevated Homocysteine Factors that affect hemostasis and thrombosis Infections: Herpes virus; Chlamydia pneumoniae Ob
4、esity, sedentary lifestyle, stress Pathogenesis of AtherosclerosisResponse to injury hypothesis Injury to the endothelium(dysfunctional endothelium)Chronic inflammatory responseMigration of SMC from media to intimaProliferation of SMC in intimaExcess production of ECMEnhanced lipid accumulationRespo
5、nse to injuryEndothelia dysfunctionInitiation of Fatty StreakFatty StreakFibro-fatty AtheromaAtherosclerosis TimelineFoamFoamCells Cells FattyFattyStreak Streak IntermediateIntermediateLesion Lesion AtheromaAtheromaFibrousFibrousPlaquePlaqueComplicatedComplicatedLesion/Lesion/RuptureRuptureAdapted f
6、rom Pepine CJ. Am J Cardiol. 1998;82(suppl 104).From FirstDecadeFrom ThirdDecadeFrom FourthDecadeEndothelial DysfunctionEndothelial DysfunctionAHA Classification of atherosclerosis动脉粥样硬化血栓形成动脉粥样硬化血栓形成: : 具具共同病理基础的进展性过程共同病理基础的进展性过程正常正常脂肪条纹脂肪条纹纤维斑块纤维斑块 粥样硬化斑块粥样硬化斑块斑块破溃斑块破溃/ /裂隙和血栓形成裂隙和血栓形成心肌梗死心肌梗死 缺血性
7、中缺血性中风风/ /TIATIA 严重的严重的下肢缺血下肢缺血临床无症状临床无症状心血管死亡心血管死亡年龄增长年龄增长稳定性心绞痛稳定性心绞痛间歇性跛行间歇性跛行不稳定性不稳定性心绞痛心绞痛ACSACS*ACS, *ACS, 急性冠脉综合征急性冠脉综合征; TIA, ; TIA, 一过性脑缺血发作一过性脑缺血发作缺血性缺血性肾病病缺血性缺血性肠病病Coronary Artery Disease冠心病冠心病Clinical classification(1979 WHO)Asymptomatic CHD(隐匿型）隐匿型）Angina pectoris CHD（心绞痛型）（心绞痛型）Myocard
8、ial infarction CHD(心肌梗死型）心肌梗死型）Ischemic cardiomyopathy CHD（缺血性心肌病型）（缺血性心肌病型）Sudden death CHD（猝死型）（猝死型）Classification of IHDChronic ischemic syndrome: stable angina asymptomatic CHD ischemic cardiomyopathy CHDAcute coronary syndrome: unstable angina STEMI/NSTEMI急性冠脉综合症的病理生理学Fuster et al. N Engl J Med
9、. 1992;326:310-318.Davies et al. Circulation. 1990;82(Suppl II):II-38, II-46.不稳定血栓不稳定血栓不稳定血栓不稳定血栓(UA/NSTEMI)(UA/NSTEMI)脂肪池脂肪池脂肪池脂肪池巨噬细胞巨噬细胞巨噬细胞巨噬细胞内在的压力，张力内在的压力，张力内在的压力，张力内在的压力，张力外部的剪切力外部的剪切力外部的剪切力外部的剪切力裂缝裂缝裂缝裂缝大裂缝大裂缝大裂缝大裂缝小裂缝小裂缝小裂缝小裂缝闭合血栓闭合血栓闭合血栓闭合血栓(STEMI)(STEMI)动脉粥样硬化斑块动脉粥样硬化斑块动脉粥样硬化斑块动脉粥样硬化斑块斑块斑
10、块斑块斑块破裂破裂破裂破裂血栓血栓血栓血栓 No ST ElevationST ElevationAcute Coronary SyndromeUnstable AnginaUnstable AnginaNQMINQMIQw MIQw MINSTEMIMyocardial InfarctionMyocardial InfarctionDavies MJ Davies MJ Heart 83:361, 2000Heart 83:361, 2000Ischemic DiscomfortPresentationPresentationWorking DxWorking DxECGECGBiochem
11、. Biochem. MarkerMarkerFinal DxFinal DxHamm Lancet 358:1533,2001Hamm Lancet 358:1533,2001ANGINA PECTORISDefinition of Angina A pain or discomfort in the chest or adjacent areas caused by insufficient blood flow to the heart muscle.Clinical classification and pathologyStable angina:fixed atheromatous
12、 stenosisUnstable angina:dynamic obstruction by plaque rupture with superimposed thrombosis and spasm斑块破裂引起急性严重事件不稳定不稳定不稳定不稳定心绞痛心绞痛心绞痛心绞痛心肌梗死心肌梗死心肌梗死心肌梗死猝死猝死猝死猝死稳定性稳定性稳定性稳定性 ( (劳力性劳力性劳力性劳力性) )心绞痛心绞痛心绞痛心绞痛不稳定斑块的进展过程不稳定斑块的进展过程稳定斑块的进展过程稳定斑块的进展过程Nissen SE. Am J Cardiol. 2000;86(suppl):12H-17H不稳定斑块不稳定斑块斑
13、块破裂斑块破裂血栓形成血栓形成稳定斑块稳定斑块斑块体积增加斑块体积增加管腔狭窄管腔狭窄Stable angina pectorisETIOLOGY.Ischemia is secondary to coronary artery disease in 95% of patients. The leading cause is certainly atherosclerotic coronary artery disease.A decreased oxygen supply or an increase in oxygen demand can lead to a worsening of s
14、ymptoms. .Ischemia can occur in patients with normal coronary arteries Clinical menifestationchest discomfortQuality - squeezing, griplike, pressurelike, suffocating and heavy”; or a discomfort but not pain. Angina is almost never sharp or stabbing, and usually does not change with position or respi
15、ration. Duration - anginal episode is typically minutes in duration. Fleeting discomfort or a dull ache lasting for hours is rarely anginaLocation - usually substernal, but radiation to the neck, jaw, epigastrium, or arms is not uncommon. Pain above the mandible, below the epigastrium, or localized
16、to a small area over the left lateral chest wall is rarely anginal. Provocation - angina is generally precipitated by exertion or emotional stress and commonly relieved by rest. Sublingual nitroglycerin also relieves angina, usually within 30 seconds to several minutes. Clinical features Physical ex
17、aminationAn S4 gallop may be transiently present during an episode, and the patient may be dyspneic or diaphoretic or have a new heart murmur.High-risk features of angina include heart failure and hypotension. A complete physical exam is crucial in making an assessment of risk.Most pt:(-) Alternativ
18、e Diagnoses to Angina for Patients with Chest PainNon-Ischemic CVaortic dissectionpericarditisPulmonarypulmonary emboluspneumothoraxpneumoniapleuritisChest Wallcostochondritisfibrositisrib fracturesternoclavicular arthritisherpes zosterGastrointestinalEsophagealesophagitisspasmrefluxBiliarycolicchol
19、ecystitischoledocholithiasischolangitisPeptic ulcerPancreatitisPsychiatricAnxiety disordershyperventilationpanic disorderprimary anxietyAffective disordersdepressionSomatiform disordersThought disordersfixed occlusionsInvestigation 12 Lead Resting ECG should be recorded in all patients with symptoms
20、 suggestive of angina pectorisnormal in 50% of patientsa normal ECG does not exclude severe CAD; however, it does imply normal LV function with favorable prognosisCHD CHD At rest:At rest: ECGECG冠心病冠心病 Episode of angina:ST-segment Episode of angina:ST-segment depressiondepressionECGECGCHD CHD HolterH
21、olterExercise testing Angina: Exercise TestingHigh Risk PatientsSignificant ST-segment depression at low levels of exercise and/or heart rate130Fall in systolic blood pressureDiminished exercise capacityComplex ventricular ectopy at low level of exerciseExercise TestingContraindicationsMIimpending o
22、r acuteUnstable anginaAcute myocarditis/pericarditisAcute systemic illnessSevere aortic stenosisCongestive heart failureSevere hypertensionUncontrolled cardiac arrhythmiasInvestigation Echocardiography.The stress echocardiogram is a widely performed test used to assess patients for coronary disease.
23、Baseline echocardiographic images are obtained at rest to evaluate left ventricular function, wall motion, and valve function.Images are then acquired during peak stress (that is, during a GXT or with dobutamine) and compared with those at rest. Regional wall-motion abnormalities with stress indicat
24、e areas of hypoperfusion or ischemia. InvestigationIsotope scanning:obtaining scintiscans of the myocardium at rest and during stress after administration of an intravenous radioactive isotope such as thallium 201Investigation Coronary angiography. Used to identify foci of coronary disease. It is th
25、e evaluation of choice in patients with angina that is (1) poorly responsive to medication, or (2) unstable. It is also indicated in patients with test results consistent with a high risk for CAD. 冠心病冠心病 Coronary angiographyCoronary angiography冠心病冠心病 冠状动脉造影冠状动脉造影冠心病冠心病 LAD:stenosis LAD:normal冠心病冠心病
26、RCA:stenosis LCX:stenosisChronic Stable Angina Treatment ObjectivesPrevent progression of coronary artery disease and optimise life expectancyRelieve symptomsManagementAspirinbeta-adrenoreceptor blocking agents ( -blockers)calcium antagonistsNitratesNCEP Primary CHD Risk Goals for Lowering LDL-CLDL-
27、C GoalNo CHD 2 RF160 mg/dLNo CHD 2 RF130 mg/dLCHD 100 mg/dLThe NCEP recommends lowering LDL-C even further than these goals, if possible.Risk CategoryNHLBI; September 1993Coronary revascularisationInvasive treatment: coronary angioplasty (PTCA); coronary artery bypass grafting (CABG)冠心病冠心病 CABG冠心病冠心
28、病 PTCA冠心病冠心病 PTCABefore PTCA after PTCA冠心病冠心病 PTCA/SAcute coronary syndromeUnstable anginaNon-ST elevation myocardial infarction (NSTEMI)ST elevation myocardial infarction(STEMI)Unstable Angina/NSTEMIUnstable AnginaClinical Presentation and ClassificationDiagnosis of unstable angina refers to new or
29、 worsening symptoms of myocardial ischemia:rest anginanew-onset severe anginaincreasing angina评估住院期间和出院后长期缺血风险n评估住院期间死亡风险 (c-index 0.83)* 及出院后6个月死亡风险 (c-index 0.81)* n多个大型数据库中验证其有效性 (c-indices分别为 0.84*和0.75*)n评价死亡/再发心梗的长期风险网络版可下载 www.outcomes-umassmed.org/GRACE*Granger CB, et al. Arch intern Med. 20
30、03;163:2345-2353.*Eagle K, at al. JAMA. 2004;291:2727-2733.Unstable AnginaChest pain syndrome, either new onset or progressive angina Transient ST-segment depression on the electrocardiogram (ECG)Without evidence of myocardial infarction by CK, CK-MB, or TroponinNSTEMIChest pain syndrome, either new
31、 onset or progressive angina Transient or persistent ST-segment depression on the electrocardiogram (ECG)With evidence of myocardial infarction by CK, CK-MB, or TroponinUnstable Angina/NSTEMISignificant likelihood of occurrence of major cardiac eventsA. Incidence of MI: 8 to 10%B. Mortality: 2 to 5%
32、Unstable Angina/NSTEMI:PathophysiologyAcute plaque fissuring and ruptureSuperimposed thrombusTransient occlusionMediator-induced vasospasm may be presentDeterminants of Plaque VulnerabilityLipid-rich core sizeCap thicknessCap inflammation and repair斑块破裂引起急性严重事件斑块破裂引起急性严重事件不稳定不稳定不稳定不稳定心绞痛心绞痛心绞痛心绞痛心肌梗
33、死心肌梗死心肌梗死心肌梗死猝死猝死猝死猝死稳定性稳定性稳定性稳定性 ( (劳力性劳力性劳力性劳力性) )心绞痛心绞痛心绞痛心绞痛不稳定斑块的进展过程不稳定斑块的进展过程稳定斑块的进展过程稳定斑块的进展过程Nissen SE. Am J Cardiol. 2000;86(suppl):12H-17H不稳定斑块不稳定斑块斑块破裂斑块破裂血栓形成血栓形成稳定斑块稳定斑块斑块体积增加斑块体积增加管腔狭窄管腔狭窄Physical ExaminatonNot that helpfulMay have evidence of CHF: JVD, rales, edemaMay have S4May have
34、 murmur of mitral regurgitation from papillary muscle dysfunctionInvestigation ECGCardiac Enzyme or TroponinCoronary angiographyAcute Coronary Syndromes评估住院期间和出院后长期缺血风险n评估住院期间死亡风险 (c-index 0.83)* 及出院后6个月死亡风险 (c-index 0.81)* n多个大型数据库中验证其有效性 (c-indices分别为 0.84*和0.75*)n评价死亡/再发心梗的长期风险网络版可下载 www.outcomes
35、-umassmed.org/GRACE*Granger CB, et al. Arch intern Med. 2003;163:2345-2353.*Eagle K, at al. JAMA. 2004;291:2727-2733.managementAdmitted to hospitalBest rest,OxygenAnti-platelet:asprin, Clopidogrel , GP IIb/IIIa inhibitors Anticoagulant: UFH or LMWHB-blocker Nitrates (intravenous)CCBStatinsACEICorona
36、ry revascularisationDefinite ACSPossible ACS() ECG;Normal biomarkersObserve; repeat ECG, markers at 4-8 hrsNo recurrent pain;() follow-up studiesRecurrent pain;(+) follow-up studiesStress test; LVfunction if ischemia() test: outpt follow-up(+) testAdmit, Use AcuteIschemia PathwayST Use MI Guidelines
37、No ST ST-T s,chest pain, markersInitial Chest Pain EvaluationSymptoms Suggestive of ACSAcute Coronary SyndromesPreparation for Discharge After UA/NSTEMIAntiplatelet RxASA 75 - 162 mg/dayClopidogrel 75 mg/day Beta BlockerACEI / ARBEspecially if DM, HF, EF 40%, HTN StatinLDL 100 mg/dL (ideally 70 mg/d
38、L)Secondary Prevention MeasuresSmoking CessationBP 140/90 mm HG or 130/80 mm HG for DM or chronic kidney disease HbA1C 7%BMI 18.5-24.9Physical Exercise 30-60 min at least 5 days/wk No ST ElevationST ElevationAcute Coronary SyndromeUnstable AnginaUnstable AnginaNQMINQMIQw MIQw MINSTEMIMyocardial InfarctionMyocardial InfarctionDavies MJ Davies MJ Heart 83:361, 2000Heart 83:361, 2000Ischemic DiscomfortPresentationPresentationWorking DxWorking DxECGECGBiochem. Biochem. MarkerMarkerFinal DxFinal DxHamm Lancet 358:1533,2001Hamm Lancet 358:1533,2001Thank you
