1、Atherosclerosis Atherosclerosis&Coronary heart diseasesCoronary heart diseasesZhengzhou University,First affiliated HospitalZhengzhou University,First affiliated HospitalDept.of CardiologyDept.of CardiologyHaiyu Li,M.D.Haiyu Li,M.D.Cardiovascular DiseasesAtherosclerosisAtherosclerosisleading cause o
2、f death and disabilityleading cause of death and disabilityCommon location:Common location:Coronary circulation:Proximal left anterior Coronary circulation:Proximal left anterior descendingdescending coronary artery(LAD)coronary artery(LAD)Proximal portion of renal arteriesProximal portion of renal
3、arteriesExtracranialExtracranial circulation to the braincirculation to the brainCarotid bifurcationCarotid bifurcationAtherosclerosisAtherosclerosisCoronary heart diseaseatherosclerosisCoronary stenosiscoronary spasmMyocardial ischemia,anoxaemiaanoxaemiaCoronary heart disease,CHDIschemic heart dise
4、aseAtherosclerosisAtherosclerosisStable angina pectoris(SAP)Stable angina pectoris(SAP)Acute coronary syndromeAcute coronary syndromeUnstable angina(UAP)and non-STEMIUnstable angina(UAP)and non-STEMI (UA/NSTEMI)(UA/NSTEMI)ST elevation myocardial infarction(STEMI)ST elevation myocardial infarction(ST
5、EMI)Three fundamental biological Three fundamental biological processes of aprocesses of atherosclerosistherosclerosis1.1.Accumulation of intimal cells:Accumulation of intimal cells:smooth muscle cells smooth muscle cells MacrophagesMacrophagesT-lymphocytesT-lymphocytes2.2.Proliferated connective ti
6、ssue matrixProliferated connective tissue matrix:collagencollagenelasticelastic fibers fibersproteoglycansproteoglycans3.Accumulation of lipid:3.Accumulation of lipid:cholestercholesterolol esters estersfree cholesterolfree cholesterolHypothesis of lipoprotein infiltrationHypothesis of lipoprotein i
7、nfiltrationAggregation of platelets and Aggregation of platelets and thrombosisthrombosisClonal theoryClonal theory the response-to-injury hypothesis the response-to-injury hypothesis Atherosclerosis-Atherosclerosis-HypothesisHypothesisResponse-to-injury Response-to-injury Atherosclerosis:hypothesis
8、Atherosclerosis:hypothesisHigh blood pressure,bacterium,virus,toxin,ox-LDL,High blood pressure,bacterium,virus,toxin,ox-LDL,immune factor,vasoactive substanceimmune factor,vasoactive substanceendothelium damageendothelium damage and dysfunction and dysfunction(vasoactive substance,adhesion and aggre
9、gation(vasoactive substance,adhesion and aggregation of monocytes-foam cell,platelets)of monocytes-foam cell,platelets)LipidosLipidosi is,growth factor,proliferation of smooth s,growth factor,proliferation of smooth mucle cells,collagen,lipolytic enzyme,mucle cells,collagen,lipolytic enzyme,atherosc
10、lerosisatherosclerosisPathology and pathophysiologyPathology and pathophysiologyFatty steakFatty steakFibrous plaqueFibrous plaqueComplicated lesionComplicated lesionAtherosclerosisAtherosclerosisInitiation of AtherosclerosisInitiation of AtherosclerosisFatty steak formationFatty steak formationInit
11、iation of AtherosclerosisInitiation of AtherosclerosisFatty steak formationFatty steak formation LipoproteinLipoprotein oxidationoxidation Nonenzymatic Nonenzymatic glycationglycationLeukocyte recruitmentLeukocyte recruitmentFoam cell formationFoam cell formationAtheroma evolution:fibrous plaqueAthe
12、roma evolution:fibrous plaqueAtheroma evolution and complicationsAtheroma evolution and complicationsAtheroma evolution:Atheroma evolution:Involvement of Involvement of arterial smooth-muscle arterial smooth-muscle cellscellsBlood coagulationBlood coagulationmicrovesselsmicrovesselsAtheroma evolutio
13、n and complicationsAtheroma evolution and complicationsComplicated lesion:thrombosisComplicated lesion:thrombosisAtheroma evolution and complicationsAtheroma evolution and complicationsAtheroma evolution and complicationsAtheroma evolution and complicationsIntravascular ultrasoundIntravascular ultra
14、soundClassicification of atherosclerotic Classicification of atherosclerotic lesion using IVUSlesion using IVUSClinicl stages and classificationClinicl stages and classificationAbsence of symptom or stage of delitescenceAbsence of symptom or stage of delitescenceischemiaischemianecrosis(target organ
15、)necrosis(target organ)fibrosisfibrosisAtherosclerosisAtherosclerosisGeneral manifestationGeneral manifestationAortic atherosclerosisAortic atherosclerosisCoronary artery atherosclerosisCoronary artery atherosclerosisCerebral atherosclerosisCerebral atherosclerosisMesenteric atherosclerosisMesenteri
16、c atherosclerosisPeripheral artery atherosclerosisPeripheral artery atherosclerosisAtherosclerosisAtherosclerosisclinical manifestationclinical manifestation laboratory examinationlaboratory examinationLack of sensitive and specific methods for Lack of sensitive and specific methods for early diagno
17、sisearly diagnosisDyslipidemiaDyslipidemia：X-rayX-ray：DSA show severity of stenosisDSA show severity of stenosisDoppler ultrasound:blood flowDoppler ultrasound:blood flowradionuclideradionuclide：detection of ischemiadetection of ischemiaEchocardiogramEchocardiogram：CHDCHDECG and stress test:CHDECG a
18、nd stress test:CHDNew techniques:intravascular ultrasound,New techniques:intravascular ultrasound,angioscopeangioscopeCT,MRICT,MRIAtherosclerosisAtherosclerosisRisk factors and Risk factors and preventionprevention1.Lifestyle modification1.Lifestyle modification2.Lipid disorders(Dyslipidemia):2.Lipi
19、d disorders(Dyslipidemia):cholesterol screening in all 20yrs cholesterol screening in all 20yrsElevated:cholesterol(Tc and LDL-c),TG,ApoB/ApoA,Lp(a),Elevated:cholesterol(Tc and LDL-c),TG,ApoB/ApoA,Lp(a),Low:HDL-c Low:HDL-c LDL lowering by HMG-CoA reductase(statins):LDL lowering by HMG-CoA reductase(
20、statins):cardiovascular events 30%cardiovascular events 30%，risk of MI 62%risk of MI 62%3.Hypertension3.Hypertension：4.DM,4.DM,Metabolic syndrome or insulin resistance syndrome:Metabolic syndrome or insulin resistance syndrome:BP,BMI,TG,serum insulin BP,BMI,TG,serum insulin HDL-c HDL-cDiabetes melli
21、tus(DM):Diabetes mellitus(DM):RR 1.9 for male,3.3 for female RR 1.9 for male,3.3 for female more diffuse lesion.more diffuse lesion.CAD equivalentCAD equivalent 75-80%cause of death in adult DM are 75-80%cause of death in adult DM are vascular diseases:vascular diseases:CAD,CAD,cerebrovascular disea
22、se,cerebrovascular disease,or peripheral vascular diseaseor peripheral vascular diseaseRisk factors and Risk factors and preventionprevention7 years incidence of death/non-fatal MI7 years incidence of death/non-fatal MI (East West Study)East West Study)*These patients had no history of myocardial in
23、farction Haffner SM,et al.N Engl J Med.1998;339:229234.0 05 5101015152020252530303535404045455050Events of MI in 7 yearsEvents of MI in 7 yearsNo history of MI OMI No history of No history of MI OMI No history of MIMI*OMI OMI non-diabetics non-diabetics diabetics diabetics n=1373n=1373n=1059n=1059P
24、P 0.001 0.001P P 0.00140yrs adults 40yrs adults，4/5 fatal myocardial 4/5 fatal myocardial infarction occured in patiens 65 yrsinfarction occured in patiens 65 yrs8.Male gender/postmenopausal state8.Male gender/postmenopausal state：male:female=2male:female=2：1,man develop CHD 10-15 yrs 1,man develop
25、CHD 10-15 yrs earlier than womanearlier than woman9.alcohol9.alcohol10.Others:diet,homocysteine,hemostatic factors10.Others:diet,homocysteine,hemostatic factors inflammation/infection inflammation/infectionRisk factors and Risk factors and preventionprevention Drug therapyDrug therapy：anti-plateleta
26、nti-platelet：aspirin,clopidogrel,GPIIb/IIIa aspirin,clopidogrel,GPIIb/IIIa inhitibor,inhitibor,Dipyridamole,cilostazol Dipyridamole,cilostazolLipid-lowering Lipid-lowering Risk factors and Risk factors and preventionprevention1.1.HMG-CoA reductase inhibitorsHMG-CoA reductase inhibitors（statinsstatin
27、s）Atorvastatin,Fluvastatin,Lovastatin,Pravastatin,SiAtorvastatin,Fluvastatin,Lovastatin,Pravastatin,Simvastatin,Cerivastatin,Rosuvastatinmvastatin,Cerivastatin,Rosuvastatin：*elevation of aminopherase,rhabdomyolysiselevation of aminopherase,rhabdomyolysis2.Bile acid-binding Resins2.Bile acid-binding
28、Resins cholestyramine cholestyramine，colestipolcolestipol3.Nicotinic Acid3.Nicotinic Acid：4.Fibric acid derivatives4.Fibric acid derivatives（fibratesfibrates）Gemifibrozil,clofibrate,FenofibrateGemifibrozil,clofibrate,Fenofibrate5.Cholesterol absorption inhibitors:ezetimibe5.Cholesterol absorption in
29、hibitors:ezetimibe6.Probucol6.ProbucolLipid-lowering drugsLipid-lowering drugsPrevention of CADPrevention of CAD A:aspirin,ACEI B:blood pressure,-blocker,C:cigarette smoking,Cholesterol D:diet,diabetes E:exercise,educationThird Report of the National Cholesterol Third Report of the National Choleste
30、rol Education Program(NCEP)Expert Panel on Education Program(NCEP)Expert Panel on Detection,Evaluation,and Treatment of Detection,Evaluation,and Treatment of High Blood Cholesterol in AdultsHigh Blood Cholesterol in Adults ATP III(adult treatment panel III)ATP III(adult treatment panel III)Circulati
31、on 2002 17/24:3144-3373AtherosclerosisAtherosclerosisCoronary heart diseaseCoronary heart disease(CHD)(CHD)Coronary heart disease Coronary heart disease(CHD)(CHD)most common cause:obstruction of most common cause:obstruction of atheromatous plaqueatheromatous plaqueother causes:other causes:spasm sp
32、asm arterial thrombi arterial thrombi coronary emboli coronary emboli ostial narrowing due to luetic aortitis ostial narrowing due to luetic aortitis congencongeni ital abnormalities tal abnormalities severe LV hypertrophy severe LV hypertrophy Factors effect myocardial oxygen Factors effect myocard
33、ial oxygen supply and demandsupply and demandOxygenOxygen supply supplyOxygen Oxygen demanddemandHeart rateHeart rateMyocardial Myocardial contractilitycontractilitySystolic wall stressSystolic wall stressoxygen carryingoxygen carryingcapacity of bloodcapacity of bloodCoronary blood flowCoronary blo
34、od flowVascular Vascular resistanceresistanceExtravascularExtravascular compressive forces compressive forcesautoregulationautoregulationMetabolic regulationMetabolic regulationHumoral Humoral factorfactorNeural Neural regulationregulationDuration of diastoleDuration of diastolePressure Pressure gra
35、dientgradientEndothelial controlEndothelial controlCoronary heart diseaseCoronary heart disease TypeType：slient ischemia:delitescenceslient ischemia:delitescence：(ECG change)(ECG change)Angina pectorisAngina pectoris：angina,caused by myocardial angina,caused by myocardial ischemiaischemia myocardial
36、 infarctionmyocardial infarction：acute myocardial acute myocardial ischemic necrosis caused by the occlusion of ischemic necrosis caused by the occlusion of coronary arterycoronary arteryIschemia cardiomyopathy(Heart failure and Ischemia cardiomyopathy(Heart failure and arrhythmia)arrhythmia)：cardia
37、c enlargement,heart failure,cardiac enlargement,heart failure,arrhythmia,caused by the myocardial fibrosis as arrhythmia,caused by the myocardial fibrosis as the consequence of chronic mycardial ischemiathe consequence of chronic mycardial ischemiaSudden deathSudden death：sudden cardiac arrest cause
38、d sudden cardiac arrest caused by by ventricular fibrillation/flutterventricular fibrillation/flutterCoronary heart disease Coronary heart disease(CHD)(CHD)TypeType：slient ischemia:delitescenceslient ischemia:delitescenceAngina pectorisAngina pectoris：myocardial infarctionmyocardial infarction：Ische
39、mic cardiomyopathy(Heart Ischemic cardiomyopathy(Heart failure and arrhythmia)failure and arrhythmia)Sudden death Sudden death Acute Coronary Syndrome(ACS)Acute Coronary Syndrome(ACS)Resting ischemiaResting ischemiaNon-ST elevationNon-ST elevationSTelevationSTelevationUnstable anginaUnstable anginaN
40、on-Q wave AMINon-Q wave AMIQ wave AMIQ wave AMI*positive serum cardiac markers*#occasionally variant anginaStable angina pectorisStable angina pectoris(SAP)(SAP)definition:definition:acute and transient myocardial ischemia and acute and transient myocardial ischemia and anoxaemia anoxaemia usually c
41、aused by coronary insufficiency during usually caused by coronary insufficiency during exertionexertion or emotional stress or emotional stressCharacteristics:Characteristics:paroxysmal precordial squeezing-like chest pain,paroxysmal precordial squeezing-like chest pain,behind the mid sternumbehind
42、the mid sternum，radiated to left shoulder and upper armradiated to left shoulder and upper armprecipitated by stress or exertionprecipitated by stress or exertionduration:2-5min duration:2-5min typicallytypically relieved rapidly by rest or nitrates relieved rapidly by rest or nitrates Stable angina
43、 pectorisStable angina pectorisCoronary stenosisCoronary stenosis(others:aortic valve disease,HOCM,MB(others:aortic valve disease,HOCM,MB)+Myocardial oxygen demand Myocardial oxygen demand（HRHR X X SBPSBP）increasedincreased myocardial hypoxiamyocardial hypoxiaacumulation of metabolic product,stimula
44、te acumulation of metabolic product,stimulate C1-5C1-5 nerve nerve to cause the sensation of chest to cause the sensation of chest painpain Stable angina pectorisStable angina pectorismechanismmechanismin angiographyin angiographySignificant coronary lesion with Significant coronary lesion with diam
45、eter stenosis 70%in 75%ptsdiameter stenosis 70%in 75%ptsNo significant stenosis in about 5-No significant stenosis in about 5-10%pts,Ischemia may be related to 10%pts,Ischemia may be related to coronary spasm or microvascular coronary spasm or microvascular dysfunction.dysfunction.PathologyPathology
46、Stable angina pectorisStable angina pectorispathophysiologypathophysiology1.Metabolic and electrophysiology1.Metabolic and electrophysiologyATP reduced,accumulation of acid substances ATP reduced,accumulation of acid substances Dysfunction of iron pump(Na+-K+,and Na+-Ca+)Dysfunction of iron pump(Na+
47、-K+,and Na+-Ca+)Early depolarization(ST deviation)Early depolarization(ST deviation)2.LV function and hemodynamic situation 2.LV function and hemodynamic situation LV contractility and speed,systolic BP,LV contractility and speed,systolic BP,stroke volume,cardiac output decreasedstroke volume,cardia
48、c output decreased LVED pressure and volume LVED pressure and volume Stunning of myocardiumStunning of myocardiumStable angina pectorisStable angina pectorissymptomsymptom：chest pain or chest pain or oppressionoppressionlocationlocation behind or slightly to the left of behind or slightly to the lef
49、t of the mid sternum the mid sternum no definite borderlineno definite borderlineradiated to the left shoulder and radiated to the left shoulder and upper armupper armAtypical location:lower jaw,the Atypical location:lower jaw,the back of neckback of neckClinical manifestationClinical manifestationS
50、table angina pectorisStable angina pectorischest painchest paincharacteristicscharacteristics：tightness,squeezing,burning,pressing,choking,tightness,squeezing,burning,pressing,choking,bursting,rarely sharp,not spasmodicbursting,rarely sharp,not spasmodic force the patient stop the activity till the
