【正文】 Atherosclerosis amp。 Coronary heart diseases Fudan University, Zhongshan Hospital Dept. of Cardiology, Shanghai Institute of CVD Juying Qian, . 2022 Cardiovascular Diseases Coronary heart disease atherosclerosis Coronary stenosis coronary spasm Myocardial ischemia, anoxaemia Coronary heart disease, CHD Ischemic heart disease ?Atherosclerosis ?Stable angina pectoris(SAP) ?Acute coronary syndrome ?Unstable angina(UAP) and nonSTEMI (UA/NSTEMI) ?ST elevation myocardial infarction(STEMI) elevation [.eli39。vei??n ] Atherosclerosis[.230。θ?r?uskli39。r?usis] ?leading cause of death and disability ?Common location: ?Coronary[39。] circulation: Proximal[39。pr?ksim?l] left anterior[230。n39。ti?ri?] descending[di39。sendi?] coronary artery(LAD) ?Proximal portion of renal arteries ?Extracranial[.ekstr?39。kreini:?l ]顱外的 circulation to the brain ?Carotid頸動(dòng) [k?39。r?tid ] bifurcation Atherosclerosis Three fundamental biological processes of atherosclerosis 1. Accumulation of intimal[39。int?m?l] cells: ? smooth muscle cells ? Macrophages[39。m230。kr?39。feid?] ? Tlymphocytes[39。limf?sait] 2. Proliferated[pr?39。] connective tissue matrix[39。meitriks] 結(jié)締組織基質(zhì)增生 : ? collagen[39。k?l?d??n] ? elastic[i39。l230。stik] fibers ? proteoglycans[.pr?uti?u39。glaik230。ns]蛋白聚糖 3. Accumulation of lipid: ? cholesteryl esters[39。ist?] ? free cholesterol[k?39。l?st?,rol] Pathology and pathophysiology ?Fatty steak ?Fibrous plaque ?Complicated lesion[39。li:??n] Atherosclerosis Initiation of Atherosclerosis Fatty steak formation Initiation of Atherosclerosis Fatty steak formation ? Lipoprotein[.lip?39。pr?uti:n] oxidation ? Nonenzymatic[39。n?nenzai39。m230。tik] glycation Leukocyte recruitment [ri39。kru:tm?nt] Foam cell formation Atheroma evolution: fibrous plaque[plɑ:k] Atheroma evolution and plications Vascular remodeling: pensatory enlargement Atheroma evolution: ?Involvement of arterial smoothmuscle cells ?Blood coagulation[k?u39。230。gju39。lei??n] ?microvessels[39。maikr?uves?l] Atheroma evolution and plications Intima[39。intim?] 炎癥 細(xì)胞 少量平滑肌 細(xì)胞 激活的巨噬細(xì)胞 血栓 Complicated lesion[39。li:??n]: thrombosis Atheroma evolution and plications Atheroma evolution and plications Vulnerable plaque: ?Thin fibrous cap ?Relatively[39。rel?tivli] large lipid core ?High content of macrophages Inflammatory mediators[39。mi:] Intravascular ultrasound[39。 Classicification of atherosclerotic lesion using IVUS Clinicl stages and classification ?Absence of symptom or stage of delitescence[deili39。tesns]潛伏 ?ischemia ?necrosis(target[39。tɑ:git] an ) ?fibrosis Atherosclerosis ?General manifestation ?Aortic atherosclerosis ?Coronary artery atherosclerosis ?Cerebral[39。seribr?l] atherosclerosis ?RA atherosclerosis ?Mesenteric[mes?n39。terik] atherosclerosis ?Peripheral[p?39。rif?r?l] artery atherosclerosis Atherosclerosis clinical manifestation laboratory[ 39。l230。br?39。t?ri examination Lack of sensitive and specific methods for early diagnosis[.dai?g39。n?usis] ?Dyslipidemia[dislipi39。demi?]： ?Xray： DSA show severity of stenosis ?Doppler ultrasound: blood flow ?radionuclide： detection of ischemia ?Echocardiogram： CHD ?ECG and stress test: CHD ?New techniques: intravascular ultrasound, angioscope ?CT, MRI Atherosclerosis Risk factors and prevention modification disorders (Dyslipidemia): cholesterol screening in all 20yrs Elevated: cholesterol (Tc and LDLc), TG, ApoB/ApoA,Lp(a), Low: HDLc LDL lowering by HMGCoA reductase(statins): cardiovascular events 30%， risk of MI 62% ： ,Metabolic syndrome or insulin resistance syndrome: BP, BMI ,TG, serum insulin HDLc, OGTT Diabetes mellitus(DM): ?RR for male, for female ?more diffuse lesion. ?CAD equivalent 7580% cause of death in adult DM are vascular diseases: CAD, cerebrovascular disease, or peripheral vascular disease Risk factors and prevention 7 years incidence of death/nonfatal MI (East West Study) * These patients had no history of myocardial infarction Haffner SM, et al. N Engl J Med. 1998。339:229–234. 0 5 10 15 20 25 30 35 40 45 50 Events of MI in 7 years No history of MI OMI No history of MI* OMI nondiabetics diabetics n = 1373 n = 1059 P P 4% 19% 20% 45% DM: CAD equivalent 5. Cigarette smoking： more thrombogenic 6. Family history： 7. Aging： 40yrs adults ， 4/5 fatal myocardial infarction occured in patiens 65 yrs 8. Male gender/ postmenopausal state： male:female = 2： 1, man develop CHD 1015 yrs earlier than woman 9. alcohol 10. Others: diet,homocysteine, hemostatic factors inflammation/infection Risk factors and prevention ?Drug therapy： ?antiplatelet： aspirin, clopidogrel, GPIIb/IIIa inhitibor, Dipyridamole, cilostazol ?Lipidlowering Risk factors and prevention 1. HMGCoA reductase inhibitors（ statins） Atorvastatin,Fluvastatin,Lovastatin,Pravastatin,Simvastatin,Cerivastatin, Rosuvastatin： *elevation of aminopherase, rhabdomyolysis 2. Bile acidbinding Resins cholestyramine， colestipol 3. Nicotinic Acid： 4. Fibric acid derivatives（ fibrates） Gemifibrozil, clofibrate, Fenofibrate 5. Cholesterol absorption inhibitors: ezetimibe 6. Probucol Lipidlowering drugs A: aspirin,ACEI B: blood pressure, βblocker, C: cigarette smoking, Cholesterol D: diet, diabetes E: exercise, education Prevention of CAD Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults ATP III (adult treatment panel III) Circul