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1、Cardiovascular Diseases Tests,Part01,Part02,Part03,Contents,目录,Atherosc-lerosis Formation,Serum Lipid Examination,Myocardial Injury Markers,Cholesterol (TC)、Triglyceride(TG) Lipoprotein HDL-C、LDL-C、Lp(a,Cardiac Troponin T, I (cTnT, cTnI) Creatine kinase (CK) ,CK-MB, Lactate dehydrogenase (LDH) Myohe
2、moglobin(Mb,Atherosclerosis Formation Endarterium hyperplasia degeneration calcification lumen: obstruction wall: disruption, hemorrhage,Endarterium,vessel,lesion,Formation of Atherosclerotic lesions,Lesion initiation Foam cell formation Chronic inflammation Fibrous plaque Thrombus formation,Normal
3、artery,Lesion Initiation,Lesion Initiation,交联,超氧自由基,切力,Foam Cell Formation,INF,SRA,TNF,凋亡,ApoE,Chronic Inflammation,MCP1,MCSF,NO,PCAM1, VCAM1,Fibrous Plaque,同型半胱氨酸,AT-II,平滑肌 细胞增殖,雌激素,NO,前列环素,CD40, CD40L,血管舒张,迁移,纤维帽,Thrombus Formation,炎症,组织因子,白细胞粘附,坏死核心,破裂,胶原酶 明胶酶,基质降解,1) 受体缺失学说 (2) 细胞激酶学说 (3) 病毒学说 (
4、4) 原癌基因学说 (5) 遗传及环境因素,其他假说,Free Cholesterol Cholesterol ester Triglyceride HDL Cholesterol LDL Cholesterol Lp(a) Apolipoprotein :ApoA1, ApoB100,Cholesterol,lipid,Serum Lipid Examination,lipoprotein,小肠,肝脏,肝外组织,毛细血管,摄食前后的血浆,Diet Synthesis release,Plasma lipid,Oxidation Reserve biomembrane transformati
5、on,source,outlet,Summary: Synthesis: liver 3/4, adrenal Excretion: bile Distribution: all over the body, adrenal cortex in brain, nerve Function: synthesize bile acid hormone vitamin D main component of cell membrane,Serum Total Cholesterol (TC,TC :risk factor of coronary heart disease Reference Val
6、ue desirable level: 5.20mmol/L(5.18) boardenline level: 5.235.69mmol/L (5.186.19) risk level: 5.72mmol/L (6.22,1) TC Physiological: Pathological: primary: Secondary: metabolic disease liver and gall disease Nephrotic Syndrome,Clinical Significance,age, sex, diet, exercise,Hyperlipidemia, Atheroscler
7、osis Diabetes Mellitus Hypothyroidism,Obstructive jaundice,type hypercholesterolemia,2) TC Hyperthyroidism Severe liver disease:cirrhosis of liver anaemia, malnutrition, malignant tumor drug: estrogen,thyroid hormone,Clinical Significance(continued,Factors affected lipid tests,biological factors: ag
8、e, sex, race behavioral factors: diet, obesity, smoking, stress, alcohol clinical factors:disease(endocrinic, metabolic, etc.) drugs(high BP) others:sample collection, fasting,Serum Triglyceride,Reference Value 0.561.70mmol/L desirable level: 1.70mmol/L boardenline level: 1.72.25mmol/L risk level:2.
9、26mmol/L,Fuction,1)TG (refer to TC) coronary heart disease:myocardial infarction atherosclerosis, diabetes mellitus primary hyperlipidemia, obesity, gout, nephrotic syndrome, obstructive jaundice,Clinical Significance,2)TG hyperthyroidism severe hepatic injury low lipoproteinemia hypoadrenocoricism,
10、Clinical Significance(continued,Easily affected by : dietary (short T1/2,Serum Lipoprotein examination,Classification,electrophoresis,density,rich TG ( livertissue) transport endogenous TC (+) AS transport TC from tissue to liver (-) AS,Chylomicrons (CM,Very Low Density Lipoprotein (VLDL,4serum - bu
11、tter like,transport endogenous TG ( livertissue) milk like, homogeneously turbid (+) AS,Low Density Lipoprotein (LDL,High Density Lipoprotein (HDL,Clinical Significance 1.Primary hyperlipoprotein: Enzyme, receptor defection type I : familial hyperchylomicronemia lipoprotein lipase(LPL) defection CM,
12、 TG,TC - acute Pancreatitis type II : IIa : familial hypercholesterolemia LDL receptor defect LDL,TC -AMI IIb : familial combined hyperlipidemia VLDL LDL TGTC,Clinical Significance (continued) type III : familial dysbetalipoproteinemia apoE synthesis deficiency ( board-) IDL , TGTC type IV : familia
13、l prebetalipoproteinemia VLDL TG CAD risk type V : combined hyperlipoproteinemia VLDL CM , TG , TC 2.Secondary hyperlipoproteinemia DM, nephrotic syndrome, AS, CAHD, Liver ,biliary disease,Low Density Lipoprotein-cholesterol(LDL-C,LDL: rich TC main risk factor of AS LDL1-IDL,LDL2-sLDL TG: LDLsLDL ox
14、LDL foam cell AS Reference Value 1 precipitation method desirable level : 3.12mmol/L boardenline level : 3.153.61mmol/L risk level: 3.64 mmol/L 2 method of elimination: 1.93.8mmol/L,Clinical Significance LDL: similar to TC To judge the chanciness of CAHD LDL CAHD TC LDL-C HDL-C- CAHD risk LDL : hype
15、rthyroidism, cirrhosis of liver,High Density Lipoprotein-cholesterol(HDL-C,Reference Value enzyme method :1.032.07mmol/L desirable level 1.04mmol/L decrease 0.91mmol/L electrophoresis: 30%40,Clinical Significance inverse correlation between HDL and TG ,CAHD HDL-C : AS, DM, NS, smoking, obesity,The s
16、tandard of desirable and risk level lipid,Item desirable boardenline increase (mmol/L) (decrease,TC 5.2 5.235.69 5.72 TG 1.70 1.70 LDL-C 3.12 3.153.61 3.64 HDL-C 1.041.55 0.91,Reference Value 0300mg/L,Lipoprotein(a) Determination Main Function: stimulate AS formation and thrombogenesis,Lp(a) is the
17、independent risk factor of AS and thrombogenesis,Clinical Significance Lp(a): (1) Ischemic cardio, cerebrovascular disease cererbral infarction, myocardial infarction (2) Acute phase protein: acute trauma inflammation (3) NS, DM, dialysis Lp(a) : Severe hepatic disease,Apolipoprotein examination,Apo
18、A ApoB,ApoA-I 构成 HDL的主要载脂蛋白 维持HDL结构的稳定与完整, 作为HDL受体的配体,被 HDL受体识别 Apo-II,apoB100 来源于肝脏 (1) 构成LDL(占其Apo的95%) (2) 作为LDL受体的配体,识别与 结合该受体 apoB48 来源于小肠, 构成CM(占其apo总量的9%), 与运输外源性TG有关,高脂血症患者开始治疗标准值及治疗目标值,饮食疗法 药物疗法 治疗 开始目标 开始目标 目标值,动脉粥样硬化病(-)TC 5.72 6.24 5.72 其他危险因子(-) LDL-C 3.64 4.16 3.64 动脉粥样硬化病(-)TC 5.20 5.
19、72 5.20 其他危险因子(+) LDL-C 3.12 3.64 3.12 动脉粥样硬化病(+)TC 4.68 5.20 4.68 LDL-C 2.60 3.12 2.60,指南的变化: 本指南的设计是取代被广泛采用的美国国家心肺血液研究所的ATP3指南。主要变化是现在指导临床医生对于四种特殊类别的患者启动中等强度或高强度他汀治疗,而不是根据特定的LDL胆固醇目标值来滴定药物。检测血脂对于病人治疗随访的目的是评价治疗的依从性,而不是看是否达到特定的LDL胆固醇目标值,AHA新指南:第IV版,AHA新指南:不再推荐血脂“达标”】指南的要点: 1. LDL胆固醇治疗目标值不再推荐;而是,临床医生
20、应该确定病人是否归属于四种特定的高危组之一,并应按照下列方案启动他汀治疗: 1.1 临床动脉粥样硬化性心血管疾病(ASCVD)患者应该使用高强度(年龄75岁)或中等强度(年龄大于等于75岁)的他汀治疗。 1.2 LDL胆固醇水平大于等于190 mg/dL(约4.2 mmol/L)的患者应该使用高强度他汀治疗。 1.3 糖尿病患者,年龄40-75岁,LDL胆固醇水平在70-189 mg/dL(约1.8-4.1 mmol/L),且没有临床ASCVD应该使用至少中等强度他汀治疗(如果估测10年ASCVD风险大于等于7.5%,则可能需要高强度他汀治疗)。 1.4 没有临床ASCVD或糖尿病的患者,如果
21、LDL胆固醇水平在70-189 mg/dL(约1.8-4.1 mmol/L),且估测的10年ASCVD风险大于等于7.5%应该使用中等或高强度他汀治疗。 2. 高强度他汀治疗是指阿托伐他汀(40-80 mg)或瑞舒伐他汀(可定;20-40 mg)。中等强度他汀治疗包括阿托伐他汀(10-20 mg),瑞舒伐他汀(5-10 mg),辛伐他汀(20-40 mg),普伐他汀(40-80 mg),以及其他一些他汀。 3. 除了个别特殊情况外,不推荐应用他汀类之外的调脂药物。 4. 10年ASCVD风险包括冠脉事件和卒中通过美国心脏协会(AHA)和美国心脏病学会(ACC)的网站的在线计算器测算。 5. 所
22、有病人均推荐生活方式改善,无论是否应用降胆固醇药物治疗。 指南的变化: 本指南的设计是取代被广泛采用的美国国家心肺血液研究所的ATP3指南。主要变化是现在指导临床医生对于四种特殊类别的患者启动中等强度或高强度他汀治疗,而不是根据特定的LDL胆固醇目标值来滴定药物。检测血脂对于病人治疗随访的目的是评价治疗的依从性,而不是看是否达到特定的LDL胆固醇目标值,Laboratory Determination of Myocardial Injury,P.252,MYOCARDIAL INJURY,Irreversible injury typically occurred in 30 minutes
23、 of ischemia Chronic O2 deficiency makes cells more resistant 30-60 min later, cell death initiated; 80% of cells at risk of death within 3 hours, almost 100% by 6 hours of ischemia,High blood cholesterol High blood pressure Smoking Obesity Lack of physical activity,Causes,MYOCARDIAL PROTEINS,Myoglo
24、bin,Actin, Myosin,Troponin,LDH,CK, AST,IDEAL CARDIAC MARKER,Detects only cardiac damage Detectable while damage reversible or preventable Correlates with amount of in injury Predicts prognosis Cheap, rapidly measured,Summary: Myocardial Injury Markers: (1) Structural protein: (2) Enzyme and micromol
25、ecule protein (3) Mitochondrion,Creatine kinase (CK) ,CK-MB, Lactate dehydrogenase (LDH) Aspartate aminotransferase (AST) Myohemoglobin(Mb,Cardiac Troponin T, I (cTnT, cTnI,ASTm, CK-mt,Dynamic curves of Heart Disease Markers,Structure of Troponin,Myocardial Protein Determination,Cardiac Troponin T,
26、I (cTnT, cTnI) compound type-most at filament free type(6% 8%)-myocardial cytoplasm,Feature: unique antigenicity-high specificity early increased, high peak value (1030 x), long persistence time correlated with myocardial ischemia time, reperfusion,infarction area,Reference Value 0.2g/L(cTnT) 1.5g/L
27、(cTnI) 0.5g/L (cTnT) Clinical Significance (1)AMI: To make a definite diagnosis,cut off value,diagnose AMI,Clinical Significance(continued) (2) Unstable angina pectoris (UAP) Minor Myocardial damage,MMD -definite diagnosis Unstable angina pectoris (UAP) -judge prognosis (3)Heart incidents of Blood d
28、ialysis patients predict Heart incidence, Hint prognosis (4)Others: evaluate operation (PTCA) effect myocardial injury, severe pyemia,Serum Myoglobin(Mb) Determination,Mb: compound protein of containing oxygen Exists in muscle and myocardium Reference Value 75g/L cut off value Clinical Significance
29、(1) AMI: 3h, 512h Peak, 1830h normal Diagnosis earlier and better than CK-MB and LD (2) Judge AMI progress : continue keep high, fluctuate infarction recurrence area increase,Cardiac Enzyme Determination Serum Creatine kinase(CK) and CK-isoenzyme,CK-MM CK-MB CK- BB Distribution skeletal myocardium b
30、rain, lung, muscle intestine, myocardium prostate Proportion 9496% 05% 0 Electrophoresis slow middle quick Subtype MM1,MM2,MM3 MB1,MB2,Clinical Significance 1. CK 25200U/L (1) CK: AMI: 38h, 1036h peak, 34day normal Myocarditis, muscular disease Progressive muscular dystrophy, polymyositis, cardiac o
31、peration Thrombolysis treatment: Reperfusion -CK (moderate sensitive) Alcoholism, hypothyroidism,Clinical Significance(continued) (2) CK: Hyperthyroidism, long-term lying in bed, Hormone therapy (3) CK-Isoenzyme CK-MB: The marker of myocardial infarction or necrosis,Clinical Significance (continued)
32、 2. CK-MB 38h, 930h peak, 23day normal Diagnose AMI : more sensitive and specific than CK peak early better progress CK-MB persistent high continuous MI infarction area new infarction angina, cardiac operation, pericarditis,1) AMI,2) Others,Clinical Significance (continued) 2. CK-MB CK-MB/CK6% (diff
33、erential diagnosis) CK-MB subtype CK-MB1 0.71U/L CK-MB2 1.0U/L diagnose AMI cut off value MB2/MB11.5 MB2/MB13.8 coronary artery recanalization,3) Muscular diseases and operation,Clinical Significance (continued) 3.CK-MM AMI : CK-MM3/CK-MM1 0.150.35 0.5 (diagnosis) Muscular diseases Polymyositis, mus
34、cular atrophy operation, trauma, convulsion, epilepsy,Clinical Significance(continued) 4. CK-BB cerebral infarction, injury, hemorrage meningitis, cerebral embolism CK-BB injury extent , area , progress lung , intestines gallbladder, prostate tumor,1) Nervous system diseases,2) Malignant tumor,CK-MB
35、的测定原理,免疫抑制法,巨CK症见于:乳腺癌、小细胞肺癌、肝硬化,M,B,抗CK-M抗体,CK-MB,2,巨CK,B,B,抗CK-M抗体,巨CK+BB,2,巨CK,B,M,凝胶电泳分析,鉴定,问题,为什么有些情况下会出现CK-MB测定值超过总CK,CK-BB增加:脑外伤、前列腺、肺疾病、昏迷,LD1 LD2 LD3 LD4 LD5 H4 H3M H2M2 HM3 M4,Lactate Dehydrogenase and Isoenzyme,Reference Value LD2LD1LD3LD4LD5 LD1 / LD2 0.7,LD : 104 245U/L,Summary,Clinical
36、 Significance 1. LD 818h, 13day peak, 6 10days retrospective diagnosis acute virus hepatitis, chronic hepatitis, cirrhosis of liver, heart failure obstructive jaundice, lymphoma, leukemia Anaemia, lung infarction, shock, muscular injury,1)AMI,2)Liver diseases,3)Malignant tumor,4) others,1) LD1,LD2:
37、AMI : LD1/LD2 1.0 , if LD5 - bad prognosis (heart failure) Malignant anemia, Renal infarction (2) LD3 : lung diseases, leukemia, carcinoma of stomach,colon, pancreas (3) LD4 : Obstructive jaundice, liver cancer (4) LD5 : liver cell damage muscular , dermatic disease,2. LD isoenzymes To distinguish h
38、eart and liver diseases,Clinical Significance (continued,Serum Aminotransferase (AST,1. AMI : 612h, 2448h peak (4 10 x),35days 2. Heart Failure : Hepatic congestion (ASTALT,Treatment,1) Stenting,a stent is introduced into a blood vessel on a balloon catheter and advanced into the blocked area of the artery the balloon is then inflated and causes the stent to expand until it fits the inner wall of the vessel, conforming to contours as needed the balloon is then deflated a
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