Zhu Jianhua M.D. 朱建华

The First Affiliated Hospital,School of Medicine, Zhejiang

University

Coronary Heart Disease

冠心病冠心病张力 li_zhang@zju.edu.cn

on behalf of

CVD—1st Cause of DeathCVD—1st Cause of DeathCVD—1st Cause of DeathCVD—1st Cause of Death

43%

27%

14%

6%3% 7% 心脑血管疾病

恶性肿瘤呼吸系统疾病意外伤害消化系统疾病其他

CVD

Cancer

Respiratory dis.

Accident

Digestive dis.

Others

In this country ， one person died from CVD per 10 seconds

Number around usNumber around usNumber around usNumber around us

中国冠心病死亡率位列世界第二

印度、中国和俄罗斯是世界上冠心病死亡人口最多的 3 个国家其中，中国的冠心病死亡人口总数列世界第二

俄罗斯： 674 ， 881

中国： 702 ， 925

印度： 1531 ， 543

单位；人

急性心肌梗死急性心肌梗死————他们离我们而去的缘由他们离我们而去的缘由

Coronary arteries--anatomyCoronary arteries--anatomy

LipidsLipids• LDL = primary target of therapy• Risk categories - > 20% risk of major coronary event in 10 years = high risk • Known CAD • Diabetes • Known atherosclerotic disease (PVD, carotid disease and abdominal

aortic aneurysm) • > 2 risk factors

• Consider causes of secondary hyperlipidemia

- Diabetes - Hypothyroidism - Obstructive liver disease - Chronic renal failure - Drugs such as progestins, anabolic steroids, corticosteroids

Major Risk FactorsMajor Risk Factors• Smoking• Hypertension (>=140/90 or on

antihypertensive treatment)• HDL < 40*• Family History premature CAD (<55

males, <65 females)• Age (men >=45; women >=55)

* HDL >60 is a negative risk factor, its presence removes one risk factor from total count

Coronary heart disease

atherosclerosis

Coronary stenosis coronary spasm

Myocardial ischemia, anoxaemia

Coronary heart disease, CHDIschemic heart disease

•Atherosclerosis

•Stable angina pectoris(SAP)

•Acute coronary syndrome

Unstable angina(UAP) and non-STEMI

(UA/NSTEMI)

ST elevation myocardial infarction(STEMI)

Atherosclerosis

•leading cause of death and disability

•Common location:

Coronary circulation: Proximal left

anterior descending coronary

artery(LAD)

Proximal portion of renal arteries

Extracranial circulation to the brain

Carotid bifurcation

Atherosclerosis

Three fundamental biological processes of atherosclerosis

1. Accumulation of intimal cells:• smooth muscle cells • Macrophages

• T-lymphocytes

2. Proliferated connective tissue matrix• Collagen

• elastic fibers• proteoglycans

3. Accumulation of lipid:• cholesteryl esters

• free cholesterol

Evolution of the atherosclerotic plaque

Pathophysiology of coronary Pathophysiology of coronary artery atherosclerosisartery atherosclerosis

1. Fatty streak

2. Fibroatheroma

3. Complicated lesions

Atherosclerosis related not only to Atherosclerosis related not only to lipidslipids

Thin fibrous cap

Much inflammatory cells

Less smooth muscle cells

Eroded endothelium

Active macrophage

Thick fibrous cap

Foam cells

Integrated endothelium

Much smooth muscle cells

Adapted from Libby. Circulation. 1995;91:2844-2850

Less inflammatory cells

Unstable plaque Stable plaque

Clinical events related to rupture Clinical events related to rupture of unstable plaqueof unstable plaque

Adapted from Weissberg. Atherosclerosis. 1999;147:S3–S10

Macrophage/T-cellSmooth muscle cell

Plaque unstable

Plaque stable

Repaired Inflammation

in balance

（ exertion or emotional stress ）

Low Demand is in balance with a diminished coronary flow （ Under

resting condition ）

Normal ECG

Normal ECG

（ CAD Under resting condition ）

Ischemia ECG

（ Angina pectoris ）

Normal coronary flow

Significant stenosis reduce coronary flow

OO22 supply supply OO22 demand demand

OO22 supply supply OO22

demanddemand

OO22

demanddemandOO22 supply supply

Significant stenosis reduce coronary flow

Prevention and Treatment Prevention and Treatment of Athrosclerosisof Athrosclerosis

1.Lifestyle modification2.Lipid disorders (Dyslipidemia): cholesterol screening in all >20yrs

Elevated: cholesterol (Tc and LDL-c), TG, ApoB/ApoA,Lp(a),

Low: HDL-c

LDL lowering by HMG-CoA reductase(statins):

cardiovascular events 30% ， risk of MI 62%

3.Hypertension：4.DM,Metabolic syndrome or insulin resistance syndrome:

BP, BMI ,TG, serum insulin

HDL-c, OGTT

5. Cigarette smoking ： more thrombogenic6. 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 10-15

yrs earlier than woman9. alcohol10. Others: diet,homocysteine, hemostatic

factors inflammation/infection

Prevention and Treatment of Prevention and Treatment of AthrosclerosisAthrosclerosis

•Drug therapy：

anti-platelet： aspirin, clopidogrel, GPIIb/IIIa inhitibor,

Dipyridamole, cilostazol

Lipid-lowering

Prevention and Treatment Prevention and Treatment of Athrosclerosisof Athrosclerosis

1. HMG-CoA reductase inhibitors （ statins ） Atorvastatin,Fluvastatin,Lovastatin,Pravastatin,Simvastatin,Cerivastatin, Rosuvastatin：

*elevation of aminopherase, rhabdomyolysis

2. Bile acid-binding Resins cholestyramine ， colestipol3. Nicotinic Acid ：4. Fibric acid derivatives （ fibrates ） Gemifibrozil, clofibrate, Fenofibrate5. Cholesterol absorption inhibitors: ezetimibe6. Probucol

Prevention and Treatment of Prevention and Treatment of AthrosclerosisAthrosclerosis Lipid-lowering drugs

Prevention and Treatment of Prevention and Treatment of AthrosclerosisAthrosclerosis

Surgery 1 Surgery : CABG 。2 PCI:

Coronary heart disease(CHD)

CHD - OverviewCHD - Overview• Stable CHD• Unstable CHD - Angina - MI

• Pathophysiology• Clinical Features - History/PE

• Differential Diagnosis• Diagnostic Testing• Treatment

How Does CHD Present?How Does CHD Present?• Chest pain is primary symptom - However, pain not always prominent in patients with CAD; Patients can

present with “anginal equivalents” • Dyspnea, faintness, fatigue, exercise intolerance - “Painless” CAD can also present as: • Silent ischemia; CHF; Arrhythmias; Sudden death

• Obstruction of coronary artery by athreomatuous plague is most common cause

- Other causes of nonatherosclerotic obstruction include • Congenital abnormalities, arteritis, “bridging”

• Myocardial Ischemia can occur in absence of obstructive CHD

- Aortic stenosis and hypertrophic cardiomyopathy

What about physical What about physical examination items in CHD?examination items in CHD?

• Physical Examination - Xanthelasma –intracellular lipid

deposits near lower lids - Blood pressure - Arterial – decrease peripheral

pulses - Cardiac examination

The Pathophysiology of Stable CHD

• Imbalance between myocardial O2 requirements and supply

- Increased requirements in tachycardia, increase wall stress, increased contractility

• Physical exertion; heavy meat; fever; thyrotoxicosis;

emotional stress (increased catecholamines) - Supply determined by coronary blood flow and

coronary arterial O2 content

• “Fixed” CHD • Transient vasoconstriction- Coronary “tone”

affected by a variety of stimuli

What else should we consider in the differential

diagnosis?More likely to be confused:• Esophageal problems – reflux; motility

disorders; spasm; - Chest pain with normal coronaries commonly due to

esophageal abnormalities - Key elements like CHD = characteristics of pain; relieved

with nitro - Key elements unlike CHD = pain changes with posture or

meals; relieved with antacids (GI cocktail);

• Pericarditis - Chest pain not relieved with rest or nitro; pericardia fiction

rub and diffuse ST elevations on ECG - Key elements like CHD = retrosternal location, abnormal

ECG - Key elements unlike CHD = pain is positional

What else should we consider in the differential

diagnosis?Less likely to be confused:• Aortic dissection - Severe, sharp, radiates to back, with or without aneurysm - Diagnosis with chest CT or TEE

• Severe pulmonary hypertension - From right ventricular ischemia

• Pulmonary emboli - From Dyspnea is cardianl symptom; pleuritic chest pain with

infarction; pleural friction rub

CHD categories ：

1 、 Absence of symptoms

2 、 Angina pectoris (AP)

3. Myocardial infarction (MI)

4. Ischemia heart disease

5. sudden death

definition: acute and transient myocardial ischemia and anoxaemia usually caused by coronary insufficiency during exertion

Characteristics: paroxysmal precordial squeezing-like chest pain, behind the mid sternum，radiated to left shoulder and upper armprecipitated by stress or exertionrelieved rapidly by rest or nitrates

Stable angina pectoris

in angiographySignificant coronary lesion with diameter stenosis > 70% in 75% pts

No significant stenosis in about 5-10% pts, Ischemia may be related to coronary spasm or microvascular dysfunction.

Pathology

Stable angina

pectoris

symptom ： chest pain or oppression•location

behind or slightly to the left of the mid sternum no definite borderlineradiated to the left shoulder and upper armAtypical location: lower jaw, the back of neck

Clinical manifestation

Stable angina

pectoris

chest pain•characteristics：

tightness, squeezing, burning, pressing, choking, bursting,rarely sharp, not spasmodic force the patient stop the activity till the symptom relieved

•precipitationexertion or emotional agitation。

•duration：3 － 5 mins

•pain relief: within several mins after rest or using nitroglycerin

Clinical manifestation

Stable angina

pectoris

What about non-invasive test?

• Metabolic abnormalities - Lipids • LDL< 100 mg/dl is optimal - Esp for patients with multiple risk

factors, DM and established CAD • HDL<40 mg/dl is an independent risk

factor • TG’s > 200 mg/dl should be treated

(lifestyle)

- Glucose • Impaired fasting glucose= 110-126 mg/dl • DM = FBS > 126 mg/dl

- Others – presence increase the risk of future CV events – no consensus on routine measurement

• C-reactive protein; homocysteine; lipoprotein Lp(a)

What about non-invasive test?

•ECG - Resting ECG is normal in 50%

patients with stable angina - Most common abnormality with

chronic CAD is non-specific ST-T wave changes

Non specific changes also seen in electrolyte abnormalities, LVH, antiarrhythmic drugs

Stable CHD: Non invasive tests

• Exercise ECG ( treadmill test ) - Looking for ST segment depression and

symptoms • 1mm (+) typical symptoms = 90% positive

predictive value • 2mm (+) typical symptoms= diagnostic • 1mm (-) typical symptoms= 70% predictive value • 2mm (-) typical symptoms = 90% predictive value • Overall sensitivity = 70%; Specificity = 80%

- Patients need to get to >85% predicted maximal

• Predicted max HR = (220 – age)

Stable CHD :Non invasive tests

•Radionuclide Perfusion imaging (“Cardiolyte”)

- Exercise ECG with images of myocardial blood flow

• Compare images at maximal exercise with images at rest

- “Defects” with exercise and not with rest = ischemia

- “Defects” with both exercise and rest = MI

• Sensitivity = 90%; Specificity = 80%

•64 slice MSCT

CHD----Diagnosis

ECGECG Chest X rayChest X ray

ECTECT AngiographAngiograph

Cardiac Echo

TreadmillTreadmill

ST segment depression

ST segment elevation

Normal ST segment

Myocardial ischemia

Myocardial infarction

Normal

Coronary stenosis

Coronary occlusions

Normal coronary flow

Treadmill testTreadmill test

Cardiac Echo

Cardiac ECTCardiac ECT （（ 201201TI TI 或或 99m99mTc-MIBTc-MIBII ）） ::

CHD-- Radionuclide CHD-- Radionuclide

Perfusion imagingPerfusion imaging

201TI perfusion defects

Chest X-ray

Soft or ‘Vulnerable’Plaque Imaging by 64 slice MSCT

Stable CHD invasive tests

Coronary angiographyCoronary angiography

- golden standard- golden standard

Coronary Coronary angiographyangiography

Left Coronary AngiogramLeft Coronary Angiogram （ （ LCLCAA ） ）

Arterial Anatomy & Arterial Anatomy & ProjectionsProjections

Left Coronary ArteryRight Anterior Oblique RAO 30

Coronary Angiography

1. General consideration ： rest ， avoid provocative factors , risk

factors control

2. Drug therapy: prevent MI and death symptom relief and quality of life

improvment

3. Coronary revascularization: percutaneous coronary intervention (PCI) Coronary artery bypass surgery (CABG) SVG, LIMA

Prevention and treatment

Stable angina

pectoris

antianginal and anti-ischemic therapy

Drug therapy

Oxygen supply

Oxygen demand

a.nitratesb.beta-adrenergic blockersc.Calcium antagonistsd.Drugs improving metabolism

Stable angina

pectoris

Drug therapy

a.nitrateslower oxygen demand: decrease arteriolar and

venous tone, reduce preload and afterload increase coronary supply: Coronary dilatation

•Nitroglycerin•Isosorbide dinitrate•isosorbide 5-mononitrate (long-acting nitrates)

Stable angina

pectoris

b. ß － blockers: reduce myocardial oxygen: reduce HR,

myocardial contractility, BP,the LV wall stress Abslute contraindications：

sever bradycardia: high-degree A-V block, SSS,

severe unstable LV failure

Relative contraindications:

asthma and bronchospastic disease

peripheral vascular disease

ß1-selective ： metoprolol, atenolol, bisoprolol

Drug therapy

Stable angina

pectoris

c.Calcium antagonists：Increase oxygen supply: dilate conduit and resistance vessels, release spasm, improve microvascular functionDecrease oxygen demand: negative inotropic effect, decrease BP Antiplatelet effect

d. Drugs improving metabolism：trimethazine （ vasorel）， selectively inhibit 3-KAT （ 3-酮酰辅酶 A硫解酶）， partly inhibit FA oxidation,

Drug therapy

Stable angina

pectoris

prevent MI and death therapy

a.antiplatelet angents ：ASA ， 75-325mg/dclopidogrel; ticlopidine: ADP receptor- antagonists:Cilostazol: phosphodiesterase inhititor,50-100mg bid

b. Lipid-lowering angents: statins

c. Angiotesin-converting enzyme inhibitor (ACEI)

Drug therapy

Stable angina

pectoris

stenting

Stable angina

pectoris

Coronary Artery Bypass Graft --CABG

Acute Coronary Syndromes

• ST segment elevation MI (STEMI)• Unstable angina (UA) • Non ST segment elevation MI

(NSTEMI) - Non Q wave MI

Plaque rupture/erosion → thrombosis→ coronary completed/incomplete occlusion

Acute Coronary SyndromesAcute Coronary Syndromes• Patients presenting to ER with

acute chest pain - 15% will be found to have an MI - 30% found to have unstable angina

• 50% of deaths from AMI occur within one hour of symptoms onset usually due to arrhythmia (V. fib)

• MI’s due to coronary atherosclerosis with superimposed coronary thrombosis – brought on by plaque rupture

- This is the cause of almost all acute coronary syndromes leading to either complete occlusion of coronaries leading to Q wave infarction or partial occlusion leading to acute coronary syndrome of unstable angina or non-Q MI

ACS—the top of icebergACS—the top of iceberg

Coronary Heart DiseaseCoronary Heart Disease

Stable plaque Unstable plaque Disrupted plaque

From Eugene Braunwald, Heart Disease, A Textbook of Cardiovascular Medicine

CHD –Sudden death (arrhythmia)

Ventriclar TachycardiaVentriclar Tachycardia

Ventricular flutterVentricular flutter

Ventricular fibrillationVentricular fibrillation

Unstable Angina and Non-ST Unstable Angina and Non-ST segment elevation myocardial segment elevation myocardial

infarction (NSTEMI)infarction (NSTEMI)• Caused by non occlusive thrombus• Risk of death and non-fatal cardiac ischemic events

can be determined• “High risk” history: • Nature of Symptoms - Accelerating ischemic in past 48 hours

and prolonged ongoing (>20 minutes) rest pain • Prior Hx MI • Age • Sex • number of traditional risk factors present

Circulation 2000; 102:1193

Unstable Angina and Non-ST Unstable Angina and Non-ST segment elevation myocardial segment elevation myocardial

infarction (NSTEMI)infarction (NSTEMI)• “ High Risk” PE Findings - Pulmonary edema - S3 gallop

- New or worse MR murmur - Hypotension, bradycardia, tachycardia

• ECG findings - ST-segment changes of >= 1mm - Sustained V. Tachy - New or presumed new BBB

Chest Pain AssessmentChest Pain Assessment

• ECG most important single source of data in the evaluation of patients with chest pain

• ECG findings in patients with acute chest pain

- New ST-segment elevation of >=1 mm • Probability of MI = 80% - ST-segment depression or T-wave inversion no know to

be old • Sensitivity = 90%; Specificity = 80%

Myocardial InfarctionMyocardial Infarction

• >75% of patients with MI have > 1 coronary artery diseased;

- However about 6% of patients with AMI will have angiographically normal coronary arteries

• Biochemical markers of necrosis are CK-MB or troponin

MI ECGCulprit lesionCulprit lesion

MI areaMI area

Total Total occluocclusionsion

Cardiac Biomarkers Cardiac Biomarkers “enzymes”“enzymes”

• Enzymes (cardiac biomarkers) diffuse into the cardiac interstitium after MI and become detectable in the blood within hours.

• CK-MB detectable 4 hours after MI and up to about 2 days

- Some CK-MB detectable in healthy patients

• Troponin I detectable 4 hours after an MI and up to a week afterwards

- Therefore, difficult to use to diagnose re-infarction - Troponin I not detectable in healthy patients - “Microinfarctions” can increase troponin I and not increase CK-MB

(30% of patients with UA)

Time Course of Cardiac Biomarkers Time Course of Cardiac Biomarkers after MIafter MI

Aspects of Diagnosis of Aspects of Diagnosis of Myocardial Infaction by Myocardial Infaction by

Different TechniquesDifferent Techniques

Therapeutics--patients with Therapeutics--patients with ACSACS

Anti-ischemic therapy• Nitrates - relieve pain and ischemia, given sublingually or IV acutely

• Morphine sulfate - Relieve pain, decreases agitation and decreases

preload (decreased venous congestion)

• B- Blockers - Decreases myocardial oxygen demand, decreases

heart rate, stabilizes membranes thereby decreasing arrhythmia risk

Do not use short acting Calcium channel blockers (nifedipine)

Therapeutics--patients with Therapeutics--patients with ACSACSAntiplatelet and anticoagulant

therapy• Antiplatelets - ASA • Give promptly - Clopridogel • Give promptly

• Anticoagulants - Heparin – LMWH or unfractionated

RE-vascularization (thrombolytics or PTCA with stent) in patients with STEMI

Treatment : myocardial reperfusion

PCI: The first choicePCI: The first choice 经皮冠脉介入治疗（ PCI ） 无论是否经溶栓治疗，冠状动脉闭塞或再

通后又再堵塞，或虽再通但仍有重度狭窄者，如禁忌可紧急施行 PCI 并安置支架。

目前认为有条件时应首选 PCI

CAD—Intervention therapy

• Percutanouse transluminal

coronary angioplasty (PTCA)

• Stent

• Rotational atherectomy （ R

A ）

Acute Myocardial Infarction

Reopen the

vesselsReduce the area of infarction

Rescue the dying myocardium

Time = Time =

Myocardium!Myocardium!

Time = Life !Time = Life !

ischemia

ischemic necrosis

Mild impairment

Moderate impairment

 severe impairment

Best time

Slightly injury

Mild injured

Severe injured

Management: onset of STEMI

Treatment : myocardial reperfusion

FibrinolysisFibrinolysis

原理：起病 3 ～ 6 小时内，使闭塞的冠状动脉再通，心肌得到再灌注，濒临坏死的心肌可能得以存活，或使坏死范围缩小。

溶栓疗法 常用药物 尿激酶、链激酶、重组组织型纤溶酶原激活剂 (rt-

PA)溶栓成功的判断 间接判断 ST 段 2 小时内回降 >50 ％；胸痛 2 小时内基本

消失；再灌注性心律失常； CK-MB 峰值提前 直接判断 冠状动脉造影

Reperfusion therapy ： PCI vs. Fibrinolysis

Reperfusion therapy ： PCI vs. Fibrinolysis

PCI : Time and outcome

PCI of STEMI

PCI of STEMI

Technique revolution → New time

CABGCABG

POBAPOBA(1977-1994)(1977-1994)

BMSBMS(1994- )(1994- )

手术要求高手术要求高费用昂贵费用昂贵

病人创伤大病人创伤大并发症多并发症多

恢复时间长恢复时间长

创伤小创伤小操作简单操作简单并发症多并发症多

病人恢复迅速病人恢复迅速

创伤小创伤小操作简单操作简单并发症少并发症少

病人恢复迅速病人恢复迅速

RestenosisRestenosis ≧50%%

RestenosisRestenosis 20%~30%20%~30%

Restenosis Restenosis <5% <5%

DESDES ！！(2002- )(2002- )

One year follow up after PCI

before before afterafter

4 m4 m 1 y1 y

TherapeuticsAcute Coronary Syndromes-Post discharge

• A: Antiplatelets / ACE-I• B: β- blockers / Bp control• C: Cholesterol lowering (Statins) /

Cigarette quitting• D: Diabetes control / Diet• E: Exercise / Education

LDL-C↓

VLDL↓, IDL↓, LDL-C↓

• Endothelium function• SMC function • Anti-inflammation• Thrombosis↓

lumen

Lipid core

Macrophages

SMC

Potential clinical benefits of Statins in ACS

Statins

Take Home MessagesTake Home MessagesAtherosclerosis is the leading cause of death and Atherosclerosis is the leading cause of death and disability, also the main cause of CHDdisability, also the main cause of CHD

Risk factors and prevention of atherosclerosisRisk factors and prevention of atherosclerosis

CHD is due to the imbalance between myocardial CHD is due to the imbalance between myocardial oxygen supply and demandoxygen supply and demand

Two large groups of CHD: chronic(stable angina Two large groups of CHD: chronic(stable angina pectoris) and ACSpectoris) and ACS

ACS composed of UAP/NSTEMI and STEMI, ACS composed of UAP/NSTEMI and STEMI, resulting from the plaque rupture or erosion, with resulting from the plaque rupture or erosion, with differing degree of thrombosis and distal differing degree of thrombosis and distal embolization, with different obstruction of the embolization, with different obstruction of the coronary artery.coronary artery.

reperfusion either by fibrinolysis or primary PCI reperfusion either by fibrinolysis or primary PCI is the mainstay of therapy of STEMIis the mainstay of therapy of STEMI

Thanks!