ATHEROSCLEROSIS

and
ACUTE CORONARY SYNDROME

ATHEROSCLEROSIS
DEFINISI :

Athero : Lemak, Sclerosis : Pengerasan / penebalan, jaringan parut

Atherosclerosis : proses inflamasi menahun dan progresif akibat penumpukan kolesterol di dinding arteri.

Risk Factors
Age : older > younger Gender : male > female Family history Smoking Hypertension Diabetes Mellitus Diet : high in saturated fat and dietary cholesterol Elevated Total-C and LDL-C Low HDL-C Obesity 3 Lack of physical activity

Type I Lesion

Red Blood Cell Monocyte/macrophage

LDL HDL Platelet

Bentuk paling ringan ( bayi dan anak-anak) Foam Cells saja ( Macrofag + LDLox)

Type II Lesion

Red Blood Cell Monocyte/macrophage

LDL HDL Platelet

Prescursor Atherosclerotic Lesion : Fatty Streak : Macrofag + deposit LDL, Otot polos + deposit LDL

Type IV Lesion

Red Blood Cell Monocyte/macrophage

LDL HDL Platelet

TIPE IV : Atheroma : Lipid ekstraseluler membentuk LIPID CORE

Type V Lesion

Red Blood Cell Monocyte/macrophage

LDL HDL Platelet

TIPE V : Fibrous Plaques/fibro atheroma: Lipid Core dibungkus dengan jaringan ikat/kolagen

Type VI Lesion

Red Blood Cell Monocyte/macrophage

LDL HDL Platelet

TIPE VI : Complicated Lesion

Atherosclerosis Timeline
Foam cells Fatty streaks Intermediate lesion
Atheroma

Fibrous plaque

Complicated lesion rupture

Endothelial Dysfunction
From First Decade From 3rd decade From 4th decade Smooth muscle and collagen Thrombosis hematoma

Growth mainly by lipid accumulation

Sequence of Events in Ischemic Heart Disease

Arrythmias Lost of muscle Remodeling

Angina Silent

MI
Ischemia

CAD
Progresif dilatation

Endothelial dysfunction
Risk Factor

Heart Failure Death

Pathogenesis of atherosclerosis

Factors influencing plaque stability

The balance of atherosclerosis

Stable atherosclerotic plaque

Unstable plaque

Cardiovascular Protective Effects of Statins

1.
2.

Lipid Lowering Effect

Pleiotropic Effects

Pleiotropic Effects

Endothelial Function

Cellular processes associated with atherogenesis Uptake of ox-LDL Inflammation Smooth Muscle Cell Proliferation Thrombotic Elements and Processes

Pleiotropic Effects of

HMG- CoA Reductase Inhibitors

Platelet activation (

TXA )

Thrombotic effect (
Plaque stability (

tPA )

macrophage, MMF )

VASCULAR INFLAMMATION (
SMC HYPERTROPHY

CRP )

ENDOTHELIAL DYSFUNCTION (

NO )

Effect of HMG-CoA reductase inhibitor on CReactive Protein Levels

CRP (mg/L)
Baseline Simvastatin 20 mg/day Pravastatin 40 mg/day Atorvastatin 10 mg/Day 2.9 2.9 2.9 On treatment 2.0 2.2 1.8 % reduction 31 24 38 P value 0.0008 0.024 0.0008

Atorvastatin Significantly Reduced CRP

C-Reactive Protein Associated with the atherosclerotic process High levels are associated with an increased risk of coronary events CRP decreased significantly in the atorvastatin group versus the simvastatin group after 2 years The reduction in CRP was associated with regression of atherosclerosis, suggesting the importance of statins in the reduction of this inflammatory marker.

The pleiotropic effects of statins on plaque biology

ACUTE CORONARY SYNDROME

No ST Elevation

ST Elevation

NSTEMI

Unstable Angina

NQ Qw Myocardial Infarction

New terminology for coronary syndromes

Adapted from Aroney C, Boyden AN, Jelinek MV, et al. Management of unstable angina: guidelines 2000. Med J Aust 2000;173(Suppl):S65S88, with permission.

CAUSES OF UA/NSTEMI
Thrombosis Mechanical Obstruction

Dynamic Obstruction Inflammation/ Infection Thrombosis

. MVO2

Mechanical Obstruction
. MVO2

Dynamic Obstruction
Braunwald, Circulation 98:2219, 1998

Inflammation/ Infection

Fibrinolytic Use in Myocardial Infarction

Absolute Contraindications
Previous hemorrhagic

Cautions/Relative Contraindications
Severe uncontrolled HT on presentation (BP >180/110 mm Hg) History of prior CV accident or known intracerebral pathology not covered in CI Current use of anticoagulants (INR 2-3); known bleeding diathesis Recent trauma ( 2-4 wks ),head trauma Noncompressible vascular punctures Recent ( 2-4 wks ) internal bleeding For streptokinase : prior exposure ( within 5d-2y ) or prior allergic rx Pregnancy Active peptic ulcer History of chronic HT

stroke at any time : other strokes or CV events within 1 yr Known intracranial neoplasm Active internal bleeding (not include menses) Suspected aortic dissection

UA/NSTEMI THREE PRINCIPAL PRESENTATIONS

Rest Angina*
New-onset Angina Increasing Angina
Angina occurring at rest and prolonged, usually > 20 minutes
New-onset angina of at least CCS Class III severity Previously diagnosed angina that has become distinctly more frequent, longer in duration, or lower in threshold (i.e., increased by > 1 CCS) class to at least CCS Class III severity.

Braunwald Circulation 80:410; 1989

UA/NSTEMI EMERGENCY ROOM TRIAGE

Chest pain or severe epigastric pain, typical of

myocardial ischemia or MI:

Substernal compression or crushing chest pain Pressure, tightness, heaviness, cramping,

aching sensation Unexplained indigestion, belching, epigastric pain Radiating pain to neck, jaw, shoulders, back or to one or both arms

Associated dyspnea, nausea and/or vomiting,

diaphoresis

RISK STRATIFICATION IN EMERGENCY DEPARTMENT

HIGH RISK-FEATURES
History Clinical findings Prolonged ischemic discomfort (>20 min), ongoing rest pain, accelerating tempo of ischemia Pulmonary edema; S3 or new rales New MR murmur Hypotension, bradycardia, tachycardia Age >75 years Rest pain with transient ST-segment changes > 0.05 mV; new bundle-branch block, new sustained VT Elevated (e.g. TnT or TnI>0.1 ng/mL)

ECG

Cardiac markers

LMWH IN UNSTABLE ANGINA EFFECT ON TRIPLE ENDPOINT*

FRISC (dalteparin; n = 1,482 FRAXIS (nadroparin; n = 2,357 ESSENCE (enoxaparin; n = 3,171) TIMI 11B (enoxaparin; n = 3,910)
0.75 1 LMWH better

Day 6

14

(P = 0.032)

14

(P = 0.029)

14

1.5 UFH better

* Triple endpoint: death, MI, recurrent ischemia + urgent revascularization

ANTIPLATELET AND ANTICOAGULATION Rx

Trials Patients with event (%)
Active Placebo N % Death or MI ASA vs placebo UFH + ASA vs ASA 2448 999 6.4 2.6 12.5 5.5 0.0005 0.018

Risk ratio (95% CI)

P-value

LMWH + ASA vs ASA

2629

2.0

5.3

0.0005

All GP IIb/IIIa + UFH + ASA vs UFH + ASA 17044

5.1

6.2 Active Treatment Superior

0.0022 Active Treatment Inferior

MEDICATIONS AT HOSPITAL DISCHARGE

Class I
1. Aspirin 75 to 325 mg/d 2. Clopidogrel 75 mg/qd for patients with contraindication to ASA 3. -Blocker 4. Lipid-lowering agent and diet in patients with LDL cholesterol >130 mg/dL 5. Lipid-lowering agent if LDL cholesterol level after diet is > 100 mg/dL 6. ACEI for patients with CHF, LV dysfunction (EF<0.40) hypertension, or diabetes

INSTRUCTIONS AT HOSPITAL DISCHARGE RISK FACTOR MODIFICATION

Class I
1. Smoking cessation and achievement or maintenance of optimal weight, daily exercise, and diet. 2. HMG-CoA reductase inhibitor for LDL cholesterol > 130 mg/dL. 3. Lipid-lowering agent if LDL cholesterol after diet is > 100 mg/dL. 4. Hypertension control to a BP < 130/85 mm Hg. 5. Tight control of hyperglycemia in diabetics. 6. Consider referral of smokers to a smoking cessation program. 7. Gemfibrozil or niacin for patients with HDL cholesterol < 40 mg/dL and triglycerides > 200 mg/dL.

POST-HOSPITAL DISCHARGE CARE

A B C D E

Aspirin and Anticoagulants Beta blockers and Blood Pressure Cholesterol and Cigarettes Diet and Diabetes Education and Exercise