Atherosclerosis & Atherotrombosis

OLEH

dr.Fatchurochman,SpJP

RS.TNI AU DR.M.SALAMUN

B A N D U N G

Atherosclerosis ( Aterosklerosis ) • Atherosclerosis = pengerasan arteri

• Adalah suatu proses inflamasi o.k gangguan metab.

Karbohidrat & Lemak pada pembuluh darah

ateroma ( deposit KH,L,darah , jar.ikat ,kalsium,) yg

menyebabkan lapisan pembuluh darah berubah

menyempit

• Kapan dimulainya proses Aterosklerosis ? Yaitu

sejak masa anak dan merupakan proses satu pro

• ses yg progresif dg terbentuk nya plaque pada

dinding arteri & menyebabkan sirkulasi koroner

terganggu

Atherothrombosis

Thrombus adalah bekuan darah

Atherothrombosis

Adalah suatu proses terjadinya bekuan darah yang menyumbat aliran pembuluh darah

Atherosclerosis Atherothrombosis oklusi mendadak

serangan mendadak

Arteri coronaria di jantung arteri di otak

↓ ↓

Acute Infark Miokard Cerebro Vasc.Accident

( PJK ) ( Stroke )

24.7% 29.9%

Coronary

disease 7.4%

Atherothrombosis is commonly found in more

than one arterial bed in an individual patient*

Cerebrovascular

disease

Peripheral arterial disease

3.8% 11.8%

19.2%

* Data from CAPRIE study (n=19,185)

Coccheri S. Eur Heart J 1998; 19(suppl): P1268.

3.3%

Major clinical manifestations

of atherothrombosis

Adapted from: Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6.

Transient ischemic attack

Angina: • Stable • Unstable

Ischemic stroke

Myocardial infarction

Peripheral arterial disease: • Intermittent claudication • Rest Pain • Gangrene • Necrosis

Manifestations of Atherothrombosis

1. CAPRIE Steering Committee. Lancet 1996; 348: 1329–1339

2. The CURE Trial Investigators. N Engl J Med 2001; 345: 494–502

3. Bertrand ME et al. Circulation 2000; 102: 624–629

4. Steinhubl SR et al. JAMA 2002; 288: 2411–2420

Stroke

TIA

Acute MI

Unstable angina

Prior MI

PCI/stenting

Atrial fibrillation

Intermittent

claudication

Peripheral

vascular

intervention

CHARISMA

CAPRIE1

ACTIVE

COMMIT

CLARITY

CURE2

CLASSICS3

CREDO4

CHARISMA

CAPRIE1

CAMPER

CHARISMA

CAPRIE1

MATCH

ACTIVE

CARESS

TIA = Transient ischemic attack

MI = Myocardial infarction

PCI = Percutaneous coronary intervention

© Teri J McDermott CMI 2003

Identifying those at risk of atherothrombosis

Yusuf S et al. Circulation 2001; 104: 2746–53. 2. Drouet L. Cerebrovasc Dis 2002;13(suppl 1):1–6.

Lifestyle

• Smoking

• Diet

• Lack of exercise

Genetic

• Genetic traits

• Gender

• Age

Generalized

disorders

• Obesity

• Diabetes

Systemic

conditions

• History of vascular

events

• Hypertension

• Hyperlipidemia

• Hypercoagulable

states

• Homocystinemia

Local factors

• Elevated prothrombotic factors: fibrinogen, CRP, PAI-1

• Blood flow patterns, vessel diameter, arterial wall structure

Atherothrombosis

manifestations

(myocardial infarction,

stroke, vascular death)

Angka Kejadian PKV:

Laporan WHO :

2004 : 7 juta orang meninggal/ tahun

2010 : 11juta orang meninggal/ tahun

( perkiraan )

Penyakit jantung koroner (PJK)

• Ialah : Penyakit jantung akibat perubahan

obstruktif (penyumbatan)pada pembuluh

darah koroner yang menyebabkan fungsi

jantung terganggu.

• Sebab utama PJK : proses aterosklerosis

Patofisiologi / Perjalanan penyakit pjk/ska :

• Lihat gambar berikut

Atherothrombosis: A Generalized and

Progressive Disease

Unstable angina

MI

Ischemic stroke/TIA

Critical leg ischemia

Intermittent claudication

CV death

ACS

Atherosclerosis

Stable angina/Intermittent claudication

Atherothrombosis

MI = Myocardial infarction

ACS = Acute coronary syndromes

CV = Cardiovascular

Adapted from Libby P. Circulation 2001; 104: 365–372

Dekade proses pembentukan trombus

Ross (1999)

Endothelial

permeability

Leucocyte

migration

Leucocyte

adhesion

Endothelial

adhesion

The normal artery wall

Endothelial cells

Contractile VSMCs

The normal artery wall

Early atherosclerosis (I)

– Endothelial

dysfunction

Lipi

d

Lipid accumulates

in the intimal space

and is associated

with abnormal

endothelial cell

function

Platelet thrombus

Platelets adhering to subendothelial space Platelets

Endothelial cells

Subendothelial space

Aggregation

of platelets into a

thrombus

Normal platelets

in flowing blood

Platelets adhering to

damaged endothelium

and undergoing activation

Platelet adhesion and activation

Adapted from: Ferguson JJ. The Physiology of Normal Platelet Function. In: Ferguson JJ, Chronos N,

Harrington RA (Eds). Antiplatelet Therapy in Clinical Practice. London: Martin Dunitz; 2000: pp.15–35.

A B C

Characteristics of the

stable atherosclerotic

plaque Fibrous cap

(VSMCs and matrix)

Lipid core

Adventitia

Endothelial

cells

Intimal VSMCs

(repair

phenotype)

Medial VSMCs

(contractile

phenotype)

Lipid core

Resolving

thrombus

Adventitia

Site of previous

plaque rupture

Recruitment

of new

VSMCs

Plaque growth

Weissberg, 1999

Plaque disruption leading to

atherothrombosis formation

Adapted from: Falk E et al. Circulation 1995; 92: 657–71.

Macrophage Tissue factor

Fibrin

Aggregated platelets

BLOOD

FLOW

Lipid core

Adventitia

Thrombus

Unstable

coronary

artery disease

(II)

Thrombus forms

and extends into the

lumen

Atherothrombosis: a Life-threatening

Disease

• Atherothrombosis is a chronic, progressive, generalized and unpredictable disease

characterized by the formation of blood clots on top of established atherosclerosis

1. Falk E et al. Circulation 1995; 92: 657–671

2. Arbustini E et al. Heart 1999; 82: 269–272

3. Aronow WS, Ahn C. Am J Cardiol 1994; 74(1): 64–65

Plaque rupture1 Plaque erosion2

• An atherothrombotic manifestation (like myocardial infarction, stroke, transient

ischemic attack, unstable angina, or peripheral arterial disease) in one vascular

territory means increased risk in all vascular beds3

• Atherothrombosis (cardiovascular and cerebrovascular disease) is one of the world’s

biggest killers4

4. World Health Organization. Cardiovascular diseases site.

www5.who.int/cardiovascular-diseases/main.cfm?p=0000000424

(last accessed 24 January 2003)

The ruptured atherosclerotic plaque

following fibrinolysis

Davies and Ho,

1998

Penyakit jantung koroner

Clinical classification of ACS

Acute Coronary Syndrome

(ACS)

No ST Elevation ST Elevation

Unstable

Angina

Pectoris

MI (NSTEMI) MI (STEMI)

No Q-wave Q-wave

National Heart Foundation of Australia, Cardiac Society of Australia and New Zealand.

Med J Aust 2000;173 (suppl):S65–S88

Tindakan Kateterisasi / Angiografi koroner

Tindakan Kateterisasi / Angiografi koroner

‘Significant’ (>70%)

stenosis

‘Insignificant’ (<70%)

stenosis

Coronary angiography and the

significance of stenosis

Angiography of Unstable Angina

Davies. Atlas of Coronary Artery Disease. Lippincott-Raven, Philadelphia, Pennsylvania: 1998:79

STENT

.

Pyridoxin Hydrochloride (Vit B6) ------- 25 mg

Cyanocobalamin (Vit B12) -------- 25 g

Folic Acid (Vit B9) ------------ 500 g

Natural Vitamin E (d- Tocopherol) ---- 400 IU

.

• .

Faktor –faktor risiko tradisional penting dan faktor –faktor

risiko non tradisional yang baru muncul dapat dilihat pada

tabel berikut ini

Faktor Risiko Tradisional Faktor Risiko Non Tradisional

. .

Merokok Homosisitein (HCy)

LDL –Kolesterol Lipoprotein (a)

Diet Lemak /Kolesterol tinggi Partikel small-dense LDL

Hipertensi Stres oksidatif

DM Inflamasi

Inaktivitas fisik Penanda-penanda hemostatik

Obesitas Disfungsi Endotel

Status post menopause Penginfeksi

Riwayat PJK pada keluarga Trigliserida

Homocystein

• Homocystein ( Hcy):

Adalah *Asam amino sulfhidril

*Merupakan senyawa antara

*Terbentuk pada metab. Methionin

*Terdapat dlm beberapa btk didlm

plasma.

*Kadar Hcy plasma

tgt pd : -kadar enzim esential yg diatur scr genetik

-dan asupan as.folat, vit B6, B12

Thrombin

Viral infectin

Oxidized lipids/ Free radicals

Leucocyte

Adhesion

Vasoactive

Substances

Procoagulant Activity

Altered

Permiability

Growth Factor

Response

Hypoxia

Shear stress Cytokines

Homocystein

Activation

Gangguan/ Kekurangan

Asupan as.folat, vit B6, B12

Hyperhomocysteinemia

Risiko

Peny. Vaskular perifer Peny. Artyeri koroner

Cerebral

B6

B6

B12

Transulfuration

Pathway

vitamin

Vitamin

vit

vit

vit

PERAN VIT. E

• Berfungsi :

* Sebagai Anti oksidan yg efektif

(memberi manfaat jangka panjang dalam

perlindungan sel tubuh akibat zat oksidatif )

* Mengurangi bahaya inflamasi

* Sebagai nutrisi essential yang dibutuhkan untuk

menjaga kesehatan

.

.