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

AtherothrombosisAdalah 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

Ischemicstroke

Myocardial infarction

Peripheral arterialdisease:• Intermittent claudication• Rest Pain• Gangrene• Necrosis

Manifestations of Atherothrombosis

1. CAPRIE Steering Committee. Lancet 1996; 348: 1329–13392. The CURE Trial Investigators. N Engl J Med 2001; 345: 494–5023. Bertrand ME et al. Circulation 2000; 102: 624–6294. Steinhubl SR et al. JAMA 2002; 288: 2411–2420

StrokeTIA

Acute MIUnstable angina

Prior MIPCI/stenting

Atrial fibrillation

Intermittent claudication

Peripheral vascular

intervention

CHARISMACAPRIE1

ACTIVECOMMITCLARITYCURE2

CLASSICS3

CREDO4

CHARISMACAPRIE1

CAMPER

CHARISMACAPRIE1

MATCHACTIVECARESS

TIA = Transient ischemic attackMI = Myocardial infarctionPCI = 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

Generalizeddisorders• Obesity• Diabetes

Systemicconditions• 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 ischemiaIntermittentclaudication

CV death

ACS

Atherosclerosis

Stable angina/Intermittent claudicationStable angina/Intermittent claudication

AtherothrombosisAtherothrombosis

MI = Myocardial infarctionACS = 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 cellsEndothelial cells

Contractile VSMCsContractile VSMCs

The normal artery wall

Early atherosclerosis (I) Early atherosclerosis (I) – Endothelial – Endothelial dysfunctiondysfunction

Lipid

Lipid accumulates in the intimal space

and is associated with abnormal endothelial cell

function

Lipid accumulates in the intimal space

and is associated with abnormal endothelial cell

function

Platelet thrombus

Platelets adhering to subendothelial spacePlatelets

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 Characteristics of the stable atherosclerotic stable atherosclerotic

plaqueplaqueFibrous cap(VSMCs and matrix)

Fibrous cap(VSMCs and matrix)

Lipid core

Adventitia

Endothelial cells

Endothelial cells

Intimal VSMCs (repair

phenotype)

Intimal VSMCs (repair

phenotype)

Medial VSMCs(contractile phenotype)

Medial VSMCs(contractile phenotype)

Lipid core

Resolving thrombusResolving thrombus

Adventitia

Site of previous plaque ruptureSite of previous plaque rupture

Recruitment of new VSMCs

Recruitment of new VSMCs

Plaque growthPlaque growth

Weissberg, 1999Weissberg, 1999

Plaque disruption leading to atherothrombosis formation

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

Macrophage Tissue factor

Fibrin

Aggregated plateletsBLOOD

FLOW

Lipid core

Adventitia

Thrombus

Unstable Unstable coronarycoronaryartery disease artery disease (II)(II)

Thrombus forms and extends into the lumen

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: 657–6712. Arbustini E et al. Heart 1999; 82: 269–2723. 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 The ruptured atherosclerotic plaque following fibrinolysisfollowing fibrinolysis

Davies and Ho, Davies and Ho, 19981998

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

‘Significant’ (>70%)stenosis

‘Insignificant’ (<70%) stenosis

‘Insignificant’ (<70%) stenosis

Coronary angiography and the Coronary angiography and the significance of stenosissignificance of stenosis

Angiography of Unstable Angina

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

STENT

.

Pyridoxin Hydrochloride (Vit B6) ------- 25 mgCyanocobalamin (Vit B12) -------- 25 gFolic Acid (Vit B9) ------------ 500 gNatural 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

AlteredPermiability

Growth Factor

Response

HypoxiaShear stress Cytokines

Homocystein

Activation

Gangguan/ Kekurangan

Asupan as.folat, vit B6, B12

Hyperhomocysteinemia

Risiko

Peny. Vaskular perifer Peny. Artyeri koronerCerebral

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

.

.