Atherosclerosis & Atherotrombosis

OLEH

dr.Fatchurochman,SpJP RS.TNI AU DR.M.SALAMUN BANDUNG

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 Acute Infark Miokard ( PJK )

arteri di otak Cerebro Vasc.Accident ( Stroke )

Atherothrombosis is commonly found in more than one arterial bed in an individual patient*
Cerebrovascular disease Coronary disease

7.4%
24.7% 3.3% 3.8% 11.8%

29.9%

19.2%

Peripheral arterial disease

* Data from CAPRIE study (n=19,185) Coccheri S. Eur Heart J 1998; 19(suppl): P1268.

Major clinical manifestations of atherothrombosis

Ischemic stroke Myocardial infarction
Transient ischemic attack

Angina:
Stable Unstable

Peripheral arterial disease:

Intermittent claudication Rest Pain Gangrene Necrosis

Adapted from: Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 16.

Manifestations of Atherothrombosis

Stroke TIA

CHARISMA CAPRIE1 MATCH ACTIVE CARESS

Acute MI Unstable angina Prior MI PCI/stenting Atrial fibrillation

CHARISMA CAPRIE1 ACTIVE COMMIT CLARITY CURE2 CLASSICS3 CREDO4 CHARISMA CAPRIE1 CAMPER

Intermittent claudication Peripheral vascular intervention

Teri J McDermott CMI 2003

1. CAPRIE Steering Committee. Lancet 1996; 348: 13291339 2. The CURE Trial Investigators. N Engl J Med 2001; 345: 494502 3. Bertrand ME et al. Circulation 2000; 102: 624629 4. Steinhubl SR et al. JAMA 2002; 288: 24112420

TIA = Transient ischemic attack MI = Myocardial infarction PCI = Percutaneous coronary intervention

Identifying those at risk of atherothrombosis

Local factors Elevated prothrombotic factors: fibrinogen, CRP, PAI-1 Blood flow patterns, vessel diameter, arterial wall structure

Generalized disorders Obesity Diabetes

Atherothrombosis manifestations (myocardial infarction, stroke, vascular death)

Systemic conditions History of vascular events Hypertension Hyperlipidemia Hypercoagulable states Homocystinemia

Genetic Genetic traits Gender Age

Lifestyle Smoking Diet Lack of exercise

Yusuf S et al. Circulation 2001; 104: 274653. 2. Drouet L. Cerebrovasc Dis 2002;13(suppl 1):16.

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

Atherothrombosis

Unstable angina MI

ACS

Ischemic stroke/TIA
Atherosclerosis Critical leg ischemia Intermittent claudication

CV death

Stable angina/Intermittent claudication

Adapted from Libby P. Circulation 2001; 104: 365372

MI = Myocardial infarction ACS = Acute coronary syndromes CV = Cardiovascular

Dekade proses pembentukan trombus

The normal artery wall

Endothelial permeability

Leucocyte migration

Endothelial adhesion

Leucocyte adhesion
Ross (1999)

The normal artery wall

Endothelial cells

Contractile VSMCs

Early atherosclerosis (I) Endothelial dysfunction

Lipid accumulates in the intimal space and is associated with abnormal endothelial cell function

Lipi d

Platelet adhesion and activation

Normal platelets in flowing blood
A

Platelets adhering to damaged endothelium and undergoing activation

B
C

Aggregation of platelets into a thrombus

Platelet thrombus

Platelets

Platelets adhering to subendothelial space

Endothelial cells Subendothelial space

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.1535.

Characteristics of the stable atherosclerotic plaque Fibrous cap

Endothelial cells (VSMCs and matrix)

Intimal VSMCs (repair phenotype)

Lipid core

Adventitia

Medial VSMCs (contractile phenotype)

Plaque growth
Site of previous plaque rupture
Resolving thrombus Recruitment of new VSMCs

Lipid core

Adventitia
Weissberg, 1999

Plaque disruption leading to atherothrombosis formation

Aggregated platelets BLOOD FLOW

Fibrin

Macrophage
Adapted from: Falk E et al. Circulation 1995; 92: 65771.

Tissue factor

Unstable coronary artery disease (II)

Lipid core

Thrombus forms and extends into the lumen

Thrombus

Adventitia

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

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 beds 3 Atherothrombosis (cardiovascular and cerebrovascular disease) is one of the worlds biggest killers4

1. 2. 3.

Falk E et al. Circulation 1995; 92: 657671 Arbustini E et al. Heart 1999; 82: 269272 Aronow WS, Ahn C. Am J Cardiol 1994; 74(1): 6465

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):S65S88

Tindakan Kateterisasi / Angiografi koroner

Tindakan Kateterisasi / Angiografi koroner

Coronary angiography and the significance of stenosis

Insignificant (<70%) stenosis

Significant (>70%) 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

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Faktor faktor risiko tradisional penting dan faktor faktor risiko non tradisional yang baru muncul dapat dilihat pada tabel berikut ini
Faktor Risiko Tradisional .. Merokok LDL Kolesterol Diet Lemak /Kolesterol tinggi Hipertensi DM Inaktivitas fisik Obesitas Status post menopause Riwayat PJK pada keluarga Homosisitein (HCy) Lipoprotein (a) Partikel small-dense LDL Stres oksidatif Inflamasi Penanda-penanda hemostatik Disfungsi Endotel Penginfeksi Trigliserida Faktor Risiko Non Tradisional

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

Activation
Oxidized lipids/ Free radicals

Viral infectin

Shear stress Cytokines

Homocystein Hypoxia

Thrombin

Response Leucocyte Adhesion

Altered Permiability

Vasoactive Substances Growth Factor

Procoagulant Activity

Gangguan/ Kekurangan
Asupan as.folat, vit B6, B12

Hyperhomocysteinemia

Risiko
Peny. Vaskular perifer Cerebral Peny. Artyeri koroner

B12

B6 Transulfuration Pathway B6

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

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