atherosclerosis & trombosis dr. faturochman
DESCRIPTION
trombosisTRANSCRIPT
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
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
Ross (1999)
Endothelial permeability
Leucocyte migration
Leucocyte adhesion
Endothelial adhesion
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
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
‘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
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
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