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): 16.
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: 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
Stroke
TIA
Acute MI
Unstable angina
Prior MI
PCI/stenting
Atrial fibrillation

Intermittent
claudication
Peripheral
vascular
intervention
CHARISMA
CAPRIE
1
ACTIVE
COMMIT
CLARITY
CURE
2
CLASSICS
3
CREDO
4
CHARISMA
CAPRIE
1
CAMPER
CHARISMA
CAPRIE
1
MATCH
ACTIVE
CARESS
TIA = Transient ischemic attack
MI = Myocardial infarction
PCI = Percutaneous coronary intervention
Teri J M
c
Dermott CMI 2003
Identifying those at risk of atherothrombosis
Yusuf S et al. Circulation 2001; 104: 274653. 2. Drouet L. Cerebrovasc Dis 2002;13(suppl 1):16.
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: 365372
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.1535.
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: 65771.
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: 657671
2. Arbustini E et al. Heart 1999; 82: 269272
3. Aronow WS, Ahn C. Am J Cardiol 1994; 74(1): 6465
Plaque rupture
1
Plaque erosion
2
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 killers
4

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

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

.
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