1.

DEFINIIE
2. TIPURI DE LEZIUNI
3. FACTORI DE RISC
4. PATOGENIE
5. EVOLUTIVILATEA LEZIUNILOR
6. CONSECINE CLINICE

1. DEFINIIE: apariia n intima arterial a unor plci formate din lipide, celule
musculare netede, macrofage, esut fibros.
Atheros = terci
Plac de
Sclerosis = induraie
aterom avansat
- intereseaz arterele musculare medii (coronare, cerebrale, carotide, renale,
mezenterice, ale membrelor inferioare) i arterele elastice mari (aorta, n special
aorta abdominal)
-ASC: b.heterogen, multifactorial si complex cu determinri clinice diferite
-ASC cauzeaz manifestri clinice distincte ce depind de patul circulator afectat
si de caracteristicile leziunilor individuale:
-ASC arterelor coronariene: AP de efort si/sau IM
-ASC art.cerebrale: AIT sau stroke
-ASC art.periferice ale membrelor: claudicaia intermitent, gangren
-ASC art.splahnice: ISM mezenteric, infarct intestinal
.ASC art.renale: rinichiul este FR si sediu pentru b.ateroembolic, poate
participa la ap.HTA, etc.

-ASC tinde s se produc:

-focal mai ales in regiunile cu aceast predispoziie: LAD, p.proximal a
a.renale, circulaia cerebrovascular, bifurcaia a.carotide
(alte regiuni nu au ac.predispoziie: a.mamar intern)
-la locul lor de ramificaii, unde fluxul sanghin este mai turbulent (factori
locali dinamici), deci lez.au o distribuie focal
-in timp si in spatiu (aspect discontinuu, nu liniar regulat); n plus, evoluia
are perioade de stagnare (silence) dar cu alte perioade cu evoluie
rapid (ASC manifest)
-ASC are expresie clinic diferit:
-cronic: AP stabil de efort, claudicaia intermitent predictibil i
reproductibil
-acut: IMA, AVC, chiar ca prima manifestare de ASC, de b.arterial
aterosclerotic
-ASC are mai multe tipuri heterogene de determinri:
-ateroame in leziunile stenotice, cu limitare de flux arterial si ocluzie
arterial, sau
-ateroamele conduc la ectazii, anevrisme (cu cretere de diametru
arterial) pe traiect arterial cu posibilitatea de ruptur sau disecie (mai ales
la nivel aortic)

2. TIPURI DE LEZIUNI: formare, progresie si complicaii specifice fiecrui tip

lezional
a) Striuri lipidice: fatty streak: leziuni precoce prin acumularea focal de
lipoproteine din stratul intimal arterial
macroscopic: proeminene sub form de striuri glbui la nivelul
endoteliului arterial
microscopic:
- celule spumoase (foam cells), provenite din macrofage, celule musculare
netede, conin colesterol i esteri de colesterol;
- celule musculare netede care conin incluziuni lipidice care se nmulesc
progresiv i sunt protruzive n lumen;
sunt precursoare ale leziunilor mai complexe
apar n copilrie, cresc i descresc n adolescen i perioada
maturitii
sunt obinuite la coronarieni
se coreleaz direct cu nivelul plasmatic al LDL i invers cu HDL

b) Placa fibroas sau placa de aterom fibroas (fibroaterom)

leziune avansat proeminent n lumen
majoritatea sunt excentrice i nu compromit fluxul sanghin,
iniial
microscopic:
- cap (acoperi): fibros dispus spe lumen, conine collagen, proteoglicani, fibre
musculare netede, acoperit de celule endoteliale
- zon celular: celule musculare, limfocite, macrofage ncrcate cu lipide (celule
spumoase);
- nucleu necrotic: resturi celulare, lipide, cristale de colesterol, calciu
se pot nsoi de modificri ale mediei i adventiciei
este o leziune metabolic activ
sunt moi - la nivelul coronarelor la bolnavii hipercolesterolemici
sunt fibroase - la fumtori
pot realiza ocluzie parial; critic (ischemie sever); total
sunt locul, leziunilor complicate

c) Placa de aterom complicat

fisur, ruptur, ulceraia plcii de aterom, care este de obicei bogat n
colesterol
este instabil
n interiorul
la nivelul ei, se produc: tromboze plachetare
hematoame
plcilor
hemoragii
tromboze protruzive n interiorul
lumenului pe care l pot obstrua

Development of Atherosclerotic Plaques

Fatty streak
Normal
Lipid-rich plaque
Foam cells
Fibrous cap

Thrombus

Lipid core

The Vulnerable Plaque

Thin, Vulnerable,
Fibrous Cap
Large Lipid Core

Reproduced with permission from Falk E, et al. Circulation. 1998;92:657-671.

Ruptured Plaque with Occlusive Thrombus Formation

Thrombus
Formation

Atherothrombosis: Thrombus
Superimposed on Atherosclerotic
Plaque

Adapted with permission from Falk E, et al. Circulation. 1998;92:657-671. Slide reproduced with permission
from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

Characteristics of Unstable and

Stable Plaque
Unstable

Few
SMCs

Thin
fibrous cap

Stable

Inflammatory
cells

Eroded
endothelium
Activated
macrophages

More
SMCs

Thick
fibrous cap

Lack of
inflammatory
cells

Intact
endothelium
Foam cells

Adapted with permission from Libby P. Circulation. 1995;91:2844-2850. Slide reproduced with permission from
Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

The Stable and

Unstable Plaque

Reproduced with permission from

Yeghiazarians Y, Braunstein JB, Askari A, et
al. Unstable angina pectoris. N Engl J Med.
2000;342:101-114.Copyright 2000,
Massachusetts Medical Society. All rights
reserved.

Plaque Rupture, Thrombosis, and Microembolization

Quiescent plaque

Process
Lipid core

Vulnerable plaque
Inflammation

TF Clotting
Cascade

Collagen
platelet
activation
Foam Cells
Macrophages Metalloproteinases

Marker

Plaque formation

Cholesterol
LDL

Inflammation
Multiple factors
? Infection

C-Reactive Protein
Adhesion Molecules
Interleukin 6, TNF
sCD-40 ligand

Plaque Rupture
MDA Modified LDL
? Macrophages
Metalloproteinases

Plaque rupture Platelet-thrombin micro-emboli

Courtesy of David Kandzari.

Thrombosis
D-dimer,
Platelet Activation Complement,
Thrombin
Fibrinogen,
Troponin, CRP,
CD40L

Plaque
Fissure or
Rupture

Platelet
Adhesion

Pathogenesis of
Acute Coronary
Syndromes:
The integral role of
platelets
Platelet
Activation
Platelet
Aggregation
Thrombotic
Occlusion

Thrombus Formation and ACS

Plaque Disruption/Fissure/Erosion
Thrombus Formation

Old
Terminology:
New
Terminology:

UA

NQMI

Non-ST-Segment Elevation Acute

Coronary Syndrome (ACS)

STE-MI
ST-Segment
Elevation
Acute
Coronary
Syndrome
(ACS)

d. Remodelarea arterial in timpul si dup formarea plcii de aterom

-vasele cu lez.ASC tind s creasc n diametru pe msur ce placa se dezvolt
spre lumenul vasului afectat: modificare compensatorie ce limiteaz progresiv
fluxul sanghin
- n timp, stenozele arteriale ce limiteaz fluxul sanghin se dezvolt i n
paralel, apar sindroamele arteriale stabile (AP sau claudicaia intermitent) n
general
-n diferite paturi circulatorii, evolutia placii chiar prin ocluzie arterial total nu
conduce n mod automat la infarct;
-hipoxia local cronica conduce la dezv.circuliei colaterale (ex. n
miocard, dup o ocluzie acut arteriala epicardic)
-multe leziuni ce dau SCAI (sindroame aterosclerotice acute sau instabile) pot
proveni din lez ASC care nu dau stenoze ce limiteaz fluxul sanghin; pe
coronarografii dau aspecte ce nu au semnificaie major;

-dar, aspectul de instabilitate al stenozelor nonocluzive explic de ce IMA

poate fi prima manifestare de BCI la cca 1/3 din cazuri; se adaug eroziunea
superficial a endoteliului, ruptura sau fisura plcii cu formarea de trombus;
clinic, poate apare API sau IMA (trombus mai mare, ocluziv si mai persistent)
-n caz de aterom carotidian, poate apare o ulceratie adnc cu formarea de
trombi plachetari i aparitie de AIT
-ruptura capului fibros al plcii conduce ca factorii de coagulare si diferii factori
tisulari trombogenici s intre n aciune;
-dac apar trombi nonocluzivi sau mici si trectori:
-nu apar simptome sau rezulta simptome ischemice (Ap de repaus)
-dac apar trombi ocluzivi, apare IMA, mai ales dac nu exist circulaie
colateral dezvoltat n teritoriul afectat
-nu toate plcile au tendina si posibilitatea de rupere, ci cele ce au ( culprit
lesion ): cap fibros subire, coninut mare n lipide si coninut mare de
macrofage; celelalte sunt rezistente la ruptur si sunt incapabile de a provoca
procesul trombotic

Atherothrombosis* is the
Leading Cause of Death Worldwide1
6.3

Pulmonary Disease
Injuries

AIDS

9.7

Cancer

12.6
19.3

Infectious Disease

22.3

Atherothrombosis*
0

10

15

20

25

30

Causes of Mortality (%)

*Atherothrombosis defined as ischemic heart disease and cerebrovascular disease.
1
The World Health Report 2001. Geneva: WHO; 2001.
Reprod.with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

Major Clinical Manifestations

of Atherothrombosis
Ischemic
stroke
Myocardial
infarction

Transient
ischemic attack

Angina:
Stable
Unstable

Peripheral arterial
disease:

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

Intermittent claudication
Rest Pain
Gangrene
Necrosis

Atherothrombosis:
a generalized and progressive process

Normal

Fatty
streak

Fibrous
plaque

Atherosclerotic
plaque

Plaque
rupture/
fissure &
thrombosis

Unstable
angina
MI

ACS

Ischemic
stroke/TIA

Clinically silent
Stable angina
Intermittent claudication
Increasing age

Critical
leg
ischemia
Cardiovascular
death

3. FACTORII DE RISC din ASC

Etiologia ateromatozei este multifactorial, complex, insuficient
cunoscut.
FR sunt caracteristici ale persoanelor sntoase asociate statistic cu
apariia BCI.
a) care in de stilul de via
- alimentaie bogat n grsimi, colesterol, calciu, fumat, alcool
- sedentarism (inactivitate fizic)
b) caracteristici biochimice sau fiziologice (modificabile)
- creterea colesterolului total plasmatic (hipercolesterolemie)
- HTA
- scderea HDL colesterolului
- diabetul zaharat
- obezitatea
- factori trombogeni (hiperfibrinogenemia, hiperhomocisteinemia)
c) caracteristici individuale nemodificabile
- vrst
- sex masculin, menopauz
- istoric familial de BCI prematur
Factori majori
- hipercolesterolemia
- hipertensiunea arterial
- fumatul

Cunoaterea FR a dus la scderea morbiditii i mortalitii prin BCV legate de

ateromatoz. Sunt nuane:
-HTA este factor independent de risc pentru ev.coronariene
-genul M si st.postmenopauz cresc riscul pentru dezvoltarea BCI
-starea premenstrual evolueaz cu HDL_C crescut si este ferit de lez.majore
ASC
-efectul vasculoprotectiv posibil al estrogenilor a condus la introducerea trat.de
nlocuire hormonala in menopauz ca strategie antiaterogenic
-DZ accelereaz aterogeneza, iar complicaiile diabetice macrovasculare sunt de
cauz aterosclerotic; se insoete de rezistena la insulina si de dislidemie
aterogen cu Tg crescute si HDL-C mic, alturi de HTA, intolerana la glucoz si
obezitate visceral (SXmetabolic)
-hiperfibrinogenemia la b cu ASC, deja prezent, este un fen. secundar dar care
poate contribui la evolutia leziunilor ASC si a riscului protrombotic
-infectiile, reactiile imune si autoimune pot induce lez de ASC (rspunsul imun,
virusuri si bacterii, v.herpetic, Clamydia), etc.

CV Disease is a Continuum
Myocardial
Infarction

CAD

Atherosclerosis

CV Risk Factors
Diabetes
Hypertension
Hyperlipidemia
Smoking

Loss of
contractility

Remodeling

Ventricular
Dilation
Congestive
Heart Failure

End-Stage
Heart Disease

Death

Adapted from Dzau V, Braunwald E. Am Heart J. 1991

Clinical Manifestations
of Atherosclerosis
Coronary heart disease
Stable angina, acute myocardial infarction, sudden death, unstable
angina

Cerebrovascular disease
Stroke, TIAs

Peripheral arterial disease

Intermittent claudication, increased risk of death from heart attack and
stroke
American Heart Association, 2000.

Deaths From
Cardiovascular Disease
Stroke 17%
Rheumatic Fever/
Rheumatic Heart
Disease 0.4%

Coronary Heart
Disease 55%

Congenital
CV Defects
0.5%
Diseases of
the Arteries 2%
Congestive Heart
Failure 6%
High Blood
Pressure 5%
American Heart Association. 2002 Heart and Stroke Statistical Update. 2001.

Other 15%

ABC Approach to Prevention

A

Antiplatelet therapy
Anticoagulant therapy
Angiotensin converting enzyme inhibitor
Angiotensin receptor blocker

Blood pressure control

-blocker

Cholesterol management
Cigarette smoking cessation

Diet and weight management

Diabetes mellitus prevention and management

Exercise
Ejection fraction assessment

The Role of Lipoproteins in Atherogenesis

HDL

Endothelial
injury

High plasma
LDL

LDL
+
VLDL

Adherence
of platelets

LDL infiltration
into intima

Liver

Cholesterol
excreted

LCAT
APO-A1
Release
of PDGF

Advanced
fibrocalcific
lesion

APO-A1=Apolipoprotein A1, LCAT=Lecithin cholesterol

acyltransferase, LDL=Low density lipoprotein,
HDL=High density lipoprotein, PDGF=Platelet-derived
growth factor, VLDL=Very low density lipoprotein,

Other
growth
factors

Oxidative
modification
of LDL
+
Macrophages
Foam cells
Fatty streak

Dac gseti un drum fr obstacole,

probabil c drumul acela nu duce
nicieri !
J.F.Kennedy