ATHEROSCLEROSIS

SCHOOL OF VETERINARY MEDICINE-UB

The Heart

Is a muscle about the size of your fist

Weighs approximately one pound

Is located behind and slightly to the left of the breastbone

Pumps about 5 quarts (4.7 liters of blood e!ery minute

The function of the heart is to circulate blood throughout the
body by:

Pumping blood through the lungs remo!es carbon

dioxide and refreshes the blood "ith oxygen

#he oxygenated blood is pumped to the body to

pro!ide oxygen and nutrients and to remo!e "aste
products.

#he coronary arteries are the blood !essels that

supply blood and oxygen to the heart muscle.


2 coronary arteries branch from the
main aorta just above the aortic
valve. No larger than drinking
straws, they divide and encircle the
heart to cover its surface with a lacy
network that reminded physicians of
a slightly crooked crown (coronary
comes from the atin coronarius,
belonging to a crown or wreath!.
"hey carry out about #$% gallons of
blood through the heart muscle
daily.& ('lark, ##(!
)lood *upply "o "he +eart
Coronary Artery Disease

$oronary artery disease is one of the most common

and serious effects of aging. %atty deposits build up in
blood !essel "alls and narro" the passage"ay for the
mo!ement of blood. #he resulting condition& called
atherosclerosis often leads to e!entual bloc'age of
the coronary arteries and a (heart attac').
,endahuluan
*eperti halnya di -*, saat ini ,.,/ menjadi penyebab kematian no.# di
0ndonesia (1lfah, 2%%%2 diakses 2%%3!.
,.4 merupakan penyebab kematian terbesar di banyak negara di
dunia. -ngka kejadian di 0ndonesia terus meningkat (1lfah, 2%%%2
diakses 2%%3!.
*45"N #(62: ,.4 urutan ke7##
*45"N #(89, menjadi urutan ke7$
*45"N #((2, menjadi ururan ke7#: #9: kematian
*45"N #((3, meningkat: #8,( : kematian
*45"N 2%%#, meningkat: 29,; : kematian (*ibarani, 2%%$!
< separo kematian di -* disebabkan oleh aterosklerosis = 3%%.%%%
orang meninggal setiap tahun karena infark miokard (>rford, 2%%3!
,.4 banyak dijumpai di 0nggris, *kotlandia "imur, ?inlandia,
*candinavia, 5usia (>rford = *elwyn, 2%%3!
$(: kematian penduduk di 14: infark miokard, stroke ()oyle, 2%%3!
Similar terms yet !istin"t in #ot$ s%ellin& an!
meanin& "an #e easily "on'(se!)

*rteriosclerosis is a general term describing any

hardening (and loss of elasticity of medium or
large arteries (the +ree' arteria, artery& sclerosis,
hardening-

*rteriolosclerosis is any hardening (and loss of

elasticity of arterioles (small arteries-

*therosclerosis is a hardening of an artery

specifically due to an atheromatous plaque.
#he term atherogenic is used for substances or
processes that cause atherosclerosis.

*therosclerosis, the +ree' "ords athero (gruel or

paste or porridge referring to the soft lipid.rich
material in the centre of atheroma& and sclerosis
(hardness.
*merican /eart *ssociation (0110& atherosclerosis is
a disease of large and medium.sized arteries
characterized by thic'ening and hardening of the
!ascular "all

It2s the term for the process of fatty substances&

cholesterol& cellular "aste products& calcium and fibrin
(a clotting material in the blood building up in the inner
lining of an artery. #he buildup that results is called
plaque.

It is commonly referred to as a hardening or

furring of the arteries. It is caused by the
formation of multiple plaques "ithin the arteries

*therosclerosis is a specific form (type of

arteriosclerosis (thic'ening 3 hardening of
arterial "alls affecting primarily the intima of
large and medium.sized muscular arteries and is
characterized by the presence of fibrofatty
plaques or atheromas.
*teros'lerosis merupa'an penya'it 'arena
membesar atau menebalnya mus'uler arteri& dan
'ara'tersti' adanya disfungsi endotel& inflamasi
!as'uler& a'umulasi lipid& 'olesterol& 'alsium&
debris seluler dalam intima dinding pembuluh
darah. *'umulasi tersebut menyebab'an
terbentu'nya pla'& remodeling !as'uler& obstru'si
luminal a'ut atau 'hroni'& abnormalitas aliran
darah& dan menurunnya suplai o'sigen pada
organ target (4rford and 5el"yn& 0115.
I6.7* TNF+
IL-,
8$*9& I$*9&
5electin
P:+%&
b%+%
%ree
radicals
monocyte
chemotac
tic
protein-1
(9$P.7
Si&ns an! Sym%toms

None: This is referred to as silent
ischemia. Blood to your heart may be
restricted due to CAD, but you dont feel
any effects.

Chest pain: If your coronary arteries cant

supply enough blood to meet the oygen
demands of your heart, the result may be
chest pain called angina.

!hortness of breath: !ome people may

not be a"are they ha#e CAD until they
de#elop symptoms of congesti#e heart
failure$ etreme fatigue "ith eertion,
shortness of breath and s"elling in their
feet and an%les.

&eart attac%: 'esults "hen an artery to

your heart muscle becomes completely
bloc%ed and the party of your heart
muscles fed by that artery dies.
Signs &
Symptoms
None
Chest
Pain
Shortness
Of Breath
Heart
Attack

9ost commonly affected arteries by atherosclerosis

include large and medium sized arteries li'e aorta&
coronary& popliteal and cerebral arteries.

9a;or complications resulting from ischemia due to

atherosclerosis include myocardial infarction
leading to heart attac's and cerebral infarction
leading to stro'es.

6ess common complications include peripheral

!ascular disease& aneurysmal dilatation due to
"ea'ened arterial "all& chronic ischemic heart
disease& ischemic encephalopathy and mesenteric
occlusion.
Ris- Fa"tors in At$eros"lerosis
9a;or ris' factors
7 9a;or $onstitutional ris' factors,
i. *ge ii. 5ex iii. +enetic factors
0 9a;or *cquired ris' factors,
i. /yperlipidemiaii. /ypertension
iii. :iabetes mellitus i!. 5mo'ing
!. /yperhomocysteinemia
Risk Factors
<ncontrollable

*e@

+ereditary

-ge
'ontrollable

+igh blood pressure

+igh blood cholesterol

*moking

,hysical activity

>besity

/iabetes

*tress and anger

$*=I=> :I*?>#>5
9>66I#<5
%>6I=> :I*?>#>5
9>66I#<5
/@P>A#>=5I4=
4?>5I#@
Ris- Fa"tors in At$eros"lerosis
9inor Ais' %actors,
7. >n!ironmental influences
0. 4besity
B. /ormones, >strogen deficiency& oral contracep.
4. Physical inacti!ity
5. 5tressful life
C. Infections ($. pneumoniae& /erpes !irus& $98
7. /omocystinuria
D. Aole of *lcohol
$hronic consumption of alcohol may result in
increased plasma le!els of homocysteine

Ais's multiply& "ith t"o factors increasing the

ris' of atherosclerosis fourfold.

/yperlipidemia& hypertension and cigarette

smo'ing together increases the ris' se!en

*ge,

9en E 55 years old

Women after menopause

5ex

Incidence and se!erity of atherosclerosis is more in

men than in "omen.

Pre!alence of atherosclerosis is about three times

higher in men in 4th decade than in "omen.

6o"er incidence in "omen& especially in

premenopausal age is probably due to high le!els of
estrogens and high.density lipoproteins& both of "hich
ha!e anti.atherogenic influence

+enetic 3 Aas

/ereditary genetic derangements of lipoprotein

metabolism predispose the indi!iduals to high
blood lipid le!el and familial hypercholesterolaemia

%amilial predisposition to atherosclerosis may be

related to other ris' factors li'e diabetes&
hypertension and hyperlipoproteinaemia.

Aacial differences too exist. ?lac's ha!e less se!ere

atherosclerosis than Whites.
Hy%er$omo"ysteinemia .&eneti"/

/omocysteine can be recycled into methionine or con!erted into

cysteine "ith the aid of ?.!itamins.

:eficiencies of the !itamins folic acid (?F& pyridoxine (?C& or ?70 (

cobalamin can lead to high homocysteine le!els

Increased le!els of homocysteine are lin'ed to high concentrations of

endothelial asymmetric dimethylarginine
/omocysteine degrades and inhibits the formation of the three main
structural components of the artery& collagen& elastin and the
proteoglycans. /omocysteine permanently degrades cysteine
disulfide bridges and lysine amino acid residues in proteins& gradually
affecting function and structure
endothelial in;ury 3 inflammation cardio!ascular disease
Dia#etes millit(s

Advanced glycosylation end productsG*+>s 3 %ree

radical endothelium-dependent relaxation
endothelial dysfunction

>nhance adhesi!eness of platellets

Hy%erli%i!aemia

#he atherosclerotic plaques contain cholesterol and

cholesterol esters largely deri!ed from the lipoproteins in
the blood.

#he lesions of atherosclerosis can be induced in

experimental animals by feeding them cholesterol.rich
diet

#he need of 6:6,

*drenal, synthesis of androgen& estrogen&

mineralo'orti'osteroid 3 glu'o'orti'oid

/epar, synthesis of bile salt

*ll of cell membrane (5imon& 7FFD.

Hy%ertension

/ypertension causes mechanical in;ury to the

arterial "all due to increased blood pressure

>ndothelial in;ury due to persistent high ?.P

leads to plaque formation as per response to
in;ury hypothesis.

* systolic pressure of o!er 7C1 mm/g or a

diastolic pressure of o!er F5 mm/g leads to 5
times higher ris' of de!eloping I/: than in
people "ith normal ?.P. (741GF1 mm/g or less.
Smo-in&

#he extent and se!erity of atherosclerosis are much greater in

smo'ers than in non.smo'ers.

Increased ris' is due to reduced le!el of /:6 and accumulation

of carbon monoxide in the blood that produces carboxy.
haemoglobin and e!entually hypoxia in the arterial "all fa!oring
atherosclerosis.

5mo'ing also promotes atherosclerosis,

increased platelet adhesi!eness

raised endothelial permeability

sympathetic ner!ous system stimulation by nicotine.

free radical produced by smo'ing causing endothelial in;ury leading

to atherosclerosis

%ree radicals oxidized 6:6 upta'e by macrophages

foam cells
Minor Ris- Fa"tors
7. /igher incidence of *thr. in de!eloped countries is
primarily because of en!ironmental influences.
0. 4besity, Ais' is increased if a person is o!er"eight by
01H or more.
B. <se of exogenous hormones li'e oral contracepti!es
by "omen or endogenous estrogen deficiency e.g.& in
post.menopausal "omen leads to increased ris'.
4. Physical inacti!ity and lac' of exercise increases ris'
5. 5tressful life style led by aggressi!eness& competiti!e
dri!e& o!er.ambitiousness and a sense of urgency is
associated "ith enhanced ris' of I/:.
#he possibility that ris' of a atherosclerosis complication
increases "ith oral contracepti!e (oral pill containing 1.1C7 mg
menstranol and 1.CC7 mg ehtynodiol diacetateG'g body "eight
on the metabolism of lipids in female rats fed a
hypercholesterolemic diet for three months.

higher le!els of triglycerides and cholesterol in plasma and

tissues& increase in aorta obser!ed to be t"o folds.

*cti!ity of lipoprotein lipase of extrahepatic tissue "as

depressed in experimental group.

*cti!ity of plasma 6$*#& an enzyme in!ol!ed in the transport

of cholesterol from tissues
*nimals treated "ith prolonged oral contracepti!es and fed
"ith atherogenic diet& may predispose to"ards
atherosclerosis.

increase in plasma and aortic cholesterol le!els&

increase in 6:6I86:6 cholesterol

decrease in /:6 cholesterol

C. Infections particularly Chlamydia pneumoniae and
!iruses such as herpes!irus and cytomegalo!irus
increases coronary atherosclerotic lesions.
C. pneumoniae:
-
Infects the endothelial cells , in;ury
-
/5P C1 similar to human endothelial protein
-
6P5, endothelial in;ury
-
Inhibits apoptosis
7. Patients "ith homocystinuria& an inborn error of
metabolism ha!e early atherosclerosis and $*:.
F. Persistent consumption of alcohol in large quantities
causes more damage.
S"reenin& an! Dia&nosis
Stress
Test
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Coronary
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Ot$er Tests In"l(!e000

)lood tests: used to evaluate kidney and thyroid

function as well as to check cholesterol levels
and the presence of anemia.

'hest A7ray: shows the siBe of your heart and

whether there is fluid build up around the heart
and lungs.

Cchocardiogram: shows a graphic outline of the

heartDs movement

Cjection fraction (C?!: determines how well your

heart pumps with each beat.

9any people are able to manage coronary artery

disease "ith lifestyle changes and medications.

4ther people "ith se!ere coronary artery disease

may need angioplasty or surgery.
#A>*#9>=#

Treatment #continued$
#! *tenting

a stent is introduced into a blood !essel on a balloon

catheter and ad!anced into the bloc'ed area of the artery

the balloon is then inflated and causes the stent to

expand until it fits the inner "all of the !essel& conforming
to contours as needed

the balloon is then deflated and dra"n bac'

#he stent stays in place permanently& holding the !essel

open and impro!ing the flo" of blood.
2! -ngioplasty

a balloon catheter is passed through the guiding

catheter to the area near the narro"ing. * guide "ire
inside the balloon catheter is then ad!anced through
the artery until the tip is beyond the narro"ing.

the angioplasty catheter is mo!ed o!er the guide "ire

until the balloon is "ithin the narro"ed segment.

balloon is inflated& compressing the plaque against the

artery "all

once plaque has been compressed and the artery has

been sufficiently opened& the balloon catheter "ill be
deflated and remo!ed.
B ?ypass surgery

healthy blood !essel is remo!ed from leg& arm or

chest

blood !essel is used to create ne" blood flo" path in

your heart

the (bypass graft) enables blood to reach your heart

by flo"ing
around (bypassing
the bloc'ed portion
of the diseased
artery. #he
increased blood flo"
reduces angina and
the ris' of heart
attac'.
P
r
e
v
e
n
t
i
o
n

(et regular medical chec%ups.

Control the blood pressure.

Chec% the cholesterol le#el.

Dont smo%e.

)ercise regularly.

*aintain a healthy "eight.

)at a heart$healthy diet.

*anage stress.
#his is a normal coronary artery "ith no atherosclerosis and a "idely
patent lumen that can carry as much blood as the myocardium requires.
T$is is mil! "oronary at$eros"lerosis0 A 'e1 s"attere!
yello1 li%i! %la2(es are seen on t$e intimal s(r'a"e o' t$e o%ene! "oronary artery
tra3ersin& t$e e%i"ar!ial s(r'a"e o' a $eart0 T$e !e&ree o' at$eros"lerosis $ere is not
si&ni'i"ant eno(&$ to "a(se !isease #(t "o(l! #e t$e $ar#in&er o' 1orse at$eros"lerosis to
"ome0
T$e !e&ree o' at$eros"lerosis is m("$ &reater in t$is "oronary artery an! t$e l(men is
narro1e! #y $al'0 A small area o' "al"i'i"ation is seen in t$e %la2(e at t$e ri&$t0
T$ese "ross se"tions o' t$e le't anterior !es"en!in& "oronary artery !emonstrate more
%rono(n"e! at$eros"lerosis 1it$ narro1in& at t$e le't 1$i"$ is t$e %ro4imal %ortion o' t$is
artery0 At$eros"lerosis is &enerally 1orse at t$e #e&innin& o' an artery 1$ere t(r#(len"e is
&reater0
Here is o""l(si3e "oronary at$eros"lerosis0 T$e "oronary at t$e le't is narro1e! #y ,5 to
6570 T$e "oronary at t$e ri&$t is e3en 1orse 1it$ e3i!en"e 'or %re3io(s t$rom#osis 1it$
or&ani8ation o' t$e t$rom#(s an! re"anali8ation s("$ t$at t$ere are t$ree small l(mens
remainin&0
T$is is t$e &ross a%%earan"e o' se3ere "oronary at$eros"lerosis 1$i"$ in3ol3es
3irt(ally 9557 o' t$e s(r'a"e o' t$e "oronary0 T$ere is e4tensi3e "al"i'i"ation
es%e"ially at t$e ri&$t 1$ere t$e l(men is narro1e!0
Mani'estasi :lini-
?efore the plaques rupture,

angina pectoris
*fter the plaques rupture,

acute myocardial infarction

sudden cardiac death

stro'e (Worthley et al.& 0117- ?oyle& 0115,

ischaemic (!an /aelst et al.& 0115.

Adaptive immunity
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