Aterosklerosis

Pembimbing :
Dr. Bambang Supriadi, Sp. S
Oleh :
Benediktus Bayu Anggoro Putro

Introduction

Atherosclerosis (also known as

Arteriosclerotic Vascular Disease or
ASVD)
the condition in which an artery wall
thickens as the result of a build-up of
fatty materials such as cholesterol
affecting arterial blood vessels, a chronic
inflammatory response in the walls of
arteries
due to the accumulation of macrophage
white blood cells and promoted by Lowdensity lipoproteins without adequate
removal of fats and cholesterol from the

 It is commonly referred to as a hardening or

furring of the arteries.
It is caused by the formation of multiple
plaqueswithin the arteries.
It can restrict blood flow. These plaques can
also burst, causing a blood clot.
Although atherosclerosis is often considered
a heart problem, it can affect arteries
anywhere in your body.
Atherosclerosis is a preventable and
treatable condition.

TERMS/Definitions
Arteriosclerosis is a general term describing
any hardening (and loss of elasticity) of medium
or large arteries

Arteriolosclerosis is any hardening (and loss

of elasticity) of arterioles (small arteries);

Atherosclerosis is a hardening of an artery

specifically due to an atheromatous plaque.

Atherogenic is used for substances or

processes that cause atherosclerosis.

Atherogenesis is the developmental process

of atheromatous plaques

Causes
Atherosclerosis starts with damage or
injury to the inner layer of an artery.
The damage may be caused by:

High blood pressure

High cholesterol
An irritant, such as nicotine
Certain diseases, such as diabetes

Epidemiology
Table:1. Estimated
10-year risk of
coronary artery
disease according
to various
combinations of
risk factor levels,
expressed as the
probability of an
event in 10 years.
HDL-C,

Epidemiology
ATHEROSCLEROSIS is less prevalent
in central and south America, Africa,
and Asia. And more prevalent in
united states and Japan.
The mortality in U.S in 5 times higher
than Japan
According to United States data for
the year 2004, for about 65% of men
and 47% of women, the first
symptom of atherosclerotic
cardiovascular disease is heart
attack or sudden cardiac death

Epidemiology
ATHEROSCLEROSIS is less prevalent
in central and south America, Africa,
and Asia. And more prevalent in
united states and Japan.
The mortality in U.S in 5 times higher
than Japan
According to United States data for
the year 2004, for about 65% of men
and 47% of women, the first
symptom of atherosclerotic
cardiovascular disease is heart
attack or sudden cardiac death

Pathophysiology
Atherosclerosis develops as a chronic
inflammatory response of the arterial
wall to endothelial injury.
Lesion progression occurs through
interactions of modified lipoproteins,
monocyte-derived macrophages, Tlymphocytes, and the normal cellular
constituent of the arterial wall.
The contemporary view of
atherosclerosis is expressed by the
response-to-injury hypothesis.

Response-to-injury hypothesis

1.
2.
3.
4.

5.

The following are

the steps involved
in the hypothesis:
Chronic
endothelial injury
Accumulation of
lipoproteins
Monocyte
adhesion to the
endothelium
SMC
proliferations
and ECM
production
factor release

Response-to-injury
hypothesis
1. Chronic endothelial injury
. with resultant endothelial
dysfunction, causing increased
permeability, leukocyte adhesion,
and thrombosis

Response-to-injury
hypothesis

2. Accumulation of lipoproteins
(mainly LDL and its oxidized forms) in
the vessel wall. Low-density
lipoprotein molecules (LDL) becoming
oxidized (ldl-ox) by free radicals,
particularly oxygen free (ROS). When
oxidized LDL comes in contact with an
artery wall, a series of reactions occur
to repair the damage to the artery wall
caused by oxidized LDL. Cholesterol
can move in the bloodstream only by

Response-to-injury
hypothesis
3. Monocyte
adhesion to the
endothelium

followed by migration into the intima and

transformation into macrophages and foam
cells. The body's immune system responds
to the damage to the artery wall caused by
oxidized LDL by sending specialized white
blood cells (macrophages and Tlymphocytes) to absorb the oxidized-LDL
forming specialized foam cells.
Unfortunately, these white blood cells are
not able to process the oxidized-LDL, and
ultimately grow then rupture, depositing a
greater amount of oxidized cholesterol into
the artery wall. This triggers more white

Response-to-injury
4.hypothesis
platelet adhesion
5. factor release
from activated platelet,
macrophages and vascular wall
cells, inducing SMC recruitment,
either from the media or from
the circulating precursors

Response-to-injury
6. SMC
proliferations and ECM
hypothesis
production.

Eventually, the artery becomes

inflamed. The cholesterol plaque
causes the smooth muscle cells to
enlarge and form a hard cover over
the affected area. This hard cover is
what causes a narrowing of the
artery, reduces the blood flow and
increases blood pressure.

Response-to-injury
7. hypothesis
Lipid accumulation
both extracellularly and within cells
(macrophages and SMCs).
accumulation if lipid-containing
macrophages in the intima gives rise
to fatty streaks, with further
evolution, a fibrofatty atheroma
consisting of proliferated SMC, foam
cells, extracellular lipid, and ECM is
formed.

Micrograph of an artery that supplies the

heart With significant atherosclerosis and
marked luminal narrowing

Kenichi Sakakura, MD, Masataka Nakano, MD, Fumiyuki

Otsuka, MD, Elena Ladich, MD, Frank D. Kolodgie, PhD and
Renu Virmani, MD. Pathophysiology of Atherosclerosis
Plaque Progression. Elsevier : Australian and New Zealand
Society of Cardiac. 2013

Kenichi Sakakura, MD, Masataka Nakano, MD, Fumiyuki

Otsuka, MD, Elena Ladich, MD, Frank D. Kolodgie, PhD and
Renu Virmani, MD. Pathophysiology of Atherosclerosis
Plaque Progression. Elsevier : Australian and New Zealand
Society of Cardiac. 2013

Symptoms
Atherosclerosis develops gradually,
typically begins in early adolescence,
and is usually found in most major
arteries. There are usually no
atherosclerosis symptoms until an
artery is so narrowed or clogged that
it can't supply adequate blood to your
organs and tissues. Sometimes a
blood clot completely obstructs blood
flow, or even breaks apart and causes
blood clots that can trigger a heart
attack or stroke.

Symptoms
Atherosclerosis symptoms depend on which
arteries are affected. For example:
Atherosclerosis in heart arteries,have
symptoms similar to those of a heart attack,
such as chest pain (angina).
Atherosclerosis in the arteries leading to
brain, have symptoms such as sudden
numbness or weakness in your arms or legs,
difficulty speaking or slurred speech, or
drooping muscles in your face.
Atherosclerosis in the arteries in arms and
legs, produces decreased blood flow is called
peripheral artery occlusive disease (PAOD).have
symptoms such as leg pain when walking
Sometimes atherosclerosis causes erectile

Symptoms

Symptoms

Table 1.Conditions That Accelerate the Progression of Atherosclerosis and the Mechanisms
Responsible.
Condition
Mechanism
Male gender (and females Estrogen increases cholesterol removal by the liver, and the progression of
after menopause)
atherosclerosis is less rapid in premenopausal women that in men
Family history of
ischemic heart disease,
stroke

Probably multiple genetic mechanisms.

Primary hyperlipidemia

Inherited disorders causing lipoprotein lipase deficiency (type I), defective LDL
receptors (type IIa), abnormal apoprotein E (type III), deficiency of apoprotein C (type
V), or unknown cause (types IIb and IV).

Secondary
hyperlipidemia

Increased circulating triglycerides produced by diuretics, b-adrenergic blocking drugs,

excess alcohol intake.

Cigarette smoking

Probably carbon monoxide-induced hypoxic injury to endothelial cells.

Hypertension

Increased shear stress, with damage to endothelium.

Diabetes mellitus (types

1 and 2)

Decreased hepatic removal of LDL from the circulation; increased glycosylation of

collagen, which increases LDL binding to blood vessel walls.

Obesity, particularly
abdominal obesity

Unsettled, but obesity is associated with type 2 diabetes, hypertriglyceridemia,

hypercholesterolemia, and hypertension, all of which are risk factors in their own right.

Nephrotic syndrome

Increased hepatic production of lipids and lipoprotein (a).

Hypothyroidism

Decreased formation of LDL receptors in the liver.

Elevated plasma
homocysteine

Unsettled. Probably increased homocysteine provides more H2O2 and other reactive
oxygen molecules that foster formation of oxidized LDL.

Complications
The complications of atherosclerosis depend on
the location of the blocked arteries. For
example:
Coronary artery disease.When
atherosclerosis narrows the arteries close to
your heart, you may develop coronary artery
disease, which can cause chest pain (angina)
or a heart attack.
Carotid artery disease.When
atherosclerosis narrows the arteries close to
Stein
Harald
Johnsen,
Signe
Helene
Forsdahl, Kulbir
Singh, artery
Bjarne Koster
your
brain,
you
may
develop
carotid
Jacobsen. Atherosclerosis in Abdominal Aortic Aneurysms: A Causal Event
which
can cause
a transient
ordisease,
a Process Running
in Parallel?
The Troms
Study. AHA : 2016. Available
on : http://atvb.ahajou1rn2a6l3s.org/ by guest on February 13, 2016
ischemic attack (TIA) or stroke.

Complications
Peripheral artery disease.When atherosclerosis
narrows the arteries in your arms or legs, you may
develop circulation problems in your arms and legs
called peripheral arterial disease. This can make you
less sensitive to heat and cold, increasing your risk of
burns or frostbite. In rare cases, poor circulation in your
arms or legs can cause tissue death (gangrene).
Aneurysms.Atherosclerosis can also cause
aneurysms, a serious complication that can occur
anywhere in your body. An aneurysm is a bulge in the
wall of your artery. Pain and throbbing in the area of an
aneurysm is a common symptom. If an aneurysm
bursts, you may face life-threatening internal bleeding.
Although this is usually a sudden, catastrophic event, a
slow leak is possible. If a blood clot within an aneurysm
dislodges, it may obstruct an artery at some distant

Tests and diagnosis

Doctors may find signs of narrowed, enlarged or
hardened arteries during a physical exam.
These include:
A weak or absent pulse below the narrowed
area of the artery
Decreased blood pressure in an affected limb
Whooshing sounds (bruits) over the arteries,
heard with a stethoscope
Signs of a pulsating bulge (aneurysm) in the
abdomen or behind knee
Evidence of poor wound healing in the area
where blood flow is restricted

Tests and diagnosis

Depending on the results of the physical
exam, doctors may suggest one or more
diagnostic tests, including:
Blood tests.
Doppler ultrasound
Ankle-brachial index.
Other imaging tests.
Angiogram.
Electrocardiogram (ECG).

Lifestyle and home remedies

Lifestyle changes can help prevent or
slow the progression of atherosclerosis.
Stop smoking.
Exercise most days of the week.
Eat healthy foods
Manage stress
manage the condition of high
cholesterol, high blood pressure,
diabetes or other chronic disease

Prevention
The same healthy lifestyle changes
recommended to treat atherosclerosis
also help prevent it. You've heard it
before stop smoking, eat healthy
foods, exercise regularly, maintain a
healthy weight, drink less alcohol. Just
remember to make changes one step at
a time, and keep in mind what lifestyle
changes are manageable for you in the
long run.

Tests and diagnosis

Blood tests.Lab tests can detect increased levels of
cholesterol and blood sugar that may increase the risk
of atherosclerosis.
Doppler ultrasound.Uses a special ultrasound device
(Doppler ultrasound) to measure blood pressure at
various points along arm or leg. These measurements
can help doctor gauge the degree of any blockages, as
well as the speed of blood flow in the arteries.
Ankle-brachial index.This test can tell if one have
atherosclerosis in the arteries in your legs and feet.
Doctor may compare the blood pressure in ankle with
the blood pressure in the arm. This is known as the
ankle-brachial index. An abnormal difference may
indicate peripheral vascular disease, which is usually
caused by atherosclerosis.

Tests and diagnosis

Electrocardiogram (ECG).An electrocardiogram
records electrical signals as they travel through your
heart. An ECG can often reveal evidence of a previous
heart attack or one that's in progress. If signs and
symptoms occur most often during exercise,
Angiogram.To better view blood flow through heart,
brain, arms or legs, doctor may inject a special dye into
your arteries before an X-ray. This is known as an
angiogram. The dye outlines narrow spots and
blockages on the X-ray images.
Other imaging tests. doctor may use ultrasound, a
computerized tomography (CT) scan or a magnetic
resonance angiogram (MRA) to study the arteries.
These tests can often show hardening and narrowing of
large arteries, as well as aneurysms and calcium
deposits in the artery walls.

Treatments and drugs

Lifestyle changes, such as eating a healthy diet
and exercising, are often the first line of
defense in treating atherosclerosis. But
sometimes, medication or surgical procedures
may be recommended as well.
Various drugs can slow or sometimes even
reverse the effects of atherosclerosis. Here
are some common choices:
Cholesterol medications.Aggressively
lowering low-density lipoprotein (LDL)
cholesterol, the "bad" cholesterol, can slow,
stop or even reverse the buildup of fatty
deposits in arteries. Boosting your high-density
lipoprotein (HDL) cholesterol, the "good"
cholesterol, may help, too. cholesterol
medications includes drugs known as statins

Treatments and drugs

Anti-platelet medications.Doctors may
prescribe anti-platelet medications, such as
aspirin, to reduce the likelihood that
platelets will clump in narrowed arteries,
form a blood clot and cause further
blockage.
Anticoagulants.An anticoagulant, such as
heparin or warfarin (Coumadin), can help
thin blood to prevent clots from forming.
Blood pressure medications.Medications
to control blood pressure such as beta
blockers, angiotensin-converting enzyme
(ACE) inhibitors and calcium channel
blockers can help slow the progression of
atherosclerosis

Treatments and drugs

Other medications. doctor may suggest
certain medications to control specific
risk factors for atherosclerosis, such as
diabetes. Sometimes medications to treat
symptoms of atherosclerosis, such as leg
pain during exercise, are prescribed.
Sometimes more aggressive treatment is
needed. If you have severe symptoms or
a blockage that threatens muscle or skin
tissue survival, you may be a candidate
for one of the following surgical
procedures:

Treatments and drugs

Angioplasty.In this procedure, your doctor
inserts a long, thin tube (catheter) into the
blocked or narrowed part of your artery. A
wire with a deflated balloon is passed
through the catheter to the narrowed area.
The balloon is then inflated, compressing the
deposits against your artery walls. A mesh
tube (stent) is usually left in the artery to
help keep the artery open. Angioplasty may
also be done with laser technology.
Endarterectomy.In some cases, fatty
deposits must be surgically removed from
the walls of a narrowed artery. When the
procedure is done on arteries in the neck (the
carotid arteries), it's known as carotid
endarterectomy.

Treatments and drugs

Thrombolytic therapy.If you have
an artery that's blocked by a blood
clot, your doctor may insert a clotdissolving drug into your artery at
the point of the clot to break it up.
Bypass surgery.Your doctor may
create a graft bypass using a vessel
from another part of your body or a
tube made of synthetic fabric. This
allows blood to flow around the
blocked or narrowed artery.

References:

Harrisons principle of internal

medicine, 17th edition.
Robbins basic pathology, 8 th edition

Kenichi Sakakura, MD, Masataka Nakano, MD, Fumiyuki Otsuka,

MD, Elena Ladich, MD, Frank D. Kolodgie, PhD and Renu Virmani,
MD. Pathophysiology of Atherosclerosis Plaque Progression.
Elsevier : Australian and New Zealand Society of Cardiac. 2013

Stein Harald Johnsen, Signe Helene Forsdahl, Kulbir Singh,

Bjarne Koster Jacobsen. Atherosclerosis in Abdominal Aortic
Aneurysms: A Causal Event or a Process Running in Parallel?
The Troms Study. AHA : 2016. Available on :
http://atvb.ahajou1rn2a6l3s.org/ by guest on February 13, 2016