CHAPTER I

INTRODUCTION
Cardiovascular disease is a class of diseases that involve the heart, the blood or both.
The causes of cardiovascular disease are diverse but atherosclerosis and/or hypertension are
the most common. Atherosclerosis is a narrowing of the arteries that can significantly reduce
the blood supply to vital organs such as the heart, brain and intestines. In atherosclerosis, the
arteries are narrowed when fatty deposits called plaques build up inside. Plaques typically
contain cholesterol from low-density lipoproteins (LDL), smooth-muscle cells and fibrous
tissue, and sometimes calcium. Over time, plaque hardens and narrows the arteries. This
limits the flow of oxygen-rich blood to the organs and other parts of the body. This
potentially causes blood clots that can result in life-threatening conditions such as heart
attack, stroke and other cardiovascular diseases.
1

Atherosclerosis is no longer considered as an aging process alone due to the
emergence of fat spots on the wall of coronary artery is a natural phenomenon even since
childhood and not always become atherosclerotic lesions. There are many interrelated factors
that can accelerate the atherogenic process. Several factors that increased the risk of
developing coronary atherosclerosis in individual have been identified such as genetic,
environment (hemodynamic, metabolic, exogenous chemical, viral and bacterial infections,
the immune factors and mechanical factors), and the interaction of various factors. Clinical
manifestations of atherosclerosis, including coronary artery disease, cerebrovascular disease,
and peripheral arterial disease, will occur in 2 of 3 men and 1 in 2 women after age 40.
2

Atherosclerosis is one of the most important and common causes of death and
disability in the United States and throughout the world. More than 25 million persons in the
United States have at least one clinical manifestation of atherosclerosis. Although
cardiovascular disease usually affects older adults, the antecedents of cardiovascular disease,
notably atherosclerosis, begin in early life, making primary prevention efforts necessary from
childhood.
3

Based on data above that many patients who suffer from atherosclerosis then
continues manifested to coronary heart disease, the authors are interested in learning more
about the atherosklerosis.
CHAPTER II
CONTENT
1. DEFINITION
Atherosclerosis is often referred to as hardening of the arteries. The word comes from the
Greek words athero(meaning gruel or paste) and sclerosis (hardness). Atherosclerosis is a
narrowing of the arteries that can significantly reduce the blood supply to vital organs such as
the heart, brain and intestines. In atherosclerosis, the arteries are narrowed when fatty
deposits called plaques build up inside. Plaques typically contain cholesterol from low-
density lipoproteins (LDL), smooth-muscle cells and fibrous tissue, and sometimes calcium.
Over time, plaque hardens and narrows the arteries. This limits the flow of oxygen-rich blood
to the organs and other parts of the body. This potentially causes blood clots that can result in
life-threatening conditions such as heart attack, stroke and other cardiovascular diseases.
1


2. EPIDEMIOLOGY
The true frequency of atherosclerosis is difficult to accurately determine because it is
a predominantly asymptomatic condition. Atherosclerosis is virtually ubiquitous among most
developed nations but is much less prevalent in Central and South America, Africa, and parts
of Asia.
3

Atherosclerosis is one of the most important and common causes of death and
disability in the United States and throughout the world. More than 25 million persons in the
United States have at least one clinical manifestation of atherosclerosis. Atherosclerosis
remains an occult but important harbinger of significant cardiovascular events. Throughout
the last half of the past century, coronary artery atherosclerosis has been a major focus for
basic and clinical investigation. Unfortunately, the current level of knowledge differs
atherosclerosis epidemiology widely by vascular territory.
4


3. ETIOLOGY
The atherosclerotic process is not fully understood. How atherosclerosis begins or
what causes it isn't known, but some theories have been proposed. Many scientists believe
plaque begins to form because the inner lining of the artery, called the endothelium, becomes
damaged.
5

Because of the damage, fats, cholesterol, platelets, cellular debris and calcium
accumulate over time in the artery wall. These substances may stimulate the cells of the
artery wall to produce other substances, resulting in the accumulation of more cells in the
innermost layer of the artery wall where the atherosclerotic lesions form. These cells
accumulate, and many divide. At the same time, fat builds up within and around these cells.
They also form connective tissue. The arterial wall becomes markedly thickened by these
accumulating cells and surrounding material. The artery narrows and blood flow is reduced,
thus decreasing the oxygen supply.
5

There are several risk factors that are contributed to the damage of the arterial
endothelium. These can be divided into various categories:
Risk Factor for Atherosclerosis
Status Risk Factor
Nonmodifiable

Age
Family history of premature atherosclerosis
Sex
Modifiable, established Certain dyslipidemias (high total or LDL level, low
HDL level, increased total-to-HDL cholesterol
ratio)
Tobacco smoking
Diabetes mellitus
Hypertension
Modifiable, under study or
emerging
Alcohol intake (other than moderate)
Heart transplantation
Chlamydia pneumoniae infection
High C-Reactive Protein level
High level of small, dense LDL
High lipoprotein (a) level
Hyperhomocysteinemia
Hyperinsulinemia
Hypertriglyceridemia
5-Lipoxygenase polymorphisms
Low intake of fruits and vegetables
Obesity or the metabolic syndrome
Prothrombotic states (eg,hyperfibrinogenemia, high
plasminogen activator inhibitor level)
Psychosocial factors (eg, type A personality,
depression, anxiety, work characteristics,
socioeconomic status)
Radiation therapy to thorax
Renal insufficiency
Sedentary lifestyle
Table 1. Risk Factor for Atherosclerosis.
6,7

4. PATHOPHYSIOLOGY
Atherosclerosis characterized by intimal lesions called atheromas or atherosclerotic
plaques that protrude into the vascular lumina. An atheroma consists of raised lesion with a
soft, yellow, grumous core of lipid covered by a firm, white fibrous cap. Atheromas have
three principal components: (1) cells, including SMCs, macrophages, and T cells; (2) ECM,
including collagen, elastic fibers, and proteoglycans; and (3) intracellular and extracellular
lipid. Atherosclerotic plaque typically causes obstruction in blood vessels, but it can also
weaken the underlying media and can themselves rupture, causing acute catastrophic vessel
thrombosis.
3

Figure 1. Typical structure of atheromas
3

The underlying pathogenesis of atherosclerosis involve imbalance in lipid metabolism
and maladaptive immune response following a chronic inflammation of the arterial wall.
8
It
usually occurs at predilection sites (e.g branch points) and causing disturbance in laminar
blood flow. The most extensively involved vessels in atherosclerosis are the lower abdominal
aorta, the coronary arteries, the popliteal arteries, the internal carotid arteries, and the vessels
of the circle of Willis.
3
Atherosclerosis of the coronary artery commonly cause myocardial
infarction and angina pectoris; Strokes and transient cerebral ischemia also commonly occurs
following atherosclerosis of arteries supplying the CNS; While atherosclerosis of the
peripheral artery may result in intermittent claudication and gangrene.
9

Atherosclerosis initiated by endothelial dysfunction and structural alterations,
including the absence of a confluent luminal elastin layer and exposure of proteoglycans,
which allows sub-endothelial accumulation of low-density lipoproteins (LDL). Endothelial
loss due to any kind of injury-whether induced experimentally by mechanical denudation,
hemodynamic forces, immune complex deposition, irradiation, or chemicals-results in intimal
thickening; in the presence of high-lipid diets, typically results in atheromas. Apolipoprotein
B100 (Apo B100) end of LDL binding to the negatively charged extracellular matrix
proteoglycans result in retention of LDL particles in the intima, where they are susceptible to
oxidation by reactive oxygen species (ROS). Oxidation of LDL and lipid particles in
atherosclerosis triggers expression of chemokines, which drives intimal immune and smooth
muscle cells infiltration.
3,8


Figure 2. Pathogenesis of Atherosclerosis
3

Early atherosclerosis lesions consists of T-cell and monocyte-derived macrophage-
like foam cells loaded with lipids. Successive accumulation of apoptotic cells, debris, and
cholesterol crystals eventually forms necrotic core at the center of the lesion. The
fibroatheromateous plaques are covered by a fibrous cap composed of collagen and smooth
muscle cells; which are replaced by macrophages in thinning inflammation caps that prone to
rupture.
8

Several pathological events may follow atherosclerosis; (1) Rupture, ulceration, or
erosion of the luminal surface of atheromatous plaques exposes the bloodstream to highly
thrombogenic substances and induces thrombus formation. Such thrombi can partially or
completely occlude the lumen and lead to downstream ischemia. (2) Hemorrhage into the
plaque may occur after rupture of the fibrous cap, in which contained edema may expand the
plaque and causing them to rupture. (3) Plaque rupture may discharge debris into the
bloodstream, producing microemboli. (4) Atherosclerosis-induced pressure or ischemic
atrophy of the underlying media, with loss of elastic tissue may cause weakness of the vessel
wall and development of aneurysm.
3


5. CLINICAL MANIFESTATION
Atherosclerosis is asymptomatic for decades because the arteries enlarge at all plaque
locations, thus no affect on blood flow. Even most plaque ruptures do not produce symptoms
until enough narrowing/closure of an artery, due to clots, occurs. Signs and symptoms only
occur after severe narrowing/closure impedes blood flow to different organs enough to induce
symptoms.

These symptoms, however, still vary depending on which artery or organ is
affected.
2
Although atherosclerosis can affect any organ or tissue, the arteries supplying the
heart, brain, kidneys, lower extremities, and small intestine are most frequently involved.
The coronary arteries supply oxygen-rich blood to the heart. If plaque narrows or blocks
these arteries the disease is called coronary heart disease (CHD), a common symptom
is angina. Angina is chest pain or discomfort that occurs when heart muscle doesn't get
enough oxygen-rich blood. The pain tends to get worse with activity and go away with rest.
Emotional stress also can trigger the pain. Other symptoms of CHD are shortness of breath
and arrhythmias.
2,9
Plaque also can form in the heart's smallest arteries. This disease is called coronary
microvascular disease (MVD). Symptoms of coronary MVD include angina, shortness of
breath, sleep problems, fatigue (tiredness), and lack of energy. The carotid arteries supply
oxygen-rich blood to the brain. If plaque narrows or blocks these arteries the disease is
called carotid artery disease. Patient whose suffer from carotid artery disease may have a
stroke.
2
Plaque also can build up in the major arteries that supply oxygen-rich blood to the
legs, arms, and pelvis it is called peripheral arterial disease. If these major arteries are
narrowed or blocked, the symptom can be numbness, pain, and, sometimes, dangerous
infections. The renal arteries supply oxygen-rich blood to the kidneys. If plaque builds up in
these arteries, it may develop chronic kidney disease. Over time, chronic kidney disease
causes a slow loss of kidney function. Early kidney disease often has no signs or symptoms.
As the disease gets worse it can cause tiredness, changes in urinating, loss of appetite, nausea,
swelling in the hands or feet, itchiness or numbness, and trouble concentrating.
2

6. DIAGNOSIS
Atherosclerosis can be diagnosed based on medical and family histories, risk factors,
physical examination, and the results from tests and procedures.
1) During a physical examination, there is signs of narrowed, enlarged or hardened arteries,
including:
10

A weak or absent pulse below the narrowed area
Decreased blood pressure in an affected limb
Bruit over the arteries
Signs of aneurysm in the abdomen or behind the knee
Evidence of poor wound healing in the area where blood flow is restricted
2) Blood Test; Lab tests can detect increased levels of cholesterol and blood sugar that may
increase the risk of atherosclerosis
.

3) Doppler ultrasound; used to measure blood pressure at various points along the arm or
leg. These measurements can help to gauge the degree of any blockages, as well as the
speed of blood flow in the arteries.


4) Ankle-brachial index; This test can tell if the patient have atherosclerosis in the arteries
in the legs and feet. The motive is to compare the blood pressure in the 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.


5) Electrocardiogram (ECG); ECG can often reveal evidence of a previous heart attack.


6) Stress test; A stress test, also called an exercise stress test, is used to gather information
about how well the heart works during physical activity. an exercise stress test can reveal
problems within the heart that might not be noticeable otherwise. In some types of stress
tests, pictures will be taken of the heart, such as during a stress echocardiogram
(ultrasound) or nuclear stress test.


7) Cardiac catheterization and angiogram; This test can show if the coronary arteries are
narrowed or blocked. A liquid dye is injected into the arteries of the heart through a
catheter. As the dye fills the arteries, the arteries become visible on X-ray, revealing
areas of blockage.


8) Other imaging tests; Ultrasound, a computerized tomography (CT) scan or magnetic
resonance angiography (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.



7. TREATMENT
Lifestyle changes, such as eating a healthy diet and exercising, are often the best
treatment for atherosclerosis. Sometimes, medication or surgical procedures may be
recommended as well. Various drugs can slow, or even reverse the effects of atherosclerosis.
Here are some common management for atherosclerosis:
11

1) Cholesterol medications; Aggressively lowering low-density lipoprotein (LDL)
cholesterol, stop or even reverse the buildup of fatty deposits in the arteries. Boosting the
high-density lipoprotein (HDL) may help too. Cholesterol medications could include
statins and fibrates.
2) Anti-platelet medications; anti-platelet medications, such as aspirin can be used to
prevent form a blood clot and further blockage.
3) Beta blocker medications; These medications are commonly used for coronary artery
disease. They lower heart rate and blood pressure, reducing the demand on the heart and
often relieve symptoms of chest pain. Beta blockers reduce the risk of heart attacks and
some heart rhythm problems.
4) Angiotensin-converting enzyme (ACE) inhibitors; These medications may help slow the
progression of atherosclerosis by lowering blood pressure and producing other beneficial
effects on the heart arteries. ACE inhibitors can also reduce the risk of recurrent heart
attacks.
5) Calcium channel blockers; These medications lower blood pressure and are sometimes
used to treat angina.
6) Water pills (diuretics); High blood pressure is a major risk factor for atherosclerosis.
Diuretics lower blood pressure.
7) Other medications; certain medications is needed to control specific risk factors for
atherosclerosis, such as diabetes.
8) Surgical; Sometimes aggressive treatment is needed. If patient have severe symptoms or
a blockage that threatens muscle or skin tissue survival surgical can be considered.
9) Angioplasty and stent placement; In this procedure catheter inserting into the blocked or
narrowed part of the artery. A second catheter with a deflated balloon on its tip is then
passed through the catheter to the narrowed area. The balloon is then inflated,
compressing the deposits against the artery walls. A mesh tube (stent) is usually left in
the artery to help keep the artery open.
10) 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 called a carotid endarterectomy.
11) Thrombolytic therapy; If an artery is blocked by a blood clot thrombolytic therapy can be
considered.
12) Bypass surgery; a graft bypass using a vessel from another part the body or a tube made
of synthetic fabric. This allows blood to flow around the blocked or narrowed artery
8. COMPLICATION
There are a number of possible complications of atherosclerosis due primarily to
ischemia or infarction of one or more organs nourished by atherosclerotic arteries. These
complications include stroke, heart attack (myocardial infarction), narrowing (stenosis) of a
kidney (renal) artery causing hypertension or ultimate loss of the kidney, decreased blood
flow to the legs with leg pain when walking (claudication) or ultimate leg amputation,
decrease blood flow to the intestines (mesenteric ischemia), and ballooning of an artery
(aneurysm) especially of the abdominal aorta.
12


9. PROGNOSIS
Atherosclerosis is a progressive disease. It is frequently associated with and
complicated by one or more of the clinical problems from ischemia or infarction. It carries a
high morbidity and mortality with coronary heart disease being the most frequent cause.
Several studies have shown that morbidity, progression, and mortality can be slowed through
use of lipid lowering drugs for as little as 18 months of therapy.
13

Atherosclerosis can be successfully treated but not cured. Recent clinical studies have
shown that atherosclerosis can be delayed, stopped, and even reversed by aggressively
lowering LDL cholesterol. New diagnostic techniques enable physicians to identify and treat
atherosclerosis in its earliest stages. New technologies and surgical procedures have extended
the lives of many patients who would otherwise have died.
13















CHAPTER III
SUMMARY

Atherosclerosis is a narrowing of the arteries that can significantly reduce the blood
supply to vital organs such as the heart, brain and intestines. In atherosclerosis, the arteries
are narrowed when fatty deposits called plaques build up inside. The true frequency of
atherosclerosis is difficult to accurately determine because it is a predominantly
asymptomatic condition.
The atherosclerotic process is not fully understood. How atherosclerosis begins or
what causes it isn't known, but some theories have been proposed. Many scientists believe
plaque begins to form because the inner lining of the artery, called the endothelium, becomes
damaged.
Atherosclerosis is asymptomatic for decades because the arteries enlarge at all plaque
locations, thus no affect on blood flow. Although atherosclerosis can affect any organ or
tissue, the arteries supplying the heart, brain, kidneys, lower extremities, and small intestine
are most frequently involved. Atherosclerosis can be diagnosed based on medical and family
histories, risk factors, physical examination, and the results from tests and procedures.

Lifestyle changes, such as eating a healthy diet and exercising, are the best treatment
for atherosclerosis. Sometimes, medication or surgical procedures may be recommended as
well. There are a number of possible complications of atherosclerosis. Recent clinical studies
have shown that atherosclerosis can be delayed, stopped, and even reversed by aggressively
lowering LDL cholesterol