Cholesterol

Updated 27 February 2018

Atherosclerosis

Atherosclerosis is a condition in which arteries become hardened and narrowed.

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Atherosclerosis is a disease process in which cholesterol and other fat from the circulation collect in the arterial wall together with cells and some scar tissue. This is part of a process called arteriosclerosis in which “hardening of the arteries” is more prominent than fat accumulation and calcification is more typical in such lesions. 

While it is unlikely that the cholesterol-rich atherosclerotic lesion will protrude into the inside of the artery to obstruct blood flow, its rupture leads to clotting, the extent of which vary from minor amounts that do not impair flow significantly, to complete obstruction. 

Atherosclerosis occurs to some extent in most people as they get older, but more rapidly in some for reasons, most of which are largely preventable.
Causes

Arterial walls develop atherosclerotic “plaques” over a long period of decades. These begin as thin, fatty streaks in the inner portion of an arterial wall. In a healthy, young person the streaks may come and go. In the setting of a strong risk factor, these can progress or in the concurrence of several less powerful risk factors the lesions may also progress 

More cholesterol attracted 

If arteries are stressed or damaged – from high blood pressure, diabetes,  smoking or excess cholesterol in the blood  – the inner lining artery is injured and  the wall attracts cholesterol-carrying particles and cells This sets in motion the series of events described below which create a fully-fledged atherosclerotic plaque.

Over time, various substances such as, cholesterol and some other lipids (fats), and cells accumulate along with platelets (particles that cause blood clotting). Cellular debris remains in the region. . Eventually, scar tissue with cholesterol crystals and sometimes calcium crystals surround the fatty plaque, making the arteries hard and inelastic. 

As a plaque grows due to ongoing injury, it produces a rough area in the artery's normally smooth inner surface. This rough area can trigger the formation of a thrombus (clot), decreasing and eventually blocking blood flow in the artery. Large amounts of fat in the wall make it more s liable to rupture and cause a clot. Portions of the plaque may break off to deposit distantly (emboli) in arteries supplying the brain from the chest or neck, or may happen elsewhere in the body.

The tissue that has been starved of blood and oxygen become severely damaged and the cells may die.

Smoking promotes injury to the endothelium (cells lining the inside of an artery) Diabetes also damages the artery. High blood pressure not only increases the stress on the artery but also induces the heart to work harder to pump blood, causing it to enlarge and ultimately heart failure. 

Outcome

Because atherosclerosis usually progresses slowly over many years, it is commonly thought of as an affliction of the elderly.

However, studies show that arterial deposits can begin in childhood, with significant plaque formation by the time a person is 30 years. In some people it progresses rapidly in their third decade; in others it doesn’t become threatening until they’re in their fifties or sixties. Women, in particular, are generally but not invariably protected before menopause.

Atherosclerosis may never seriously affect the overall health of some people who have it. In many others, however, it is an important cause of illness and early death.

In most cases, improvements in lifestyle (see "Treatment" and "Prevention") and appropriate medical treatment, can retard or even reverse the progress of the disease.
Physical effects

Atherosclerosis is the most common cause of coronary artery disease in adults. The changes that result from atherosclerosis can be divided into reversible and irreversible:

 The potentially reversible changes generally occur in the first three decades of life. These do not result in clinical disease and can disappear with appropriate treatment, leaving behind an entirely normal artery. The reversible changes result in some swelling of the wall of the artery due mainly to some accumulation of lipids inside the cells which have gathered in the wall of the artery itself.

 The irreversible changes are called atherosclerotic plaque – or just “plaque”. These occur later in life, except in unusually severe cases in which they may appear earlier. They can go on to cause chronic (ongoing) or acute (sudden) symptoms or a combination of the two. Plaque can be modified by vigorous treatment and the risks associated with it can be significantly reduced when the plaque is “stabilised”. O once formed, plaque never regresses completely but can regress. 

After a plaque has formed it can cause problems in a number of different ways. If an established plaque ruptures, the resulting events can cause a heart attack or stroke.

Plaque ruptures if the tissue covering it erodes sufficiently to allow blood to come into contact with the lipid core. This causes the blood to clot (thrombose). If the clot is in one of the coronary arteries it can cause symptoms such as chest pain or it can cause a fatal heart attack. It can also lodge in the brain and cause a stroke.

Plaque can also become thickened with calcium deposits, or the lipid core can crystallise. A fibrous cap can form; protecting the plaque from rupturing as easily, but further stiffens the artery – so-called hardening of the arteries.

Associated risk factors

Atherosclerosis is the major cause of death and disability in developed nations through the clinical mechanisms described above. Coronary artery disease and its complications, together with stroke, are responsible for more deaths than all other causes combined.

There is also an emerging epidemic of heart attacks in Africa and other developing countries as more people adopt the sedentary western lifestyle including a high-fat, high-cholesterol diet, and little exercise and becoming obese. Heart disease is one of the leading causes of premature death in South Africa, notably in the white and Indian communities but increasingly in the black population as well.

Most people will develop some arterial deposits over time, but certain factors significantly account for this process. These are called risk factors:

Age. The risk of developing atherosclerosis increases after age 35 years, although it can begin much earlier. Blood vessels lose a certain amount of elasticity with ageing.

Gender. Premenopausal women are much less likely than men of the same age to have atherosclerosis. But after menopause, women's risk increases to equal – or even exceeds – that of men.

Heredity. A family history of atherosclerosis or other circulatory diseases may denote increased risk in closely related family members. This is particularly relevant in South Africa, where there is a high incidence of familial hypercholesterolaemia in several communities.

Obesity. Obese people are more likely to have atherosclerosis because they are predisposed to high triglyceride, low HDL-cholesterol and raised total cholesterol levels, as well as high blood pressure, thrombus formation and diabetes mellitus.

Physical inactivity. Too little exercise is detrimental through many changes that may appear minor but over years may contribute significantly to disease.

Diabetes mellitus. This is a risk factor for large vessels and medium vessels with complications discussed above, but also harm small vessels in the kidney and retina. 

High level of blood cholesterol (hypercholesterolaemia): especially the cholesterol carried in LDL ( low-density lipoproteins)  from the liver to the tissues.

Low levels of high-density lipoprotein (HDL), which transport cholesterol from cells to the liver, are also associated with a high risk of heart disease. This is often associated with raised concentrations of triglyceride (also a fatty substance similar to cholesterol, obesity and diabetes.

Hypertension (high blood pressure). This should be treated. 

Smoking. A smoker's risk of coronary artery disease is directly related to the number of cigarettes smoked daily. In people who already have a high risk of heart disease, smoking is particularly dangerous. 

Symptoms and signs

Atherosclerosis usually produces no symptoms for a long time but may suddenly or slowly reduces the blood supply to an organ. This may be partial or complete, acute or chronic. Complete obstruction is generally the result of a thrombus or an embolus. The symptoms and outcome (prognosis) will vary accordingly.

The first symptom of inadequate blood supply is generally pain, and may only happen during exercise (of the heart or legs at which times the blood flow can't keep up with the tissue’s demand for oxygen).

Chest pain

For instance, during exercise, you may feel chest pain (angina) because of lack of oxygen to the heart; or leg cramps because of lack of oxygen to the leg muscles (claudication). These symptoms may set in suddenly when a clot forms; and could improve when the clot is digested by normal processes or could progress if this does not happen. This may be the presenting event without previous warning symptoms.

Symptoms may vary from quite characteristic to atypical depending on the several incidental factors.

It is important to note that persons with diabetes often do not experience pain as an early warning sign. They may thus have advanced disease, e.g. coronary artery disease, without being aware of it – until it reaches a critical phase and causes a heart attack.

Subtle symptoms 

Women, also, generally do not have the same “classical” symptoms and signs listed below. In these two categories of patient – women and diabetics – there must be a greater awareness and index of suspicion than in others. These patients should thus be tested sooner and more frequently.

The more characteristic clinical presentations are described below which depend on the organ mainly affected and the severity of the obstruction:

Heart

The complications resulting from atherosclerosis can arise slowly over time as blood flow is reduced or may be of sudden onset.

The common ways in which the heart is affected are through:
Stable or exercise-induced angina
Unstable or crescendo angina
Heart attack (acute myocardial infarction)

Coronary artery disease (coronary heart disease): occurs when atherosclerosis results in narrowing of the coronary arteries (arteries supplying blood to the heart muscle). As the coronary arteries narrow, angina (chest pain) may result – especially on exertion.

In a heart attack, a portion of the heart muscle actually dies and is repaired by a scar; the technical term is "myocardial infarction". If this occurs very suddenly and rapidly it is called an acute myocardial infarction.

Symptoms may include:
a pressing, centrally located chest pain (angina), which may also be felt in the arms and hands as tingling or numbness or may rise to the neck. 
shortness of breath

Less characteristic features include:
sweating
nausea
dizziness or light-headedness
palpitations
pain in the jaw or shoulder/upper arm

Brain

Stroke: A thrombus may form in an artery to the brain that has been affected by atherosclerosis, or a piece of atherosclerotic plaque in an artery supplying the brain can break off to form an embolus dislodged piece that travels and downstream causes a blockage or the weakened arterial wall may rupture and bleed. The end result in all cases is greater or lesser damage to the brain, which presents as a stroke. A bleed into the brain can also cause a stroke by interrupting blood supply at this region. 

Warning signs may include:
Atherosclerosis of cerebral arteries does not present with pain, but may cause progressively diminished mental functioning, and episodes of light-headedness.
It may also present with very minor strokes, called transient ischaemic attacks, accompanied by temporary dizziness or confusion, incoordination, numbness and loss of speech, loss of vision and many other complaints. These features are relieved within 24 hours.

An acute, more severe obstruction or bleed may present with:
Headache – often severe – is more suggestive of a bleed 
Unconsciousness and collapse may occur if vital parts are affected
Weakness or paralysis on one side of the body
Sudden, severe numbness in any part of the body
Speech and visual disturbances or severe muscle incoordination.
The presentation may be progressive over a short period of time or may be sudden and overwhelming. In the case of a stroke, the neurological abnormalities are persistent, often taking months to improve. Full restoration of normal function is rare. Strokes can result in a bizarre variety of neurological problems, sometimes very localised and specific.

Legs

Peripheral arterial disease: Atherosclerosis can impair the flow of blood in the major arteries to the legs. The resultant reduced blood flow may cause crampy leg pain during exercise, which is called "intermittent claudication".

If blood flow is severely restricted, parts of the leg may become pale on exertion or "blue" (cyanotic), feel cool and develop skin sores and ulcers or even gangrene (tissue death). A bruit (specific type of noise) may be heard with a stethoscope over a partly blocked artery. If the artery is totally blocked, there may be no pulse at all.

Abdomen

Abdominal angina and bowel infarction: When atherosclerosis narrows arteries that supply blood to the intestines, it causes abdominal pain called abdominal angina. Blockage of intestinal blood supply causes a bowel infarction. This is similar to a myocardial infarction, but involves the intestines instead of the heart.

Symptoms include:
Dull or cramping pain in the middle of the abdomen, usually beginning 15 to 30 minutes after eating.
Severe abdominal pain, vomiting, diarrhoea or constipation caused by complete blockage of an artery in the intestine.

Other conditions

Atherosclerosis may contribute to the development of an aortic aneurysm (a weakening and "bulging or ballooning" of the aorta, the main artery leading from the heart) or in renal artery stenosis (narrowing of the kidney arteries).

An aneurysm may rupture, causing a massive haemorrhage (bleed). Narrowing of renal arteries can reduce kidney function and cause high blood pressure.

Diagnosis

Atherosclerosis may not cause any complaints. The doctor needs to establish whether a patient is at increased risk for this process in order that it is intercepted, or whether the patent has already developed the clinical complications associated with it.

The risk or predisposing factors have already been discussed. Part of a general medical examination is to enquire into important lifestyle factors such as:
dietary habits
levels of physical activity
smoking habits
the amount and kind of alcohol consumed
less frequently, levels of emotional stress during daily living

It is also important to determine whether the patient suffers from the important predisposing condition of diabetes mellitus or has already developed symptoms suggestive of early arterial obstruction without even noticing them, for example erectile dysfunction in men. In women, menstrual status is significant since risk increases substantially in post-menopausal women. Hypertension is usually symptom-free until a significant clinical complication results. The doctor also needs to know what medication the patient is currently taking.

After the history has been taken, a physical examination will also help determine risk or the presence or absence of atherosclerosis:

Since obesity is an important risk factor, the doctor should determine your weight and height. The circumference of your waist and hip may also be measured. From this, he can calculate important indices, such as body mass index or waist: hip ratio which provides additional useful information.
Hypertension is another significant contributory factor, so blood pressure will be measured.
Your heart will be assessed for size and normality of rhythm and the retina of your eyes examined for changes indicating arterial damage due to hypertension or diabetes mellitus.
Your pulse should be felt in your neck, groin and legs in order to determine whether the arteries supplying these regions function normally. The doctor may also use his stethoscope to listen for the noise (bruit) made by blood passing over an atherosclerotic plaque. Skin colour, appearance and temperature also convey important information regarding blood supply.

Once the history and clinical and urine examinations are done, an important next step is a blood test to measure the amount and type of cholesterol in the blood. Urine should be examined for sugar and protein. If positive, or if other suggestive evidence is present, a glucose tolerance test and other assays may be performed to ascertain whether diabetes mellitus or some other predisposing condition is present.

Blood may be withdrawn after an overnight fast for what is often called a lipoprotein profile. This comprises total cholesterol, LDL-cholesterol, triglyceride and HDL-cholesterol. This is an important aspect, because measuring only the total cholesterol level can be misleading: even if the value of the total falls in the normal range, if that total is composed of all "bad" cholesterol, you are at great risk. Other less common assays may also be carried out. . Glucose determinations are important as well.

In women especially, reduced thyroid function, or hypothyroidism, is not uncommonly a cause of high cholesterol levels. Tests may also be done to determine menopausal status.
There are other rarer disorders which may occasionally require specific investigation.

Of course, if the patient comes in the first place with obvious symptoms and features of one of the clinical complications of atherosclerosis already described, the doctor will then need to determine the extent and severity of the underlying process in order to recommend appropriate treatment.

There is no simple correlation between the severity of clinical symptoms and the extent and severity of atherosclerosis. In such cases, other complications such as thrombosis or even vascular spasm or embolism may have contributed to the presentation.

The impact of the atherosclerosis on the function of the heart is indirectly but usefully assessed by electrocardiography, at rest or during and after exercise. In addition, more direct assessment is increasingly possible through a series of sophisticated and expensive imaging techniques.

These may involve craterisation and injection of a dye so as to visualise the coronary arteries or non-invasive techniques of various kinds which include ultrasound and X-rays amongst others.

 

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