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Cholesterol

Updated 20 July 2018

Atherosclerosis

Atherosclerosis is a disease process in which cholesterol and other fat collect in the arterial wall.

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Atherosclerosis is a disease process in which cholesterol and other fat collect in the arterial wall along with cells and some scar tissue (plaques). In arteriosclerosis, the arteries become hardened and stiff.

While it’s 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 don’t impair flow significantly to complete obstruction.

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

1. What causes atherosclerosis?

Arterial walls develop atherosclerotic plaques over several 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, or where several less powerful risk factors occur concurrently, the lesions may progress.

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

Over time, various substances such as cholesterol, some other lipids (fats) and cells accumulate along with platelets (particles that are involved in 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 as a result of 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 liable to rupture and clot formation. Portions of the plaque may break off to deposit distantly (emboli) in arteries supplying the brain from the chest or neck, or elsewhere in the body. The tissue that’s been starved of blood and oxygen becomes severely damaged, and the cells may die.

Smoking promotes injury to the endothelium (the cells lining the inside of an artery), and diabetes also damages the artery. High blood pressure increases stress on the artery and makes it harder for the heart to pump blood, causing it to enlarge. This ultimately leads to heart failure.

2. What is the course and prognosis of atherosclerosis?

Since atherosclerosis usually progresses slowly over many years, it’s 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 50s or 60s. 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’s an important cause of illness and early death. In most cases, improvements in lifestyle 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 it can be divided into those that are reversible and those that aren’t:

  • The potentially reversible changes generally occur in the first three decades of life. These don’t 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, mainly as a result of some accumulation of lipids inside the cells that 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”. Once formed, plaque never regresses completely (only partially).

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. This, however, further stiffens the artery.

3. What are the risk factors for atherosclerosis?

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

There’s also an emerging epidemic of heart attacks in Africa and other developing countries as more people adopt a western lifestyle, characterised by a high-fat, high-cholesterol diet and too little exercise. 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, and include:

  • 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’s a high incidence of familial hypercholesterolaemia in several communities.
  • Obesity. Obese people are more likely to have atherosclerosis because they’re 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 condition is a risk factor for damage to the large and medium vessels. It can also harm small vessels in the kidneys and eyes.
  • High levels of blood cholesterol (hypercholesterolaemia). The cholesterol carried in LDL (low-density lipoproteins) from the liver to the tissues are particularly significant.
  • Low levels of high-density lipoprotein (HDL), which transports 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 (a fatty substance similar to cholesterol), obesity and diabetes.
  • Hypertension (high blood pressure).
  • 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.

4. Symptoms and signs of atherosclerosis

Atherosclerosis usually produces no symptoms for a long time, but may suddenly or slowly reduce 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 embolus. The symptoms and outcome (prognosis) will vary accordingly.

The first symptom of inadequate blood supply is generally pain, which may only occur during exercise. Pain in the heart or legs is a sign that the blood flow can't keep up with the tissue’s demand for oxygen.

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. Alternatively, it could progress. This may be the presenting event without previous warning symptoms. Symptoms may vary from quite characteristic to atypical, depending on several incidental factors.

It’s important to note that people with diabetes often don’t 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. Women, also, generally don’t experience the same “classical” symptoms and signs listed below.

The more characteristic clinical presentations are described below. These depend on the organ that’s 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 it may be of sudden onset.

The common ways in which the heart is affected are through:

  • Stable or exercise-induced angina (chest pain)
  • Unstable or crescendo angina
  • Heart attack (acute myocardial infarction)

Coronary artery disease (or coronary heart disease) occurs when atherosclerosis results in narrowing of the coronary arteries (the 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. If this occurs very suddenly and rapidly, it’s called an acute myocardial infarction.

Symptoms may include:

  • A pressing, centrally located chest pain (angina). This may also be felt in the arms and hands as tingling or numbness, or it 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
A thrombus may form in an artery to the brain that’s been affected by atherosclerosis, or a piece of atherosclerotic plaque in an artery supplying the brain can break off to form an embolus (a dislodged piece that travels and 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 in this region.

Atherosclerosis of cerebral arteries doesn’t 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, loss of speech and loss of vision. These features are relieved within 24 hours.

An acute, more severe obstruction or bleed may present with:

  • Headache (often severe). This is more suggestive of a bleed.
  • Unconsciousness and collapse.
  • Weakness or paralysis on one side of the body.
  • Sudden, severe numbness in any part of the body.
  • Speech and visual disturbances.
  • Severe problems with muscle coordination.

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
Atherosclerosis can impair the flow of blood in the major arteries to the legs (peripheral arterial disease). 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
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 15-30 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.

5. How is atherosclerosis diagnosed?

Atherosclerosis may not present with any obvious signs or symptoms. Your doctor needs to establish whether you’re at increased risk for the disease process to intercept it, or whether you’ve already developed the clinical complications associated with it.

As part of a general medical examination, your doctor will ask you about the following lifestyle factors:

  • Your dietary habits
  • Your levels of physical activity
  • Your smoking habits
  • The amount and kind of alcohol you consume
  • Less frequently, your levels of emotional stress

It’s also important to determine whether you suffer from the important predisposing condition of diabetes mellitus and if you’ve 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; tests may be done to determine your menopausal status. Your doctor will also ask you about your blood pressure and all the medication you’re currently taking.

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

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

Once these examinations are done, an important next step is a blood test to measure the amount and type of cholesterol in your blood. Your 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 or some other predisposing condition is present.

Your blood may be drawn after an overnight fast for what is often called a lipoprotein profile. This comprises total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. This is an important aspect of the examination, 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 the "bad" cholesterol, you’re at great risk.

In women, especially, reduced thyroid function (hypothyroidism) is sometimes a cause of high cholesterol levels. This may be checked. And there are other rarer disorders that may require specific investigation.

If you present with any obvious symptoms or features of one of the clinical complications of atherosclerosis, your doctor will need to determine the extent and severity of the underlying process in order to recommend appropriate treatment.

There’s no simple correlation between the severity of clinical symptoms and the extent and severity of atherosclerosis. Other complications such as thrombosis, or even vascular spasm or embolism, may contribute to the presentation.

The impact of the atherosclerosis on the function of your heart can be 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 imaging techniques. These may involve craterisation and injection of a dye so as to visualise the coronary arteries, or non-invasive techniques such as ultrasound and X-rays.

6. How is atherosclerosis treated?

Atherosclerosis is a condition in which arteries accumulate lipid (chiefly cholesterol in the form of an oil or crystals) and attract cells as an “inflammatory” response. This may lead to scarring and calcification (hardening). These changes are regional and form recognisable plaques. Such plaques may be stable for long times, but upon rupture initiate clot formation that can obstruct blood flow.

The best approach is to prevent or retard the atherosclerotic process during the silent phase, thus avoiding the urgent treatment (or even death) that may arise from complications. The preventive treatment is best initiated when risk factors for atherosclerosis have been identified, and before any significant damage has occurred. While all risk factors should be addressed, the focus should be on managing raised blood cholesterol levels.

If your cholesterol level isn’t too high, lifestyle changes (e.g. correct diet, sufficient exercise and smoking cessation) may be enough to retard or arrest the process and reduce your risk for a cardiovascular event. After implementing these measures for a couple of months, a follow-up evaluation of all your risk factors and cholesterol levels must be done. Note that the improvements will only remain while the lifestyle changes remain – as soon as your old habits are resumed, your cholesterol levels will return to what they were before.

If your blood cholesterol levels are too high, your doctor will prescribe medication. The different medications work in different ways to lower blood cholesterol. Cholesterol absorption in the body can be impaired by dietary fibre, binding of bile salts, and by blocking the uptake of cholesterol in the bowel (plant sterols and ezetimibe).

The contribution that the synthesis of cholesterol in the liver makes can be lowered by statins. This leads to a greater importation of cholesterol from the blood, and so the blood cholesterol level decreases. Lowering blood cholesterol levels after a complication (e.g. a non-fatal heart attack) is also important to prevent future events.

You may not notice the rupture of a plaque when a small clot forms and the blood flow to the organ remains normal. If incomplete blockage of arteries results in problematic angina pectoris (chest pain due to an inadequate supply of oxygen to the heart muscle) or places the heart at risk of severe damage (e.g. a narrowing near the origin of the large left main stem artery), the diseased arteries may be bypassed surgically. A "detour" can be created to carry adequate blood past the narrowing of the arteries. This area may be opened with a balloon on a catheter (angioplasty) and the placing of a stent.

Blockages in the arteries to the brain (carotid arteries) may be also be opened by bypass surgery or a stent in order to prevent strokes.

How is angina treated?

This decision is best made by a cardiologist and will be based on clinical and investigational findings.

If your symptoms are relatively mild, they may improve with lifestyle changes that can have a significant impact in the long term. The drugs for angina pectoris are designed to either reduce your heart’s demand for oxygen, or to allow your blood vessels to relax and widen so that more blood can be supplied.

If you smoke, you must stop immediately. You should also look carefully at your diet – preferably with the help of a dietician – and cut down on fats, lose weight and do supervised exercise.

But some people aren’t helped by these relatively simple measures. The next step is to perform an investigation that outlines the coronary arteries (angiography). The catheter through which the dye is injected is inserted into the groin and then advances to the heart.

This procedure assesses whether there are critical narrowing of the arteries that require repair (angioplasty, possibly to place a stent) or surgery to bypass a diseased region. This can be done with one of the less important arteries in the chest, forearm or a vein from the leg.

For many people angioplasty offers a safe and relatively easy way to deal with blocked arteries. The procedure is called percutaneous transluminal coronary angioplasty (PTCA).

During the procedure, a hollow tube called a catheter is inserted into an artery in the groin (the area will be numbed first with local anaesthetic). A thinner catheter is then inserted through the first catheter. This has a miniature, deflated balloon at its tip. The cardiologist is able to watch the position of the catheter using X-ray images on a television screen, and the catheter is guided through your arteries until it arrives at the blocked artery. It’s then carefully threaded through the blockage. Once in position, the balloon is inflated. This widens the artery and improves the flow of blood through the area. The balloon is then deflated and removed.

The procedure can take between 30 minutes to two hours, depending on what is done, and often only requires one day in hospital. Coronary angioplasty is done under local anaesthesia and is generally no more than mildly uncomfortable.

Stents after angioplasty
In around 80% of patients, a stent is also inserted after PTCA. This is a mechanical device that is used to keep a hollow tube open. A coronary stent looks like a coiled spring, and is inserted into the artery using a catheter. The insertion of a stent improves the outcome of the whole procedure, ensuring that the formerly blocked artery remains open. Before stents were developed, the blocked arteries would often narrow again – called restenosis.

A stent is intended to remain in place permanently to keep the artery open. It’s inserted under high pressure and, over time, becomes incorporated into the wall of the artery. This means that there’s no danger of it moving later.

Bare metal stents may, however, also become obstructed with clot or growing cells. This is why drugs such as clopidogrel are prescribed for a long period of time after placing of a stent, or a drug-eluting stent is used to suppress the process.

But there are risks involved in the use of drug-eluting stents: the potent anticlotting medication may lead to uncontrolled bleeding, particularly if you’re involved in a road accident or suffer severe physical trauma.

Take special care to get to an emergency unit as soon as possible if there’s any serious injury, bruising and/or bleeding.

What about bypass surgery?
It used to be the case that the only option available to treat blocked coronary arteries was coronary artery bypass surgery. However, newer techniques (angioplasty and stents) have replaced the coronary artery bypass graft (CABG) in around half of people with blocked coronary arteries.

A bypass is a major operation. An artery from your chest wall or a vein from your leg is attached (grafted) to the aorta to conduct blood past the blocked part of your coronary artery. This allows your heart muscle to receive enough blood flow to provide oxygen and nutrients.

The cost is generally higher than angioplasty, and the procedure requires a fairly long stay in hospital. However, for some people with blockage of many of the arteries of the heart, it remains the only option.

What are the advantages of angioplasty?
For many people, coronary angioplasty is as effective as bypass surgery in reducing chest pain and improving their ability to live a normal life.

However, it hasn’t yet been proven that angioplasty and bypass surgery actually prolong life expectancy, except in certain very specific circumstances. In spite of this, the technique is so much more effective than drugs in relieving symptoms that it’s preferred in many instances.

Angioplasty offers around a 98% immediate success rate. Recovery from the procedure is quick, relatively pain free and much less expensive than bypass surgery.

What are the disadvantages of angioplasty?
In around 10-15% of people, the artery opened with PTCA re-narrows within six months. It’s more likely to narrow again if the blockage was very long or in a very small artery. The good news is that angioplasty can be repeated. However, in some patients bypass surgery will be recommended.

The chances of suffering a heart attack or needing an emergency bypass during coronary angioplasty are less than 2%, and the risk of dying during the procedure is less than 1%.

New research shows that the initial higher success rate of angioplasty evaporates after about two years. After this time period, the survival rates are no better than with bypass surgery.

Is angioplasty for you?
When you have chest pain or experience other symptoms that aren’t being sufficiently relieved with medication, you should see a cardiologist. He or she will then assess the different treatment options open to you.

Around half of people who have blocked coronary arteries are offered angioplasty. The rest are better treated with bypass surgery. People with diabetes often do better with coronary artery bypass grafting, and there are instances in which technical difficulties make bypass surgery the better option.

Even relatively mild angina, which is controlled by medication, can be relieved by angioplasty. It’s a question of weighing up the risks, benefits and costs of this procedure.

Remember that lifestyle changes must be made even after angioplasty or bypass surgery. In particular, you must never smoke again.

Reviewed by Prof David Marais, FCP(SA), Head of Lipidology at Groote Schuur Hospital and the University of Cape Town. February 2018.

 

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