Summary

• Atherosclerosis is a condition in which arteries become hardened and narrowed due to the deposition of cholesterol-rich plaques in the artery wall. This is associated with high blood cholesterol levels and other conditions such as hypertension and diabetes, and may be familial.
• The effects of the condition will be determined by the organ most affected, e.g. the heart, brain or limbs, giving rise to conditions such as heart attack, stroke or claudication.
• Diagnosis is simple and treatment may include lifestyle changes, medication and even surgery such as heart bypass grafting.
• Cure and total prevention is not realistically possible, but a prudent lifestyle and appropriate medication can significantly delay the onset of problems.
• Those with a family history of high cholesterol or any of the associated risk factors should regularly be screened from a young age by means of a full fasting lipogram.

What is atherosclerosis?

Atherosclerosis, also known as arteriosclerosis or "hardening of the arteries", is a disease process that causes narrowing of the arteries and thickening of the artery walls.

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

It is caused by build-up of deposits such as cholesterol, accompanied by fibrous tissue and calcification.

What causes atherosclerosis?

Arterial narrowing is caused by the formation of "plaques", or areas of abnormality and thickening in the wall of an artery. 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.

But if arteries are damaged – from high blood pressure or smoking or excess cholesterol and related fatty substances, for example – the inner lining of the wall can start to deteriorate. This sets in motion the series of events described below which create a fully-fledged atherosclerotic plaque.

Over time, various substances such as fats, cholesterol, platelets (particles that cause blood clotting) and cellular debris are deposited at these sites. Eventually, scar tissue and sometimes calcium crystals surround the fatty plaque, making the arteries hard and inelastic.

As a plaque grows, 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 excess fat also accumulate in the wall which is liable to rupture into the lumen of the artery.

Atherosclerosis itself also predisposes towards the formation of a blood clot or thrombus that is often the precipitating cause of the acute event. Portions of the plaque may break off to deposit emboli in arteries supplying the brain particularly, and elsewhere in the body.

Through any of these processes the affected tissue is then starved of blood and oxygen with the result that the cells may die or become severely damaged.

Development of a plaque also deforms the arterial wall, increasing turbulence and resistance to blood flow. As resistance to flow increases, blood pressure increases. Therefore, the heart has to work harder to pump blood, causing it to enlarge. This may lead to abnormalities of heart action and ultimately heart failure. High blood pressure also has deleterious effects on cerebral arteries and the small arteries to the eyes and kidneys, resulting in failure of these organs.

What are the 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 aspects of the sedentary western lifestyle including a high-fat, high-cholesterol diet. 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 encourage this process. These are called risk factors:

• Age. The risk of developing atherosclerosis increases after age 35, 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.
• 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.
• Diabetes mellitus.
• High level of blood cholesterol (hypercholesterolaemia): especially the cholesterol carried in LDL or 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).
• 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. Smoking:
• decreases the level of "good" HDL cholesterol and increases the level of "bad" LDL cholesterol.
• raises the blood carbon monoxide level, which may increase the risk of injury to the lining of arterial walls.
• constricts arteries already narrowed by atherosclerosis, further decreasing blood flow to the tissues.
• increases the blood's clotting tendency, thus increasing the risk of peripheral arterial disease, coronary artery disease, stroke and obstruction of an arterial graft after surgery.

What are the symptoms and signs?

Atherosclerosis usually produces no symptoms until arterial narrowing significantly reduces 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 a narrowed artery is generally pain at times when the blood flow can't keep up with the tissue’s demand for oxygen.

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. Typically, these symptoms develop gradually and episodically as the artery is slowly narrowed. However, when an obstruction occurs rapidly, the onset of symptoms is sudden and severe. This may be the presenting event without previous warning symptoms.

Symptoms may be quite characteristic or atypical.

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.

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

The risk of heart attack also increases, often due to the formation of a thrombus over the atherosclerotic area. In a heart attack, a portion of the heart muscle actually dies; 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 be felt in the arms and hands as tingling or numbness
• 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 narrowed by atherosclerosis, or a piece of atherosclerotic plaque in an artery supplying the brain can break off to form an embolus (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.

Warning signs may include:

• Chronic atherosclerosis of cerebral arteries does not present with pain, but may cause progressively diminished mental functioning and episodes of light-headedness, especially on rising suddenly.
• It may also present with very minor strokes, called transient ischaemic attacks, accompanied by temporary dizziness or confusion, incoordination, numbness and loss of speech. These features are relieved within 24 hours.

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

• Headache – often severe and sudden
• 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 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 narrow 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 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, this 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 "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 or bleed. Narrowing of renal arteries can reduce kidney function and cause high blood pressure.

How is atherosclerosis diagnosed?

Since atherosclerosis is a pathological or disease process rather than an illness in itself, a doctor needs to establish whether a patient is at increased risk or whether he/she 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 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 provide 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 examinations are done, the single most important next step is a blood test to measure the amount and type of cholesterol in the blood.

Blood may be withdrawn after an overnight fast for what is often called a lipoprotein profile. This must include total cholesterol, LDL-cholesterol, triglyceride and HDL-cholesterol and glucose determinations. 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.

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.

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 is also a host of 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 often 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 extent of functional atherosclerosis 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 catherisation 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.

How is it treated?

The treatment will depend on the problems experienced by the patient. If he/she has no symptoms, but is found to have a raised blood cholesterol, then steps will be taken to correct this.

If the cholesterol level is not too high, lifestyle changes (correct diet, sufficient exercise, smoking cessation) may be enough to manage the condition. However, this MUST be checked by follow-up blood tests. The patient must also be made aware that the improvement will only remain while the lifestyle changes remain, and that as soon as old habits are resumed, the cholesterol levels will return to what they were before.

If blood levels are too high, then medication of various sorts may be used. These work in different ways to help the body get rid of excess stored cholesterol, prevent the recycling of existing cholesterol (thereby gradually reducing the total cholesterol present in the body) and by reducing the amount of cholesterol manufactured. (For more details, please refer to our article on hypercholesterolaemia.)

If blockages to arteries have already caused damage to an organ (e.g. heart attack) or are in danger of doing so (e.g. angina), the diseased arteries may be bypassed surgically and a "detour" inserted to carry adequate blood to the organ. This is the principle used in heart bypass surgery. Blockages in the arteries to the brain (carotid arteries) may be also be opened (and stents inserted to keep them open) in order to prevent strokes.

What is the 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. 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.

Untreated, it can lead to the conditions listed under "Symptoms and Signs". In most cases, improvements in lifestyle (see "Treatment" and "Prevention") and appropriate medical treatment, can retard or even reverse the progress of the disease.

Can atherosclerosis be prevented?

For most people clinically important atherosclerosis can be prevented or markedly retarded by means of lifestyle changes alone. In some, cholesterol-lowering medication may be required; and in a few it may be impossible at the present time.

Lifestyle changes involve:

• an appropriate diet
• regular exercise
• the elimination of harmful substances

Diet and exercise work together in a synergistic fashion and can also help reduce stress which can contribute to clinical complications.

The principles are easy to understand but putting these into practice can be difficult in developed countries. It requires commitment and understanding plus a refusal to be misled by a host of popular fads which promote specific foods or substances as the secret of success. These are almost universally ineffective and are occasionally harmful.

Principles of a healthy diet

Obesity contributes to atherosclerosis directly and indirectly. Most South Africans are overweight. In such people, loss of weight is important in lowering blood pressure, reducing the risk of diabetes mellitus in predisposed individuals and in reducing triglyceride and raising "good" HDL-cholesterol levels. These changes are strongly protective against atherosclerosis and its complications.

Loss of weight is achieved by reducing energy intake, especially energy contained in fat, and by increasing energy expenditure through regular exercise. In addition to fat, over-indulgence in simple carbohydrates – e.g. sugar, sweets and many soft drinks – also contributes to obesity.

The worst way to approach weight loss is by means of crash diets. These result in large weight fluctuations, called cycling, and rarely have benefit.

Besides weight normalisation, it is desirable to cut down on saturated fat, cholesterol and trans fatty acid intake. This can be accomplished by reducing the consumption of:

• red meats, the skin of poultry and, especially, processed meats such as salamis and polony
• full-cream dairy products such as full-cream milk, cream, most cheeses and yoghurts, many pastries and desserts
• eggs or egg-based products in desserts, pastries and pies
• fried foods, especially those cooked in repeatedly used oils
• commercially produced cookies, crisps and crackers and baked products that contain hard "brick" margarine

Antioxidants and other food 'fads'

• These vary from mildly useful to neutral to positively harmful. The most authoritative opinion is that there is no solid evidence in favour of antioxidant vitamin supplementation and harmful effects may occur.
• Soluble fibre contained in fruits, wholewheat bread and certain oats has a variety of health promoting effects and a mildly cholesterol-lowering action.
• Garlic has a mildly beneficial effect on cholesterol levels.
• Fat-free substitutes in foods can assist with weight loss and lowering of cholesterol and triglycerides, but can have other side effects.

The bottomline is this: an appropriate mixed diet with a healthy balance of fruit and vegetables and a reduction in saturated fat, regular exercise, normalisation of weight or at least some weight reduction in obese persons and avoidance of smoking will contribute 90% to the lowering of atherosclerotic risk.

Additional measures can make a small contribution but some are actually harmful – especially if they divert attention from the known effective means of prevention.

Most people will need the advice of a qualified dietician, a clear strategy and goals, regular monitoring and some form of support – until good practice becomes habitual.

Many of the foods mentioned are also high in salt and most Westernised individuals eat salt far in excess of need, which may promote high blood pressure in susceptible people and have other adverse effects.

Exercise

The evidence is overwhelming that regular aerobic exercise at virtually any age reduces atherosclerosis and its complications. It has a variety of directly beneficial effects as well as being an important component of weight normalisation.

The baseline should be set at five hours of aerobic activity dispersed throughout the week, such as walking, cycling, jogging, aerobics, rowing or swimming. This can be varied to prevent boredom and to maximise effect, and can be adjusted in intensity and duration according to the health status, age and objectives of the individual. The addition of mild to moderate resistance training can help strengthen muscles and bone and promote weight loss.

Once again, the advice of a professional trainer is useful, especially in the early stages. The support of a family member, friend or group is very valuable.

Consult your doctor if you have any symptoms or concerns over your health status. It is vital to start slowly: in the long run it will do far more good than a crash start.

Avoidance of harmful substances

First and foremost among these is cigarette smoking. Risk of coronary artery disease is at least doubled in most smokers and often more than that. It interacts with other risk factors, elevating risk 10-fold or more. Besides heart disease, smoking promotes lung disorders such as emphysema and causes cancer.

The good news is that the risk of vascular disease drops rapidly after stopping smoking, reaching baseline within two years. Professional help and support is again important, especially since stopping smoking promotes weight gain. Thus exercise and diet are part of the anti-smoking programme.

Excessive alcohol consumption, e.g. over 10 tots per week, can induce atherosclerosis and hypertension in susceptible individuals. Moderate alcohol consumption may be beneficial and wine, particularly red wine, reduces risk of atherosclerosis and cardiovascular disease. Binge drinking is definitely risky and should be strongly avoided.

When to call your doctor

Because atherosclerosis is such an insidious condition, and starts at an early age, the best approach is one of prevention. A screening fasting lipogram will quickly identify any patient at risk.

The Clinical Guidelines recently published jointly by the South African Medical Association and the Lipid and Atherosclerosis Society of Southern Africa, recommends that all young adults be assessed at least once for the risk or presence of atherosclerotic vascular disease. This can be done as part of a normal medical visit.

This provides you with the essential information (e.g. blood pressure, total, LDL- and HDL-cholesterol levels, triglyceride concentration, body weight and height, fasting glucose value) to modify your lifestyle so as to promote health and reduce risk. Occasionally, the results may indicate the need for further investigation and more vigorous treatment, but generally a five year follow-up is recommended even for relatively low-risk individuals. In older people, above 60 years, more frequent examination is desirable.

In addition to such baseline examination, you should consult your doctor under the following circumstances:

• If you experience symptoms for the first time of a possible atherosclerosis-related medical condition. These include: chest pain, undue breathlessness, tingling or numbness in your arms, palpitations, visual, speech or coordination disturbances, any unexplained loss of consciousness or mental confusion, pain in your legs when walking, which improves on rest, undue fatigue or excessive thirst, or passing urine frequently.
• If you have an increase in any of the above symptoms.
• If you are at increased risk through family history, poor lifestyle habits, obesity or the presence of diabetes mellitus (or, more rarely, some other predisposing condition). If you develop discolouration or unusual skin sores in your legs or feet. This may indicate severe atherosclerosis and possibly a circulatory blockage that needs treatment to prevent gangrene.

It is possible to have atherosclerosis for many years without having symptoms and sometimes the clinical complications are worse than may be expected from the degree of atherosclerosis present. Despite these difficulties, a careful medical work-up provides the important information required for effective prevention and treatment.

Reviewed by Dr A.G. Hall (B.Soc.Sc.(SW), MB,Ch.B)
Last updated: 2008/01/11

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