1. Normal artery (at birth)

This is a simplified view of a normal artery wall with no vascular disease present. The inner layer (or intima) is where vascular disease occurs. In Western society, vascular disease gradually increases from early in life. Even at the age of 10, many children would have signs of the early stages of vascular disease.

2. Early vascular disease (called a ‘fatty streak’)

A small deposit of cholesterol containing cells (‘foam cells’) and cholesterol itself has formed in the inner (‘intima’) section of the artery. These lesions often start because the inner part of the artery wall at this location was injured in some way. There are numerous possible causes for this injury, including forces associated with high blood pressure, chemical injury from compounds originating outside the body, such as chemicals from cigarette smoke, raised blood levels of normal body compounds (such as homocysteine), and perhaps even infection. Turbulent blood flow around areas where blood vessels branch is a factor that causes lesions to commonly occur in these regions.

What causes excess cholesterol to accumulate in an artery wall?

Cholesterol is necessary for cells to live and its entry into cells is usually tightly controlled. Injury to the cells lining the inner artery wall makes them more prone to interact with and take up LDL cholesterol (bad cholesterol) in the blood. Other factors that increase LDL cholesterol uptake into the developing lesion include:

• A higher than normal blood LDL level. This can be caused by a high intake of cholesterol in the diet or, more importantly, by a high intake of saturated fats in the diet. (See appendix 1 at the end of this section for more details.)
• Oxidation of LDL cholesterol or of the outer membrane of the cells lining the blood vessel. LDL cholesterol that has been oxidized is more likely to be taken up into these lesions and increase lesion size. Thus, chemicals that cause oxidation of LDL cholesterol act to make lesions worse. (Cigarette smoke is one source of such chemicals.) On the other hand, anti-oxidants act to reverse the oxidation of LDL cholesterol and thus act to reduce cholesterol deposition into 'evolving' artery lesions, thus slowing lesion formation.)

The ‘cholesterol deposit’ lesion shown above has caused a slight thickening of the intima layer of the artery and consequently reduced the size of the lumen. (This has resulted in a slight reduction in blood flow through the artery.)

3. Further progression of vascular disease

(Occurs from the third decade of life onwards)

Further enlargement of the lesion has occurred and distinct cholesterol deposits have developed. As well as containing cholesterol, the lesion has started to accumulate some fibrous connective tissue and calcium, a process that hardens the lesion.

The rate of this enlargement process depends on the number of risk factors for vascular disease the person processes and their severity. Important risk factors include:

• A high level of LDL cholesterol (bad cholesterol) in the blood. (A high total blood cholesterol is also a risk factor as it usually indicates a high LDL cholesterol level.)
• High blood pressure
• Diabetes
• Smoking
• Severe kidney disease
• Abdominal obesity
• Physical inactivity
• Increasing age (unfortunately!!)

Vascular lesions usually take about 10 to 20 years to reach this stage and such lesions are relatively common in adults in their fifties and sixties. They occur even earlier in people with a high overall risk of vascular disease.

Early lesions often expand outwatrds and thus don't cause much blockage:

In the early to middle stages of lesion formation, thinkening of the artery wall often results in the artery wall expanding outwards rather than inwards. (Not shown in the above diagram.) This means that, although a lesion is present, it tends to cause less blockage. Angiograms done to determine the extent of lesions often therefore underestimate the severity of the underlying lesion because what they see is the blockage. Lesions that go on to cause heart attacks are thus not always the ones causing significant blockages.

4. Established lesion with a thick capsule – A stable lesion

(Generally occurs after the age of fifty and is most common in people aged over seventy years.)

If the inner wall cap is thick, the lesion usually just continues to gradually increase in size, resulting in a corresponding decrease in the size of the vessel lumen. These are called stable lesions.

The body can compensate, to a degree, for the gradual decrease in the lumen size of a vessel by making new smaller vessels to bypass the increasingly blocked vessel (artery). However, the blockage will eventually become large enough to cause problems due to inadequate supply of blood (and thus inadequate supply of oxygen) to the tissue the artery supplies. Initially this causes symptoms only when the person is exercising, as muscle tissue requires more oxygen during exercise. However, the blockage may eventually become large enough to cause symptoms even when the person is resting. (An example of this process is chest / heart pain (angina), which occurs when heart muscle tissue does not receive enough oxygen. Angina pain is more likely to occur during exercise.)

These types of lesions are more common in people with more favourable vascular disease risk factors and these people are also more likely to develop such lesions later in life.

5. Established lesion with a thin capsule – An unstable lesion

(Generally occurs after the age of fifty and is most common in people aged over seventy years.)

If the vascular lesion is covered by a thin and thus weaker fibrous cap, it is more likely to tear or rupture. These are called unstable lesions. Thin fibrous caps form over lesions for several reasons, including increasing pressure on the fibrous cap from a relatively rapidly enlarging underlying cholesterol deposit and further injury (and inflammation) to the inner lining of the vessel or the cap itself.  Lesions with thin caps are more likely to occur in people with multiple, more severe risk factors.

These lesions are far more likely to rupture. (See Diagram 6.)

Aggressively reducing risk factors can reduce the size of the cholesterol deposits in these unstable lesions, thus reducing both the pressure exerted on the thin cap and the irritation that the cholesterol deposit exerts on the cap tissue. This can reduce the likelihood of 'cap rupture'. It’s a bit like letting some air out of an overfilled balloon that is likely to rupture.

 6. Lesion breakdown

a. Lesion rupture (sudden, larger and more dramatic) - 50% of cases

(Generally occurs after the age of fifty and is most common in people aged over seventy years.)

When this weakening process is severe enough, the thin cap of the unstable lesion will tear or rupture. This brings the underlying cholesterol deposit into direct contact with blood in the artery lumen. The natural response of the body is to repair this break and the body starts this process by quickly (in few minutes) establishing a blood clot over the rupture site. This clot formation is important a it often significantly increases the blockage the lesion causes.

The consequence of this rupture and clot formation depends on the degree of blockage it causes. A large blockage will cause a dramatic reduction in blood flow through the artery and an equally large reduction in the oxygen it delivers to the tissues it supplies and this usually results in the death of this tissue. This is how almost all heart attacks and many strokes occur. If the rupture is not this large, it may just cause symptoms to occur with exercise and no permanent damage. Smaller ruptures may even give no symptoms but all such ruptures act to further weaken the inner vessel wall and make future larger ruptures much more likely.

About half of all heart attacks (and the majority of severe heart attacks and deaths due to heart attacks) occur from ruptures to unstable lesions that, prior to rupturing, caused much less severe blockage; usually a blockage of less than 40% of the artery lumen. These smaller blockages are usually not able to be detected by stress tests or ECGs and give no warning symptoms before the heart attack occurs. Thus, many, many heart attacks occur 'out of the blue', with no prior warning. Prevention is the only hope!!

b. Lesion errosion (less dramatic) - also about 50% of cases

When the build up of fat in the vascular lesion causes less pressure, the breakdown process can be more gradual and less dramatic. In this case, the tissue lying between the lesion and the lumen can just errode and the area of breakdown occurs more gradually and issmaller. The clot that forms over this area is therefore also smaller and thus causes less blockage. Thus, these lesions cause smaller less significant heart attacks or just angina pain with exercise.

As stated previously, there are no tests available that can reliably tell whether an existing lesion is going to breadown and whether this breakdown will occur as a rupture or an errosion.

Removal of clots

When a heart attacks occurs, quickly removing the clot that forms over a vessel rupture (by drugs or surgery) can avoid or significantly reduce permanent damage to heart muscle. This is one reason why anyone with symptoms suggestive of a heart attack needs to go to hospital as quickly as possible (by ambulance). Every minute counts!

Aspirin: A single aspirin tablet can help this ‘clot-removing’ process and should be taken as soon as a heart attack is suspected unless the person is allergic / has serious side effects to aspirin.) Heart attack symptoms are described in the section 'Heart attacks and strokes - General information'.

Similarly, people with a suspected stroke need to be assessed in hospital quickly to minimise brain damage.