Atherosclerosis
Epidemiology
- Cardiovascular disorders are the leading cause of death in western society
- In England and Wales, they account for 40% of all deaths:
- Ischaemic heart disease is 27%
- Cerebral vascular disorders 13%
- Atherosclerosis is by far the most important cause
- In the developed world the incidence has increased massively
- In the US and some European countries, incidence has actually peaked and in declining
- In the rest of Europe, and in the middle and far east, incidence is rising rapidly
Pathology
Atherosclerosis can have 3 main types of manifestation:
These situations often co-exist, and the pathology is very similar. For example, patients presenting with
stroke or claudication will very likely have coronary artery disease – and this co-existing disease is an important cause of mortality.
Normal artery structure:
There are 3 layers of arterial tissue:
- Tunica Intima – this is the innermost layer, and has a single layer of endothelium, with a sparse supportive tissue. This layer is very very thin!
- Tunica Media – this is separated from the intima by the internal elastic lamina. The media is made up of smooth muscle and elastic tissue. In the heart, the elastic tissue is most predominant, but in most arteries, this layer is mostly made up of smooth muscle.
- Tunica Adventitia – this is a fibrous connective tissue. The external elastic lamina separates this from the media. Very small blood vessels can be found in this layer called vasa vasorum and these filter down to supply the media.
- The intima and innermost media receive their nutrients from the arterial lumen via diffusion.
Normal age-related changes
These will usually be inconsequential by age 40, and very common by age 70. They are often termed arteriosclerosis. the changes affect all blood vessels, right down to the arterioles. They include:
- Progressive fibrous thickening of the intima
- Fibrosis and scarring of the muscular and elastic media
- Accumulation of mucopolyysaccharide ground substance
- Fragmentation of the elastic laminae
Ultimately these changes reduce the strength and elasticity of the vascular wall. Clinically, this will mean there is dilation of the aorta and coronary arteries – and this finding is common.
- In the aorta this can lead to stretching of the aortic ring – resulting in valve incompetence
- Dilation of the aortic arch and thoracic aorta can also lead to ‘unfolding’ of the aorta – which can be seen in chest x-rays as a loss of the aortic notch, and a widened appearance of the central vascular column in the x-ray.
To compensate for these changes, there is often smooth muscle hypertrophy and production of extra layers of collagen in the internal elastic laminae.
Atherosclerosis
This is a disease of the medium and large sized arteries only. It is very uncommon in arteries of less than 2mm diameter. It is caused by 3 types of lesion:
- Fatty streaks
- Fibrolipid plaques
- Complicated lesions
The major risk factors are:
- Age
- Male gender – pre-menopausal women in particular seem to be a very low risk – being pre-menopausal is a preventative factor. After the menopause, gender differences disappear rapidly. HRT also has no role in reducing the risk – infact oestrogen therapy appears to increase the risk.
- Hypertension – anti-hypertensive therapy reduces coronary mortality, stroke and heart failure.
- Smoking – this link is also dose related
- Diabetes
- High levels of LDL
- Low levels of HDL
- Obesity
- Sedentary lifestyle
- Increased levels of blood coagulation factor VII
- Low birth weight – this is thought to be particularly important. Those with a low birth / infant weight are at higher risk of adult obesity. Those with a low birth weight and a subsequent level of obesity in adulthood are 2-3x more likely to die from heart disease than those with a high infant weight. A low infant weight is often (in the past at least) associated with low socio-economic status.
- Low socio-economic status
- Genetic factors – often things like hypertension, hyperlipiedaemia and diabetes run in families, and are multi-genetic. HOWEVER – it is also important to remember than families often share the same environment – and environmental factors may be involved in the apparent family history link.
- Clinically – we say a significant family history is present when first degree relatives have had acute events at <50 years for men and <55 years for women.
However – it is important to note that there are wide variations in the severity of the disease, even within similar populations. These variations are possibly due to genetic factors. For example;
- There is an inherited genetic abnormality whereby an individual has a lack of LDL receptors – familial hyperlipidaemia? - about 1 in 500 caucasians are heterozygous for this abnormality to cope with their reduced number of receptors, they
