This article provides an overview of atherosclerosis Ischaemic Heart Disease. For more information on Acute Coronary Syndromes, see the Acute Coronary Syndromes article, and for info on Stable Angina, see the Stable Angina Article
- 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
- Coronary heart disease – angina, MI, sudden death
- Cerebrovascular disease – stroke, TIA
- Peripheral vascular disease – claudication, critical limb disorder
- 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.
- 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
- 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.
- Fatty streaks
- Fibrolipid plaques
- Complicated lesions
- 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
- High levels of LDL
- Low levels of HDL
- 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.
- 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 produce increased amount of LDL’s. These people develop coronary heart disease in their 40’s or 50’s.
- Some patients may even be homozygous for this gene – in this case these patients will often die from coronary heart disease in their infancy or teens.
- Lipid deposition
- Chronic inflammation
- These will occur at areas of turbulent flow, such as bifurcations, and they are associated with abnormal endothelial function.
- They themselves are of no clinical significance, and occur in all populations
- They are basically a yellow linear elevation of the intimal lining.
- Endothelial cells will begin to show unusual adhesion molecules (e.g. ICAM-1 and E-selectin). These may be similar to those seen in acute inflammation.
- This attracts monocytes (macrophages) to the site – and these can be seen both entering and leaving the endothelium.
- At the same time, high levels of LDL in the blood will begin to accumulate in the arterial wall. It may be that these lipid deposition sets off an inflammatory reaction, and the macrophages are attracted like they would be to any type of inflammation.
- The macrophages entering the arterial wall will come into contact with these lipid cores, and will take up the oxidized LDL, becoming foam cells. The macrophages will also be activated by the inflammatory products released by the arterial wall.
- The foam cells can die, and they release their products, causing the formation of a pool of lipid. This pool is called a lipid core.
- The activated macrophages will release lots of their own products. These include cytokines and growth factors, particularly PDGF. These growth factors lead to proliferation of the smooth muscle layer. It will proliferate towards the lipid pool, and in an attempt to repair and stabilise the lesion, it may form a layer around the pool. The smooth muscle cells change their phenotype from contractile, to repair – they now permanently become repair type cells.
- If this process of repair is successful, the plaque will be a stable atherosclerotic plaque and will remain asymptomatic, unless it grows big enough to occlude an artery.
- Many more products are released by the macrophages, including, IL-1, TNF-α, interferon gamma, PDGF and matrix metalloproteinases.
- These can cause the smooth muscle cells overlying the plaque to thin, and thus the protective ‘fibrous cap’ covering the plaque can become weak.
- The macrophages themselves can also digest collagen struts that are holding the cap in place.
- These changes in themselves don’t completely destroy the cap, but make it more vulnerable to external shearing forces
- When the contents of the plaque become exposed to the lumen, this can trigger thrombus formation. This may cause complete occlusion at the site of the plaque, but the thrombus may also break off, and cause a blockage somewhere else.
- More plaques
- A greater number of macrophages and t-lymphocytes within the plaques
- Release of more cytokines and growth factors (including IL-1 and IL-6 that are chemotactic for macrophages
- Elevated levels of antibodies to pathogens, such as Chlamydia pneumoniae. Some people aregue that such organisms (also including cytomegalo virus, herpes and helicobacter) have a causatory role (to initially start the inflammation) although the evidence for this is limited.
- In coronary artery disease – elevated levels of inflammatory markers; such as CRP – this is an indicator of future acute events.
- In transplanted hearts – patients with transplanted hearts may have a particularly quickly progressing form of the disease in the transplanted heart. The pathology of this disease is also slightly different from that of normal atheroma. This further supports the theory that the disease is a result of an immune problem. To minimize the risk all heart transplant patients are given lipid lowering drugs.
- It is thought that lipid lowering therapy helps to stabilise vulnerable plaques.
Thrombus formation on plaques
- Chylomicrons – these consist of 95% triglyceride. These carry absorbed lipids from the gut to the liver.
- VLDL’s – very low density lipoproteins – these carry triglycerides manufactured by the liver, as well as small amounts of phospholipid and cholesterol. The primary function of these is to transport triglycerides to peripheral tissues. These are the largest of the ‘-DLs’.
- LDL’s – low density lipoproteins – these contain very few triglycerides, a few more lipoproteins, and lots and lots of cholesterol! These are the ‘bad cholesterol’. Their primary role is to deliver cholesterol to peripheral tissue.
- HDL’s – high density lipoproteins – these are the smallest of the ‘-DLs’. They have roughly equal amounts of lipid and protein. The lipids are mainly phospholipid and cholesterol. These will transport excess cholesterol back from peripheral tissue to the liver to excretion in the bile! They are ‘good cholesterol’.
Prevention of atherosclerosis
- Cessation of smoking
- Control of BP
- Weight reduction
- Regular exercise
- Dietary modifications
- Diets that are low in saturated fat are particularly associated with a reduced risk of disease
- Fatty acids found in fish also have cardio-protective effects – thus it is recommended you eat at least 2 portions of oily fish per week.
- ACE inhibitor
- C – Clopidogrel – anti-platelet agent
- O – Omacar – Omega 3
- B – Bisoprolol – β-blocker
- R – Ramipril – ACE-i
- A – Aspirin
- A – Atorvastatin – very potent statin!