Atherosclerosis – why do we get it?
Heart disease – prevention or cure?
Cardiovascular Magnetic Resonance in Research
Using ultrasound to detect atherosclerosis before it develops.
Virtually all cardiovascular deaths and debilitating strokes are due to one disease, atherosclerosis.
Atherosclerosis is responsible for more deaths in the UK than any other condition.
The disease affects the wall of the artery. Plaques (atheroma) form in the vessel walls, causing the inner layer to thicken and narrow, which cause the arteries to become stiff and narrowed or even blocked.
Atheromatous plaques are pools of lipids (fats like cholesterol) with a fibrous cap.
The disease often produces no symptoms until the damage to the arteries is severe enough to restrict blood flow. Restrictions can give warning signs that include angina, pains in the legs or episodes of dizziness.
The first stages of atherosclerosis can develop in children before they are five years old. By the time we were teenagers, virtually all of us had atheromatous plaques in our arteries. The danger usually comes later in life and depends on the state of the plaques in our arteries.
Plaques that have a large pool of lipids can rupture and leave a raw area on which blood may clot, blocking the blood vessel.
These days, everyone knows that smoking is one of the major risk factors for heart disease. But there are many other causes:
Half of all people who suffer a heart attack or stroke have no warning symptoms, nor do they have any significant risk factors. And other people with risk factors may live to a great age.
Atherosclerosis was virtually unknown in Europe before 1900, but steadily increased until the 1940s. After a short decline, it increased again until the mid 1980s.
It is more common in rich countries, but there are variations. Incidence is high in Scotland, Northern Ireland, England and Wales, Finland and the USA, but lower in France, Japan and some Mediterranean countries. Rates are rapidly increasing in Asia.
All of this suggests environmental factors are significant and, most importantly, that the development of atherosclerosis can be arrested by the use of lipid lowering drugs and lifestyle changes.
CORDA has always focused research on the prevention of heart and arterial disease rather than curing it or just treating the symptoms.
Prevention involves the elimination of a disease, either by removing its known cause or by making the population immune. It can also involve the detection of disease at an early stage, when it can be stopped or reversed by simple measures. For example atherosclerosis can be prevented from worsening after a heart attack through the use of lipid lowering drugs.
Treatment of a disease may involve a complete cure, such as the removal of an aortic aneurysm, but more often treatment is only the relief of symptoms.
There are several medical techniques used to treat atherosclerosis, but these generally only treat the symptoms and reduce the risk of further complications.
Surgery such as cardiac artery bypass grafts and angioplasty (blowing up a balloon in the blood vessel) do nothing to reduce the incidence of atherosclerosis. Drug treatment is very effective at treating symptoms and lowering risk factors.
However, all of these procedures only treat the symptoms. They are expensive and do not cure the patient.
Our ambition is to prevent atheroma from being formed. How can we do that?
By discovering how and why it develops. We are currently funding important research at Great Ormond Street Hospital, where very early signs of damage in the lining of arteries of children are being detected.
By identifying even small plaques in arteries using the most modern MR scanners and developing the technology needed to provide the quickest and most accurate methods of identifying problems.
By looking at normal people in the community without symptoms using our own special mobile scanner. In this way we have been able to track the development of atheroma and determine the risk of sudden heart attacks or strokes.
Cardiovascular Magnetic Resonance – how it works and what it does
Cardiovascular magnetic resonance (CMR) does not involve harmful x-rays, yet it provides the most comprehensive pictures of the body available without surgery, showing both the interior and exterior of blood vessels.
Magnetic Resonance Imaging (MRI) works because most of the human body is water. Each molecule of water is made up of two hydrogen atoms and one oxygen atom. The nucleus, or inner core, of each hydrogen atom consists of a single proton that constantly spins on its axis. This works like a small electromagnet and generates a tiny magnetic field.
Although each atom produces its own field, the atoms are usually randomly orientated so there is no overall effect. However, placing a person in a CMR scanner (basically a powerful magnet) makes all the protons in the body line up, either with or against the direction of the scanner’s magnetic field.
To make an image, short pulses of radio waves are directed at the area being examined through a special antenna (the coil). This knocks the spinning protons off balance and they flip orientation. When the pulse is turned off the protons relax back to their original directions. As they do so, they emit very weak radio signals. The strength of the signal from any particular body tissue depends mainly on water content. The signals are picked up by a receiver and analysed by a computer to produce a series of cross-sectional images of the body.
The fact that CMR can be repeated regularly without any harm to the patient means it is the ideal way to check the progress of disease and allow accurate evaluation of treatment.
CMR is not only useful for the detection of atherosclerosis. Scientists and doctors at Royal Brompton CMR Unit have been involved in many great advances in the field of CMR.
The problems are caused by the repeated treatments. The body has only a limited capacity to recycle excess iron and each transfusion adds extra iron, overloading the process, leading to an accumulation of iron in the heart and other organs. There are treatments that promote the elimination of iron, but these are difficult, painful and potentially dangerous for the patient. Without CMR it is impossible to determine the level of iron in a patient’s heart. This meant that some patients underwent unnecessary treatment whilst others went without it.
CMR allows cardiac iron levels to be assessed accurately, enabling efficient and effective use of treatment.
CORDA has funded the salaries of two members of Professor John Deanfield’s research team in the Vascular Physiology Unit at Great Ormond Street Hospital since 1992. The team investigate the very earliest signs of atherosclerosis.
Every artery is lined with endothelium. This layer is only one cell thick, but is extremely important in helping the blood to move around the body. In a healthy person, the walls of the blood vessels constantly produce nitric oxide and this regulates the vessel walls, for example by expanding them for increased blood flow during exercise. The nitric oxide also prevents platelets, blood cells and fatty deposits from sticking to the artery, blocking blood flow and stiffening the artery walls. However, if any of the endothelial cells are damaged these benefits are lost and atherosclerosis develops.
Although it has been known for many years that damage to the artery walls often occurs in the first decade of life, it was not possible to identify and measure this before John Deanfield’s team developed a non-invasive technique, flow mediated dilation (FMD), which is now used all over the world. FMD enables them to identify arterial damage in children as young as seven. In addition, the team have used FMD to show that endothelial damage in young children has the same risk factors as atherosclerosis: high cholesterol levels, smoking (or living with smokers), diabetes or high blood pressure. In addition, several unexpected novel influences such as pre-natal factors have been shown to affect arterial function in later life.
The simplicity of FMD enables the team to evaluate the effectiveness of treatments. They have shown that both oral L-arginine and lifestyle changes can help in the repair of arterial endothelium. They are investigating whether they can actually alter and manipulate the function of the artery to protect against the consequences of arterial disease.
An FMD scan involves the subject having a series of ultrasound scans of the brachial artery. First, a segment of artery that provides a clear image is identified and selected. A baseline resting image is obtained and blood flow is estimated using the pulsed Doppler velocity. A blood pressure cuff is then inflated to cut off as much of the blood flow as possible. When the cuff is released there is a brief rush of blood through the brachial artery, causing it to dilate.
The image of the artery is recorded continuously from three seconds before to two minutes after the cuff deflation and the blood flow velocity is measured upon cuff release and 15 seconds. The patterns of blood flow and measurement of the change in the artery allow any changes in the endothelium to be identified and measured.
The early detection of changes in the artery before any major damage has developed has important research benefits and the convenience of FMD helps assess the effectiveness of treatments in children in a clinical setting.
