Watch: Research into abdominal aortic aneurysm
Abdominal aortic aneurysm is relatively common in older men and can be life-threatening. Four genes have recently been found to be involved in the condition, and a new study could shed light on how it develops, as Sarah Brealey explains.
aortic aneurysm (AAA) is a bulging of one of the main blood vessels in your body, located at the back of your abdomen (tummy). If it bursts, it causes massive internal bleeding which can be fatal. It mostly affects older men, so in the UK men are routinely invited for screening at the age of 65 to detect the condition.
At the moment, there is no treatment except for surgery.
Now BHF-funded researchers have recently discovered four new genes which are linked to the condition. They’re starting a new piece of research to find out more about what role these genes play in the speed at which aneurysms grow, and which common medications, if any, might be able to slow down the growth of the aneurysm, and if other factors are involved.
An international team led by Matt Bown, a vascular surgeon from the University of Leicester BHF Cardiovascular Research Centre/National Institute of Health Research Leicester Cardiovascular Biomedical Research Unit, and funded by the Wellcome Trust, looked at more than 10,000 patients with AAA. They have identified four genes that are linked to the development of AAA specifically, rather than cardiovascular disease in general.
Professor Bown says: “Since AAA often runs in families, we compared the genes of people with AAA to those without and discovered four genes that are associated with AAA.
“This is a tremendously exciting discovery that is the culmination of over a decade of a global research effort. In particular, this research would not have been possible without the patients who have provided samples for analysis over the last 10 years.”
This brings the number of genes known to be associated with AAA to 10 - Professor Bown has been involved in the discovery of eight of these. There are thought to be more genes yet to be discovered.
Studying growth of AAA
The next step is to study large numbers of people over a five-year period, to see how aneurysms grow and what factors affect this.
Professor Bown says: “There’s a long time period between when the aorta starts to swell and before we would consider surgery. Men aged 65 are invited to join the screening programme. If it’s normal they get discharged, and if it’s abnormal (but not yet large enough to be operated on) they will be invited back for yearly scans.
“A normal aorta is about 1.7cm in diameter. We class it as an aneurysm once it gets to 3cm, but we don’t operate until it gets to 5.5cm, because it’s quite high-risk surgery and aneurysms are at very low risk of bursting when they are less than 5.5.cm. Most aneurysms do grow slowly over time but on average it takes about 7 years for an aneurysm to grow from 3cm to 5.5cm. My research is focussed on this time period because it represents an opportunity to improve the health of patients with AAA and potentially, slow down the speed at which AAA grow.
“We could try to improve people’s health in that time, and there’s also the question of whether we could prevent aneurysms forming in the first place.
“Sometimes by the time the AAA is large enough to need an operation on people are not
physically fit enough to undergo surgery, so to slow down the growth of the aneurysm would be useful.”
Currently there are no treatments proven to prevent or slow down an aneurysm, although giving up
smoking is the biggest thing you can do.
Professor Bown says: “Currently, as a surgeon who specialises in this area, patients are asking me simple clinical questions like ‘Is there any
medication that will help’, ‘What about statins, do they make a difference’, and at the moment we don’t know – all we can do is tell people to stop smoking.”
“Our lack of knowledge in this area is because we have never had good data from a single large group of people about how their aneurysms grow and progress. For example, we’ve never been able to look at the effect of changes in medication over time before.
There are no treatments proven to prevent or slow down an aneurysm ... giving up smoking is the biggest thing you can do
“We may see that some classes of
blood pressure medication (such as angiotensin receptor blockers ( ARBs) are better than others. We may be able to give some simple quick answers just by collecting basic medical information.
The research will also look at the 10 genes now known to have a link to aortic aneurysm. The professor says: “The same genes that cause you to get an aneurysm probably cause your aneurysm to grow quicker. So the first step will be to establish whether that’s true. The second step will be to look at the whole genome in one go and look at whether there are areas of the genome associated with the speed at which AAA grow. That’s quicker and less expensive than genome sequencing of individuals – and it’s more appropriate because at the moment we don’t definitely know there’s a genetic link to AAA growth.
“Our genetic work may seem to be the most exciting part of this research but it can be a long pathway from finding genes involved to finding new treatments. That is why in this study we are looking at the effects of medication first as this should provide us with some quick, clinically useful answers for patients. Following on from that we will start the more complicated work of genetic analysis.”
Volunteers with AAA needed for research
In order for the research to be successful, Professor Bown and his team need more patients to enrol in their study.
He says: “We are collecting blood and urine samples from men who have been screened by the NHS and found to have an aneurysm. We ask them to consent to the study, go to their GP, have a blood and urine sample taken, and fill in a questionnaire.
“We have just reached 3,000 men with aneurysms recruited into the study and we hope to reach 5,000 by the end of 2017.”
Currently, the research is aimed only at men: “We are interested in women with aneurysms but we don’t have a project for them at the moment. Because the UK NHS screening programmes are for men, women would make up such a small proportion of the data that it would be difficult to learn from it – although I am doing another piece of research about whether women would benefit from screening.”
If you’re a man with an AAA that has been detected in one of the NHS AAA screening programmes, you can sign up to the study or
find out more.
Each year there are 3000 deaths in England and Wales because of AAA rupture and over 4000 patients undergo surgery to prevent or treat AAA rupture.
In the UK AAA affects 1.2% of men aged 65 and account for around 1 per cent of all deaths in men over the age of 65.
The incidence in women is about 6 times lower.
Around 9 in 10 cases of ruptured aortic aneurysm are fatal.