Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation (BHF) explains the work they are doing to find the next breakthrough treatment for cardiovascular disease.
Since the BHF was formed over 50 years ago, the number of people in the UK dying of cardiovascular disease each year has halved. This impressive reduction is largely down to an improvement in our understanding of heart disease, and the lifestyle changes and treatments that this new knowledge has led to.
Take statins, for example. Entering clinical use in the 1980s, statins tackle the most common type of cardiovascular illness – coronary heart disease. They are the most commonly prescribed medicine in the UK, and save lives by reducing a person’s risk of heart attack and stroke by stopping fatty deposits from building up inside their arteries.
However, even after the development of statins, around 150,000 people in the UK still die each year from cardiovascular disease. And over 7 million people across the UK are living with various heart and circulatory conditions. It’s important that we don’t become complacent, as it is clear there is still plenty of work to be done. That’s why the BHF is investing £100million every year into research towards improved prevention, diagnosis and treatment of cardiovascular disease. With such a vast programme of funding comes hope and the promise of new breakthroughs to help save more lives.
Prevention of common conditions
Coronary heart disease affects 2.3 million people in the UK, but present diagnostic techniques do not allow identification of people whose coronary arteries are not significantly narrowed but are inflamed and therefore still at high risk of triggering a heart attack. These tests only detect changes in the shape and structure of the coronary arteries once damage has already taken place.
Professor Charalambos Antoniades and colleagues at the University of Oxford are trying to develop a new test that could transform how we prevent and treat these diseases.
The test analyses heart scan images to identify changes in the fat surrounding the coronary arteries and uses this to look for atherosclerotic plaques that are unstable. If a plaque is unstable or vulnerable it is at a higher risk of rupturing and causing a blood clot to form and block the artery. Professor Antoniades has discovered that these plaques release chemicals that prevent small immature fat cells turning in to bigger mature ones. As part of his BHF-funded research Professor Antoniades is examining whether the test can be used to predict plaque rupture and therefore risk of heart attack, thus allowing preventive treatments to be given before the attack occurs. He is also investigating whether this technique can identify people who are more prone to developing new plaques, or those whose plaques are likely to worsen, again helping doctors prescribe preventive treatments.
New treatments for rare conditions
Research into rare conditions is incredibly important, as these conditions can be devastating but have limited treatment options. Pulmonary arterial hypertension (PAH) is one such example – at present this life changing condition, which affects around 6,500 people in the UK, has no cure.
Yet PAH is serious, and causes high blood pressure in the blood vessels between the heart and the lungs. It leaves sufferers weak and short of breath and can lead to heart failure.
Recently, scientists the BHF funds at the University of Edinburgh have made exciting new progress, which could lead to the development of new treatments for people with PAH. By studying muscle cells from pulmonary arteries in mice, and clones of human cells, the team were able to show that they can use the existing treatments for PAH to regulate a new calcium channel, called TPC2. How these drugs work against the condition has been hotly debated as they were initially designed for other targets. Using them as a template to develop new drugs could speed up the road to new specific treatments for PAH.
Although this research is in early stages, it is really encouraging to see new targets emerge that could help develop treatments for conditions that blight the lives of thousands of people and their families.
Learning from ticks
Sometimes a viral or bacterial infection can spread, leading to severe inflammation of the heart muscle, known as myocarditis. In extreme cases this can cause lasting damage to the heart, or even death. Occasionally, a viral or bacterial infection can lead to severe and potentially fatal inflammation of the heart muscle, known as autoimmune myocarditis. Around 20% of people who suffer from this develop heart failure, which in severe cases can result in the person needing a transplant.
Myocarditis has, so far, proven difficult to diagnose and treat. This is because although the dangerous inflammation of the heart muscle seen in the disease is known to be caused by a certain type of white blood cells, called T-cells, researchers do not yet know exactly how this process occurs.
Researchers funded by the BHF at the University of Oxford think that we may be able to learn to design drugs targeted at this problem from an unlikely source, parasitic ticks.
During autoimmune myocarditis, chemicals called chemokines are released in the heart and attract cells that cause inflammation. If you’ve ever been bitten by a tick you will know that, unlike a mosquito bite, you do not feel it. Ticks need to feed for a long time, so they inject proteins that block your body’s chemokines and prevent painful inflammation.
BHF Professor Shoumo Bhattacharya and his team have identified 31 of these tick proteins, called evasins, and are now studying which chemokines they block, and are planning to trial them in autoimmune myocarditis in mouse models. The aim is to take inspiration from the tick’s anti-inflammatory strategy and design a life-saving medicine for this dangerous heart condition.
Gene-editing – providing hope for thousands
If left undetected and untreated, inherited heart conditions can sadly lead to heart failure or even sudden death from cardiac arrest. For many families, the first sign there’s a problem is when someone dies suddenly with no obvious cause or explanation.
Hypertrophic cardiomyopathy (HCM) is a genetic condition caused by a change or mutation in one or more genes and is passed on through families. If you have HCM, the muscular wall of your heart – the myocardium – becomes thickened, making the heart muscle stiff. This thickening makes it harder for your heart to pump blood out of your heart and around your body and can also lead to life-threatening arrhythmias.
Decades of BHF research has discovered many of the genes responsible for HCM so that genetic testing can be carried out for families at risk. However, there is no cure.
Gene-editing is a relatively new and hugely exciting field which could see the cure for inherited heart disease by simply swapping a faulty, disease-causing gene for a ‘healthy’ gene. Of course, this type of genetic manipulation has unique ethical considerations and has not been tested in humans, but there are already examples of success in animal models.
There are many diseases which fall under the cardiovascular disease ‘umbrella’ for which treatments are at best limited and at worst non-existent. A standout example is heart failure, where the only treatment for many is a heart transplant.
Our great strides in cardiovascular research have resulted in a dramatically reduced death-rate from heart attack. Now we must strive to find treatments for those heart attack patients left with heart failure, and to enable advances that will end the heartbreak for the millions of people who suffer from the consequences of both common and rare forms of heart and circulatory disease.
