Understanding statins side effects and stroke risks: discover the research we’re funding

Between December 2018 and February 2019, we granted £19.7 million of funding for life-saving research. That’s 60 new research projects across the UK. Here are 5 of the most exciting projects we’re funding. 
1st May 2019

1. We want: to prevent stroke by studying how your genes can raise your risk. 

We’re investing: £259,756 to Professor Hugh Markus at the University of Cambridge. 

Doctor analysing MRI scan

A doctor examining MRI scans of the head

Around a quarter of all strokes occur due to narrowing of the large vessel carrying blood to the brain (the carotid artery). We already know that obesity, smoking and high blood pressure increase your risk of stroke. Now a particular form of one gene – found in one in every five Europeans - has been discovered to be a risk factor too. 
This is a variation of a gene known as HDAC9. The team will find out how and why this particular variant increases your risk of stroke. 
In this research project, they will use stem cells (derived from skin) donated by people who’ve had a stroke and carry the HDAC9 stoke-prone variant. From the stem cells, they’ll create blood vessel cells mimicking the patients’ carotid arteries in the lab. They will then study how the variant changes the way blood vessel cells behave, compared to those carrying an unchanged HDAC9 gene. 
In future, these results could help identify new therapies to prevent stroke in thousands of people. 

2. We want: to improve how GPs give weight loss advice. 

We’re investing: £169,488 to Professor Paul Aveyard at the University of Oxford. 

A tape measure wrapped around a calendar
More than one in four adults in the UK is obese, and levels are rising. Obesity increases the risk of developing heart and circulatory diseases, and is estimated to cost the NHS over £5 billion each year. GPs are in a good position to encourage and support patients to take action. However, they rarely give advice because they don’t feel they know how to talk about weight. 
Surveys show that the way doctors talk about weight is important in motivating people. However, we don't currently know which ways are most helpful. In this project, researchers will analyse recorded doctor-patient conversations in 200 consultations where advice to lose weight was offered. They will then see how patients felt afterwards, and what they did about their weight in the following months. 
This research will identify the most effective approach, words, phrases and tone that GPs could use to motivate people to lose weight. This will inform a new training package, which will be tested by GPs.The new training tools could give many more GPs the confidence and skills to support obese patients to reach a healthy weight. 

3. We want to: understand who might have side effects when taking statins. 

We’re investing: £90,639 to Dr James Sheppard at the University of Oxford. 

Two statin tablets next to a glass of water
Statins are cholesterol-lowering drugs that help to reduce your risk of heart attack and stroke. However, some people don’t take them because of concerns about side effects.  
It can be very difficult to tell whether symptoms experienced when taking statins are genuinely caused by the statin. So, this project aims to determine whether these side effects are truly linked to statins. Dr James Sheppard’s team will compare previous clinical trials testing statins and will perform something called a ‘network meta-analysis’. This is an analysis of lots of separate studies at the same time, to pool all the data to be able to look for a more informed answer. 
This will produce a ranked list of each type of statin and dose levels, based on how well they work and the rate of side effects. 
Dr Sheppard will also compare the GP health records of statin users and non-users between 1998 and 2019 to look for evidence of new muscle symptoms, new-onset diabetes, liver damage, kidney dysfunction, haemorrhagic stroke (bleed in to the brain) and eye diseases.  
This information will be used to work out which types of patients are most at risk of side effects. These predictions will then be cross-checked against the data from patient records.  
The goal is to create risk calculators that doctors can use to estimate a person’s risk of side effects from statins. This will allow doctors and their patients to make a shared decision about whether to start, stop, change, or continue statin treatment. 

4. We want: to understand and prevent heart disease in older athletes. 

We’re investing: £238,271 to Professor Sanjay Sharma at St George’s, University of London. 

Older athletes running outside
Coronary heart disease is the build-up of fatty material, called atherosclerosis, in the vessels that supply the heart with blood. Some athletes, usually considered at low risk for heart disease, can still develop more coronary heart disease and show more evidence of silent heart attacks than healthy people who exercise in moderation.  
In this fellowship, Professor Sharma aims to address the question: Why are they more at risk?  
220 healthy male endurance athletes aged 40-65 will be assessed with a variety of tests to understand their heart function and risk factors.  
These tests include: 
The goal is to understand the relationship between years of endurance exercise and the development of atherosclerosis. Dr Sharma expects that endurance athletes who have done the most exercise over many years will have more fatty plaques in their coronary arteries.  
The team believe this could be down to not the exercise itself, but high blood pressure (both during exercise and resting) and diets that increase inflammation in the body, for example because they are high in red meat and fatty foods. Being able to confirm that these factors contribute to the development of coronary heart disease in athletes will provide guidance for doctors when advising about the potential risks of endurance exercise. This will allow older athletes to enjoy their active lifestyles in a safer way. 

5. We want: to understand the changes that occur in heart cells during heart failure, so that it can be prevented. 

We’re investing: £864,825 to Dr Michela Noseda at Imperial College London. 

Heart muscle cells under the microscope

Cross section of cells found in the heart muscles.

This is a partnership grant between the BHF and the German Centre for Cardiovascular Research (DZHK).  
Heart failure affects up to 26 million people around the world. During heart failure, the heart is unable to pump strongly enough to meet the day-to-day demands of the body. It can also lead to electrical faults in the heart, which can result in abnormal heart rhythms.  
Now, researchers in London and Berlin are joining forces to try to build a more precise understanding of what happens to cells during heart failure.  
A healthy heart is made of billions of cells, including muscle cells, which function and contract in perfect harmony. But we don’t yet know the precise types and combinations of cells that make up different parts of the heart.  
We know that physical symptoms of heart failure come about due to changes in the way these cells work together, and now Dr Noseda and her colleagues in Berlin are investigating how the individual cells change.  
Working together, these British and German teams will use cutting-edge research technologies to analyse thousands of heart cells at once. They hope to reveal the exact types of cells that make up different parts of the heart, and when, where and what changes take place in each type of cell during heart failure. This will help them find potential ways to develop much-needed medicines to try to prevent or reverse heart damage. 

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