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Welcome to the BHI Newsletter Autumn 2021

Professor Andy Judge, Head of Section for Cardiovascular Surgery and Vascular Biology, reflects on recent successes.

With the new academic year underway, we welcome our new cohorts of postgraduate taught master’s degree students for the MSc in Perfusion Science and the MSc in Translational Cardiovascular Medicine (TCM). The teaching sessions are now back in person for the campus based TCM students and Perfusion students, and our student numbers are good.

I’m pleased to report that the labs, which closed for three months at the start of the pandemic, have been open since June 2020. Staff are gradually returning to the office at Level 7 of the BRI as the University has launched its blended working trial policy, and we are now seeing more staff in both the labs and offices.

Within our section for Cardiovascular Surgery and Vascular Biology at the University, we are delighted to have been able to appoint staff to new posts. Dr Kerry Wadey has been appointed as Lecturer in Cardiovascular Medicine on an open-ended core funded post. Francesco Paneni has been appointed as a Professor in Cardiology and Tom Johnson as an Associate Professor in Cardiology and they are expected to begin working with us at the start of 2022.

A number of staff in our section have had success following the annual University promotions procedure. Jason Johnson has been promoted to Professor of Cardiovascular Pathology, and Umberto Benedetto becomes Professor of Cardiac Surgery. Staff from the Teaching and
Learning for Health Professionals (TLHP) programme have recently joined our department of Translational Health Sciences and come under
the umbrella of our cardiovascular section, where we are delighted to congratulate Andrew Blythe on being promoted to Professor of Medical Education in this year’s annual promotion procedure.

Huge congratulations to all those recently promoted: we wish them continued success in their careers.

Bristol Heart Institute researchers feature in World Heart Day campaign

 

Four Bristol Heart Institute researchers have shared their work in a campaign to mark World Heart Day, 29 September 2021.

The interviews, which appear in the Guardian newspaper’s Cardiovascular Health supplement, cover a broad aspect of the BHI’s work, from tissue engineering to population health.

BHI Director, Professor Gianni Angelini, outlines the BHI’s innovative link between clinicians and scientists, citing the combination of people from different disciplines – basic scientists, clinicians, engineers, epidemiologists and statisticians – as one of the Institute’s key strengths.

Professor of Congenital Cardiac Surgery, Massimo Caputo, talks about how tissue engineering and stem cell therapies could lead to better treatment options for young patients with congenital heart disease.

Dr Giovanni Biglino, Senior Lecturer in Biostatistics, explains how patients and the public are playing an increasing role in cardiovascular research through closer collaborations with clinicians, researchers and artists. This is supporting clinical training and medical research as well as helping patients have a better understanding, and acceptance, of their heart conditions.

Finally, Deborah Lawlor, Professor of Epidemiology, talks about using population health data to identify causes of cardiovascular disease and to predict who is at risk of it. which can lead to prevention, early detection and effective treatment of disease.

See the full BHI World Heart Day campaign

Fat matters more than muscle for heart health, research finds

New research has found that changes in body fat impact early markers of heart health more than changes in body muscle, suggesting there are greater benefits to be expected from losing fat than from gaining muscle.

The observational study, led by researchers from the University of Bristol, was published today [9 September] in PLoS Medicine.

More than 3,200 young people in Bristol’s Children of the 90s birth cohort study were measured repeatedly for levels of body fat and lean mass using a body scanning device. These scans were performed four times across participants’ lives, when they were children, adolescents, and young adults (at ages 10, 13, 18 and 25 years). Handgrip strength was also tested when they were aged 12 and 25 years.

When the participants were 25 years old, blood samples were collected and a technique called “metabolomics” was used to measure over 200 detailed markers of metabolism including different types of harmful cholesterol, glucose, and inflammation, which together indicate one’s susceptibility to developing heart disease and other health conditions.

Dr Joshua Bell, senior research associate in epidemiology and lead author of the report, said:

“We knew that fat gain is harmful for health, but we didn’t know whether gaining muscle could really improve health and help prevent heart disease. We wanted to put those benefits in context.”

The findings showed that gaining fat mass was strongly and consistently related to poorer metabolic health in young adulthood, as indicated, for example, by higher levels of harmful cholesterol. These effects were much larger (often about 5-times larger) than any beneficial effect of gaining muscle. Where there were benefits of gaining muscle, these were specific to gains that had occurred in adolescence – suggesting that this early stage of life is a key window for promoting muscle gain and reaping its benefits.

Dr Bell added:

“Fat loss is difficult, but that does seem to be where the greatest health benefits lie. We need to double down on preventing fat gain and supporting people in losing fat and keeping it off.

“We absolutely still encourage exercise – there are many other health benefits and strength is a prize in itself. We may just need to temper expectations for what gaining muscle can really do for avoiding heart disease – fat gain is the real driver.”

The study also found that improving strength (based on handgrip) has slightly greater benefits for markers of heart health than gaining muscle itself, suggesting that the frequent use of muscle, rather than the bulking up of muscle, may matter more.

Professor Nic Timpson, the Principal Investigator of the Children of the 90s and one of the study’s authors, said:

“This research provides greater clarity in the relative roles of fat and lean mass in the basis of cardio-metabolic disease. This is an important finding and clearly part of a complex picture of health that involves weight gain, but also the other indirect costs and benefits of different types of lifestyle. It is only through detailed, longitudinal, studies like Children of the 90s that these relationships can be uncovered. We extend our thanks to the participants of the Children of the 90s who make all of this work possible.”

Read the paper

Body muscle gain and markers of cardiovascular disease susceptibility in young adulthood: A cohort study‘ by Joshua A. Bell, Kaitlin H. Wade, Linda M. O’Keeffe, David Carslake, Emma E. Vincent, Michael V. Holmes, Nicholas J. Timpson and George Davey Smith in PLoS Medicine

Further information

The research was funded by the Elizabeth Blackwell Institute for Health Research at the University of Bristol and the Wellcome Trust. The research was also supported by the UK Medical Research CouncilHealth Research Board of IrelandDiabetes UKWorld Cancer Research FundBritish Heart FoundationNational Institute for Health Research (NIHR); Cancer Research UK.

About Children of the 90s
Based at the University of Bristol, Children of the 90s, also known as the Avon Longitudinal Study of Parents and Children (ALSPAC), is a long-term health-research project that enrolled more than 14,000 pregnant women in 1991 and 1992. It has been following the health and development of the parents and their children in detail ever since and is currently recruiting the children and the siblings of the original children into the study. It receives core funding from the Medical Research Council, the Wellcome Trust and the University of Bristol. Find out more at www.childrenofthe90s.ac.uk.

BHI scientist wins national science image contest with heart vessel image

Recreating heart blood vessels
Recreating heart blood vessels. Image credit : Dr Elisa Avolio

A scientist from the Bristol Heart Institute has won the British Heart Foundation’s (BHF) annual ‘Reflections of Research’ image competition. Where science and art collide, the competition challenges BHF-funded scientists to showcase their state-of-the-art heart and circulatory disease research through the generation of captivating images.

Dr Elisa Avolio’s entry ‘recreating heart blood vessels’ was chosen as this year’s judges’ winner. Although at first glance it appears to resemble a luminous jelly fish, the image shows new blood vessel-like structures – pictured in green in the centre – sprouting from a 3D gel.

Dr Avolio of the Bristol Medical School created the structures using a mixture of two types of heart cells – cardiac endothelial cells, which line the inside of every blood vessel, and pericytes, which ‘hug’ the outside of blood vessels to support the vessel and help it function.

During a heart attack, the arteries that supply blood to the heart are blocked, cutting off blood flow. The area of the heart starved of blood and oxygen dies, and it no longer functions to help the heart pump blood around the body. Dr Avolio is researching ways to encourage the formation of new blood vessels to replace those that have died, to restore blood supply to damaged areas of the heart.

Dr Avolio, a post-doctoral research associate, said:

“It is fantastic to have won this year’s Reflections of Research competition. Each year the entries display such variety in the BHF’s work to support heart and circulatory disease research.

“By recreating models of the heart blood vessels, we can see how the cells in blood vessel walls interact with and talk to other cells. This knowledge, along with understanding what molecules promote or block the formation of blood vessels, could be used in the future to develop new treatments for patients after a heart attack.”

Dr Neil Dufton, Lecturer in Inflammatory Sciences at Queen Mary University of London, was this year’s guest judge. He said:

“All of the images shortlisted in this year’s competition offer a stunning glimpse into the cutting-edge work being carried out by BHF scientists.

“The winning image is truly eye-catching. The chaotic mixture of different cells around the outside contrasts perfectly with a ‘through the looking glass’ moment where we see new and exquisitely detailed blood vessels forming in the centre.”

Dr Charmaine Griffiths, Chief Executive at the British Heart Foundation, was also a competition judge. She added:

“All of this year’s entries beautifully capture aspects of the heart and circulatory system, bringing to life the challenges that BHF scientists work tirelessly to solve.

“The images show how far we’ve come over 60 years of BHF research, and would have been barely imaginable to our founders. I love the winning image not just because of its circular beauty, but also because of the hope it represents for the future of healing damaged hearts.”

New research lifts the lid on cardiac microvascular dysfunction

New research has shown abnormalities in the tiny blood vessels of human hearts in regions well beyond the large arteries with atherosclerotic blockages that trigger the need for stents or bypass surgery. The findings could lead to the development of new treatments for patients with angina-like symptoms without blockages or those recovering from a heart attack or unexplained heart failure.

Normal intrinsic constriction of these micro-arteries in response to changing blood pressure is called myogenic (automatic) tone. Myogenic tone controls blood flow distribution within the heart muscle, and in other parts of the human body.

Current heart scans can identify blockages in large coronary arteries, but they are unable to show these tiny, hair size micro-arteries in patients, making it impossible to diagnose poor myogenic tone, which is thought to develop independent of disease in the larger arteries. This study used tissue biopsies to study the function, structure and alterations in pathways in the micro-arteries that link to abnormalities in myogenic tone.

The study, led by Professor Raimondo Ascione (Clinical Lead) at the University of Bristol and Professor Kim Dora (Basic Science Lead) at the University of Oxford, and funded by the BHF, is published in Cardiovascular Research.

The research team took small heart samples, that are otherwise discarded, from 88 patients with no large coronary artery blockages and undergoing valvular cardiac surgery at the Bristol Heart Institute. In addition, cardiac samples were obtained from three human organ donors from the Newcastle Institute of Transplantation Tissue Biobank and 45 pigs treated at the University of Bristol Translational Biomedical Research Centre (TBRC).

The research team found that 44 per cent of the micro-arteries from patients had abnormal myogenic tone despite retaining their cell viability. This abnormality was associated with an excessive presence of a molecule called caldesmon within the muscle cells in the wall of the abnormal micro-arteries and with poor alignment of these contracting cells compared to micro-arteries with normal myogenic tone from the other 66 per cent of patients, and all the organ donors and pigs.

Abnormalities in the micro-arteries affects the blood supply within the beating heart, and other organs in the body, affecting people’s quality of life and life expectancy.

The findings offer new insights on coronary microvascular dysfunction that could predate the development of clinically known heart disease such as heart failure.

Professor Raimondo Ascione, NHS Consultant Cardiac Surgeon and Head of the TBRC at the University of Bristol, said:

“It has been a pleasure to work with Professor Dora on this landmark study over the last seven years. No study had focused on ex vivo poor myogenic tone of the cardiac microcirculation before. These tiny arteries are sited deep within the cardiac wall, well beyond the blocked arteries we treat in the NHS with stents or bypass surgery and cannot be seen with a naked eye.

“Our study lifts the lid on cardiac microvascular dysfunction. It could help to develop new treatments to help patients with angina-like symptoms without coronary blockages, or those recovering from a heart attack or unexplained heart failure.”

Kim Dora, Professor of Microvascular Pharmacology at the University of Oxford, explained:

“I am so excited with the results of this study and the excellent teamwork with Professor Ascione in Bristol.  Not only will our findings enhance the development of new medical treatments and possibly new patient imaging modalities, but they represent a new ex-vivo research model for thousands of scientists globally working on microvascular dysfunction in the heart and other organs.”

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, added:

“This study is the first to develop techniques to understand the links between the structure of micro-arteries and impaired myogenic tone, representing the outcome of years of painstaking work to develop the methods and apply them to micro-arteries from human hearts. The findings provide new information that will help to develop treatments for the many patients whose angina occurs without significant narrowing of their coronary arteries.”

There is now a new area of research that confirms thousands of patients, mostly postmenopausal women, have angina-like symptoms despite their coronary angiogram showing no obvious blockages of the large epicardial arteries in the heart that are usually treated with stent or bypass. Other patients seem to develop heart failure associated with either the contraction or the relaxation of their heart for no obvious reasons.

The human coronary micro-arteries the Bristol and Oxford team has studied in the laboratory represent the microvascular area in human organs (lung, heart, brain and elsewhere) where COVID-19 has caused most of the problems during the ongoing pandemic.

Paper

Human coronary microvascular contractile dysfunction associates with viable 2 synthetic smooth muscle cells‘ by Kim A Dora, Raimondo Ascione et al in Cardiovascular Research [open access]

Early adulthood education and employment experiences play independent role in later life cardiovascular health

New research has found that education and employment experiences in early adulthood contribute to cardiovascular health inequalities in later life, independent of occupation and family income in mid-adulthood. The findings, published today in the Journal of Epidemiology and Community Health, involve researchers from the University of Cambridge, University of Bristol and UCL Social Research Institute.

There are important differences in health between different sectors of our society, with those who are less educated and in lower status jobs shown to be less healthy and have shorter life expectancy on average than the more privileged. While early adulthood is an important time for both the development of adult socioeconomic position and for development of behaviours related to cardiovascular health, until now the degree to which early adulthood socioeconomic trajectories contribute directly to health differences observed in later life has not been clear.

Researchers from the University of Cambridge, University of Bristol and UCL Social Research Institute analysed health and socioeconomic data collected over several decades from over 12,000 members of the 1970 British Birth Cohort, to determine the contribution of early adulthood to differences in cardiovascular health in mid-adulthood. The scientists used a data-driven method to divide the population into different socioeconomic trajectory groups based on their participation in education, different job types, unemployment or economic inactivity across early adulthood (ages 16-24). They studied the association of these groups with cardiovascular risk factors at age 46, including blood pressure, cholesterol levels, waist circumference. To determine if the association of early adulthood socioeconomic trajectories with cardiovascular health was mediated by socioeconomic status later in life, they examined how correcting for occupation or family income at age 46 affected the link.

Professor Kate Tilling from the MRC Integrative Epidemiology Unit at the University of Bristol, and senior author on the paper, said:

“Measuring socioeconomic position in early adulthood has always been difficult as this is a period of transition when most people’s occupations change over time. The method we’ve developed provides a flexible way to identify early adulthood socioeconomic position, and we hope that it will be used in future to answer other research questions related to this period of life.”

The researchers found that those who spent a longer time in education, going on to employment in professional or managerial roles during early adulthood, had better cardiovascular health more than 20 years later (at age 46) than other groups. Importantly this association wasn’t entirely because of a higher income or higher level job at age 46, suggesting an independent and long-term association of early adulthood influences with health.

The findings indicate that that material factors in mid-adulthood do not contribute to the pathway through which early adulthood socioeconomic trajectory affects mid-life health, and the authors suggest that the development of health behaviours or psychosocial factors such as stress, depression, and job control in early adulthood may play an important role.

Dr Eleanor Winpenny from the MRC Epidemiology Unit at the University of Cambridge, and first author on the paper, said:

“We found that an individual’s education and employment experiences in early adulthood had a far larger impact on measures of cardiovascular health more than twenty years later than their occupation or income at that time did.

“These results suggest that we need to provide more support for young adults to allow healthy development into middle age and prevent disease in later life. Given the added disadvantage to young adults as a result the current coronavirus pandemic, there is an urgent need to understand and mitigate the effect these circumstances may be having on their future health.”

The research was funded by the Medical Research Council and the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence. Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and Wellcome, under the auspices of the UK Clinical Research Collaboration.

Paper

Early adulthood socioeconomic trajectories contribute to inequalities in adult cardiovascular health, independently of childhood and adulthood socioeconomic position‘ by Winpenny, E. et al in the Journal of Epidemiology and Community Health

The beating heart of Royal Fort Garden

Bristol Heart Institute interpretation sign

The new interpretation sign for the University of Bristol brings a whole new meaning to the phrase ‘living statue’.

The solid oak monolith is the third instalment in a series of iconic totems dedicated to the University’s research institutes. This sign embodies the work of the Bristol Heart Institute and has been designed to reflect the relationship between human life and nature. Joining many other works of art in the Royal Fort Garden this piece stands proud at three metres high, and if you get close enough you can hear the low thud of a heartbeat coming from deep within the structure day and night.

Previous designs highlighted the work of the Bristol Population Health and the Bristol Bio Design Institutes.

The new monolith is built from four solid oak panels which have been laser cut and hand painted to represent a human cardiovascular system. Following a couple of years of pandemic enforced hiatus, it’s great to add to the collection and celebrate the work of the Bristol Heart Institute in such a creative way.  

(Photo by Green Hat. Words adapted from text supplied by Green Hat)

Study shows aspirin can reduce the risk of heart attacks and strokes in patients with pneumonia

Aspirin can reduce the risk of serious cardiovascular events such as ischemic stroke and heart attack in patients with pneumonia, according to new research.

Serious cardiovascular complications are common in cases of pneumonia and are strongly associated with long-term mortality. A study by Dr Fergus Hamilton and colleagues at the University of Bristol looked at whether aspirin could reduce the risk of ischemic stroke (stroke caused by blockage of blood vessels, representing some 80 per cent of strokes) and heart attack, and if the drug could have a preventative role to play in primary care settings. 

The team analysed the details of all patients aged over 50 with pneumonia from the Clinical Practice Research Datalink (CPRD), a large UK primary care database of more than 61 million patients. The primary outcome was defined as the occurrence of both ischemic stroke and myocardial infarction (MI – heart attack), while either of those events happening individually was defined as the secondary outcome. 

Of the 48,743 patients identified as being eligible for inclusion in the study, the researchers found 8,099 aspirin users who were matched to 8,099 non-users also selected from the sample group. 

The authors found that the risk of the primary outcome (stroke and MI) was 36 per cent lower in aspirin users compared to non-users. The drug was also associated with a reduced risk of both secondary outcomes with ischemic stroke and MI rates being 30 per cent and 54 per cent lower, respectively, in aspirin users. 

The researchers conclude: “This study provides supporting evidence that aspirin use is associated with reduced ischaemic events after pneumonia in a primary care setting. This drug may have a future clinical role in preventing this important complication.”

Dr Fergus Hamilton, Wellcome Doctoral Fellow at the University of Bristol and an NIHR Academic Clinical Fellow at North Bristol NHS Trust, said: “This research really paves the foundation for a clinical trial of aspirin in pneumonia, which remains the most common reason for admission to hospital in many countries.”

Paper

‘Aspirin reduces cardiovascular events in patients with pneumonia: a prior event rate ratio analysis in a large primary care database’ by F. Hamilton, D. Arnold, W. Henley and R. Payne in the European Respiratory Journal

Cardiovascular researchers visit Bristol primary school

Giovanni Biglino shows Year 6 students a 3D printed heart model
Giovanni Biglino shows Year 6 students a 3D printed heart model

Drs Lucy Culliford, Andrew Shearn and Giovanni Biglino took part in an outreach activity at Parson Street Primary School in Bedminster, south Bristol. in May 2021.

The visit was organised by Lucy on behalf of the Bristol Trials Unit. The group explained some of their research to the Year 6 students (aged 10 and 11) and, as the visit happened in the same week as Clinical Trials Day, it was also an opportunity for Lucy to ask the students to think about clinical studies, the idea of randomisation and ‘what is a clinical trial?’. The group showed the THERMIC 3 animation video, which was developed as part of the TRECA study exploring children’s and young people’s engagement with clinical trials.

Giovanni gave an overview of the technology involved in 3D printing and Andrew brought a series of heart models, both adult and paediatric, including examples of babies’ hearts with congenital heart disease, which sparked some stimulating conversations with the 53 students who attended.

They explained that 3D printing technology can produce models of human organs using scans taken during routine visits to the hospital. Bristol Royal Hospital for Children use this technique to create heart models from patients with congenital heart disease. Being able to hold a life-size model of the patient’s heart can complement information the surgeon or cardiologist can get from medical imaging – for example, they can practice aspects of the surgery or decide the best route to access a specific part of the heart. The models are also used when explaining the details of the case to a patient or a parent.

The children asked lots of questions about ‘hole in the hearts’, as some had had siblings with this condition. They also asked how smoking can affect the heart, and if the researchers could show them a video of a beating heart.

Lucy said:

“This is the first time we’ve done a talk in a school as part of our outreach activities around Clinical Trials Day, and it was a real pleasure to talk to the children. They were very engaged and although they had only started learning about the heart the day before, they already knew lots about heart anatomy, and had more questions than we had time to answer!”

How to get involved in schools outreach

If you would like to run a schools outreach activity, contact your local school.

Schools often have science weeks, or may be doing a topic related to cardiovascular research. For example, Parson Street Primary School use the Cornerstones curriculum and the year 6s had just started the ‘blood heart’ topic – the following week they had a visitor demonstrating a heart dissection.

Smoking during pregnancy associated with child’s risk of having congenital heart disease

Children born to mothers who smoked during pregnancy were at increased risk of having congenital heart disease, a new study published today [27 May] in the Journal of the American Heart Association has found.

The study was led by the University of Bristol, in an international collaboration with researchers from seven institutions. It brings together data on more than 230,000 families from seven European birth cohorts from the UK, Ireland, the Netherlands, Denmark, Norway and Italy, including the world-renowned Children of the 90s study at the University of Bristol. The research was supported by the British Heart Foundation and the H2020 program of the European Commission.

Each day, around 13 babies in the UK are diagnosed with congenital heart disease. This means the heart or the large blood vessels surrounding the heart have not developed properly in the womb. Identifying causes of congenital heart disease could help prevent some of these cases and ultimately save lives.

Lead author, Kurt Taylor, a PhD student at the University of Bristol said:

“Birth cohorts are unique in that many possess a wealth of data not only in mothers and children, but also in fathers. Crucially, having access to data in the fathers as well as mothers and children allowed us to use a novel study design to investigate possible causes of congenital heart disease.”

The study analysed associations between body mass index, smoking, and alcohol consumption on offspring congenital heart disease. Data on these characteristics were obtained through measurements of weight and height and questionnaires administered during early pregnancy when most of the cohorts began recruitment. Measurements were harmonised across cohorts as part of the LifeCycle project; an initiative that aims to research the role of pregnancy and infancy factors on offspring health and wellbeing across childhood and into adulthood. The researchers were able to test the reliability of their findings by using an approach that compares the results from mothers and fathers to help discern whether the effects they see are “real” or are as a result of other factors.

Kurt continued:

“Here, we have shown that mothers who smoke during pregnancy are more likely to have a child with congenital heart disease. Our results also suggest that being overweight or obese at the start of pregnancy or consuming alcohol may not be causes of congenital heart disease, despite previous research suggesting otherwise. These results might help in supporting women of reproductive age not to start smoking. Meanwhile it continues to be appropriate to recommend that women, and men, maintain a healthy weight and limit alcohol consumption prior to and during pregnancy.”

Professor Deborah Lawlor, British Heart Foundation Chair in Cardiovascular Science and Clinical Epidemiology of the University of Bristol, who oversaw the study, added:

“Smoking rates are declining but remain high in more deprived groups in the UK and other high-income countries and are promoted in low- and middle-income countries. These findings further highlight the need to support smoking cessation globally. Also, if we can work out exactly how maternal smoking increases risk of congenital heart diseases this could identify new ways of preventing these diseases even in the absence of smoking.”

Dr Sonya Babu-Narayan, Associate Medical Director at the British Heart Foundation and cardiologist, said:

“Smoking is one of the biggest risk factors for developing heart and circulatory disease. It is also the greatest cause of health inequality across Europe, but supporting people to quit smoking is one of the most effective things we can do to reduce these inequalities. We need to make it easier for everyone to quit by offering them appropriate smoking cessation support and advice.”

Read the paper

Effect of maternal prepregnancy/early-pregnancy body mass index and pregnancy smoking and alcohol on congenital heart diseases: A parental negative control study‘ by Kurt Taylor et al in The Journal of the American Heart Association [open access]