̽��ֱ�� of Cambridge - stroke

Cambridge research receives £5 million boost for ‘world-leading’ cardiovascular research

cjb250 — Tue, 28 May 2024 11:10:58 +0000

̽��ֱ��funding will support the university to cultivate a world-class research environment that encourages collaboration, inclusion and innovation, and where visionary scientists can drive lifesaving breakthroughs.

Professor Martin Bennett, BHF Professor of Cardiovascular Sciences at the ̽��ֱ�� of Cambridge, said: “This is a fantastic achievement from the whole Cambridge team. This award will support our multiple research programmes identifying new targets and treatments for vascular disease and heart failure, new ways to reduce the consequences of diabetes and obesity, and how we can get our research used to treat patients.”

̽��ֱ��Cambridge award is part of a £35 million boost to UK cardiovascular disease research from the British Heart Foundation. It comes from the charity’s highly competitive Research Excellence Awards funding scheme. ̽��ֱ��£5 million award to the ̽��ֱ�� of Cambridge will support researchers to:

Combine their expertise to work on cardiovascular diseases and in populations with high unmet need.
Identify new markers and disease targets for a wide range of cardiovascular diseases, and test new drugs in clinical trials.
Develop new ways to diagnose cardiovascular disease and harness the power of artificial intelligence from imaging and health records to identify people at highest risk.
Generate user-friendly risk communication and management tools to improve the prevention and management of cardiovascular disease.

Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, said: “We’re delighted to continue to support research at the ̽��ֱ�� of Cambridge addressing the biggest challenges in cardiovascular disease. This funding recognises the incredible research happening at Cambridge and will help to further its reputation as a global leader in the field.

“With generous donations from our supporters, this funding will attract the brightest talent, power cutting-edge science, and unlock lifesaving discoveries that can turn the tide on the devastation caused by heart and circulatory diseases.”

Research Excellence Awards offer greater flexibility than traditional research funding, allowing scientists to quickly launch ambitious projects that can act as a springboard for larger, transformative funding applications.

̽��ֱ��funding also aims to break down the silos that have traditionally existed in research, encouraging collaboration between experts from diverse fields. From clinicians to data scientists, biologists to engineers, the funding will support universities to attract the brightest minds, nurture new talent and foster collaboration to answer the biggest questions in heart and circulatory disease research.

̽��ֱ�� ̽��ֱ�� of Cambridge has previously been awarded £9 million funding through the BHF’s Research Excellence Awards scheme. This funding has supported research that will lay the foundations for future breakthroughs, including:

Research showing that low doses of a cancer drug could improve recovery after a heart attack. ̽��ֱ��drug boosts activity of anti-inflammatory immune cells that can cause harmful inflammation in blood vessels supplying the heart. It’s currently being tested in clinical trials to see if it benefits patients.
A new risk calculator to enable doctors across the UK and Europe predict who is at risk of having a heart attack or stroke in the next 10 years with greater accuracy. ̽��ֱ��calculator has been adopted by the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice.
Developing imaging and artificial intelligence tools to improve diagnosis of heart and vascular disease by enhancing analysis of scans for disease activity and high-risk fatty plaques. These tools can be rapidly implemented to support diagnosis, treatment and prevention.
A study investigating whether an epilepsy medication could help to prevent strokes in people with a common gene variant. ̽��ֱ��change in the gene HDAC9 can cause it to become ‘overactive’ and increase stroke risk. ̽��ֱ��epilepsy medication sodium valproate blocks the HDAC9 activity, so could reduce stroke risk in people with the variant.
Discovery of rare and common changes in the genetic code that influences proteins and small molecules in the blood, helping us understand the development of cardiovascular diseases and identify novel drug targets.

Adapted from a press release by BHF

̽��ֱ�� ̽��ֱ�� of Cambridge has received £5 million funding from the British Heart Foundation (BHF) to support its world-class cardiovascular disease research over the next five years, the charity has announced.

This is a fantastic achievement from the whole Cambridge team. This award will support our multiple research programmes.

Martin Bennett

Lloyd Mann

Professor Martin Bennett standing outside the Victor Phillip Dahdaleh Heart and Lung Research Institute

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Lab-grown ‘small blood vessels’ point to potential treatment for major cause of stroke and vascular dementia

cjb250 — Thu, 16 Nov 2023 16:00:19 +0000

̽��ֱ��study, published today in Stem Cell Reports, also identifies a drug target to ‘plug’ these leaks and prevent so-called small vessel disease in the brain.

Cerebral small vessel disease (SVD) is a leading cause of age-related cognitive decline and contributes to almost half (45%) of dementia cases worldwide. It is also responsible for one in five (20%) ischemic strokes, the most common type of stroke, where a blood clot prevents the flow of blood and oxygen to the brain.

̽��ֱ��majority of cases of SVD are associated with conditions such as hypertension and type 2 diabetes, and tend to affect people in their middle age. However, there are some rare, inherited forms of the disease that can strike people at a younger age, often in their mid-thirties. Both the inherited and ‘spontaneous’ forms of the disease share similar characteristics.

Scientists at the Victor Phillip Dahdaleh Heart and Lung Research Institute, ̽��ֱ�� of Cambridge, used cells taken from skin biopsies of patients with one of these rare forms of SVD, which is caused by a mutation in a gene called COL4.

By reprogramming the skin cells, they were able to create induced pluripotent stem cells – cells that have the capacity to develop into almost any type of cell within the body. ̽��ֱ��team then used these stem cells to generate cells of the brain blood vessels and create a model of the disease that mimics the defects seen in patients’ brain vessels.

Dr Alessandra Granata from the Department of Clinical Neurosciences at Cambridge, who led the study, said: “Despite the number of people affected worldwide by small vessel disease, we have little in the way of treatments because we don’t fully understand what damages the blood vessels and causes the disease. Most of what we know about the underlying causes tends to come from animal studies, but they are limited in what they can tell us.

“That’s why we turned to stem cells to generate cells of the brain blood vessels and create a disease model ‘in a dish’ that mimics what we see in patients.”

Our blood vessels are built around a type of scaffolding known as an extracellular matrix, a net-like structure that lines and supports the small blood vessels in the brain. ̽��ֱ��COL4 gene is important for the health of this matrix.

In their disease model, the team found that the extracellular matrix is disrupted, particularly at its so-called ‘tight junctions’, which ‘zip’ cells together. This leads to the small blood vessels becoming leaky – a key characteristic seen in SVD, where blood leaks out of the vessels and into the brain.

̽��ֱ��researchers identified a class of molecules called metalloproteinases (MMPs) that play a key role in this damage. Ordinarily, MMPs are important for maintaining the extracellular matrix, but if too many of them are produced, they can damage the structure – similar to how in ̽��ֱ��Sorcerer’s Apprentice, a single broom can help mop the floor, but too many wreak havoc.

When the team treated the blood vessels with drugs that inhibit MMPs – an antibiotic and anti-cancer drug – they found that these reversed the damage and stopped the leakage.

Dr Granata added: “These particular drugs come with potentially significant side effects so wouldn’t in themselves be viable to treat small vessel disease. But they show that in theory, targeting MMPs could stop the disease. Our model could be scaled up relatively easily to test the viability of future potential drugs.”

̽��ֱ��study was funded by the Stroke Association, British Heart Foundation and Alzheimer’s Society, with support from the NIHR Cambridge Biomedical Research Centre and the European Union’s Horizon 2020 Programme.

Reference
Al-Thani, M, Goodwin-Trotman, M. A novel human 1 iPSC model of COL4A1/A2 small vessel disease unveils a key pathogenic role of matrix metalloproteinases. Stem Cell Reports; 16 Nov 2023; DOI: https://doi.org/10.1016/j.stemcr.2023.10.014

Cambridge scientists have grown small blood vessel-like models in the lab and used them to show how damage to the scaffolding that supports these vessels can cause them to leak, leading to conditions such as vascular dementia and stroke.

Despite the number of people affected worldwide by small vessel disease, we have little in the way of treatments because we don’t fully understand what damages the blood vessels and causes the disease

Alessandra Granata

Alessandra Granata/ ̽��ֱ�� of Cambridge

Disease mural cells stained for calponin (mural cells marker, green), collagen IV (magenta) and DAPI (nuclei, blue)

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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New Heart and Lung Research Institute opens

cjb250 — Mon, 11 Jul 2022 06:31:58 +0000

A major new institute opens today, bringing together the largest concentration of scientists and clinicians in heart and lung medicine in Europe.

Epilepsy drug could help prevent stroke in people with ‘furred’ arteries

cjb250 — Mon, 04 Apr 2022 07:45:01 +0000

A drug used to treat epilepsy patients could help prevent stroke in people whose arteries show signs of atherosclerosis – furring of the arteries – scientists will tell audiences at the Cambridge Festival.

New risk calculator to help save many more lives from heart attack and stroke

Anonymous — Sun, 13 Jun 2021 23:12:13 +0000

̽��ֱ��risk calculator, SCORE2, will be adopted by the upcoming European Guidelines on Cardiovascular Disease Prevention in Clinical Practice, and enables doctors across Europe to predict who’s at risk of having a heart attack or stroke in the next 10 years with greater accuracy.

̽��ֱ��researchers say this new prediction tool will help save many more people across Europe from having a potentially deadly heart attack or stroke, ultimately saving lives. People who are flagged as having an increased risk can be put on personalised preventative treatment, such a statins, or will receive lifestyle advice to lower their risk.

Researchers from the ̽��ֱ�� of Cambridge played a leading role in a major collaborative effort involving around 200 investigators to develop SCORE2. Researchers across Europe analysed data from nearly 700,000 participants - mostly middle-aged - from 45 different studies. ̽��ֱ��tool has also been tailored for use in different European countries.

Participants had no prior history of heart and circulatory disease when they were recruited to the studies, and in the 10 years they were followed up, 30,000 had a ‘cardiovascular event’ – including fatal or non-fatal heart attack or stroke.

̽��ֱ��risk tool was then statistically ‘recalibrated’, by using regional-specific cardiovascular and risk factor data from 10.8 million people, to more accurately estimate cardiovascular risk for populations split into four European risk regions. ̽��ֱ��tool uses known risk factors for heart and circulatory diseases such as age, sex, cholesterol levels, blood pressure and smoking.

This is a much-needed upgrade from the previous prediction tool that was developed using data before 1986 and underestimated the cardiovascular risk in some countries. ̽��ֱ��new SCORE2 risk calculator now accounts for current trends in heart and circulatory diseases, can predict both fatal and non-fatal conditions and is adaptable to countries with different levels of risk.

̽��ֱ��researchers say that this upgrade will better estimate the cardiovascular risk amongst younger people, and will improve how treatment is tailored for older people and those in high-risk regions across Europe.

Professor Emanuele Di Angelantonio at the ̽��ֱ�� of Cambridge British Heart Foundation (BHF) Centre of Research Excellence, said: “This risk tool is much more powerful and superior than what doctors have used for decades. It will fit seamlessly into current prevention programmes with substantial real-world impact by improving the prevention of cardiovascular diseases across Europe before they strike.”

Dr Lisa Pennells, also at Cambridge’s BHF Centre of Research Excellence, said: “This project was a highly collaborative effort that has brought together key experts and extensive data sources to develop improved risk prediction tools for cardiovascular disease for use across the UK and Europe.

“A key feature is that our calculators are relevant to current day rates of cardiovascular disease in different regions of Europe. Importantly, our methods allow them to be easily updated using routinely collected data in the future to ensure they stay relevant as trends in heart and circulatory diseases change.”

This study was carried out by the SCORE2 Working Group and the European Society of Cardiology Cardiovascular Risk Collaboration. It was supported by organisations including the British Heart Foundation, the Medical Research Council, National Institute for Health Research Cambridge Biomedical Research Centre and Health Data Research UK.

Professor Sir Nilesh Samani, Medical Director at the BHF and cardiologist, said: “Heart and circulatory diseases are the world’s biggest killers, impacting the lives of 7.6 million people across the UK alone.

“This new risk tool is a major advance and will save many more people from developing heart attacks, stroke and heart disease, all of which develop silently over many years and strike without warning. It will be the new gold standard for doctors to determine which patients are at the highest risk of these conditions, and enable tailored treatment and lifestyle advice to be given much earlier.”

Reference
SCORE2 risk prediction algorithms: revised models to estimate 10-year risk of cardiovascular disease in Europe. European Heart Journal; 14 June 2021; DOI: 10.1093/eurheartj/ehab309

Adapted from a press release from the British Heart Foundation

A new risk calculator will better predict people at high risk of heart and circulatory diseases years before they strike, and is ready for use across the UK and Europe, according to research published in the journal European Heart Journal.

This risk tool... will fit seamlessly into current prevention programmes with substantial real-world impact by improving the prevention of cardiovascular diseases across Europe before they strike

Emanuele Di Angelantonio

Pexels

Man clutching his heart

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Could a vaccine protect us against heart attacks?

cjb250 — Thu, 20 May 2021 07:15:46 +0000

Professor Ziad Mallat and his team have been shortlisted for a £30 million grant from the British Heart Foundation. If successful, atherosclerosis – hardening of the arteries – could become a thing of the past.

New genetic clues point to new treatments for ‘silent’ stroke

cjb250 — Thu, 25 Mar 2021 23:30:09 +0000

Researchers discovered changes to 12 genetic regions in the DNA of people who have had a lacunar stroke – a type of stroke caused by weakening of the small blood vessels deep within the brain. Over time, damage to the blood vessels and subsequent interruption to blood flow can lead to long-term disability, causing difficulty with thinking, memory, walking and ultimately dementia.

There are few proven drugs to prevent or treat lacunar strokes. ̽��ֱ��blood vessels affected are less than a millimetre wide and a lacunar stroke can strike without the person knowing. It’s not usually until someone has had a number of these strokes and starts to see signs of dementia that they realise something is wrong.

To date, only one genetic fault has been associated with lacunar strokes. However, after over a decade of research, Professor Hugh Markus and his team at the ̽��ֱ�� of Cambridge working with researchers from around the world now believe their genetic breakthrough holds the key to finding much-needed treatments for lacunar stroke and vascular dementia.

In research funded by the British Heart Foundation, the team scanned and compared the genetic code of 7,338 patients who had a lacunar stroke with 254,798 people who had not. Participants were recruited from across Europe, United States, South America and Australia after they attended hospital and had an MRI or CT brain scan.

They discovered that many of the 12 genetic regions linked to lacunar strokes were involved in maintaining the neurovascular unit – the part of the brain that separates the blood vessels from the brain and ensures that nerves function normally. These genetic changes are thought to make the small blood vessels ‘leakier’, causing toxic substances to enter the brain, and meaning that messages travelling around the brain slow down or don’t arrive at all.

̽��ֱ��team now plan to test whether new treatments can correct these abnormalities on brain cells in the lab. They hope to begin human clinical trials in the next ten years.

̽��ֱ��study also highlighted that high blood pressure, type 2 diabetes and a history of smoking are causally associated with an increased risk of lacunar stroke, identifying things that we can immediately tackle.

Professor Hugh Markus, leader of the study and neurologist at the ̽��ֱ�� of Cambridge, said: “These small and often silent lacunar strokes have gone under the radar for a long time, and so we haven’t been able treat patients as well as we’d like to. Although small, their consequences for patients can be enormous. They cause a quarter of all strokes and they are the type of stroke which is most likely to lead to vascular dementia.

“We now plan to use this new genetic blueprint as a springboard to develop much needed treatments to prevent lacunar strokes from occurring in the first place and to help stave off dementia.”

Dr Matthew Traylor, first author of the study at Queen Mary ̽��ֱ�� of London, said: “Genetics offers one of the few ways we can discover completely new insights into what causes a disease such as lacunar stroke. It is only by better understanding of what causes the disease that we will be able to develop better treatments.”

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, said:

“This is the most extensive genetic search to date which truly gets to grips with what cause lacunar strokes. These findings are a significant leap forward and we now have a much greater understanding of the genetics and biology behind what causes the small blood vessels deep in the brain to become diseased.

“Lacunar strokes affect around 35,000 people in the UK each year. This research provides real hope that we can prevent and treat this devastating type of stroke much better in the

Reference

Traylor, M et al. Genetic basis of lacunar stroke: a pooled analysis of individual patient data and genome-wide association studies. Lancet Neurology; 26 Mar 2021.

Adapted from a press release by the British Heart Foundation

Scientists have identified new genetic clues in people who have had small and often apparently ‘silent’ strokes that are difficult to treat and a major cause of vascular dementia, according to research led by the ̽��ֱ�� of Cambridge and published in ̽��ֱ��Lancet Neurology.

These small and often silent lacunar strokes have gone under the radar for a long time, and so we haven’t been able treat patients as well as we’d like to. Although small, their consequences for patients can be enormous

Hugh Markus

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Elderly man's hands

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Age and pre-existing conditions increase risk of stroke among COVID-19 patients

cjb250 — Wed, 28 Oct 2020 15:34:55 +0000

COVID-19 has become a global pandemic, affecting millions of people worldwide. In many cases, the symptoms include fever, persistent dry cough and breathing difficulties, and can lead to low blood oxygen. However, the infection can cause disease in other organs, including the brain, and in more severe cases can lead to stroke and brain haemorrhage.

A team of researchers at the Stroke Research Group, ̽��ֱ�� of Cambridge, carried out a systematic review and meta-analysis of published research into the link between COVID-19 and stroke. This approach allows researchers to bring together existing – and often contradictory or under-powered – studies to provide more robust conclusions.

In total, the researchers analysed 61 studies, covering more than 100,000 patients admitted to hospital with COVID-19. ̽��ֱ��results of their study are published in the International Journal of Stroke.

̽��ֱ��researchers found that stroke occurred in 14 out of every 1,000 cases. ̽��ֱ��most common manifestation was acute ischemic stroke, which occurred in just over 12 out of every 1,000 cases. Brain haemorrhage was less common, occurring in 1.6 out of every 1,000 cases. Most patients had been admitted with COVID-19 symptoms, with stroke occurring a few days later.

Age was a risk factor, with COVID-19 patients who developed stroke being on average (median) 4.8 years older than those who did not. COVID-19 patients who experienced a stroke were on average (median) six years younger than non-COVID-19 stroke patients. There was no sex difference and no significant difference in rates of smokers versus non-smokers.

Pre-existing conditions also increased the risk of stroke. Patients with high blood pressure were more likely to experience stroke than patients with normal blood pressure, while both diabetes and coronary artery disease also increased risk. Patients who had a more severe infection with SARSCoV2 – the coronavirus that causes COVID-19 – were also more likely to have a stroke.

̽��ֱ��researchers found that COVID-19-associated strokes often followed a characteristic pattern, with stroke caused by blockage of a large cerebral artery, and brain imaging showing strokes in more than one cerebral arterial territory. They argue that this pattern suggests cerebral thrombosis and/or thromboembolism are important factors in causing stroke in COVID-19. COVID-19-associated strokes were also more severe and had a high mortality.

An important question is whether COVID-19 increases the risk of stroke or whether the association is merely a result of COVID-19 infection being widespread in the community.

“ ̽��ֱ��picture is complicated,” explained Dr Stefania Nannoni from the Department of Clinical Neurosciences at the ̽��ֱ�� of Cambridge, the study’s first author. “For example, a number COVID-19 patients are already likely to be at increased risk of stroke, and other factors, such as the mental stress of COVID-19, may contribute to stroke risk.

“On the other hand, we see evidence that COVID-19 may trigger – or at least be a risk factor for – stroke, in some cases. Firstly, SARSCoV2 more so than other coronaviruses – and significantly more so than seasonal flu – appears to be associated with stroke. Secondly, we see a particular pattern of stroke in individuals with COVID-19, which suggests a causal relationship in at least a proportion of patients.”

̽��ֱ��researchers say there may be several possible mechanisms behind the link between COVID-19 and stroke. One mechanism might be that the virus triggers an inflammatory response that causes thickening of the blood, increasing the risk of thrombosis and stroke. Another relates to ACE2 – a protein ‘receptor’ on the surface of cells that SARS-CoV-2 uses to break into the cell. This receptor is commonly found on cells in the lungs, heart, kidneys, and in the lining of blood vessels – if the virus invades the lining of blood vessels, it could cause inflammation, constricting the blood vessels and restricting blood flow.

A third possible mechanism is the immune system over-reacting to infection, with subsequent excessive release of proteins known as cytokine. This so-called ‘cytokine storm’ could then cause brain damage.

̽��ֱ��team say their results may have important clinical implications.

“Even though the incidence of stroke among COVID-19 patients is relatively low, the scale of the pandemic means that many thousands of people could potentially be affected worldwide,” said Professor Hugh Markus, who leads the Stroke Research Group at Cambridge.

“Clinicians will need to look out for signs and symptoms of stroke, particularly among those groups who are at particular risk, while bearing in mind that the profile of an at-risk patient is younger than might be expected.”

While the majority of strokes occurred after a few days of COVID-19 symptoms onset, neurological symptoms represented the reason for hospital admission in more than one third of people with COVID-19 and stroke.

Dr Nannoni added: “Given that patients admitted to hospital with symptoms of stroke might have mild COVID-19-related respiratory symptoms, or be completely asymptomatic, we recommend that all patients admitted with stroke be treated as potential COVID-19 cases until the results of screening in the hospital are negative.”

̽��ֱ��research was supported by the Medical Research Council, the National Institute for Health Research (NIHR), the NIHR Cambridge Biomedical Research and the British Heart Foundation.

Reference
Nannoni S, de Groot R, Bell S, Markus HS. Stroke in COVID-19: a systematic review and meta-analysis. Int J Stroke; 26 Oct 2020; DOI: 10.1177/1747493020972922. Epub ahead of print. PMID: 33103610.

Fourteen out of every 1,000 COVID-19 patients admitted to hospital experience a stroke, a rate that is even higher in older patients and those with severe infection and pre-existing vascular conditions, according to a report published this week.

Even though the incidence of stroke among COVID-19 patients is relatively low, the scale of the pandemic means that many thousands of people could potentially be affected worldwide

Hugh Markus

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Brain inflammation stroke

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