̽��ֱ�� of Cambridge - Cardiovascular Epidemiology Unit

Moderate drinking linked to lower risk of some – but not all – heart conditions

cjb250 — Wed, 22 Mar 2017 23:30:27 +0000

̽��ֱ��finding that moderate drinking is not universally associated with a lower risk of all cardiovascular conditions suggests a more nuanced approach to the role of alcohol in prevention of cardiovascular disease is necessary, say the researchers.

Moderate drinking is thought to be associated with a lower risk of developing cardiovascular disease compared with abstinence or heavy drinking.

In the UK, moderate drinking is defined as no more than 14 units of alcohol a week, the equivalent of 7 pints of ordinary strength beer or just over one and a half bottles of ordinary strength wine.

There is, however, a growing scepticism around this observation, with some experts pointing out several shortcomings in the evidence, for example grouping non-drinkers with former drinkers, who may have stopped drinking due to poor health.

Researchers at the ̽��ֱ�� of Cambridge and ̽��ֱ�� College London set out to investigate the association between alcohol consumption and 12 cardiovascular diseases by analysing electronic health records for 1.93 million healthy UK adults as part of the CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records) data resource.

All participants were free from cardiovascular disease at the start of the study, and non-drinkers were separated from former and occasional drinkers to provide additional clarity in this debate.

̽��ֱ��researchers looked at the effect of different levels of drinking on the risk of ‘first presenting’ to a doctor with a number of cardiovascular diseases; for example, did moderate drinking make it more or less likely that an individual’s first diagnosis of cardiovascular disease was a heart attack.

After several influential factors were accounted for, moderate drinking was associated with a lower risk of several, but not all, cardiovascular conditions, including angina, heart failure and ischaemic stroke (the most common type of stroke, when a blood clot blocks the flow of blood and oxygen to the brain), compared with abstaining from alcohol.

“This doesn’t mean that it is advisable for individuals to take up drinking as a means of lowering their cardiovascular risk,” says Dr Steven Bell from the Department of Public Health and Primary Care at the ̽��ֱ�� of Cambridge. “Alcohol consumption is associated with other diseases, such as liver disease and certain types of cancer. There are other, safer and more effective ways, such as being more physically active, maintaining a healthy diet and stopping smoking.

“Ultimately an individual’s decision to drink, and at what level, should not be considered in isolation of other health behaviours or risk factors and instead be motivated by their own personal circumstances.”

Heavy drinking (exceeding recommended limits) conferred an increased risk of a range of cardiovascular diseases, including heart failure, cardiac arrest (when the heart malfunctions and stops beating suddenly) and ischaemic stroke compared with moderate drinking. However, it carried a lower risk of heart attack (when blood flow to the heart is blocked) and angina.

Again, the authors explain that this does not mean that heavy drinkers will not go on to experience a heart attack in the future, just this was less likely to be their first diagnosis compared with moderate drinkers.

This is an observational study, so no firm conclusions can be drawn about cause and effect. Added to which, the authors point to some study limitations that could have introduced bias.

Nevertheless, they say it is the first time this association has been investigated on such a large scale and their findings have implications for patient counselling, public health communication, and disease prediction tools.

In a linked editorial, researchers at Harvard Medical School and Johns Hopkins School of Public Health in the US say this study “sets the stage for ever larger and more sophisticated studies that will attempt to harness the flood of big data into a stream of useful, reliable, and unbiased findings that can inform public health, clinical care, and the direction of future research”.

Reference
Bell, S et al. Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records. BMJ; 23 Mar 2017; DOI: 10.1136/bmj.j909

Adapted from a press release from ̽��ֱ��BMJ.

Moderate drinking is associated with a lower risk of several, but not all, cardiovascular diseases, according to a large study of UK adults led by researchers at the ̽��ֱ�� of Cambridge and ̽��ֱ�� College London published today in ̽��ֱ��BMJ.

This doesn’t mean that it is advisable for individuals to take up drinking as a means of lowering their cardiovascular risk. There are other, safer and more effective ways, such as being more physically active, maintaining a healthy diet and stopping smoking

Steven Bell

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A BLUEPRINT for blood cells: Cambridge researchers play leading role in major release of epigenetic studies

cjb250 — Thu, 17 Nov 2016 17:00:15 +0000

̽��ֱ��studies are part of BLUEPRINT, a large-scale research project bringing together 42 leading European universities, research institutes and industry entrepreneurs, with close to €30 million of funding from the EU. BLUEPRINT scientists have this week released a collection of 26 publications, part of a package of 41 publications being released by the International Human Epigenome Consortium.

One of the great mysteries in biology is how the many different cell types that make up our bodies are derived from a single stem cell and how information encoded in different parts of our genome are made available to be used by different cell types. Scientists have learned a lot from studying the human genome, but have only partially unveiled the processes underlying cell determination. ̽��ֱ��identity of each cell type is largely defined by an instructive layer of molecular annotations on top of the genome – the epigenome – which acts as a blueprint unique to each cell type and developmental stage.

Unlike the genome, the epigenome changes as cells develop and in response to changes in the environment. Defects in the proteins that read, write and erase the epigenetic information are involved in many diseases. ̽��ֱ��comprehensive analysis of the epigenomes of healthy and abnormal cells will facilitate new ways to diagnose and treat various diseases, and ultimately lead to improved health outcomes.

“This huge release of research papers will help transform our understanding of blood-related and autoimmune diseases,” says Professor Willem H Ouwehand from the Department of Haematology at the ̽��ֱ�� of Cambridge, one of the Principal Investigators of BLUEPRINT. “BLUEPRINT shows the power of collaboration among scientists across Europe in making a difference to our knowledge of how epigenetic changes impact on our health.”

Among the papers led by Cambridge researchers, Professor Nicole Soranzo and Dr Adam Butterworth have co-led a study analysing the effect of genetic variants in our DNA sequence on our blood cells. Using a genome-wide association analysis, the team identified more than 2,700 variants that affect blood cells, including hundreds of rare genetic variants that have far larger effects on the formation of blood cells than the common ones. Interestingly, they found genetic links between the effects of these variants and autoimmune diseases, schizophrenia and coronary heart disease, thereby providing new insights into the causes of these diseases.

A second study led by Professor Soranzo looked at the contribution of genetic and epigenetic factors to different immune cell characteristics in the largest cohort of this kind created with blood donors from the NHS Blood and Transplant centre in Cambridge.

Dr Mattia Frontini and Dr Chris Wallace, together with scientists at the Babraham Institute, have jointly led a third study mapping the regions of the genome that interact with genes in 17 different blood cell types. By creating an atlas of links between genes and the remote regions that regulate them in each cell type, they have been able to uncover thousands of genes affected by DNA modifications, pointing to their roles in diseases such as rheumatoid arthritis and other types of autoimmune disease.

Dr Frontini has also co-led a study with BLUEPRINT colleagues from the ̽��ֱ�� of Vienna that has developed a reference map of how epigenetic changes to DNA can program haematopoietic stem cells – a particular type of ‘master cell’ – to develop into the different types of blood and immune cells.

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, which helped fund the research, said: “Our genes are critical to our health and there’s still a wealth of information hidden in our genetic code. By taking advantage of a large scale international collaboration, involving the combined expertise of dozens of research groups, these unprecedented studies have uncovered potentially crucial knowledge for the development of new life saving treatments for heart disease and many other deadly conditions.

“Collaborations like this, which rely on funding from the public through charities and governments across the globe, are vital for analysing and understanding the secrets of our genetics. Research of this kind is helping us to beat disease and improve millions of lives.”

Departmental Affiliations

Professor Nicole Soranzo – Department of Haematology
Dr Adam Butterworth – Medical Research Council (MRC)/British Heart Foundation (BHF) Cardiovascular Epidemiology Unit
Dr Mattia Frontini – Department of Haematology, and Senior Research Fellow for the BHF Cambridge Centre for Research Excellence
Dr Chris Wallace – Department of Medicine and MRC Biostatistics Unit

References

Astle, WJ et al. ̽��ֱ��allelic landscape of human blood cell trait variation. Cell; 17 Nov 2016; DOI: 10.1016/j.cell.2016.10.042
Chen, L et al. Genetic drivers of epigenetic and transcriptional variation in human immune cells. Cell; 17 Nov 2016; DOI: 10.1371/journal.pbio.0000051
Javierre et al. Lineage-specific genome architecture links enhancers and non-coding disease variants to target gene promoters. Cell; 17 Nov 2016; DOI: 10.1016/j.cell.2016.09.037
Farlik et al. Cell Stem Cell; 17 Nov 2016; DOI: 10.1016/j.stem.2016.10.019

Cambridge researchers have played a leading role in several studies released today looking at how variation in and potentially heritable changes to our DNA, known as epigenetic modifications, affect blood and immune cells, and how this can lead to disease.

BLUEPRINT shows the power of collaboration among scientists across Europe in making a difference to our knowledge of how epigenetic changes impact on our health

Willem Ouwehand

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‘Good’ cholesterol doesn’t always lower heart attack risk

cjb250 — Fri, 11 Mar 2016 09:48:43 +0000

̽��ֱ��discovery, published today in Science, could move researchers away from potentially ineffective HDL-raising drugs to treat coronary heart disease, and lead to the development of new treatments, helping to reduce their risk of heart attack.

̽��ֱ��researchers studied people with a rare genetic mutation in the SCARB1 gene, called the P376L variant, which causes the body to have high levels of ‘good’ HDL-C. High levels of ‘good’ cholesterol are commonly associated with reduced risk for coronary heart disease. Challenging this view, the researchers unexpectedly found that people with the rare mutation, who had increased levels of HDL-C, had an 80 per cent increased relative risk of the disease – a figure almost equivalent to the increased risk caused by smoking.

Coronary heart disease is responsible for nearly 70,000 deaths every year, almost entirely through heart attacks, making it the UK’s single biggest killer. ̽��ֱ��disease involves the build-up of fatty material, or plaque, in the coronary artery walls. If large quantities accumulate in the vessel walls, blood flow to the heart can become restricted or blocked, increasing risk of a heart attack.

̽��ֱ��international team of scientists included BHF-funded researchers Professor Sir Nilesh Samani at the ̽��ֱ�� of Leicester and Professor John Danesh at the ̽��ֱ�� of Cambridge. They initially looked at the DNA of 328 individuals with very high levels of HDL-C in the blood and compared them to 398 people with relatively low HDL-C. As the P376L variant they found was so rare, they then looked at its effects on HDL-C and heart disease in more than half a million additional people.

Dr Adam Butterworth, from the Cardiovascular Epidemiology Unit, ̽��ֱ�� of Cambridge, and co-investigator of this study, said: “We found that people carrying a rare genetic mutation causing higher levels of the so-called ‘good’ HDL-cholesterol are, unexpectedly, at greater risk of heart disease. This discovery could lead to new drugs that improve the processing of HDL-C to prevent devastating heart attacks.

“Large-scale collaborative research like this paves the way for further studies of rare mutations that might be significantly increasing people’s risk of a deadly heart attack. These discoveries also give researchers the knowledge we need to develop better treatments.”

Professor Peter Weissberg, Medical Director at the BHF, added said: “This is an important study that sheds light on one of the major puzzles relating to cholesterol and heart disease, which is that despite strong evidence showing HDL-C reduces heart disease risk, clinical trials on the effects of HDL-C-raising drugs have been disappointing.

“These new findings suggest that the way in which HDL-C is handled by the body is more important in determining risk of a heart attack than the levels of HDL-C in the blood. Only by understanding the underlying biology that links HDL-C with heart attacks can we develop new treatments to prevent them. These unexpected findings pave the way for further research into the SCARB1 pathway to identify new treatments to reduce heart attacks in the future.”

Additional funding for the study in the USA came from the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institute of Health.

Reference
Zanoni, P et al. Rare Variant in Scavenger Receptor BI raises HDL Cholesterol and Increases Risk of Coronary Heart Disease. Science; 10 Mar 2016; DOI: 10.1126/science.aad3517

Adapted from a press release from the British Heart Foundation

Some people with high levels of ‘good’ high density lipoprotein cholesterol (HDL-C) are at increased risk of coronary heart disease, contrary to earlier evidence that people with more HDL-C are usually at lower heart disease risk. This finding comes from an international study involving researchers at the ̽��ֱ�� of Cambridge, funded by the British Heart Foundation (BHF).

Large-scale collaborative research like this paves the way for further studies of rare mutations that might be significantly increasing people’s risk of a deadly heart attack

Adam Butterworth

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