̽��ֱ�� of Cambridge - hypertension

Extending weight loss programme helps overweight people keep more weight off and is cost-effective

cjb250 — Thu, 04 May 2017 07:52:57 +0000

Although upfront costs for the longer programme are higher, the study estimates that offering more sessions would be cost-effective to the NHS in the long-term because it would help to prevent more people from developing diseases as a result of their weight.

“This trial provides important data that offering support to lose weight – by referring people to a community weight loss group – is more successful than a self-help approach, and that providing classes for longer helps people keep weight off for longer,” says Professor Susan Jebb, senior author of the study from ̽��ֱ�� of Oxford. “Our results also show that, in the long-term, weight loss groups are cost-effective for society as a whole because they are likely to reduce future healthcare expenditure by preventing costly conditions such as diabetes and coronary heart disease.”

̽��ֱ��NHS currently refers people who are obese to 12-week long weight loss programmes run by commercial groups and provides vouchers for free attendance. These are among the most commonly commissioned programmes to treat obesity in the UK and the National Institute for Health and Care Excellence recommends that programmes last at least 12 weeks. However, there is little evidence to suggest how long these programmes should last to be most effective.

̽��ֱ��new study involves 1,267 participants with a body mass index (BMI) of 28 or above and compares the effectiveness of a 12-week and a year-long programme of free Weight Watchers sessions to one-off advice together with a self-help booklet.

After a year, those given the self-help booklet had lost 3.3kg, those referred to the 12-week programme had lost 4.8 kg, and those referred to the year-long programme had lost 6.8kg on average. Two years after they began treatment, participants in all groups regained some weight but all groups were still lighter on average than at the start of treatment. ̽��ֱ��self-help group were 2.3kg lighter, the 12-week programme were 3.0kg lighter, while the group offered a one-year programme were 4.3kg lighter.

Compared to participants in the other groups, those in the year-long programme also had significantly greater reductions in fasting blood glucose and glycosylated haemoglobin, which are important markers of the risk of developing diabetes. After a year, those on the year-long programme saw their blood glucose level reduce by 0.54mmol per litre of blood (compared to reductions of 0.27mmol/litre for the 12-week group and 0.11mmol/litre for the self-help group).

̽��ֱ��researchers also modelled the impact of the three programmes over the next 25 years to predict how many people would develop different weight-related illnesses. They also estimated the impact of the programmes on quality of life, the cost of providing the programmes, as well as cost-savings to health services from preventing future diseases.

̽��ֱ��12-week programme was predicted to prevent more illnesses than the self-help intervention due to greater weight loss. Over 25 years, the cost to the NHS of providing the programme would be more than offset by the later savings as a result of reductions in disease, making it overall cost-saving.

Offering a year-long programme was estimated to prevent an additional 1,786 cases of disease (including 642 fewer cases of hypertension, 373 fewer cases of diabetes and 104 fewer cases of heart disease) for every 100,000 people, compared to the 12-week programme. So, although it was more expensive upfront, the study shows that the year-long programme is cost-effective over 25 years by preventing more cases of weight related illness.

“We’ve seen before that a 12-week programme can help people lose weight, but for the first time we’ve shown that extending this to a full year leads to greater weight loss over a longer period and a lower risk of diabetes,” says lead author Dr Amy Ahern from the MRC Epidemiology Unit at ̽��ֱ�� ̽��ֱ�� of Cambridge.

“Although the initial costs of the year-long programme are greater, it’s very likely that it will be good value for money over the long term because of the reduction in weight-related illnesses. ̽��ֱ��results from the one-year programme are comparable to what has been seen in previous trials that used much more costly interventions, usually involving multiple contacts with health professionals.”

Professor Jebb adds: “We know that many local authorities are questioning how best to spend their limited budgets. We have shown that the longer programmes bring greater benefits, with only modest extra costs. But at a time when some areas are reducing their expenditure on obesity treatment, the first step is to ensure that people who want help to lose weight have access to at least a standard 12-week weight loss programme, which we have shown is likely to be cost-saving for the NHS.”

Reference
Ahern, AL et al. Extended and standard duration weight-loss programme referrals for adults in primary care (WRAP): a randomised controlled trial. Lancet; 4 May 2017; DOI: 10.1016/S0140-6736(17)30647-5

Adapted from a press release by ̽��ֱ��Lancet

Extending NHS weight loss programmes from one session per week for 12-weeks to one session per week for a year helped people who are overweight to lose more weight and keep it off for longer, according to a study published in ̽��ֱ��Lancet, and led by researchers from the ̽��ֱ�� of Cambridge, ̽��ֱ�� of Liverpool and ̽��ֱ�� of Oxford.

Although the initial costs of the year-long programme are greater, it’s very likely that it will be good value for money over the long term because of the reduction in weight-related illnesses

Amy Ahern

Quinn Dombrowski

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High fat, high sugar diet during pregnancy 'programs' for health complications in mother and child

tdk25 — Thu, 06 Apr 2017 03:00:53 +0000

In a study carried out in pregnant mice, a team of academics found that an obesity-causing high fat and high sugar diet disrupted processes within the pregnant mother’s body, leading to poor metabolic control. These changes were found just prior to birth and may make her more susceptible to conditions such as type 2 diabetes and heart disease, as well as to further fat accumulation, in later motherhood.

̽��ֱ��exact impact on her child during pregnancy was harder to ascertain, but the researchers found that metabolic dysfunction in the mother compromised the flow of nutrients to the foetus, altering its growth and metabolism at critical stages during its development. This strongly suggests that an obesogenic diet (a diet which promotes obesity) also has consequences for foetal development. It may also explain why babies from mothers who are obese or eat obesogenic diets during pregnancy have a tendency to develop conditions such as obesity, hypertension and type 2 diabetes as adults.

In particular, the researchers found that a higher than recommended intake of fat and sugar exacerbates and distorts metabolic changes which occur naturally as a result of the pregnancy, so that the mother can appropriately allocate nutrients to the foetus.

̽��ֱ��study was carried out by a team of researchers at the ̽��ֱ�� of Cambridge. ̽��ֱ��lead author is Dr Amanda Sferruzzi-Perri, from St John’s College, Cambridge, and the Centre for Trophoblast Research in the Department of Physiology, Development and Neuroscience. She said that the findings were especially relevant for women in western countries.

“In places like the UK, the US and Australia, many women of child-bearing age are also eating higher amounts of fat and sugar than the National Dietary Recommendations,” she said. “We know that obesity during pregnancy is a risk factor for health complications for mother and baby both during and after pregnancy. This study offers insight into the mechanisms operating during pregnancy that may cause this.”

̽��ֱ��study involved feeding a diet that contained high amounts of fat and sugar to pregnant mice. ̽��ֱ��researchers then assessed the impact of this on both the metabolism of the mother and her levels of body fat, compared to mice which were fed a more balanced diet.

They related these changes in whole-body metabolism to the expression of proteins in the mother’s tissues, which are responsible for processing and storing nutrients, as well as to the supply of nutrients, growth and metabolism of her developing foetuses. All of the experiments were carried out in line with the UK Home Office Animals (Scientific Procedures) Act 1986.

Overall, the researchers found that excessive consumption of sugar and fat compromised the mother’s glucose tolerance and her sensitivity to insulin – the hormone that controls blood sugar levels.

Specifically, they found that the mother’s ability to respond to insulin was reduced in tissues like her muscle and fat, which take up glucose from the circulation. By contrast, the sensitivity of the maternal liver to insulin was increased, which reduces glucose production during pregnancy. As a result, the mother was unable adequately to control glucose levels or produce enough glucose to support the pregnancy.

̽��ֱ��high fat, high sugar diet also changed the expression of proteins in the mother’s body that control fat storage, leading to an increase in body fat. Collectively, the researchers suggest that these effects promote a “pre-diabetic state” in the mother, resembling many aspects of gestational diabetes; a pregnancy complication which affects up to 5% of women in the UK.

One of the main reasons for this may be that an obesogenic diet exaggerates natural metabolic changes associated with pregnancy. “During a normal pregnancy, the mother’s body will change the way it handles nutrients so that some can be freed up for the foetus,” Sferruzzi-Perri explained. “ ̽��ֱ��mother’s metabolism is shifted to an insulin resistant, glucose intolerant state, such that her own glucose use is limited in favour of foetal supply. We think that in cases where the mother has a high fat, high sugar diet, these metabolic changes are exacerbated or perturbed.”

These effects, the researchers suggest, may alter the mother’s disposition to develop health complications after she has given birth as well – a phenomenon that they refer to as a “metabolic memory”, putting her at greater risk of type 2 diabetes, obesity and cardiovascular problems in later life.

̽��ֱ��study also found that the defects in the mother’s metabolism impaired nutrient flow to the foetus, as they resulted in the preferential storage of nutrients within the mother’s tissues, in favour of allocating these to the developing foetus.

Because the placenta also plays an important role in nutrient allocation (as previous studies have shown), the babies of mice fed the obesogenic diet were still born at a normal size. However, because the foetus receives different amounts of nutrients and shows defects in its ability to use these during development, the researchers believe that the child will still be more susceptible to metabolic dysfunction later in life.

“We still don’t know what the exact consequences for the foetus are, but the findings match existing research which already suggests that the individual will suffer from these metabolic problems during adulthood,” Sferruzzi-Perri said. “This is because changes to the nutrient and oxygen supply, at a stage when individual organs are developing, can cause a permanent change in the structure and function of certain tissues.”

̽��ֱ��full study, A Western-style obesogenic diet alters maternal metabolic physiology with consequences for fetal nutrient acquisition in mice is published in ̽��ֱ��Journal of Physiology. DOI: 10.1113/JP273684.

Eating a high fat and high sugar diet when pregnant leads to metabolic impairments in both the mother and her unborn child, which may 'program' them for potential health complications later in life, a study in mice has shown.

We know that obesity during pregnancy is a risk factor for health complications for mother and baby both during and after pregnancy. This study offers insight into the mechanisms operating during pregnancy that may cause this.

Amanda Sferruzzi-Perri

Free image via Max Pixel

̽��ֱ��researchers found that a high fat and high sugar diet exaggerates metabolic changes in the mother which occur naturally during pregnancy, potentially rendering her more susceptible to health complications.

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Major global study reveals new hypertension and blood pressure genes

sc604 — Mon, 12 Sep 2016 15:00:00 +0000

̽��ֱ��discoveries include DNA changes in three genes that have much larger effects on blood pressure in the population than previously seen, providing new insights into the physiology of hypertension and suggesting new targets for treatment.

High blood pressure or hypertension is a major risk factor for cardiovascular disease and premature death. It is estimated to be responsible for a larger proportion of global disease burden and premature mortality than any other disease risk factor. However, there is limited knowledge on the genetics of blood pressure.

̽��ֱ��teams investigated the genotypes of around 347,000 people and their health records to find links between their genetic make-up and cardiovascular health. ̽��ֱ��participants included healthy individuals and those with diabetes, coronary artery disease and hypertension, from across Europe, (including the UK, Denmark, Sweden, Norway, Finland and Estonia), the USA, Pakistan and Bangladesh. ̽��ֱ��study brought together around 200 investigators from across 15 countries.

Study author Professor Patricia Munroe from QMUL said: “We already know from earlier studies that high blood pressure is a major risk factor for cardiovascular disease. Finding more genetic regions associated with the condition allows us to map and understand new biological pathways through which the disease develops, and also highlight potential new therapeutic targets. This could even reveal drugs that are already out there but may now potentially be used to treat hypertension.”

Most genetic blood pressure discoveries until now have been of common genetic variants that have small effects on blood pressure. ̽��ֱ��study, published in Nature Genetics, has found variants in three genes that appear to be rare in the population, but have up to twice the effect on blood pressure.

“ ̽��ֱ��sheer scale of our study has enabled us to identify genetic variants carried by less than one in a hundred people that affect blood pressure regulation,” said study author, Dr Joanna Howson from Cambridge’s Department of Public Health and Primary Care. “While we have known for a long time that blood pressure is a risk factor for coronary heart disease and stroke, our study has shown that there are common genetic risk factors underlying these conditions.”

RBM47 is a gene that encodes for a protein responsible for modifying RNA. RRAS is involved in cell cycle processes and has already been implicated in a syndrome related to ‘Noonan syndrome’ which is characterised by heart abnormalities. COL21A1 is involved in collagen formation in many tissues, including the heart and aorta. COL21A1 and RRAS warrant particular interest since both are involved in blood vessel remodelling, with relevance to hypertension.

̽��ֱ��team also found a mutation in a key molecule ENPEP that affects blood pressure. This gene codes for an enzyme that is a key molecule involved in regulating blood pressure through the dilation and constriction of blood vessels, and is currently a therapeutic target.

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation which part-funded the research, said: “Large scale genetic studies continue to expand the number of genes that may contribute to the development of heart disease, or risk factors such as high blood pressure. But so far most of the genes discovered in these studies individually have only very small effects on risk – though they may still provide valuable clues for new drug targets.

“This study has increased the number of genes implicated in control of blood pressure to almost 100 and, in the process, has also identified three genes that have larger effects on blood pressure than previously found.”

̽��ֱ��study was also funded by the National Institute for Health Research (NIHR), National Institute of Health (NIH), Wellcome Trust and the Medical Research Council.

Reference:
Surendran et al. ‘Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension’. Nature Genetics 2016. DOI: 10.1038/ng.3654

Thirty-one new gene regions linked with blood pressure have been identified in one of the largest genetic studies of blood pressure to date, involving over 347,000 people, and jointly led by Queen Mary ̽��ֱ�� of London (QMUL) and the ̽��ֱ�� of Cambridge.

While we have known for a long time that blood pressure is a risk factor for coronary heart disease and stroke, our study has shown that there are common genetic risk factors underlying these conditions.

Joanna Howson

Yale Rosen

Pulmonary hypertension-associated vasculitis

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New research leaves tumours with nowhere to hide

Anonymous — Thu, 24 Sep 2015 09:25:29 +0000

̽��ֱ��small tumours concealed in the adrenal gland are “unmasked” in early pregnancy, when a sudden surge of hormones fires them into life, leading to raised blood pressure and causing risk to patients.

New research published today in the New England Journal of Medicine conducted by a team led by Professor Morris Brown, professor of clinical pharmacology at Cambridge ̽��ֱ�� and a Fellow of Gonville & Caius College, identifies this small group of lurking tumours for the first time, and explains why they behave as they do.

̽��ֱ��study means that, when patients are found to have high blood pressure early in pregnancy, doctors will now be encouraged to consider that the cause could be the tumours, which can be easily treated. Currently, adrenal tumours are not usually suspected as the cause of high blood pressure in pregnancy, and so go undiagnosed.

Brown and an international group of PhD students including first-author Ada Teo of Newnham College used a combination of state-of-the-art gene “fingerprinting” technology and old-fashioned deduction from patient case histories to work out that the otherwise benign tumours harbour genetic mutations that affect cells in the adrenal gland.

̽��ֱ��mutation means the adrenal cells are given false information and their clock is effectively turned back to “childhood”, returning them to their original state as ovary cells. They then respond to hormones released in pregnancy, producing increased levels of the salt-regulating hormone aldosterone.

Aldosterone in turn regulates the kidneys to retain more salt and hence water, pushing up blood pressure. High blood pressure – also known as hypertension – can be fatal, since it greatly increases the risk of stroke and heart attack.

̽��ֱ��new findings build on a growing body of research focusing on the adrenal gland and blood pressure. Sixty years ago, the American endocrinologist Dr Jerome Conn first observed that large benign tumours in the adrenal gland can release aldosterone and increase blood pressure (now known as Conn’s Syndrome).

Brown and his team have previously found a group of much smaller tumours, arising from the outer part of the gland, that have the same effect. ̽��ֱ��latest discovery drills down still further, revealing that roughly one in ten of this group has a mutation that makes the cells receptive to pregnancy hormones.

Brown said: “This is an example of what modern scientific techniques, and collaborations among doctors and scientists, allow you to do [through a form of genetic fingerprinting]. Conditions are often around for 60 years which we have had no explanation for, and now we can get to the heart of what has gone wrong.”

But the discovery also relied on what doctors call “clinical pattern recognition” – using experience to spot similarities. Brown was able to link together the cases of two pregnant women almost ten years apart and a woman in early menopause. All suffered high blood pressure, leading him to screen their adrenal tumours and identify a matching genetic mutation.

Pregnant women found to have the newly identified subset of tumours can now be identified more readily, and the tumours either treated with drugs or potentially even removed.

̽��ֱ��research was funded by the Wellcome Trust, National Institute for Health Research, British Heart Foundation and A* Singapore.

Hidden tumours that cause potentially fatal high blood pressure but lurk undetected in the body until pregnancy have been discovered by a Cambridge medical team.

Conditions are often around for 60 years which we have had no explanation for, now we can get to the heart of what has gone wrong

Morris Brown

11C metomidate PET CT of small Conn's tumour

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Old drug performs new tricks

Anonymous — Mon, 21 Sep 2015 08:24:54 +0000

Spironolactone, one of a range of drugs given according to doctors' preference to patients with resistant hypertension (high blood pressure that doesn't respond to a standard drug treatment), is in fact "outstandingly superior" to the alternatives, researchers have found. They recommend it should now be the first choice for such patients, and say that – for most – this well-known but under-valued drug will bring their condition fully under control.

̽��ֱ��discovery could have a profound impact globally, since hypertension, a major contributor to stroke and heart disease, is so common, affecting as many as one in three adults in some countries. It challenges what the authors describe as "a growing perception" that severe hypertension was beyond the control of existing drug treatments, and gives more clues into what causes the condition.

̽��ֱ��latest research, published today in the Lancet to coincide with their presentation to the British Hypertension Society, emerged from the PATHWAY-2 trial, part of the PATHWAY programme of trials in hypertension funded by the British Heart Foundation and led by Professor Morris Brown, professor of clinical pharmacology at Cambridge ̽��ֱ�� and a Fellow of Gonville & Caius College.

̽��ֱ��findings are drawn from what authors Brown and Professor Bryan Williams of ̽��ֱ�� College London describe as an experimental "shoot-out" between three different drugs used by doctors for years to treat patients if the standard initial cocktail of three hypertension drugs do not work.

Spironolactone 'slugged it out' against a betablocker (bisoprolol) and an alpha-blocker (doxazosin) in the trial, which took six years and involved 314 patients in 14 different centres.

̽��ֱ��patients all suffered from resistant high blood pressure that had not responded to the standard treatment for hypertension: a combination of three drugs (an ACE-inhibitor (or angiotensin-receptor blocker), a calcium channel blocker and a thiazide-type diuretic). They continued with this basic combination throughout, but each of the three trial drugs – and a placebo – was added one at a time, in random order, for 12 weeks each.

In what is known as a "double blind" trial, neither the patients nor the researchers knew which patient was taking which drug when. In a pioneering step, the study also used patients' own blood pressure readings taken at home to minimise so-called "white coat syndrome", in which the stress of being in a clinic causes blood pressure to rise artificially.

Once the resulting data had been analysed, it emerged that almost three quarters of patients in the trial saw a major improvement in blood pressure on spironolactone, with almost 60% hitting a particularly stringent measure of blood pressure control. Of the three drugs trialled, spironolactone was the best at lowering blood pressure in 60% of patients, whereas bisoprolol and doxazosin were the best drug in only 17% and 18% respectively.

"Spironolactone annihilated the opposition," said Brown. "Most patients came right down to normal blood pressure while taking it."

He added: "This is an old drug which has been around for a couple of generations that has resurfaced and is almost a wonder drug for this group of patients. In future it will stimulate us to look for these patients at a much earlier stage so we can treat and maybe even cure them before resistant hypertension occurs."

Doctors appear to have been wary of giving patients spironolactone because it raises the level of potassium in the body. But the study revealed the rise to be only marginal and not dangerous.

̽��ֱ��causes of resistant of hypertension are still poorly understood, but one theory is that the condition could be the result of sodium retention: too much salt in the body.

Spironolactone is a diuretic and helps the body get rid of salt. In the trial, it worked even better than average on patients whom tests showed had high salt levels. Brown said the findings appeared to confirm that, in most patients with resistant hypertension, excessive salt was the problem, probably caused by too much of the adrenal hormone aldosterone.

Instead of seeing the treatment-resistant form of high blood pressure as simply the result of having the condition for a long time or of poor treatment, it should be regarded as a different sub-group of hypertension which would need different investigations and treatments, Brown said.

Patients with the most dangerous type of high blood pressure will be able to receive far more effective treatment after Cambridge-led research reveals the powers of a "wonder drug" that has lain under the noses of doctors for 50 years.

jasleen_kaur

Sphygmomanometer

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New test could help thousands of patients with high blood pressure

gm349 — Wed, 30 Nov 2011 16:01:56 +0000

A new test developed by researchers at the ̽��ֱ�� of Cambridge could help doctors diagnose thousands of people with the most common curable cause of high blood pressure (hypertension). Research funded by the British Heart Foundation (BHF) and National Institute for Health Research (NIHR), showed a high-tech PET-CT scan could detect Conn’s syndrome, which causes up to five per cent of hypertension cases.

Around 12 million people in the UK are diagnosed with hypertension, a condition which greatly increases the risk of having a heart attack or stroke. For most people with hypertension there is no single underlying cause, but in a small minority there is a specific condition that causes blood pressure to rise. One of these conditions is called Conn’s syndrome – the most common curable cause of high blood pressure.

Conn’s syndrome is difficult to diagnose but an accurate diagnosis often leads to successful treatment. It’s caused by a benign tumour called an adenoma – about the size of a 5-pence coin – in one of the adrenal glands, which lie close to the kidneys. ̽��ֱ��tumour causes the over-production of a key blood pressure-regulating hormone called aldosterone. It can be treated either by surgically removing an affected gland, or by using a drug to block the effects of aldosterone.

̽��ֱ��new test, studied in 44 patients at Addenbrooke’s Hospital in Cambridge, scans the abdomen using ‘positron emission tomography with x-ray computer tomography’ technology, better known as a PET-CT and more commonly used in cancer diagnosis. ̽��ֱ��researchers developed a special radioactive tracer called 11C-metomidate, which lights up culprit adenomas in the scan. ̽��ֱ��test takes around 45 minutes.

̽��ֱ��current standard test for Conn’s syndrome relies on taking blood samples from a vein supplying the adrenal gland to measure the aldosterone level, a complex and difficult procedure which often fails to confirm the diagnosis. However, the researchers showed that their scan picked up adenomas causing hypertension in the majority of study patients, making it a potentially useful alternative to the standard test.

Morris Brown, Professor of Clinical Pharmacology at the ̽��ֱ�� of Cambridge, who led the study, said: “We were excited to see our technique work so well, and shortcut the delays and discomforts associated with the alternative test. We’re using PET-CT on our patients already, but we also plan a larger study to work out who will benefit the most. ̽��ֱ��test could be especially important for older patients – we often see growths in the adrenal glands during a routine CT scan. Often these growths are not Conn’s adenomas, but it’s difficult to be sure and they create a lot of anxiety in patients and doctors. In the future PET-CT could be a quick way to reassure a lot of patients without the need for detailed investigations.”

Dr Shannon Amoils, Research Advisor at the BHF, said: “Conn’s syndrome is the most common curable cause of high blood pressure. And although it affects only a small fraction of people with hypertension, it’s almost certainly more widespread than we previously thought. There are drugs that can control the high blood pressure caused by Conn’s syndrome, but the only cure is surgery, so making the diagnosis is very important. This new approach, using a PET-CT scan, offers real hope that more people with Conn’s syndrome will be accurately diagnosed in the future.”

Chris Wood, 56, who was diagnosed as having Conn’s syndrome by the new test, said: “When I had blood tests before, the results were never clear. I enrolled in Professor Brown’s study I had the scan, which took less than an hour, and immediately after the scan they showed me the pictures of the lump in my adrenal gland that was causing the problem. Getting the definitive diagnosis is fantastic because it removes all the worry, and because I’m on much much less medication than I had been for 15 years. I feel absolutely great.”

̽��ֱ��study was published online in the Journal of Clinical Endocrinology and Metabolism. ̽��ֱ��work was funded mainly by the BHF and the National Institute for Health Research (NIHR), the research funding arm of the NHS.

Scan can detect 5p-sized growth that causes hypertension.

̽��ֱ��test could be especially important for older patients – we often see growths in the adrenal glands during a routine CT scan.

Morris Brown, Professor of Clinical Pharmacology at the ̽��ֱ�� of Cambridge

Morris Brown

Conn's adenoma

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Blood pressure breakthrough holds real hope

bjb42 — Thu, 07 Oct 2010 00:00:00 +0000

After 20 years of research, scientists from the ̽��ֱ�� of Cambridge have now cracked the first step in the main process that controls blood pressure. Their findings, published today in the journal Nature, are likely to have significant implications for the treatment of pre-eclampsia as well as high blood pressure (also known as hypertension).

Blood pressure is controlled by hormones called angiotensins, which cause the blood vessels to constrict. These hormones are released by the protein angiotensinogen. Until now, it was not understood how this occurred.

Dr Aiwu Zhou, a British Heart Foundation (BHF) Fellow at the ̽��ֱ�� of Cambridge, who made the breakthrough, said: "Although we primarily focused on pre-eclampsia, the research also opens new leads for future research into the causes of hypertension in general."

To make the discovery, the researchers solved the structure of angiotensinogen with the help of an extremely intense X-ray beam produced by Diamond Light Source, the UK synchrotron. Their results revealed that the protein is oxidised and changes shape

to permit ready access to angiotensinogen by an enzyme, renin. Renin cuts off the tail of the protein to release the hormone angiotensin, which then raises blood pressure.

Taking their lab results into the clinic at the ̽��ֱ�� of Nottingham, the research team showed that the amount of oxidised, and hence more active, angiotensinogen was increased in women with pre-eclampsia.

Professor Robin Carrell at the ̽��ֱ�� of Cambridge, who led the 20-year research project, explained: "During pregnancy oxidative changes can occur in the placenta. These changes, the very ones we have found stimulates the release of the hormone angiotensin and lead to increased blood pressure, can arise as the circulation in the placenta readjusts the oxygen requirements of the growing foetus with the delivery of oxygen to the placenta from the mother."

Drugs currently used to treat high blood pressure - such as ACE inhibitors - focus on the later stages of the mechanism that controls blood pressure. Today's findings, which give insight into the previously mysterious early stages of the regulation process, provide scientists with new opportunities to research novel treatments for hypertension.

Professor Peter Weissberg, Medical Director of the BHF, which largely funded the study, said: "Every year in the UK pre-eclampsia is responsible for the deaths of around six women and several hundred babies. This research is of the highest quality and offers real hope for developing strategies to prevent or treat this dangerous condition by targeting the process that these scientists have identified. And of course, although the researchers only looked at pre-eclampsia in this study, similar strategies may be useful for those people with high blood pressure that is not effectively controlled by current medicines."

High blood pressure frequently affects pregnancy. However, in 2-7 per cent of pregnancies this develops into pre-eclampsia, which threatens the health and survival of both the mother and child. In Britain, it affects about one in 20 women during pregnancy, and every year 50,000 women and 500,000 infants die globally as a result of pre-eclampsia. There is no treatment for pre-eclampsia and often the mother is either induced early or undergoes a Caesarean.

̽��ֱ��research was largely funded by the British Heart Foundation, with additional funding provided by the Medical Research Council, the Wellcome Trust and the Isaac Newton Trust.

Photo credit: House of Sims

Scientists have discovered a mechanism which raises blood pressure in pre-eclampsia, a potentially deadly condition which occurs during pregnancy.

This research is of the highest quality and offers real hope for developing strategies to prevent or treat this dangerous condition by targeting the process that these scientists have identified."

Professor Peter Weissberg, Medical Director of the BHF

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blood pressure

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