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AUGUSTA, Ga. (Aug. 27, 2018) - Problems like obesity and alcoholism appear to chronically trigger in the liver a receptor known to amplify inflammation in response to invaders like bacteria, scientists report.

The relentless, increased activity of TREM-1 in turn accelerates injury and scarring of the liver, a first step toward cirrhosis and liver cancer, says Dr. Anatolij Horuzsko, reproductive immunologist in the Georgia Cancer Center and Department of Medicine at the Medical College of Georgia at Augusta University.

TREM-1, or triggering receptor expressed on myeloid cells-1, is known to help turn up inflammation short-term to help us deal with external invaders. It has increased activity immediately after an injury as well, when increased inflammation, damage cleanup and collagen production aid healing.

But Georgia Cancer Center scientists report in the Journal of Clinical Investigation the first evidence that when activated by chronic offending agents, like obesity and hepatitis, TREM-1 instead contributes to a destructive level of inflammation that results in liver damage and possibly cancer.

The unhealthy transformation can occur in five to 50 years, depending on factors like the level of insult, and may be largely reversible up to the point of cirrhosis, if the offending agent is stopped, and the liver's natural ability to regenerate takes over.

Horuzsko and his colleagues think TREM-1 could one day be another point of intervention, possibly with a drug that could return TREM-1 activation to normal levels on resident, garbage-eating, watchdog immune cells called Kupffer cells.

"Right now we have treatment for hepatitis C, for example, which is very efficient, if we treat it before too much damage is done. But we don't have treatment for alcohol- or obesity-related damage," Horuzsko says.

They already are doing experiments with a drug that, because of its structure, should enable tamping down of TREM-1, but long-term goals include a drug that would target this receptor on Kupffer cells.

It's known that inflammation is a key process in the thickening and scarring of the liver called fibrosis, and that tamping down inflammation can help prevent fibrosis progression. But just how inflammation and fibrosis happen at the cellular and molecular level is largely unknown, say Horuzsko, the study's corresponding author.

Their work in both animal models and human tissue indicate TREM-1 is essential to both.

In the liver, TREM-1 is found primarily on Kupffer cells, the liver's resident macrophages, as well as monocytes, a type of white blood cell that can also become garbage-eating macrophages.

TREM-1's expression is limited in a healthy human liver but its activation goes up short-term following an insult, like a laceration.

To look at what happens in the face of a chronic problem, the scientists created a model of chronic liver disease - like obesity or high alcohol consumption might - using carbon tetrachloride, a poisonous solvent found in oils, varnishes and resin. They found TREM-1 activation went up and stayed up on a larger number of Kupffer cells in the liver as well as other immune cells circulating in the body.

When they deleted TREM-1 from the model, it reduced inflammation, injury and subsequent fibrosis. When they gave TREM-1 back to the mice, inflammation and related damage came back with a vengeance, leading them to dub TREM-1 the main target that drives fibrogenesis.

They found TREM-1 even recruits other pro-inflammatory cells from the bone marrow to the liver, many of which could become macrophages as well, which further multiplies the inflammation, liver cell damage and death.

"This creates a loop," says Horuzsko, of increased activity on many fronts. "This creates chronic inflammation - with no bacterium or virus involved - which is important to the development of liver disease."

As liver cells die in the face of chronic inflammation, they release their innards, called damage associated molecular patterns, or DAMPs, when they get outside the cells. DAMPs further activate TREM-1 on the macrophages and the damaging momentum builds, he says.

That's where collagen and fibrosis set in. Stellate cells in the liver are normally quiescent and mainly store vitamin A. When TREM-1 gets activated on the macrophages, it also activates the macrophages themselves which, in turn, activate stellate cells.

Stellate cells literally change their shape, release vitamin A and start to make collagen. Collagen is a component of connective tissue that typically helps hold tissues and blood vessels together and aids wound healing. The liver already has some collagen, but in this scenario too much gets deposited and liver function suffers.

"Efficiency goes down and it causes additional damage to liver cells that already have been damaged by something like hepatitis or obesity," Horuzsko says. The liver of a patient with cirrhosis, for example, is overrun with collagen, he notes.

Blood levels of the enzymes alanine aminotransferase, or ALT, and aspartate aminotransferase, or AST, are indicators of liver injury and both went up and remained high in their models. However, in mice where TREM-1 was knocked out, rates went up only short- term before returning to pre-injury levels, another indicator of TREM-1's role in persistent inflammation and resulting damage, Horuzsko says.

They also found that while mice with and without TREM-1 both recruited additional immune cells, such as more macrophages and monocytes, from their bone marrow immediately after the injury, 72 hours later the levels were much higher both in the blood and livers of the mice that also still had TREM-1.

To look further at the role of Kupffer cells when TREM-1 is out of the picture, they first removed the cells from both mice models, then gave Kupffer cells that contained TREM-1 back to both, and both were able to cause localized damage and recruit immune cells from the marrow to further bolster inflammation. But when they put TREM-1-deficient Kupffer cells back in normal mice, the exaggerated inflammation and liver damage did not happen.

Likewise, they found markedly increased infiltration of TREM-1 expressing cells in patients with liver fibrosis.

"TREM-1 is a molecule that can be very dangerous and is normally very controlled in the body," Horuzsko says. In fact, one of the diagnostic criteria for body-wide infection, or sepsis, is the level of TREM-1 protein in the fluid portion of a patient's blood. And, in hepatitis B related liver cancer in humans, high levels of TREM-1 expression on stellate cells is considered an indicator of poor prognosis.

"The balance in our body is very, very tightly regulated and important. Alcohol, obesity, hepatitis viruses all change the balance," Horuzsko says.

The scientists suspect their findings of TREM-1 gone wild will hold true in other organs including the lungs, heart and kidneys, which also have TREM-1 on their macrophages.

Liver cancer rates have risen dramatically in the United States, 43 percent in men and 40 percent in women, from 2000-16, according to a report released this summer by the Centers for Disease Control and Prevention. In May 2017, the CDC reported that newly reported cases of hepatitis C tripled between 2010-15 and the American Cancer Society says liver cancer rose from ninth to the sixth leading cause of cancer death from 2000-16.

The most common causes of liver cancer include infection with the hepatitis B or C virus, heavy alcohol use, obesity and diabetes, according to the CDC.

The liver is part of the gastrointestinal tract and filters blood coming from the GI tract before the blood circulates to the rest of the body. Its myriad of functions include secreting bile, which helps us absorb fats and eliminate waste; producing cholesterol, triglycerides and blood clotting factors; and detoxifying chemicals. The liver is the heaviest solid organ in the body and sits on the right sight of the body behind the lower ribs.

Scientists have discovered that beluga whales and narwhals go through the menopause - taking the total number of species known to experience this to five.

Aside from humans, the species now known to experience menopause are all toothed whales - belugas, narwhals, killer whales and short-finned pilot whales.

Almost all animals continue reproducing throughout their lives, and scientists have long been puzzled about why some have evolved to stop.

The new study, by the universities of Exeter and York and the Center for Whale Research, suggests menopause has evolved independently in three whale species (it may have evolved in a common ancestor of belugas and narwhals).

"For menopause to make sense in evolutionary terms, a species needs both a reason to stop reproducing and a reason to live on afterwards," said first author Dr Sam Ellis, of the University of Exeter.

"In killer whales, the reason to stop comes because both male and female offspring stay with their mothers for life - so as a female ages, her group contains more and more of her children and grandchildren.

"This increasing relatedness means that, if she keeps having young, they compete with her own direct descendants for resources such as food.

"The reason to continue living is that older females are of great benefit to their offspring and grand-offspring. For example, their knowledge of where to find food helps groups survive."

The existence of menopause in killer whales is well documented due to more than four decades of detailed study.

Such information on the lives of belugas and narwhals is not available, but the study used data on dead whales from 16 species and found dormant ovaries in older beluga and narwhal females.

Based on the findings, the researchers predict that these species have social structures which - as with killer whales - mean females find themselves living among more and more close relatives as they age.

Research on ancestral humans suggests this was also the case for our ancestors. This, combined with the benefits of "late-life helping" - where older females benefit the social group but do not reproduce - may explain why menopause has evolved.

Senior author Professor Darren Croft said: "It's hard to study human behaviour in the modern world because it's so far removed from the conditions our ancestors lived in.

"Looking at other species like these toothed whales can help us establish how this unusual reproductive strategy has evolved."

Although individuals of many species may fail to reproduce late in life, the researchers looked for evidence of an "evolved strategy" where females had a significant post-reproductive lifespan.

Munich, Germany - 27 Aug 2018: Percutaneously reducing secondary mitral regurgitation appears futile when tested in all heart failure patients, according to late breaking research presented today in a Hot Line Session at ESC Congress 2018 and published in the New England Journal of Medicine.1

European guidelines state that percutaneous edge-to-edge repair may be considered in patients with secondary mitral regurgitation and heart failure considered high risk for open heart surgery.2 The intervention involves inserting one or more clips through the femoral vein then attaching the two mitral valve leaflets together so that they close more effectively.

Professor Jean-Francois Obadia, principal investigator, Civil Hospices of Lyon, France, said: "We show for the first time that despite reducing secondary mitral regurgitation, percutaneous repair of the mitral valve does not improve survival or symptoms, or reduce heart failure hospitalisations compared to standard medical treatment alone. This strongly suggests that this procedure is futile in patients with heart failure and secondary mitral regurgitation."

Around 2% of adults in developed countries have heart failure, rising to more than 10% of people over 70 years of age.3Typical symptoms include breathlessness, ankle swelling, and fatigue, caused by the heart's inability to pump enough blood out of the left ventricle to meets the body's needs.

In the advanced stages of heart failure the left ventricle dilates, causing the mitral valve to close insufficiently and incorrectly allow blood to leak back into the left atrium (called mitral regurgitation). It is labelled "secondary" because the mitral valve is structurally normal, but does not work properly due to a dilated left ventricle. Although associated with a worse prognosis, there is no evidence that reducing secondary mitral regurgitation improves survival.3

The MITRA.fr study examined whether this procedure could reduce the rate of all-cause death or unscheduled hospitalisation for heart failure over 12 months compared to optimal medical treatment alone.

A total of 304 patients with symptomatic heart failure, poor left ventricular function (left ventricular ejection fraction 15-40%), and severe secondary mitral regurgitation were enrolled from 37 hospitals in France. Patients received optimal medical treatment with an angiotensin-converting enzyme inhibitor (if not tolerated, an angiotensin receptor blocker was substituted), a beta-blocker, a mineralocorticoid receptor antagonist, and a diuretic.

Patients were then randomly assigned to undergo percutaneous mitral valve repair or no intervention (control group). Patients were followed-up for 12 months.

More than 90% of procedures were performed successfully and there were no significant safety concerns. Mitral regurgitation was substantially reduced in patients who underwent the procedure compared to those who received medical therapy alone. Nevertheless, there was no statistically significant difference in the primary endpoint of death and unscheduled heart failure rehospitalisation at 12 months, which occurred in 55% of patients receiving the intervention and 52% of patients treated with medical therapy alone (p=0.53).

Professor Obadia said: "The reduction in mitral regurgitation that was achieved with the intervention did not translate into a clinical benefit in patients with heart failure. There is therefore no reason to perform this procedure in all patients with heart failure and secondary mitral regurgitation. Other randomised trials could examine whether there are subgroups that might be more suitable candidates."

The cholera-causing bacterium, Vibrio cholerae, is commonly found in aquatic environments, such as oceans, ponds, and rivers. There, the bacterium has evolved formidable skills to ensure its survival, growth, and occasional transmission to humans, especially in endemic areas of the globe.

One of the ways the pathogen defends itself against predatory aquatic amoebas involves "hitchhiking" them and hiding inside the amoeba. Once there, the bacterium resists digestion and establishes a replication niche within the host's osmoregulatory organelle. This organelle is essential for the amoeba to balance its internal water pressure with the pressure exerted by the environment.

In a new study, the group of Melanie Blokesch at EPFL in collaboration with the BioEM facility headed by Graham Knott has deciphered the molecular mechanisms that V. cholerae uses to colonize aquatic amoebas. The researchers demonstrated that the pathogen uses specific features that allow it to maintain its intra-amoebal replication niche and to ultimately escape from the succumbed host. Several of these features, including extracellular enzymes and motility, are considered minor virulence factors as they also play a role in human disease.

The study suggests that the aquatic milieu provides a training ground for V. cholerae and that adaptation towards amoebal predators might have contributed to V. cholerae's emergence as a major human pathogen.

"We are quite excited about these new data, as they support the hypothesis that predation pressure can select for specific features that might have dual roles - in the environment and within infected humans," says Blokesch. She also highlights that continuous funding by the ERC (StG & CoG) has been crucial for this project, "as studying the environmental lifestyle of the pathogen is a bit outside the mainstream research on pathogenesis".

Munich, Germany - 26 Aug 2018: Blood pressure and cholesterol lowering drugs continue to improve survival in patients with hypertension after more than a decade, according to late breaking results from the ASCOT Legacy study presented today at ESC Congress 20181 and published in The Lancet.

Dr Ajay K. Gupta, of the William Harvey Research Institute, Queen Mary University London, UK, said: "Patients in their mid-60s with high blood pressure were less likely to die from heart disease or stroke by age 75-80 if they had taken both calcium channel blocker-based blood pressure lowering treatment and a statin."

The ASCOT Legacy study is the long-term follow-up of 8,580 patients from the UK who took part in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), which between 1998 and 2000 recruited patients with high blood pressure and three or more additional risk factors for cardiovascular disease.

Patients who took a newer blood pressure lowering treatment (based on a calcium channel blocker) for 5.5 years were 29% less likely to have died from a stroke ten years later than those taking an older regimen (based on a beta-blocker). There was a non-significant trend towards 10% fewer cardiovascular deaths with the newer therapy.

Patients with average (6.5 mmol/l) or below average blood cholesterol levels at the start of the trial who took a statin for 3.3-5.5 years were 15% less likely to have died from cardiovascular causes such as heart disease and stroke 16 years later than those randomised to placebo.

A subgroup of patients with above average cholesterol who received standard lipid-lowering therapy for 5.5 years had 21% fewer cardiovascular deaths over ten years of follow-up with the newer blood pressure therapy compared to the older one. There was a non-significant trend towards lower all-cause and stroke deaths with the newer treatment.

"These results are remarkable," said Professor Peter Sever, of the National Heart and Lung Institute at Imperial College London, UK, who jointly led the study with Dr Gupta. "We have previously shown that statins confer long-term survival benefits after trials have stopped, but this is the first time it has been found with a blood pressure treatment."

Dr Gupta said: "The findings provide further support for the use of an effective blood pressure lowering therapy plus a statin in most patients with high blood pressure."

A main objective of the initial ASCOT trial was to find out whether a new treatment strategy for high blood pressure was more effective in preventing heart attacks than an old strategy. Patients with high blood pressure were randomly allocated to the new treatment of amlodipine (a calcium channel blocker) plus perindopril (an angiotensin-converting enzyme inhibitor) if needed to achieve the target blood pressure, or the old therapy of atenolol (a beta-blocker) plus bendroflumethiazide (a diuretic) and potassium if needed. The medicines were taken for a median of 5.5 years, when the trial was stopped because the newer treatment prevented more strokes and deaths.2 After the trial, patients went on to receive usual (or routine) care.

A second aim of the trial was to discover if a statin would provide added protection against coronary heart disease in patients with high blood pressure and cholesterol levels below 6.5 mmol/L. Patients with a blood cholesterol level of 6.5 mmol/l or less were randomly allocated to atorvastatin or placebo for 3.3 years, when the trial was prematurely stopped because atorvastatin prevented more heart attacks and strokes.3 Following this, patients were offered atorvastatin for the remainder of the blood pressuring lowering arm of the trial. During this 2.2 year period approximately two-thirds of patients previously assigned to either atorvastatin or placebo took atorvastatin.

A third aim of the trial was to evaluate the effectiveness of the newer versus older blood pressure lowering treatment in patients with high blood pressure and high cholesterol (above 6.5 mmol/l). These patients did not participate in the randomised lipid-lowering arm of the trial and all received standard lipid-lowering therapy for 5.5 years.

Professor Mark Caulfield, Director of the William Harvey Research Institute, said: "This study confirms the importance of lowering blood pressure and cholesterol to prevent disabling and life-shortening cardiovascular disease."

We use them for everything from banking to workouts, and now research from the University of Sydney shows mobile apps could potentially save lives by helping people with coronary heart disease keep on top of their medication.

Published today in Heart, and presented at the European Society of Cardiology Congress in Germany, the study shows the use of high-quality medication reminder apps increases people's adherence to cardiovascular medication.

While medication apps have long been available online, this is some of the first research to explore the evidence around their effectiveness in people with heart disease and whether they work in terms of health and behaviour.

Senior author Associate Professor Julie Redfern said coronary heart disease is the leading cause of death globally and around 40 percent of patients do not adhere to their medications, therefore increasing their risk of subsequent heart attacks.

"Patients with coronary heart disease can become overwhelmed with the amount of pills they are taking as they are often prescribed up to four different types of medication, which need to be taken sometimes up to three times a day," said Associate Professor Redfern from the University of Sydney's Westmead Applied Research Centre.

The randomised clinical trial followed 160 predominately male patients over a three month period and compared the medication usage of patients in usual care to those supported to download and use medication apps.

Researchers also compared the use of basic apps (with one-time reminder alarms) to those with more advanced features. They found no additional benefits were gained from the advanced apps with elements such as the ability to snooze reminders and track taken and missed doses, adherence statistics and social support structures including alerting a friend or family member to missed doses.

Lead author Dr Karla Santo from the University of Sydney said the results from the trial are very encouraging.

"It's exciting that a basic app - some of which can be accessed for free - could help improve people's medication use and prevent further cardiovascular complications."

In 2016, Dr Santo and colleagues from the University of Sydney and George Institute for Global Health conducted a review of medication reminder apps available via iTunes and Google app stores.

The review rated Medisafe as the top ranking interactive app, and My Heart my Life (currently being updated) and Pill reminder among the top basic apps available at the time. However, the vast majority of the apps on the market were judged to be low quality.

Dr Santo said the next step is to carry out further research to see if apps can be used to sustain medication adherence over a longer period and the impact this has on health outcomes. Also, to trial the apps for other health conditions such as cancer, lung disease and stroke.

"Participants in our trial were followed up after 3 months but longer term and larger studies are more likely to be able to show benefits or challenges of app usage, as well as the impact on additional measures such as blood pressure and cholesterol."

Munich, Germany - 26 Aug 2018: A weight loss drug does not increase cardiovascular events, according to late breaking results from the CAMELLIA-TIMI 61 trial1 presented today in a Hot Line Session at ESC Congress2 and published in the New England Journal of Medicine.

Lorcaserin is an appetite suppressant, increasing the sense of fullness after a meal and reducing hunger before meals. It is not approved as a weight loss drug in Europe. The European Medicines Agency has expressed concerns about the potential risk of tumours based on animal data, psychiatric disorders including depression, and problems with heart valves.

The US Food and Drug Administration (FDA) in June 2012 approved the medication for weight loss in overweight adults with a body mass index (BMI) of 30 kg/m2 or greater, or with a BMI of 27 kg/m2 or greater and at least one weight-related health condition such as high blood pressure, type 2 diabetes, or high cholesterol. As with all weight loss agents, the FDA's approval was contingent on postmarketing studies assessing the risk for major adverse cardiovascular events.

The CAMELLIA-TIMI 61 trial was conducted as part of the FDA's postmarketing requirement. The trial examined the safety and efficacy of the drug with regard to major adverse cardiovascular events (MACE) and progression to diabetes in overweight or obese individuals with, or at risk for, cardiovascular disease.

The trial enrolled 12,000 adults from 473 centres in eight countries between January 2014 and November 2015. Participants had a BMI of at least 27 kg/m2 and either 1) established cardiovascular disease3 (with or without diabetes) or 2) diabetes and at least one other cardiovascular risk factor.4 Participants were randomly allocated in a 1:1 ratio to lorcaserin (10 mg twice a day) or matching placebo. All participants were advised to exercise and eat healthily.

The primary safety endpoint was noninferiority of the drug compared to placebo for MACE (cardiovascular death, myocardial infarction, or stroke) after 460 events had occurred. If the safety endpoint was met, the trial would proceed to completion and assess the primary efficacy endpoint of superiority of the drug for MACE plus hospitalisation for unstable angina, heart failure, or any coronary revascularisation. Secondary endpoints included delay or prevention of conversion to type 2 diabetes in those with pre-diabetes at baseline, and the effect on weight, heart rate, blood pressure, lipids, and blood sugar.

The average age of participants was 64 years, 64% were male, and the median BMI was 35 kg/m2. Three-quarters (8,958; 75%) had a history of at least one established cardiovascular disease: 8,153 (68%) had coronary artery disease, 1,129 (9.4%) had cerebrovascular disease, and 657 (5.5%) had peripheral artery disease. More than half (57%) had diabetes, 90% had hypertension, 94% had hyperlipidaemia, and 20% had renal insufficiency.

The interim analysis after 460 events showed that the trial met its primary safety objective. At study completion with a median follow-up of 3.3 years, MACE occurred in 6.1% of those taking lorcaserin and 6.2% of those on placebo, demonstrating noninferiority (p

The trial did not meet its superiority endpoint. The composite of MACE plus hospitalisation for unstable angina, heart failure, or any coronary revascularisation occurred in 11.8% of participants taking the drug and 12.1% of those on placebo (p=0.55).

On top of lifestyle counselling, those taking lorcaserin lost an average of 4.2 kg in the first year compared to 1.4 kg for those taking placebo (p

Regarding secondary endpoints, compared to placebo, the medication reduced the conversion rate to diabetes in participants with pre-diabetes at baseline. The drug also led to small improvements in levels of triglycerides, blood glucose, heart rate and blood pressure.

In the CAMELLIA-TIMI 61 study, the most common side effects possibly related to the drug and leading to drug discontinuation were dizziness, fatigue, headache and nausea - all of which are listed on the FDA-approved label. There was no difference in the occurrence of malignancy between the drug and placebo groups. In a dedicated echocardiographic substudy, there was a non-significant imbalance in the incidence of valvular disease at one year between the drug and placebo groups (1.8% versus 1.3%; p=0.24). Serious hypoglycaemia was more common in patients on lorcaserin, a side effect observed in prior studies.

Lorcaserin is not approved for use in women who are pregnant, breastfeeding, or planning to become pregnant. It should be used with caution in patients with congestive heart failure. If signs or symptoms of valvular heart disease develop, such as dyspnoea or a new cardiac murmur, patients should be evaluated and discontinuation of the drug considered. People taking the drug should be monitored for depression, changes in mood, and suicidal thoughts or behaviours - the drug should be discontinued if the latter are experienced.

"We have been able to show for the first time that this weight loss drug does what it is intended to do. It helps people lose weight without causing an increase in major adverse cardiovascular events in a population at higher risk for heart attacks and strokes," said Dr Erin Bohula, an investigator with the CAMELLIA-TIMI 61 trial and TIMI Study Group investigator at Brigham and Women's Hospital, Boston, US.

"One of our hypotheses was that losing weight with this medication might also lead to a cardiovascular benefit but we did not see that," she continued. "While there were improvements in multiple cardiovascular risk factors, including weight, lipids and blood glucose, the magnitude of impact on these risk factors was relatively small."

Dr Bohula said: "Nevertheless, the CAMELLIA-TIMI 61 study is notable as it provides the first demonstration of cardiovascular safety of any weight loss agent in a dedicated cardiovascular outcomes trial."

Munich, Germany - 26 Aug 2018: Impaired mental status is associated with a doubled risk of death one year after a heart attack in elderly patients, according to research presented today at ESC Congress 2018.1

"Cardiologists should consider conducting simple tests to assess mental status in elderly people after a heart attack," said study author Professor Farzin Beygui of Caen University Hospital, France. "Patients with reduced mental status can then receive more intensive management such as regular follow-up appointments with their general practitioners or nurses, more specific assessment for an early diagnosis of dementia and tailored therapy."

The risks of dementia, Alzheimer's disease, confusion and delirium increase with age. Elderly people are also at higher risk of having a heart attack and dying afterwards. People aged 75 and over account for approximately a third of heart attack admissions and more than half of those dying in hospital after admission for a heart attack. Until now it was not known whether impaired mental status affects the prognosis of elderly heart attack patients.

This study assessed the impact of mental status on the risk of death in 600 patients aged 75 and above consecutively admitted for heart attack and followed-up for at least one year. Mental status was assessed using the Mini-Mental State Examination (MMSE) and the Confusion Assessment Method (CAM) - both simple bedside tests routinely used in clinical practice.

Cognitive impairment was detected in 174 (29%) patients. Patients with impaired mental function were more than twice as likely to be dead one year after their heart attack than those with healthy mental function (see figure). The association was independent of other potential predictors of death such as age, sex, invasive treatment, type of myocardial infarction, heart failure, and severity of the heart attack.

Impaired mental status was also associated with a nearly four-fold higher rate of bleeding complications while in hospital and a more than two-fold higher risk of being readmitted to hospital for cardiovascular causes within three months after discharge.

Professor Beygui said: "Almost one-third of elderly heart attack patients in our study had reduced mental capacity. These patients had higher risks of bleeding, rehospitalisation, and death. This may be because they forget to take their medicines or take them more than prescribed, rather than because of poor cognitive function itself."

He concluded: "Assessing mental status is a simple way to identify elderly patients at particularly high risk of poor outcomes following a heart attack. Identifying these patients may help us target treatment to those who need it most."

Munich, Germany - 26 Aug 2018: Bleeding in patients treated with anticoagulants should stimulate a search for cancer, according to late breaking results from the COMPASS trial1 presented today at ESC Congress 2018.2

Professor John Eikelboom, principal investigator, of the Population Health Research Institute, McMaster University, Hamilton, Canada, said: "In patients with stable coronary artery disease or peripheral artery disease, the occurrence of major gastrointestinal bleeding predicts a substantial increase in new gastrointestinal cancer diagnoses, while major genitourinary bleeding predicts a substantial increase in new genitourinary tract cancer diagnoses."

Up to one in ten patients with cardiovascular disease have recurrent events each year. As previously reported, the COMPASS trial found that in patients with coronary artery disease or peripheral artery disease, the combination of rivaroxaban (2.5 mg twice daily) and aspirin reduced cardiovascular events compared to aspirin alone, but there were more major bleeding events in the combined drug group.3

For the first time today, the investigators report details on the effect of bleeding on subsequent cancer diagnoses.

Briefly, the trial enrolled 27,395 patients with chronic stable coronary or peripheral artery disease from 602 centres in 33 countries. Patients were randomly allocated to one of three groups: 1) rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily 2) rivaroxaban 5 mg twice daily, or 3) aspirin 100 mg once daily. Results in each of the rivaroxaban groups were compared with the aspirin alone group. The mean duration of follow up was 23 months.

The combination increased major bleeding, as defined by the International Society on Thrombosis and Haemostasis (ISTH), compared with aspirin (3.1% versus 1.9%, hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.40-2.05, p

Major gastrointestinal bleeding was associated with a 20-fold increase in new diagnoses of gastrointestinal cancer (9.3% versus 0.7%, HR 22.6, 95% CI 14.9-34.3, p

Major non-gastrointestinal bleeding was associated with a five-fold increase in new non-gastrointestinal cancers (9.4% versus 3.0%, HR 5.49, 95% CI 3.95-7.62, p

Professor Eikelboom said: "More than one in ten patients with major bleeding were subsequently diagnosed with cancer, and more than 20% of new cancer diagnoses were in patients who experienced bleeding. By reducing major cardiovascular events and mortality, the combination of rivaroxaban and aspirin already produces a clear net benefit, and if bleeding unmasks cancer it could potentially lead to the added benefit of improved cancer outcomes."

Munich, Germany - Aug. 26, 2018: Long-term use of coal, wood, or charcoal for cooking is associated with an increased risk of death from cardiovascular disease, according to a study presented today at ESC Congress 2018.1

Dr Derrick Bennett, study author, University of Oxford, UK, said: "Our study suggests that people who use solid fuels for cooking should switch to electricity or gas as soon as possible."

It has been suggested that air pollution from cooking with solid fuels, such as coal, wood, or charcoal, may lead to premature death from cardiovascular disease, but there is limited evidence. This study assessed the association between solid fuel use for cooking and cardiovascular death, as well as the potential impact of switching from solid to clean fuel (electricity or gas).

The study included 341,730 adults aged 30-79 years recruited from ten areas of China in 2004 to 2008. Participants were interviewed about how often they cooked and the main fuel used at their three most recent homes. The researchers then estimated the duration of exposure to solid fuels. The analysis was restricted to those who cooked at least weekly at their three most recent residences and did not have cardiovascular disease. Information on mortality up to 1 January 2017 was collected from death registries and hospital records.

The average age of participants was 51.7 years and three-quarters were female. Nine out of ten had spent at least 20 years in their three most recent residences. Overall, 22.5% of participants had primarily used solid fuels for cooking for 30 years or more, 24.6% for 10-29 years, and 53.0% for less than ten years. Among the latter, 45.9% had never used solid fuels in their most recent three homes and 49.1% had switched from solid to clean fuels during this period.

During 3.4 million person-years of follow-up, 8,304 participants died from cardiovascular disease. After adjusting for education, smoking and other cardiovascular risk factors, each decade of exposure to solid fuel was associated with a 3% higher risk of cardiovascular death (95% confidence interval [CI] 1-4%, p=0.0002). Participants who had used solid fuels for 30 years or longer had a 12% greater risk of cardiovascular death than those who had used them for less than ten years (95% CI 3-21%, p=0.0045) (see figure 1).

Compared to persistent long-term use of solid fuels, adopting clean fuels was associated with a lower risk of death from cardiovascular disease. Each decade earlier switch from solid to clean fuels was associated with a 5% lower risk of cardiovascular death (95% CI 1-8%, p=0.0067). Participants who had changed for ten years or longer had risks comparable to persistent clean fuel users (see figure 2).

Professor Zhengming Chen, principal investigator, University of Oxford, UK, said: "We found that long-term use of solid fuels for cooking was associated with an excess risk of cardiovascular death, after accounting for established risk factors. Switching to electricity or gas weakened the impact of previous solid fuel use, suggesting that the negative association may be reversible."

Munich, Germany – 25 Aug 2018: Confusion over how to diagnose a heart attack is set to be cleared up with new guidance launched today. The 2018 Fourth Universal Definition of Myocardial Infarction is published online in European Heart Journal1, and on the ESC website.2

“Unless there is clarity in the emergency room on what defines a heart attack, patients with chest pain may be wrongly labelled with heart attack and not receive the correct treatment,” said Professor Kristian Thygesen, Aarhus University Hospital, Denmark.

“Many doctors have not understood that elevated troponin levels in the blood are not sufficient to diagnosis a heart attack and this has created real problems,” continued Professor Thygesen, who is joint chair of the Task Force that wrote the document, together with Professor Joseph S. Alpert, University of Arizona, USA and Professor Harvey D. White, Auckland City Hospital, New Zealand.

The international consensus document spells out that a heart attack (myocardial infarction) has occurred when the heart muscle (myocardium) is injured and has insufficient oxygen. Troponin is a protein normally used by the heart muscle for contraction, but is released into the blood when the muscle is injured. Oxygen shortage (ischaemia) is detected by electrocardiogram (ECG) and symptoms such as pain in the chest, arms, or jaw, shortness of breath, and tiredness.

Myocardial injury on its own is now considered a separate condition. There are numerous situations which can cause myocardial injury, and therefore a rise in troponin. These include infection, sepsis, kidney disease, heart surgery, and strenuous exercise. The first step of treatment is to address the underlying disorder.

As for myocardial infarction, there are different types which require specific treatment. Type 1 is the situation which most people associate with a heart attack. Here a fatty deposit in an artery, called a plaque, ruptures and blocks blood flow to the heart which deprives it of oxygen. Treatment can include antiplatelet medication to stop platelets clumping together and forming a clot, inserting a stent via a catheter to open up the artery, or surgery to bypass the artery.

In type 2, oxygen deprivation is not caused by plaque rupture in an artery but is due to other reasons such as respiratory failure or severe hypertension. Professor Alpert said: “Some doctors have incorrectly called this type 1 and given the wrong treatment, which can be harmful. Treatment should be directed at the underlying condition, for example blood pressure lowering medications for patients with hypertension.”

Efforts by doctors to correctly diagnosis myocardial infarction and its subtypes have not been helped by the lack of diagnosis codes in the International Classification of Diseases (ICD). The subtypes of myocardial infarction were first introduced by the joint Task Force in 2007, but were not incorporated into the ICD until October 2017.3,4

Professor White said: “In the consensus document we have expanded the section on type 2 myocardial infarction and included three figures to help doctors make the correct diagnosis. The incorporation of type 2 into the ICD codes is another step towards accurate recognition followed by appropriate treatment. A code for myocardial injury will be added to the ICD next year.”

The international consensus document was produced by the European Society of Cardiology (ESC), American College of Cardiology (ACC), American Heart Association (AHA), and World Heart Federation (WHF).

Munich, Germany - 25 Aug 2018: The initial findings of a study on spontaneous coronary artery dissection, a major cause of heart attacks in women, are reported today in a late breaking science session at ESC Congress 2018.1

Professor Jacqueline Saw, principal investigator, of the University of British Columbia, Vancouver, Canada, said: "Spontaneous coronary artery dissection (SCAD) causes around one-third of heart attacks in women under 60 years of age. SCAD was previously under-diagnosed and considered rare. Advances in intracoronary imaging techniques have improved diagnosis, yet we still know very little about the cause and natural history of SCAD."

SCAD occurs when the lining of an artery supplying blood to the heart tears away from the artery's outer layer. Blood leaks into the space between layers and forms a clot, which narrows the artery and restricts blood flow. Symptoms are similar to a heart attack and include chest pain, rapid heartbeat, pain in the arms, shoulders or jaw, and feeling sick, short of breath, sweaty, and light headed. If you have chest pains or other symptoms, call emergency immediately.

Treatment aims to restore blood flow to the heart. Some patients receive medication only, while others undergo a procedure to open the artery, either with a stent or by surgically bypassing the artery.

The Canadian SCAD Study examined the clinical presentation, natural history, treatment, and outcomes of SCAD. The researchers prospectively enrolled 750 patients presenting acutely with SCAD at 20 centres in Canada and two centres in the US between 2014 and 2018. Diagnosis of SCAD was adjudicated by an angiographic core laboratory. At the start of the study, information was collected on demographics, stressors and conditions that could have caused SCAD, and treatments. Patients are being followed for three years for major adverse cardiovascular events (MACE).

Today researchers report the baseline characteristics and outcomes in-hospital and at one month. The average age of patients in the study was 52 years and 89% were women.

Regarding possible causes for SCAD, about half of patients (49%) reported emotional stress prior to the event, and 30% reported physical stress (in 10% this was lifting more than 23 kg). The most common predisposing condition was fibromuscular dysplasia (40% of those assessed), which causes abnormal cell development in the arteries and can lead to narrowing (stenosis), aneurysms, or tears (dissections). Other predisposing conditions were five or more pregnancies (10%), being peripartum (5.3%), fertility treatment (5.1%), systemic inflammatory conditions (4.7%), and connective tissue disorders (3.5%).

Professor Saw said: "Emotional stress appears to be a major trigger for SCAD. Fibromusclar dysplasia, which is more common in women than men, also played a major role - it often has no symptoms but in some patients it causes headaches or a swooshing sound in the ears called pulsatile tinnitus."

All patients presented with an acute coronary syndrome with their acute SCAD event, with 99.3% having a heart attack and 0.7% having unstable angina. The main symptom was chest pain, which occurred in nine out of ten patients. On angiography, the left anterior descending artery was most commonly affected (52%), and long diffuse narrowing was the most common feature (called type 2 SCAD; 58%).

The majority of patients were treated with medication only (85%), while 14% underwent percutaneous coronary intervention, and less than 1% had coronary bypass surgery.

Almost all patients (99.9%) survived to 30 days. The rate of MACE to 30 days was 7.5% (including recurrent heart attack in 5.1%, cardiac arrest in 3.3%, unplanned revascularisation in 2.1%, severe heart failure in 1.5%, mechanical haemodynamic support in 1.5%, stroke in 1.2%, heart transplant in 0.1%, and death in 0.1% of patients). Within 30 days after discharge, 5.1% had a repeat visit to the emergency room, and 2.5% were admitted for chest pain.

Professor Saw said: "Our study shows that SCAD primarily affects middle-aged women and most acute presentations occur at the same time as a heart attack. The vast majority of patients survived to 30 days with medication alone. However, recurrent heart attacks and emergency room visits were high within 30 days. More research is needed to determine the most appropriate treatment for patients with SCAD."

Munich, Germany - Aug. 25,2018: A single pill with two drugs could transform blood pressure treatment, according to the 2018 European Society of Cardiology (ESC) and European Society of Hypertension (ESH) Guidelines on arterial hypertension published online today in European Heart Journal1, and on the ESC website.2

The guidelines recommend starting most patients on two blood pressure lowering drugs, not one. The previous recommendation was for step-wise treatment, which meant starting with one drug then adding a second and third if needed. This suffered from "physician inertia", in which doctors were reluctant to change the initial strategy despite its lack of success. At least 80% of patients should have been upgraded to two drugs, yet most remained on one drug.

It is now recognised that a major reason for poor rates of blood pressure control is that patients do not take their pills. Non-adherence increases with the number of pills, so administering the two drugs (or three if needed) in a single tablet "could transform blood pressure control rates", state the guidelines.

Professor Bryan Williams, ESC Chairperson of the Guidelines Task Force, University College London, UK, said: "The vast majority of patients with high blood pressure should start treatment with two drugs as a single pill. These pills are already available and should massively improve the success of treatment, with corresponding reductions in strokes, heart disease, and early deaths."

More than one billion people have hypertension (high blood pressure) worldwide. Around 30-45% of adults are affected, rising to more than 60% of people over 60 years of age. High blood pressure is the leading global cause of premature death, accounting for almost ten million deaths in 2015, of which 4.9 million were due to ischaemic heart disease and 3.5 million were due to stroke. High blood pressure is also a major risk factor for heart failure, atrial fibrillation, chronic kidney disease, peripheral artery disease, and cognitive decline.

High blood pressure does not usually cause symptoms. However, people with very high blood pressure may have headaches, blurred or double vision, regular nosebleeds, difficulty breathing, chest pain, irregular heartbeat, blood in the urine, confusion, or pounding in the chest, neck, or ears. See your doctor if you have any of these symptoms.

Treatment thresholds in the 2018 Guidelines are less conservative, with drugs recommended for patients who would previously have received lifestyle advice only. These are patients with low to moderate risk grade I hypertension (140-159/90-99 mmHg), including 65-80 year-olds, and those with high normal blood pressure (130-139/85-89 mmHg).

Professor Williams said: "Many more millions of people, particularly in the older age groups, should be receiving treatment for high blood pressure. See your doctor if you are 65 to 80 years old and your blood pressure is above 140/90 mmHg. The evidence suggests that treatment would reduce your risk of stroke and heart disease."

The guidelines state that "treatment should never be denied or withdrawn on the basis of age". It is increasingly recognised that frailty, independence and biological, rather than chronological, age determine the tolerability and likely benefit of blood pressure lowering medications. For people over 80 years who have not yet received blood pressure treatment, therapy should be started if systolic blood pressure is 160 mmHg or above. People already taking medication should not have it withdrawn at 80 years of age if it is well tolerated.

Blood pressure targets for patients of all ages are lower than in previous guidelines. Systolic blood pressure targets are now 120-129 mmHg for patients under 65 years of age, and 130-139 mmHg for patients over 65 years of age, taking into account treatment tolerability, independence, frailty, and comorbidities. Blood pressure below 120 mmHg should not be the target for any patient since the risk of harm outweighs the potential benefits.

When blood pressure is not controlled by three drugs given in a single pill, a condition known as resistant hypertension, a second pill containing a diuretic such as spironolactone should be added. Device-based therapy is not recommended for routine treatment of these patients and should only be administered within clinical trials.

A healthy lifestyle is recommended for all patients, regardless of blood pressure level, as it can delay the need for drugs or complement their effects. Advice includes salt restriction, alcohol moderation, healthy eating, regular exercise, weight control, smoking cessation, and a new recommendation to avoid binge drinking.

A new section on hypertension and cancer therapy states that temporary discontinuation of anticancer therapy may be considered when blood pressure values are exceedingly high despite multidrug treatment. A section on blood pressure during exercise and high altitude has been added, with the advice that patients with severe, uncontrolled hypertension should avoid exposure to very high altitude (above 4000 metres).

Professor Giuseppe Mancia, ESH Chairperson of the Guidelines Task Force, University of Milano-Bicocca, Milan, Italy, said: "We have effective treatments and, theoretically, 90-95% of patients should have their blood pressure under control, but in reality only 15-20% achieve target levels. The 2018 Guidelines aim to improve these poor rates of blood pressure control by introducing a treatment strategy that is simple and easier to follow."

The effects of a heavy drinking session on our thoughts and performance may last longer we think, according to a new study.

The research, published in the journal Addiction from psychologists at the University of Bath, highlight that impairments in cognition seen when individuals are drunk are still present the day after, when there little to no alcohol left in the bloodstream.

Across the board, they highlight how hungover individuals have poorer attention, memory and psychomotor skills such as coordination and speed when compared to when sober.

The researchers suggest their findings have important implications when it comes to activities performed when hungover, including driving.

For example, while hungover, individuals might typically wait until they believe there is no alcohol in the system before driving. These new results suggest that we could still be impaired in terms of the cognitive processes required, even after alcohol has left the bloodstream. In addition, the researchers warn that although many workplaces have clear policies in place regarding alcohol intoxication at work, few cover the next day effects of alcohol.

For certain jobs, they suggest, employees should be aware of the real effects that hangovers can have, and employers might do well to consider revising guidelines on safety grounds.

Hangover is the most commonly-reported negative consequence of alcohol use, and is already estimated to cost the UK economy £1.9 billion a year due to absenteeism. Despite this, up until this point little has been done to examine the effects of being hungover 'on the job'.

Leader author Craig Gunn of the Department of Psychology at the University of Bath explained: "In our review of 19 studies we found that hangover impaired psychomotor speed, short and long term memory and sustained attention. Impaired performance in these abilities reflects poorer concentration and focus, decreased memory and reduced reaction times the day after an evening of heavy drinking. Our review also indicated limited and inconsistent research on alcohol hangover and the need for future studies in the field."

Senior author Dr Sally Adams added: "Our findings demonstrate that hangover can have serious consequences for the performance of everyday activities such as driving and workplace skills such as concentration and memory.

"These findings also highlight that there is a need for further research in this field where alcohol hangover has implications at the individual level in terms of health and wellbeing, but also more widely at the national level for safety and the economy."

The researchers are now developing this work to further examine the true health and economic costs of hangover and associated risks with the next day effects of heavy drinking. The meta-analysis involved in this study involved a review of 770 articles relating to the topic.

Munich, Germany - 25 Aug 2018: Unnecessary heart procedures can be avoided with a non-invasive test, according to late breaking research presented today at ESC Congress 20181 and published in Journal of the American College of Cardiology.

Dr Bjarne Linde Norgaard, principal investigator, of Aarhus University Hospital, Denmark, said: "This study showed that a non-invasive method can be used to identify which patients with chest pain and clogged coronary arteries (coronary artery disease) can be safely treated with drugs and do not require invasive diagnostic tests."

Chest pain is a warning sign of coronary artery disease which can cause a heart attack or death if the blockage stops blood flow to the heart. The severity of the blockage and its impact on blood flow determines whether treatment should be drugs, inserting a stent to open the artery, or surgery to replace the artery.

Patients with chest pain are initially assessed with coronary computed tomography angiography (CTA), a non-invasive scan that determines the degree of artery narrowing (stenosis), which is expressed as a percentage. An invasive technique called fractional flow reserve (FFR) then assesses whether the stenosis is obstructing blood flow (called ischaemia). FFR involves inserting a pressure wire into the artery then calculating the ratio between the maximum blood flow in the narrowed artery and the maximum blood flow in a normal artery.

A new non-invasive technique for assessing ischaemia uses anatomic information from standard coronary CTA scans and applies a mathematical algorithm simulating blood flow to calculate FFR. Several clinical trials have shown that this method, called FFRCT, accurately reflects invasively measured FFR. However, there is little information on clinical outcomes using coronary CTA followed by FFRCT to decide treatment.

This is the first study to show the clinical benefit of FFRCT in patients with moderate stenosis. The study included 3,674 patients with stable angina who had new onset chest pain between 2014 and 2016. All patients had coronary CTA to determine the degree of stenosis. A total of 2,540 patients had mild stenosis (less than 30%) and had no additional testing.

A total of 677 patients with moderate stenosis (30-70%) had FFRCT to guide further management. Of those, 410 (61%) patients had normal FFRCT (more than 0.80) and were treated with drugs alone, with no referral to invasive testing (coronary angiography).

Over the next three years, the incidence of a combined endpoint of all-cause death, myocardial infarction, hospitalisation for unstable angina, and unplanned revascularisation was similar in patients with mild stenosis on coronary CTA (2.8%) and patients with moderate stenosis on coronary CTA but normal FFRCT (3.9%).

"Patients with moderate stenosis on coronary CTA who had normal FFRCT were deemed at low risk of heart attack and received drugs alone," said Dr Norgaard. "Our study shows that this is a safe strategy, since their prognosis was equally favourable to patients with no or mild stenosis who we know have good outcomes. The findings suggest that coronary CTA followed by FFRCT could be used as a gatekeeper to invasive diagnostic testing, and that patients with moderate stenosis and a normal FFRCT result do not need the invasive test."

Patients with abnormal FFRCT (0.80 or less) either received medical therapy alone or were referred for invasive coronary angiography, depending on the number of affected arteries and their location. Dr Norgaard said: "These patients had more severe disease and a less favourable outcome, particularly those who received only medication. More research is needed to determine the best management strategy for these patients."

Data for the study were obtained from the Western Denmark Cardiac Computed Tomography (WDCT) Registry, the Danish National Patient Registry, and the Civil Registration System.