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Exposure to arsenic, lead, copper, and cadmium is associated with increased risk of cardiovascular disease and coronary heart disease, finds a comprehensive analysis of the evidence published today in The BMJ. An accompanying editorial by Ana Navas-Acien at the Columbia Mailman School of Public Health and colleagues points to metals as an important but neglected source of cardiovascular risk.

"Despite widespread distribution of toxic metal contaminants, technical reports from environmental and public health agencies often disregard the mounting evidence of associated cardiovascular risk," Navas-Acien and her co-authors write. "Similarly, metal exposures are neglected by the organizations that produce cardiovascular prevention guidelines."

The editorial calls the new meta-analysis an "important call for attention," adding that because metals are associated with cardiovascular disease even at relatively low levels of exposure, "population-wide strategies to minimize exposure can further contribute to overall cardiovascular prevention efforts."

In their meta-analysis, Sara Shahzad at the University of Cambridge and colleagues identified 37 separate studies involving almost 350,000 participants. A total of 13,033 coronary heart disease, 4,205 stroke and 15,274 cardiovascular outcomes were reported across the studies, which include several by Columbia Mailman Environmental Health Sciences Professors Navas-Acien and Joseph Graziano. Shahzad and colleagues conclude exposures to arsenic, lead, cadmium, and copper are associated with an increased risk of cardiovascular disease and death.

The editorial cites national surveys documenting a marked reduction in population exposure to lead and cadmium (the metals monitored for longest), which the authors say largely reflect public health policies on the control of tobacco, reduction of air pollution, remediation of hazardous waste, renovation of drinking water infrastructures, and banning of lead in gasoline. Concomitant with these reductions, cardiovascular mortality rates decreased by 43 percent; nearly a third of this decline is explained by a decline in lead and cadmium exposures.

However, Navas-Acien and co-authors highlight substantial sources of exposure today: widespread soil contamination; persistence of past uses (house paint and plumbing for lead); continuing industrial uses (plastics and batteries); and presence in tobacco and tobacco smoke, drinking water and ambient air, and dust near industrial and waste sites. Particularly, in low- and middle-income countries, including many countries in Africa and Asia, exposure to high levels of arsenic and lead "is still a serious threat to public health that requires urgent action," they write.

An emerging source of metals is electronic cigarettes, where exposure seems to be the heating coil, from where metals leach into the inhaled aerosol. (Navas-Acien is the co-author of a National Academies of Sciences, Engineering, and Medicine report on e-cigarettes published earlier this year.)

Exposure to arsenic, lead, copper and cadmium is associated with an increased risk of cardiovascular disease and coronary heart disease, finds a comprehensive analysis of the evidence published by The BMJ today.

In recent years, exposure to environmental toxic metals such as arsenic, lead, copper, and mercury have become a major global health concern.

Arsenic and cadmium, for example, are known carcinogens, but there are increasing suggestions that exposure to toxic metals may be an independent risk factor for cardiovascular disease.

To investigate further, an international research team, led by Rajiv Chowdhury at the University of Cambridge, reviewed and analysed the results of epidemiological studies that had looked at the association of arsenic, lead, copper, cadmium, and mercury with coronary heart disease, stroke and composite cardiovascular disease.

They identified 37 separate studies published before December 2017 involving almost 350,000 participants. A total of 13,033 coronary heart disease, 4,205 stroke and 15,274 cardiovascular outcomes were reported across the studies.

The studies were designed differently, and were of varying quality, but the researchers were able to allow for that in their analysis.

Exposure to arsenic was found to be significantly associated with a 23% greater relative risk of coronary heart disease and a 30% greater relative risk of composite cardiovascular disease, but there was no evidence of an association with risk of stroke.

Exposure to cadmium and copper was also associated with increased relative risks of coronary heart disease and cardiovascular disease, while lead and cadmium were associated with an increased relative risk of stroke (63% and 72% respectively).

In contrast, mercury was not found to be associated with cardiovascular risk.

The researchers point out that their review was solely based on observational data, which might be affected by unmeasured factors, making it difficult to draw firm conclusions about cause and effect.

Nevertheless, they say their findings "reinforce the (often under-recognised) importance of environmental toxic metals in enhancing globalcardiovascular risk, beyond the roles of conventional behavioural risk factors, such as smoking, poor diet and inactivity."

Furthermore, they say their study highlights the potential need for additional worldwide efforts and strategies "to reduce human exposures even in settings where there is a relatively lower average level of exposure (such as many Western countries)."

And they call for further detailed work "to better characterise these associations and to assess causality."

In a linked editorial, Maria Tellez-Plaza at the Carlos III Health Institute in Madrid, and colleagues, agree that metals are an important but neglected source of cardiovascular risk.

This review is "an important call for attention to an emerging group of risk factors with a high prevalence in populations around the world," they say.

Since metals are associated with cardiovascular disease even at relatively low levels of exposure, "population wide strategies to minimize exposure will further contribute to overall cardiovascular prevention efforts," they conclude.

Munich, Germany - 28 Aug 2018: Uric acid reduction with the gout treatment febuxostat reduces adverse events in elderly patients with hyperuricaemia, according to late breaking research presented today in a Hot Line Session at ESC Congress 2018.1

Hyperuricaemia, an abnormally high serum uric acid level, causes gout and is associated with coronary artery disease, hypertension, stroke, renal failure, and death. The FREED study2 examined whether lowering uric acid with febuxostat prevents cerebral, cardiovascular and renal events and death in elderly patients with the condition.

The study enrolled 1,070 patients aged 65 years and older with hyperuricaemia (serum uric acid 7-9 mg/dL) and at risk for cerebral, cardiovascular, or renal events as defined by the presence of hypertension, type 2 diabetes, renal disorder, or a history of cerebral or cardiovascular disease.3

Patients were randomly assigned in a 1:1 ratio to receive oral febuxostat for 36 months or not. In the febuxostat group, the dose was increased stepwise from 10 to 40 mg per day if tolerated. In the non-febuxostat group, allopurinol 100 mg was considered if serum uric acid was elevated. In both groups, the dose of febuxostat or allopurinol was adjusted to avoid a serum uric acid level less than 2 mg/dL. All patients were advised to consume a healthy diet, quit smoking, and exercise to help manage their hyperuricaemia.

Patients were followed-up for 36 months for the primary endpoint which was a composite of cerebral, cardiovascular, and renal events, and death from any cause. This consisted of death due to cerebral or cardiorenal vascular disease, new or recurring cerebrovascular disease, new or recurring coronary artery disease, cardiac failure requiring hospitalisation, arteriosclerotic disease requiring treatment, renal disease (development of microalbuminuria, progression to overt proteinuria, or worsening of overt proteinuria to ?300 mg/g albumin/creatinine, doubling of serum creatinine level, progression to end stage renal disease defined as estimated glomerular filtration rate

A total of 537 patients received febuxostat and the average dose at the end of the study was 29 mg. Of the 533 patients in the non-febuxostat group, 27% received allopurinol 100 mg. Average serum uric acid levels reached 4.4 mg/dL in the febuxostat group and 6.7 mg/dL in the group not receiving febuxostat.

The primary endpoint occurred in 125 (23%) patients in the febuxostat group and 153 (29%) patients in the non-febuxostat group. Febuxostat significantly reduced the rate of the primary endpoint, with a hazard ratio of 0.75 (95% confidence interval 0.59-0.95, p=0.017) (see figure).

When the individual components of the primary endpoint were analysed separately, the most frequent event was renal impairment, which occurred in 16.2% of the febuxostat group and 20.5% of the non-febuxostat group. Among those with renal impairment, the development of microalbuminuria or mild proteinuria was common in both treatment groups.

Adverse events were observed in 132 (24.6%) patients in the febuxostat group and 135 (25.3%) patients in the non-febuxostat group, with no significant difference between the two groups (p=0.83). Two patients in the febuxostat group died. Also in the febuxostat group, mental disorder, headache, hypertension, abdominal pain, diarrhoea, maculopapular rash, acute kidney injury, and oedema of the extremities occurred in two patients each.

Professor Sunao Kojima, principal investigator, Kawasaki Medical School, Okayama, Japan, said: : "We found that patients receiving febuxostat were 25% less likely to die or experience strokes, heart disease, or kidney disease over a three-year period than patients who did not receive febuxostat. The findings suggest that lowering uric acid with febuxostat provides clinical benefit."

Munich, Germany - Aug. 28, 2018: Low carbohydrate diets are unsafe and should be avoided, according to a large study presented today at ESC Congress 2018.1

Study author Professor Maciej Banach, of the Medical University of Lodz, Poland, said: "We found that people who consumed a low carbohydrate diet were at greater risk of premature death. Risks were also increased for individual causes of death including coronary heart disease, stroke, and cancer. These diets should be avoided."

Obesity is a major health issue worldwide and raises the risk of several chronic conditions, including cardiovascular disease, hypertension, type 2 diabetes, and cancer. Different diets have been suggested for weight loss, such as diets low in carbohydrates and high in protein and fat. The long-term safety of these diets is controversial, with previous studies reporting conflicting results of their influence on the risk of cardiovascular disease, cancer, and death.

This study prospectively examined the relationship between low carbohydrate diets, all-cause death, and deaths from coronary heart disease, cerebrovascular disease (including stroke), and cancer in a nationally representative sample of 24,825 participants of the US National Health and Nutrition Examination Survey (NHANES) during 1999 to 2010. Compared to participants with the highest carbohydrate consumption, those with the lowest intake had a 32% higher risk of all-cause death over an average 6.4-year follow-up. In addition, risks of death from coronary heart disease, cerebrovascular disease, and cancer were increased by 51%, 50%, and 35%, respectively.

The results were confirmed in a meta-analysis of seven prospective cohort studies with 447,506 participants and an average follow-up 15.6 years, which found 15%, 13%, and 8% increased risks in total, cardiovascular, and cancer mortality with low (compared to high) carbohydrate diets (see figure for total mortality).

Professor Banach said: "Low carbohydrate diets might be useful in the short term to lose weight, lower blood pressure, and improve blood glucose control, but our study suggests that in the long-term they are linked with an increased risk of death from any cause, and deaths due to cardiovascular disease, cerebrovascular disease, and cancer."

Participants in the NHANES study had an average age of 47.6 years, and 51% were women. They were divided into quartiles based on the usual percentage of carbohydrates in their diet. The risks of all-cause and cause-specific death over an average 6.4-year follow-up rose with each fall in carbohydrate intake (see table), and remained significant after adjusting for all available factors that might have influenced the association (model 2 in the table).

The researchers also examined the link between all-cause death and low carbohydrate diets for obese (body mass index [BMI] 30 kg/m2 or greater) and non-obese (BMI under 30 kg/m2) participants in two age groups (55 years and older versus under 55) and found that the link was strongest in the non-obese older participants.

Regarding the mechanisms underlying the correlation between low carbohydrate diets and death, Professor Banach noted that animal protein, and specifically red and processed meat, has already been linked with an increased risk of cancer. He said: "The reduced intake of fibre and fruits and increased intake of animal protein, cholesterol, and saturated fat with these diets may play a role. Differences in minerals, vitamins and phytochemicals might also be involved."

He concluded: "Our study highlights an unfavourable association between low carbohydrate diets and total and cause-specific death, based on individual data and pooled results of previous studies. The findings suggest that low carbohydrate diets are unsafe and should not be recommended."

Munich, Germany - 28 Aug 2018: The optimal timing of invasive evaluation after a heart attack has been examined in a randomised trial. The late breaking results from the VERDICT trial are presented today in a Hot Line Session at ESC Congress 2018.1

Clinical outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) has progressively improved within the last two decades, in part because of faster diagnosis with invasive coronary angiography, followed by the method of revascularisation deemed most appropriate (bypass surgery or inserting a stent). NSTE-ACS includes a type of heart attack labelled non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina.

ESC guidelines on NSTE-ACS recommend invasive examination and treatment within two hours (immediate invasive strategy) in patients at very high risk of death or myocardial infarction following an initial acute coronary syndrome, within 24 hours in those at high risk (early invasive strategy), and within 72 hours in patients at intermediate risk.2

The VERDICT trial3 examined in a randomised set-up whether invasive coronary angiography and treatment (if deemed necessary) within 12 hours (very early invasive strategy) was superior to evaluation and treatment if necessary within 48 to 72 hours in high risk patients with NSTEMI and unstable angina.

The trial enrolled 2,147 patients with NSTEMI or unstable angina (inclusion criteria were either troponin rise and/or ST-segment/T-wave changes). Patients were randomised in a 1:1 ratio to very early coronary angiography and possible treatment within 12 hours or deferred coronary angiography and possible treatment within 48 to 72 hours. Patients were followed-up for at least 18 months for all-cause death, non-fatal myocardial infarction, hospital admission for refractory ischaemia, or hospital admission for heart failure (the primary endpoint).

The average age of patients was 64 years and 66% were men. A total of 1,075 patients were assigned to very early testing which was performed a median of 4.7 hours after randomisation, whereas the 1,072 in the deferred group were examined a median of 61.6 hours after randomisation. Eight in ten patients had elevated biomarkers, 60% had ECG changes indicating new ischaemia, and nearly 50% had a GRACE score4 above 140 at the time of randomisation - all factors which qualify patients as high risk.

During a median follow-up of 4.3 years the primary endpoint occurred in 27.5% of the very early group and 29.5% of the deferred group (p=0.29). In the subgroup of patients with a GRACE score above 140, however, a very early invasive strategy improved outcome compared to a deferred strategy (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.67-1.00). There was no difference between groups in the rate of complications. There were fewer recurrent myocardial infarctions in the very early, compared to deferred, group (HR 0.73, CI 0.56-0.96, p=0.025).

Professor Thomas Engstrøm, study author, Copenhagen University Hospital, Denmark, said: "Very early diagnosis and treatment was not superior to the deferred strategy. The results suggest that postponing invasive examination and treatment for up to 72 hours is as good as a very early approach in patients with NSTE-ACS. In line with ESC guidelines, for the subgroup of NSTE-ACS patients with a GRACE score above 140, a very early invasive strategy may be indicated."

When paramedics resuscitated cardiac arrest patients with a new type of breathing tube, their patients were more likely to survive, according to a University of Texas Health Science Center at Houston (UTHealth)-led study in today's JAMA.

"Based upon these results, use of the newer, more flexible laryngeal breathing tube could result in thousands of saved lives every year," said lead author Henry E. Wang, M.D., M.S., professor and vice chair for research in the Department of Emergency Medicine at McGovern Medical School at UTHealth.

"This is one of the first randomized trials to show that a paramedic airway intervention can improve cardiac arrest survival," said Wang, who described the study as a multicenter head-to-head comparison between the newer intubation tube and a traditional one.

Funded by the National Heart, Lung, and Blood Institute (NHLBI), the study is the largest of its kind to test oxygen delivery methods used by firefighters, emergency medical technicians and paramedics.

"For over three decades, emergency medical services personnel in the U.S. have performed intubation to deliver oxygen into the lungs of cardiac arrest victims. While identical to techniques used by doctors in the hospital, intubation in the prehospital setting is very difficult and fraught with errors," Wang said. "Our trial showed that cardiac arrest patients treated using the newer and easier laryngeal tube device may have a higher survival rate."

Sudden cardiac arrest, or loss of mechanical activity of the heart, is usually caused by a heart attack. More than 400,000 individuals are treated for out-of-hospital cardiac arrest each year, with the vast majority occurring at home, according to the American Heart Association. Studies show that only about 10 percent of people who suffer cardiac arrest outside the hospital survive. Delivery of oxygen to the lungs is a critical part of reviving a patient from cardiac arrest.

The research study - Pragmatic Airway Resuscitation Trial - compared survival rates among 3,000 adults with cardiac arrest treated by paramedic crews from 27 emergency medical services (EMS) agencies from December 2015 to November 2016. Approximately half received the newer laryngeal tube airway, while the other half received traditional endotracheal intubation.

The study (NHLBI grant UH2/UH3-HL125163) was conducted by the Resuscitation Outcomes Consortium research network and included the Birmingham, Dallas-Fort Worth, Milwaukee, Pittsburgh and Portland communities.

Overall, survival was higher in the new tube device group than the standard intubation group. With the new tube, 18.3 percent survived three days in the hospital, while in the intubation group, 15.4 percent survived three days. A total of 10.8 percent in the new tube group survived to leave the hospital, while 8.1 percent in the intubation group survived to leave the hospital. The proportion of patients surviving with good brain function was also higher for the new device than standard intubation.

While additional research is needed to support the study's findings, the researchers believe that the benefits of the newer airway device are due to its easier technique, leading to better blood flow and oxygen delivery. They are continuing to analyze the data to gain additional insight into the study results.

Munich, Germany - 28 Aug 2018: The foods that make up a heart healthy diet for people worldwide may differ from what was previously thought, according to late breaking results from the observational Prospective Urban Rural Epidemiological (PURE) study presented today in a Hot Line Session at ESC Congress 20181 and simultaneously published in the Lancet.

Professor Salim Yusuf, senior author and director of the Population Health Research Institute (PHRI) at McMaster University in Hamilton, Canada, said: "Thinking on what constitutes a high quality diet for a global population needs to be reconsidered. For example, our results show that dairy products and meat are beneficial for heart health and longevity. This differs from current dietary advice."

Recommendations for a high quality diet to avoid cardiovascular disease are largely based on studies conducted decades ago in high income countries. There is little information on what people eat today across the world.

This study aimed to clarify the constituents of a modern and international diet that promotes heart health and longevity. A dietary quality score was developed based on foods associated with a lower risk of death in previous studies (fruit, vegetables, nuts, legumes, fish, dairy products, and meat).

Participants of five studies including more than 218,000 people from over 50 countries in five continents2 were divided into five groups according to the quality of their diet. The risks of cardiovascular disease and death in those with the highest quality diet (18 points or more) were compared to those with the poorest quality diet (11 points or less).

"People who consumed a diet emphasising fruit, vegetables, nuts, legumes, fish, dairy products, and meat had the lowest risks of cardiovascular disease and early death," said co-principal investigator Dr Andrew Mente, of the PHRI. "Regarding meat, we found that unprocessed meat is associated with benefit."

The results suggest that we should limit the amount of refined carbohydrates we eat and that dairy foods and unprocessed meat can be included as part of a healthy diet.

Co-principal investigator Dr Mahshid Dehghan, also a PHRI investigator, added: "Our results appeared to apply to people from different parts of the world and so the findings are globally applicable."

To conduct the study, the association between diet quality, cardiovascular disease and death was first examined in 138,527 people aged 35 to 70 years without cardiovascular disease from the PURE study. It was then validated in 31,546 patients with vascular disease from the ONTARGET and TRANSCEND studies, 27,098 patients with a first heart attack from the INTERHEART study, and 20,834 patients with a first stroke from the INTERSTROKE study.

During a median follow-up of 9.1 years in PURE, there were 6,821 deaths and 5,466 major cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, stroke, heart failure). After adjusting for factors that could influence the relationship, compared with the poorest quality diet, the highest quality diet was associated with significantly lower risks of major cardiovascular events (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80-1.00, p=0.0193), stroke (HR 0.83, 95% CI 0.71-0.97, p=0.0402), cardiovascular death (HR 0.71, 95% CI 0.59-0.85, p

Similar results were found in patients with vascular diseases in ONTARGET and TRANSCEND. The highest quality diet was associated with significantly lower risks of major cardiovascular events (HR 0.86, 95% CI 0.78-0.94), cardiovascular death (HR 0.79, 95% CI 0.69-0.91), non-cardiovascular death (HR 0.89, 95% CI 0.75-1.05), and total deaths (HR 0.75, 95% CI 0.67-0.83).

In the INTERHEART and INTERSTROKE studies, the highest quality diet was associated with a lower risk of myocardial infarction (odds ratio [OR] 0.77, 95% CI 0.70-0.84) and stroke (OR 0.78, 95% CI 0.70-0.86), respectively.

Clinicians should consider how the way we think can make us vulnerable to obesity, and how obesity is genetically intertwined with brain structure and mental performance, according to new research.

The study, led by researchers at the Montreal Neurological Institute and Hospital (The Neuro) and published in the Proceedings of the National Academy of Sciences on Aug. 28, 2018, was an examination of magnetic resonance imaging (MRI) and cognitive test data from 1,200 individuals, supplied as part of the Human Connectome Project.

Researchers found that people with higher a body mass index (BMI) showed reduced cognitive flexibility, ability to delay gratification, visuospatial ability and verbal memory. They also found that people with increased BMI tended to have a thicker left prefrontal cortex and a thinner right prefrontal cortex. Previous studies have shown damage to the right prefrontal cortex can lead to increased eating.

Subjects with higher BMI also had increased volume in the left amygdala, which is believed to play a role in response to food cues. They also had decreased volume in the entorhinal-parahippocampal structures, which are associated with episodic memory and context mediation. This suggests a model where people prone to obesity are more sensitive to visual food cues, and less able to resist them by considering the negative context of eating, like weight gain.

Many of the subjects were siblings, including fraternal and identical twins. This allowed researchers to determine the heritability of the traits as well as obesity, measured by BMI. Using statistical methods, researchers found that many of the cognitive and neurological traits have genetic links with obesity. This suggests the role genetics play in obesity is manifested at least partially through brain anatomy and cognitive functions.

"This research will be useful in developing interventions to help people with obesity," says study's lead author, Uku Vainik, a researcher at The Neuro and the Institute of Psychology at University of Tartu, Estonia. "Modifying neurobehavioural factors with cognitive training, to improve people's ability to resist food, for example, could hold promise. Interventions shouldn't just focus on diet, but also acknowledge the neurobehavioural profile that obesity is genetically intertwined with. Such interventions might help people to stay lean despite their genetic signature."

"This work adds support to the theory that body weight in humans is partly under control of higher-level brain systems involved in cognition, decision-making and motivation," says Dr. Alain Dagher, the paper's senior author. "Furthermore, individual differences in these brain systems that regulate food intake appear to be moderately heritable."

New York, NY (August 27, 2018)--A phase three clinical trial has shown that a drug called tafamidis significantly reduces deaths and hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), a progressive form of heart failure that may be more common than doctors realize.

The findings were published in the New England Journal of Medicine by the trial's co-chair Mathew S. Maurer, MD, a heart failure specialist at Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, and colleagues.

The takeaway

If tafamidis receives FDA approval for transthyretin amyloid cardiomyopathy, it would be the first medical therapy for this life-threatening disease.

Compared to a placebo, the drug reduced deaths by 30 percent, reduced cardiovascular-related hospitalizations by 32 percent, and slowed the decline in quality of life among the 441 patients enrolled in the 2½-year study.

Background

Once diagnosed, patients with ATTR-CM only live on average three to five more years.

"ATTR-CM is considered to be a rare disease, but it is underdiagnosed," Maurer says. "Until recently, cardiologists rarely tested for ATTR-CM, because diagnosis required a heart muscle biopsy and there has been no treatment for the disease. But now that we can detect the disease with noninvasive imaging, we're finding more cases."

ATTR-CM occurs when a protein called transthyretin becomes unstable and clumps together and forms sticky amyloid in heart muscle. (Amyloid deposits also occur in Alzheimer's disease, but those plaques develop through a different mechanism and cannot be treated with the drug tested in this study.)

The disease is most common in men over the age of 60 and is caused by heritable genetic mutations or age-related changes in the regulation of transthyretin.

Tafamidis acts by stabilizing transthyretin, preventing its dissociation and ability to form amyloid.

What the study means for patients

"Based on this study, tafamidis may offer the first treatment for patients with this type of heart disease," Maurer says. "Right now, the best we can do is manage the symptoms of ATTR-CM."

The drug, the study found, also slowed decline in heart function and quality of life without causing more adverse effects.

A different drug, patisiran, was recently approved by the FDA to treat nerve damage - but not heart disease - caused by transthyretin.

What's next

The U.S. Food and Drug Administration will consider whether to approve tafamidis for the treatment of transthyretin amyloid cardiomyopathy.

Patients can receive tafamidis at certain sites through an early access program established by Pfizer. NewYork-Presbyterian/Columbia University Irving Medical Center is the program's first site and is now accepting and enrolling patients.

Caveats

"Tafamidis prevents progression of the disease, and like other preventive drugs, it should be given as early as possible," Maurer says. "We'll need to diagnose people with ATTR-CM earlier for this drug to have the biggest benefit. Currently, patients are diagnosed with advanced disease, and we need to change that."

Tokyo, Japan - Researchers from Tokyo Metropolitan University have studied how microswimmers, like bacteria or sperm, swim through fluids with both solid and liquid-like properties e.g. gels. They found that subtle changes in swimmer features, its structure and how it moves, invoke a dramatically different response from the fluid. They also discovered that the similarity in size between the structure of the fluid and the swimmer led to a wide range of interesting behavior.

Swimming is a tricky business for the microorganism. It might not seem that hard when we take a dip in the pool, but at microscopic scales, or at low-Reynolds number, the effect of the viscosity of the surrounding fluid imposes severe constraints on how one can swim. Yet, nature succeeds in achieving it; microswimmers play vital roles in a wide range of phenomena. Take reproduction i.e. sperm, or the active motion of bacteria. Understanding how they work is important business.

To understand swimmers, previous studies have focused on how minimal models of swimmers behave in uniform fluids. A particularly popular model is the so-called three-sphere microswimmer, a string of three microscopic spheres attached to each other by arms; the string can be propelled forwards by pumping the arms backwards and forwards in a liquid. This simple structure lets us overcome the limitations of the "scallop" theorem of Purcell, which says that motion which looks the same when played backwards (time-reversal symmetry), like a scallop opening and closing, cannot be used for locomotion.

But what about the fluid? Take how sperm travels through cervical mucus to reach eggs in mammalian reproduction; the mucus is an example of soft matter, where the internal structure, in this case made of sugars and proteins, responds in a complex fashion to the motion of the swimmer. To address this issue, a team consisting of Kento Yasuda and Associate Professor Shigeyuki Komura of Tokyo Metropolitan University and Ryuichi Okamoto, a Lecturer at Okayama University, studied how three-sphere microswimmers behave in a structured fluid, a polymer gel e.g. jelly.

Their analysis revealed that there were broadly two mechanisms for achieving motion, one by breaking time-reversal symmetry, the other by modulating the amplitudes in the beating of the two arms of the swimmer. With the latter, it was found that swimming could be achieved without breaking the former symmetry, a loophole in the scallop theorem. Through further detailed analysis, they succeeded in deriving expressions for how the velocity of the swimmer was related to how a structured fluid resists the motion of a swimmer. Interestingly, they found that when swimmers were larger than the mesh size of the gel, there was greater resistance with faster beating, a somewhat counterintuitive conclusion.

This work marks significant progress in bringing a popular minimal swimmer model closer to experimentally relevant cases, including the beating of hairs ("cilia") on cells and the motility of bacteria. It may also see application to more exotic scenarios e.g. the locomotion of robots through debris after landslides.

Munich, Germany - 27 Aug 2018: Long-term antiplatelet monotherapy after stenting is safe but does not reduce the risk of death or heart attack compared to standard dual antiplatelet therapy, according to late breaking results from the GLOBAL LEADERS trial presented today in a Hot Line Session at ESC Congress 20181 and published in The Lancet.

Ischaemic heart disease is the top global cause of death.2 In this condition, arteries supplying oxygen-rich blood to the heart become narrowed due to the build-up of fatty material. Treatments include medication, surgery to bypass the arteries, and keyhole surgery to open clogged arteries by inserting a stent (percutaneous coronary intervention; PCI).

Among patients undergoing PCI, dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor) reduces the risk of blood clots and heart attacks but also increases the risk of bleeding.3-7 A shorter duration of dual antiplatelet followed by single antiplatelet therapy with a P2Y12 inhibitor might reduce adverse events with no increase in bleeding.8

GLOBAL LEADERS is the largest trial to date testing one month of dual antiplatelet therapy versus the standard of more prolonged dual antiplatelet therapy after drug eluting stent implantation.9 The trial enrolled 15,991 patients scheduled to undergo PCI for stable coronary artery disease or acute coronary syndromes. Patients were recruited from 130 centres in 18 countries in Europe, North and South America, and Asia Pacific.

Patients underwent PCI with a drug-eluting stent, were treated with the direct thrombin inhibitor bivalirudin, and then randomly assigned in a 1:1 ratio to the experimental or standard treatment arm.

The experimental arm received one month of dual antiplatelet therapy with aspirin plus the P2Y12 inhibitor ticagrelor, followed by ticagrelor monotherapy for 23 months. The standard treatment arm received 12 months of dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor (clopidogrel for patients with stable coronary artery disease, ticagrelor for those with acute coronary syndromes), followed by aspirin monotherapy for 12 months.

Patients were followed up for the primary endpoint of all-cause death or non-fatal myocardial infarction at two years. Myocardial infarction diagnoses were confirmed by a central committee that examined electrocardiograms (ECGs) at discharge, three and 24 months. The secondary endpoint was the rate of moderate or severe bleeding (grade 3 or 5 on the Bleeding Academic Research Consortium scale) within two years.

At two years the primary endpoint had occurred in 304 (3.8%) patients in the monotherapy group and 349 (4.4%) in the standard treatment group (rate ratio [RR] 0.87, 95% confidence interval [CI] 0.75-1.01, p=0.073). All-cause mortality occurred in 224 (2.8%) patients in the monotherapy group and 253 (3.2%) in the standard treatment group (RR 0.88, 95% CI 0.74-1.06, p=0.186), and the incidence of non-fatal myocardial infarction was 1.0% versus 1.3%, respectively (RR 0.80, 95% CI 0.60-1.07, p=0.142). Rates of moderate or severe bleeding were 2.0% versus 2.1%, respectively (RR 0.97, 95% CI 0.78-1.20, p=0.766).

Professor Patrick Serruys, principal investigator, Imperial College London, UK, said: "Ticagrelor, in combination with aspirin for one month, followed by ticagrelor alone was not superior to one-year standard dual antiplatelet therapy followed by aspirin alone for reducing deaths or heart attacks during the two years after stenting."

Professor Serruys noted that the trial was not designed to assess non-inferiority, meaning that further studies are needed to confirm that monotherapy is not less effective than extended dual antiplatelet therapy. But he said: "The risk of monotherapy compared to extended dual therapy was 0.75-1.01, suggesting that monotherapy is relatively safe."

Munich, Germany - 26 Aug 2018: Fish oil supplements do not prevent heart attacks or strokes in patients with diabetes, according to late breaking results from the ASCEND trial presented today in a Hot Line Session at ESC Congress 20181 and published in the New England Journal of Medicine.

In observational studies, higher consumption of fish is associated with lower risks of coronary artery disease and stroke. However, previous randomised trials have not been able to show that taking fish oil supplements containing omega-3 fatty acids reduce the risk of having cardiovascular events.

The ASCEND trial (A Study of Cardiovascular Events iN Diabetes)2 examined whether fish oil supplements reduce the risk of a cardiovascular event in patients with diabetes. Between 2005 and 2011, 15,480 patients with diabetes but no history of cardiovascular disease were randomly assigned to fish oil supplementation (1 g daily) or matching placebo.

The primary efficacy outcome was first serious vascular event, which included non-fatal heart attacks, non-fatal strokes or transient ischaemic attacks (sometimes called "mini-strokes"), or deaths from a cardiovascular cause (but excluding any intracranial haemorrhage; i.e. bleeding in the head or brain3).

During an average of 7.4 years of follow-up, a first serious vascular event occurred in 689 (8.9%) participants allocated fish oil supplements and 712 (9.2%) participants allocated placebo. There was no significant difference between the two groups: rate ratio of 0.97 (95% confidence interval 0.87-1.08, p=0.55).

Dr Louise Bowman, principal investigator, Nuffield Department of Population Health, University of Oxford, UK, said: "Our large, long-term randomised trial shows that fish oil supplements do not reduce the risk of cardiovascular events in patients with diabetes. This is a disappointing finding, but it is in line with previous randomised trials in other types of patient at increased risk of cardiovascular events which also showed no benefit of fish oil supplements. There is no justification for recommending fish oil supplements to protect against cardiovascular events."

Munich, Germany - UNDER EMBARGO UNTIL 26 Aug 2018: Patients with high blood pressure are relying solely on medication to reduce their risk of heart attack, stroke and heart failure, rather than decreasing salt intake as instructed by their physicians, according to research presented today at ESC Congress 2018, the annual meeting of the European Society of Cardiology1.

Lack of adherence to recommended lifestyle changes is leading to higher salt intake for hypertensive patients, more medications needed to treat their condition and more side effects from those medications, according to lead author Dr Kazuto Ohno, Enshu Hospital, Hamamatsu, Japan.

"Patients may be able to improve this vicious cycle by restricting salt intake," Dr Ohno said. "In consequence, they may avoid diseases caused by hypertension, such as heart attacks, stroke and heart failure. Moreover, they may be able to avoid side effects from antihypertensive drugs, such as dizziness and fainting."

Excess salt intake is one of the most important causes of hypertension and salt restriction is a key strategy to manage it, but few studies have been done on the relationship between salt intake and blood pressure in hypertensive patients undergoing antihypertensive drug treatment.

Study authors enrolled 12,422 patients taking medication for hypertension who visited the hospital for a physical checkup from 2010-2016. Individual salt intake was estimated in grams per day using a spot urine calculation formula shown to be effective in previous studies2.

Blood pressure levels and patients maintaining the target blood pressure of less than 140/90mmHg improved during the seven-year study among all groups, but individual salt intake increased across all groups as well.

"Although blood pressure values in hypertensive patients had lowered, salt intake was gradually increased," Dr Ohno added. "We think improvement in blood pressure control is not due to salt restriction but due to drug treatment."

Guidelines for the Management of Hypertension 20143 published by the Japanese society of hypertension, recommend less than six grams of salt intake per day, Dr Ohno said, but less than four percent of study participants were following those recommendations.

Patients in the study were divided into three groups according to whether they were currently prescribed one, two, three or more antihypertensive drugs.

"The observational study in hypertensive patients with antihypertensive drugs found two comparative facts: an improvement of blood pressure levels and an increase in salt intake," Dr Ohno explained. "In particular, in hypertensive patients with multiple antihypertensive drugs, salt intake was higher than those taking only one antihypertensive drug."

Salt intake for healthy people was targeted less than 8 g/day for men and less than 7 g/day for women in Dietary Reference Intakes for Japanese (2015) published by Ministry of Health, Labor and Welfare4.

"However, the National Health and Nutrition Examination Survey 2016 5 reported 10.8 g/day in men, 9.2 g/day in women," Dr Ohno said. "More awareness about the harms of higher salt intake is needed in both hypertensive patients and healthy people. We can check the amount of salt in a lot of food and seasoning, such as soy sauce, miso paste, mayonnaise and so on, which are printed on the food labels. It is impossible to measure salt intake in every meal, so all of us should try to take food with reduced salt by referring to food labels."

Dr Ohno said future research should consider whether nutritional guidance can improve the accomplishment rate of the target blood pressure and decrease the number of antihypertensive drug prescriptions.

"As a new attempt, we have explained their estimated salt intake value and gave nutritional guidance including salt, calories and so on to participants since 2017. We think salt restriction is an important modifiable factor of lifestyle to treat and prevent high blood pressure," he concluded.

Munich, Germany - 26 Aug 2018: The ten-year outcomes of the Arterial Revascularisation Trial (ART) are presented today in a Hot Line Session at ESC Congress 2018.1

Coronary artery bypass graft (CABG) surgery is indicated in patients with angina and advanced coronary artery disease. With about one million operations per year globally, it is one of the most common major surgical procedures undertaken worldwide. Establishing the best methods for CABG is therefore a key element of successful management of patients with advanced coronary artery disease, who have narrowed coronary arteries and are at higher risk of limited exercise capacity due to angina (chest pain on exertion), myocardial infarction (heart attack), and death.

While it is firmly established that the use of one internal thoracic artery (arteries that supply the inner part of the chest wall) can improve life expectancy compared to vein grafts it is not known if there are additional benefits with the use of a second artery. ART tested whether routine use of two internal thoracic arteries, compared to the standard single internal thoracic artery, could reduce the risk of dying over a ten-year period in patients undergoing CABG surgery.

Between 2004 and 2007, the trial enrolled 3,102 patients with symptomatic coronary disease scheduled to undergo CABG at 28 centres in seven countries (UK, Poland, Australia, India, Brazil, Austria and Italy). A total of 1,548 patients were randomly allocated to bilateral and 1,554 patients to single internal thoracic artery grafts. Additional arterial or vein grafts were used at the discretion of the responsible surgeon. The primary outcome was death from any cause at ten years. The secondary outcome was a composite of death from any cause, myocardial infarction, or stroke.

The average age of participants was 64 years and 24% were women. In the bilateral graft group, 14% actually received a single internal thoracic artery graft, while 22% in the single internal thoracic artery group also received an additional radial artery graft.

At ten years 315 (20.4%) and 329 (21.2%) patients died in the bilateral and single graft groups, respectively (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.82-1.12, p=0.58). The secondary outcome occurred in 385 (24.9%) and 425 (27.4%) patients in the bilateral and single graft groups, respectively (HR 0.90, 95% CI 0.78-1.03, p=0.12). Results appeared to be more favourable in patients who had bilateral graft surgery done by surgeons who performed more operations in the trial.

In an exploratory analysis, patients who received any two arterial grafts (internal thoracic or radial) appeared to have a lower mortality (HR 0.79, 95% CI 0.64-0.97) and composite of death, myocardial infarction or stroke (HR 0.80, 95% CI 0.69-0.93) compared to those who received a single arterial graft. Although these findings are relevant they are not a randomised comparison and require confirmation in future trials.

Overall ART was not able to confirm that a strategy of routine bilateral internal thoracic artery grafting was superior to routine single internal thoracic artery grafting for patients undergoing CABG. Possible explanations include the high rate of patients who were randomised to receive a bilateral internal thoracic artery but actually received a single internal thoracic artery and in those assigned a single internal thoracic artery graft about one fifth actually received an additional arterial graft in the form of a radial artery. Both factors could have reduced the true efficacy of bilateral internal thoracic artery grafts. Furthermore, a high use of guideline directed medical therapy, including aspirin, statins, beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, in both groups may have narrowed any potential differences between the groups.

Professor David Taggart, Chief Investigator and Professor of Cardiac Surgery at the University of Oxford, UK, said: "ART is one the largest trials with the longest duration of follow-up ever undertaken in cardiac surgery to guide future practice with regards to conduit selection for CABG. While the trial did not show that using two internal thoracic arteries is superior to one, it raises the possibility that any two arterial grafts (internal thoracic or radial) may provide better outcomes than a single graft for patients undergoing CABG surgery."

Munich, Germany - Aug. 26, 2018: Four out of ten patients with atrial fibrillation but no history of stroke or transient ischaemic attack have previously unknown brain damage, according to the first results of the Swiss Atrial Fibrillation Cohort Study (Swiss-AF) presented today at ESC Congress 2018.1

"Our results suggest that clinically unrecognised brain damage may explain the association between dementia and atrial fibrillation in patients without prior stroke," said Co-Principal Investigator Professor David Conen of McMaster University, Hamilton, Canada.

Patients with atrial fibrillation have a significantly increased risk of stroke, which is why most are treated with blood thinners (oral anticoagulation). This increased stroke risk is probably the main reason why patients with atrial fibrillation also face an increased risk of cognitive dysfunction and dementia. However, the relationship between atrial fibrillation and dementia has also been shown among patients without prior strokes, meaning that additional mechanisms have to be involved.

Clarifying the mechanisms by which atrial fibrillation increases the risk of cognitive dysfunction and dementia is a first step towards developing preventive measures.

Swiss-AF is a prospective, observational study designed to pinpoint the mechanisms of cognitive decline in patients with atrial fibrillation.2 This analysis investigated the prevalence of silent brain damage in atrial fibrillation patients.

The study enrolled 2,415 patients aged over 65 years with atrial fibrillation between 2014 and 2017 from 14 centres in Switzerland. All patients without contraindications underwent standardised brain magnetic resonance imaging and the images were analysed in a central core laboratory. Scans were available in 1,736 patients. Of those, 347 (20%) patients had a history of stroke and/or transient ischaemic attack and were excluded from the analysis.

The final analysis included 1,389 patients with atrial fibrillation but no history of stroke or transient ischaemic attack. The average age of participants was 72 years, and 26% were women. The scans showed that 569 (41%) patients had at least one type of previously unknown brain damage: 207 (15%) had a cerebral infarct, 269 (19%) had small bleeds in the brain (microbleeds), and 222 (16%) had small deep brain lesions called lacunes.

"Four in ten patients with atrial fibrillation but no history of stroke or transient ischaemic attack had clinically unrecognised 'silent' brain lesions," said Professor Conen. "This brain damage could trigger cognitive decline."

Most study participants (1,234; 89%) were treated with oral anticoagulants. Co-Principal investigator Professor Stefan Osswald of University Hospital Basel, Switzerland, noted that the cross-sectional analysis looked at the data at a single point in time and cannot address the question of whether the cerebral infarcts and other brain lesions occurred before or after initiation of oral anticoagulation. But he said: "The findings nevertheless raise the issue that oral anticoagulation might not prevent all brain damage in patients with atrial fibrillation."

Professor Conen said: "All Swiss-AF participants underwent extensive cognitive testing. These data will be analysed to see whether patients with silent brain lesions also have impaired cognitive function." Collaborations with other study groups will help to sort out whether these findings are specific to patients with atrial fibrillation.