Hypertension researcher encourages colleagues to expand their focus

Dr. David Pollock has a simple message for fellow hypertension researchers: think endothelin.

15sept 2013--In a country where better than 30 percent of adults have high blood pressure and 50-75 percent of those have salt-sensitive hypertension, he believes the powerful endothelin system, which helps the body eliminate salt, should not be essentially ignored.

However, the research and clinical world focus on suppressing a better-known system, which prompts the body to hold onto salt, said Pollock, Chief of the Section of Experimental Medicine at the Medical College of Georgia at Georgia Regents University.

Pollock is giving the 2013 Lewis K. Dahl Memorial Lecture Sept. 14 during the American Heart Association's High Blood Pressure Research 2013 Scientific Sessions in New Orleans.

"If you look at blood pressure regulation and salt-controlled sodium excretion, everybody sees the renin-angiotensin-aldosterone system. That is what the books say." Pollock said. No doubt the system is important. When blood volume is low, the kidneys secret renin to make the hormone angiotensin. Angiotensin drives blood pressure up by promoting sodium retention directly and by stimulating release of aldosterone, a hormone that prompts the kidneys to resorb sodium rather than eliminate it in the urine.

It's a protective system intended to ensure that the body has enough sodium to keep blood pressure at sufficient levels to sustain life. It's also a system that's somehow dysregulated in some hypertensive patients who take ACE inhibitors or angiotensin receptor blockers to turn it down.

Since most Americans already turn down this system by eating too much salt, Pollock argues that enhancing sodium excretion might be a better approach, particularly for those not responding to existing therapies.

In fact, when an animal on a high-salt diet is given a drug to block endothelin's B receptor, blood pressure goes up 50 points, Pollock said. He regularly reminds research colleagues that blocking angiotensin receptors won't produce nearly such dramatic results. In fact, he thinks problems with the endothelin system – possibly resulting from a developmental defect or high-salt exposure early in life – may help explain why some folks who eat a high-sodium diet get high blood pressure and others don't. But this leads to one of the weak points of endothelin and probably part of the reason it's not been top of mind for hypertension researchers, he said.

When the salt-eliminating B receptor is inactive for whatever reason, endothelin's A receptor, which actually constricts blood vessels, gets activated so blood pressure goes up, Pollock said. An interesting aside is that, at least in the short term, higher blood pressure makes it easier for the kidneys to eliminate sodium without the help of the B receptor.

Endothelin was labeled the most potent vasoconstrictor ever described when it was first purified in the late 1980s, but it was a long time before there was any attention paid to the diametrically opposed actions of the B receptors, Pollock said. Receptor antagonists didn't exist in those early days anyway and efforts to block endothelin synthesis didn't work well because there were so many forms of the enzyme that make endothelin scattered throughout the body, he said.

While still working for a pharmaceutical company, Pollock helped develop on one of the first A receptor antagonists that's now in the final stage of clinical trials for chronic kidney disease. Since the early patents on the endothelin-blocking drugs are about to run out, it's unlikely that new drug development dollars will be in the offing, Pollock said. The good news is that drugs already in use for pulmonary hypertension, which shut down the A receptors, likely have crossover potential for salt-sensitive hypertension, Pollock said.

Pollock's studies have shown that the kidney's endothelin B receptor plays a critical role in eliminating both acute and chronic salt loads by activating nitric oxide, a potent dilator of blood vessels, in the kidneys. In fact, the kidneys make more endothelin than any place in the body.

"We had no idea it was going to be this important in salt regulation," Pollock said. "The main point I want to make is that people studying hypertension, salt-sensitivity particularly, need to consider what is happening to the endothelin system when they are doing their research. There are only a handful of us who have been studying it with any real intensity."

Key questions include how the B receptor gets turned off. Interestingly, researchers already know that the angiotensin system shuts the receptor down when patients are on a low-salt diet. Do hypertensive patients on a low-salt diet also have their B receptors turned off? "It's a good question and another reason that targeting the renin-angiotensin-aldosterone system may not give you the whole answer," Pollock said.

The Lewis K. Dahl Memorial Lecture was established in 1988 by the Council for High Blood Pressure Research in honor of Dahl's pioneering work on the relations between salt, the kidney and hypertension, and for establishing the Dahl salt-sensitive rat, a major genetically based experimental model of hypertension. Pollock has been a fellow of the council since 2000.

Provided by Medical College of Georgia

Americans living longer, more healthy lives

Thanks to medical advances, better treatments and new drugs not available a generation ago, the average American born today can expect to live 3.8 years longer than a person born two decades ago. Despite all these new technologies, however, is our increased life expectancy actually adding active and healthy years to our lives? That question has remained largely unanswered – until now. In a first-of-its-kind study, researchers at the University of Massachusetts Medical School (UMMS) have found that the average 25-year-old American today can look forward to 2.4 more years of a healthy life than 20 years ago while a 65-year-old today has gained 1.7 years.

14sept 2013--Synthesizing data from multiple government-sponsored health surveys conducted over the last 21 years, Allison Rosen, MD, associate professor of Quantitative Health Sciences at UMMS, Susan Stewart, researcher at the National Bureau of Economic Research, and David Cutler, professor of economics at Harvard University, were able, for the first time, to measure how the quality-adjusted life expectancy (QALE) of all Americans has changed over time. The study's findings are described in a paper published today in the American Journal of Public Health.

"QALE tells us more than how long a person can expect to live," said Dr. Rosen, senior author on the study. "It tells us what the relative quality of those added years are in terms of physical, emotional and mental well-being. Though many studies have measured this in different ways, this is really the first time we've been able to capture this type of information across the whole U.S. population over an extended period."

The data shows that Americans are living longer, reporting fewer symptoms of disease, have more energy and show fewer impairment in everyday tasks such as walking than a generation ago. According to the study authors, a 25-year-old person today can expect to live 6 percent or 2.4 quality years longer than their 1987 counterpart. Meanwhile, a 65-year-old person will gain 1.7 quality years, a 14 percent increase from a generation ago.

Thanks to improvements in health care, many conditions are far more treatable today than 25 years ago, Rosen said. Heart disease, for instance, was potentially much more debilitating a generation ago and patients often suffered a decline in quality of life as a result. "Today, it is far less likely that a patient recovering from a heart attack will become institutionalized or need around-the-clock care the way they once might have," Rosen said. They also found that health gains made as a result of smoking cessation programs were being off-set, in part, by increases in obesity.

Today, Americans are more likely to see quality of life declines related to chronic, degenerative diseases such as Alzheimer's and dementia, while younger Americans appear to be experiencing problems related to a sedentary lifestyle.

The authors also identified some troubling health trends. Among these was an increase in anxiety among young and middle-aged people beginning in 2001. Problems with walking have increased significantly among non-elderly over the last decade.

In the past, researchers have had a difficult time measuring population health beyond simple life expectancy because quality of life incorporates so many variables – physical well-being, mental health, pain, vitality, energy, emotional state – that it's difficult to bring all these things together cohesively into a single number. Making it even more challenging, the surveys that measure quality of life are rarely consistent with each other because they all define health and quality of life differently.

Using multiple national surveys that asked Americans about their health in various ways over the last 21 years, the authors solved this problem by identifying areas where the studies overlapped, allowing them to build a single, large data set which covered the entire adult population over more than two decades.

"Comprehensive measures of the overall health of the nation are practically nonexistent," said Rosen. "This study shows how existing national data can be used to systematically measure whether the population is getting healthier – not just living longer."

As the Affordable Care Act goes into effect in 2014, the value of a single, consistent way of measuring improvements in health over a large population will be invaluable in assessing the impact of these pending changes according to the authors.

"Having a consistent measure of population health represents a major advance in our ability to measure the impact of health care reform on the health – not just the health care use – of all Americans," said Rosen. "The bottom line in assessing the success of the ACA is whether or not we are getting the most health from our investment of increasingly limited resources. Are we getting the most health bang for our bucks?"

Provided by University of Massachusetts Medical School

Obstructive lung disease linked with decline in memory and information processing

Obstructive lung disease (OLD) has been linked with a decline in cognitive functioning, including memory and information processing.

13 sept 2013--A new study, which will be presented today (11 September 2013) at the European Respiratory Society (ERS) Annual Congress, suggests that impaired cognitive functioning could be an important factor in OLD.

Previous research has found that people with OLD, including COPD, often experience global cognitive impairments, but this new study – using the UK Biobank Resource – focused on which domain-specific cognitive functions were affected in persons with OLD.

The researchers analysed 5,764 people with OLD and 37,275 people without this condition. All participants completed a number of cognitive tests to examine cognitive functioning.

The results of the study showed that people with OLD performed significantly worse than people without this condition in memory tests, pairs matching tests and a reaction time test.

The authors concluded that people with OLD are more likely to experience cognitive impairment, particularly in memory and information processing.

Lead author, Fiona Cleutjens MSc from the CIRO+, Centre of Expertise for Chronic Organ Failure in the Netherlands, said: "We know that OLD can often exist alongside other conditions and our new study has found evidence that OLD is linked with problems with memory and information processing. This can be very debilitating, especially for someone who is already dealing with the symptoms of OLD. Our findings suggest that healthcare professionals need to be aware of the possible impact of cognitive impairment in the self-management, clinical management and pulmonary rehabilitation of OLD patients."

Provided by European Lung Foundation

Screening for minor memory changes will wrongly label many with dementia, warn experts

A political drive led by the UK and US to screen older people for minor memory changes (often called mild cognitive impairment or pre-dementia) is leading to unnecessary investigation and potentially harmful treatment for what is arguably an inevitable consequence of ageing, warn University of Sydney experts in in a paper published in the British Medical Journal (BMJ) today.

12sept 2013--A team of specialists in Australia and the UK say that expanding diagnosis of dementia will result in up to 65 percent of people aged over 80 having Alzheimer's disease diagnosed - and up to 23 percent of non-demented older people being labelled with dementia.

They argue this policy is not backed by evidence and ignores the risks, harms and costs to individuals, families and societies. It may also divert resources that are badly needed for the care of people with advanced dementia.

Their views come as the Preventing Overdiagnosis conference opens in New Hampshire next week, partnered by BMJ's Too Much Medicine campaign, where experts from around the world will gather to discuss how to tackle the threat to health and the waste of money caused by unnecessary care.

Paper co-author, Professor David Le Couteur from the University's Charles Perkins Centre, said dementia is an age related condition and with an ageing global population, it is predicted to become an overwhelming and costly problem.

"Although evidence suggests that only five to 10 percent of people with mild cognitive symptoms will develop dementia each year, current policy in many countries is aimed at encouraging more widespread and earlier diagnosis of dementia," he said.

"For example, in the US, the Medicare insurance programme will cover an annual wellness visit to a physician that includes a cognitive impairment test. In England, the government has announced that it will reward general practitioners for assessing brain function in older patients - and has committed to have "a memory clinic in every town and every city" despite no sound evidence of benefit.

"This has led to the development of imaging techniques and tests that are increasingly used in diagnosis, despite uncertainty over their accuracy.

"Furthermore, there are no drugs that prevent the progression of dementia or are effective in patients with mild cognitive impairment, raising concerns that once patients are labelled with disease or pre-disease, they may try untested therapies and run the risk of adverse effects."

The paper co-authors also question whether ageing of the population is becoming a "commercial opportunity" for developing screening, early diagnosis tests and medicines marketed to maintain cognition in old age.

The desire of politicians, dementia organisations, and academics and clinicians in the field to raise the profile of dementia is understandable, write the authors, "but we risk being conscripted into an unwanted war against dementia."

Yet they suggest that the political rhetoric expended on preventing the burden of dementia would be much better served by efforts to reduce smoking and obesity, given current knowledge linking mid-life obesity and cigarettes with the risk of dementia.

"Current policy is rolling out untested and uncontrolled experiments in the frailest people in society without a rigorous evaluation of its benefits and harms to individuals, families, service settings, and professionals," Professor Le Couteur concluded.

More information: www.bmj.com/content/347/bmj.f5125

Provided by University of Sydney

US faces crisis in cancer care, says new IOM report

Delivery of cancer care in the U.S. is facing a crisis stemming from a combination of factors—a growing demand for such care, a shrinking oncology work force, rising costs of cancer care, and the complexity of the disease and its treatment, says a new report from the Institute of Medicine. The report recommends ways to respond to these challenges and improve cancer care delivery, including by strengthening clinicians' core competencies in caring for patients with cancer, shifting to team-based models of care, and communicating more effectively with patients.

11 sept 2013--"Most clinicians caring for cancer patients are trying to provide optimal care, but they're finding it increasingly difficult because of a range of barriers," said Patricia Ganz, chair of the committee that wrote the report and a professor at the School of Medicine and School of Public Health, University of California, Los Angeles. "As a nation we need to chart a new course for cancer care. Changes are needed across the board, from how we communicate with patients, to how we translate research into practice, to how we coordinate care and measure its quality."

Changing demographics will place new demands on the nation's cancer care delivery system, as the number of adults older than 65—the segment of the population that accounts for most cancer diagnoses—rapidly increases, the report says. In the United States, more than 1.6 million new cases are diagnosed each year; by 2030, cancer incidence is expected to rise by 45 percent to 2.3 million new diagnoses per year. The oncology work force may soon be too small to care for the rising number of people diagnosed with cancer, and training programs lack the ability to rapidly expand, the report says.

Adding to stresses on the system is the complexity of cancer and its treatment, which has grown in recent years with the development of new therapies targeting specific abnormalities often present only in subsets of patients. Incorporating this new information into clinical care is challenging, the report says. Given the disease's complexity, clinicians, patients, and patients' families can find it difficult to formulate care plans with the necessary speed, precision, and quality; as a result, decisions about cancer care are often not sufficiently evidence-based.

Another challenge is the cost of cancer care, which is rising faster than other sectors of medicine, having increased from $72 billion in 2004 to $125 billion in 2010, says the report. At the current rate, it will increase another 39 percent to $173 billion by 2020. And the single largest insurer for those over 65, the Centers for Medicare and Medicaid Services (CMS), is struggling financially.

The report recommends strategies for improving the care of cancer patients, grounded in six components of high-quality cancer care. The components are ordered based on the priority level with which they should be addressed.

Engaged patients. The cancer care system should support patients in making informed medical decisions that are consistent with their needs, values, and preferences. Cancer care teams should provide patients and their families with understandable information about the cancer prognosis and the benefits, harms, and costs of treatments. The National Cancer Institute, the Centers for Medicare and Medicaid Services, and other stakeholders should improve the develop¬ment and dissemination of this critical informa¬tion, using decision aids when possible.

Patients with advanced cancer face specific communication and decision-making needs, and cancer care teams need to discuss their options, such as revisiting and implementing advance care plans. However, these difficult conversations do not occur as often as they should; recent studies found that 65 percent to 80 percent of cancer patients with poor prognoses incorrectly believed their treatment could result in a cure.

An adequately staffed, trained, and coordinated work force. New models of team-based care are an effective way to promote coordinated cancer care and to respond to existing work-force shortages and demographic changes. And to achieve high-quality cancer care, the work force must include enough clinicians with essential core competencies for treating patients with cancer. Professional organizations that represent those who care for patients with cancer should define these core competencies, and organizations that deliver cancer care should ensure their clinicians have those skills.

Evidence-based cancer care. A high-quality cancer care delivery system uses results from scientific research to inform medical decisions, but currently many medical decisions are not supported by sufficient evidence, the report says. Clinical research should gather evidence of the benefits and harms of various treatment options so that patients and their cancer care teams can make more informed treatment decisions. Research should also capture the impacts of treatment regimens on quality of life, symptoms, and patients' overall experience with the disease. Additional research is needed on cancer interventions for older adults and those with multiple chronic diseases. The current system is poorly prepared to address the complex care needs of these patients.

A learning health care information technology system for cancer care. A system is needed that can "learn" by enabling real-time analysis of data from cancer patients in a variety of care settings to improve knowledge and inform medical decisions. Professional organizations and the U.S. Department of Health and Human Services should develop and implement the learning health care system, and payers should create incentives for clinicians to participate as it develops.

Translation of evidence into practice, quality measurement, and performance improvement. Tools and initiatives should be delivered to help clinicians quickly incorporate new medical knowledge into routine care. And quality measures are needed to provide a standardized way to assess the quality of cancer care delivered. These measures have the potential to drive improvements in care, inform patients, and influence clinician behavior and reimbursement.

Accessible and affordable cancer care. Currently there are major disparities in access to cancer care among individuals who are of lower socio-economic status, are racial or ethnic minorities, lack health insurance coverage, and are older. HHS should develop a national strategy that leverages existing commu¬nity interventions to provide accessible and afford¬able cancer care, the report says. To improve the affordability of care, professional societies should publicly disseminate evidence-based information about cancer care practices that are unnecessary or where the harm may outweigh the benefits. CMS and other payers should design and evaluate new payment models that incentivize cancer care teams to provide care based on the best available evidence and that aligns with their patients' needs. The current fee-for-service reimbursement system encourages a high volume of care, but fails to reward the provision of high-quality care.

The Patient Protection and Affordable Care Act is expected to make significant changes in accessibility and affordability of care, the report notes. Because much of the law has not been implemented, these issues will need to be revisited once the law's full impact is known.

Provided by National Academy of Sciences

DO-HEALTH a multi-center clinical trial on healthy ageing achieves first milestone

Europe's largest healthy ageing study – DO-HEALTH – which aims to provide evidence for the safety of three simple preventive interventions: vitamin D, omega-3 fatty acids and a simple home exercise programme, has recruited 532 of its target 2,000 seniors. In Europe, the number of seniors aged 70 and over will increase by 40 per cent in the next 20 years, and those aged 80 and above will more than double. If action to ensure people age healthily is not taken, not only will it impact their quality of life but it will result in a huge economic burden on health systems in the future.

10 sept 2013--This is the first large European multi-centre clinical trial which seeks to provide evidence for effective, affordable, and well-tolerated strategies that prevent or delay chronic disease at older age and prolong healthy life expectancy. "We are pleased to announce that the DO-HEALTH study is on track and on target in achieving the 25% recruitment milestone," announced Professor Heike Bischoff-Ferrari, Director of the Centre on Aging and Mobility of Zurich University and DO-HEALTH Principal Investigator.

The seven participating DO-HEALTH study centres in Switzerland, Austria, France, Germany, Portugal and Switzerland are recruiting participants who are 70 years or older, mobile and living independently at home, to take part in the three-year study. Five of the centres are above their targets with 26 to 36% of participants already recruited.

As the European population rapidly ages, age-related chronic diseases in seniors have become a central concern. Chronic diseases prevent millions of seniors from leading longer, more active and independent lives while placing a heavy burden on health care systems and society as a whole.

Among the most promising affordable strategies to promote healthy ageing are vitamin D, marine omega-3 fatty acids and physical exercise. However, their individual and combined effects have yet to be confirmed in a large clinical trial. DO-HEALTH will investigate the impact of these simple strategies in the prevention of chronic disease at older age and will study their role in the prevention of fractures and falls, functional decline, high blood pressure, cognitive decline and pain from osteoarthritis.

International Osteoporosis Foundation CEO, Judy Stenmark stated "Chronic diseases are by far the leading cause of mortality in the world, imposing an enormous burden on patients, their families and on society as a whole. With its ageing population, Europe will have to deal with a dramatic increase in chronic diseases in the next decade therefore, studies such as DO-HEALTH are essential in helping us to better understand and control the disease burden."

She continued, "DO-HEALTH is set to make a vital contribution to the development of low-cost, universally accessible strategies in the fight against age-related chronic diseases. IOF congratulates the DO-HEALTH centres for their dedication to this important study."

Provided by International Osteoporosis Foundation

Stressful life events significantly raise the risk of falls in older men

A study of around 5,000 older men has shown that stressful life events such as death of a loved one, or serious financial problems, significantly raised the risk of falls in the year following the incident. The research is published online today in the journal Age and Ageing.

09 sept 2013--Dr Howard A. Fink of the VA Medical Center in Minneapolis and colleagues conducted a study of 5,994 community-dwelling men over the age of 65 who were enrolled in the Osteoporotic Fractures in Men (MrOS) study in six locations across the United States. 5,125 participated in a second study visit and answered questions on stressful life events in the prior year. A further subset of 4,981 men reported complete data on falls for one year after the second visit.

During the second visit, participants were asked their marital status, and if widowed, their spouse's date of death. They were also asked to report occurrence of any of the following stressful life events: serious illness or accident of wife/partner; death of other close relative or close friend; separation from child, close friend, or other relative on whom the participant depended on for help; loss of pet; given up important hobby or interest; serious financial trouble; move or change in residence. Following the second visit, the participants were contacted every four months for one year regarding falls or fractures. Any fractures were confirmed by central review of radiographyreports. Overall response rates exceeded 99%.

Among the 4,981 men with complete stressful life event and falls data, 27.7% fell and 14.7% fell multiple times during the year after visit two. Among men who reported stressful life events, falls occurred in 29.9% of cases where one type of stressful event had been reported; 35.5% of cases with two types of stressful events, and 39.9% of cases where three or more types of stressful life events were reported.

In age-adjusted analyses, any stressful life event was associated with a 41% increase in risk of fall, and a nearly two-fold increase in risk for multiple falls in the following year. However, there was no statistically significant increase of risk for fractures.

Dr Fink said: "To my knowledge, this is the first prospective study to examine the independent association between stressful life events and the risk of falls in community-dwelling older men. We believe it provides the strongest evidence to date supporting stressful life events as a risk factor for falls. However, the mechanism connecting stressful life events to falls is uncertain."

In the paper, the authors discussed possible reasons for this association. One potential explanation, based on previous studies, is that stressful events trigger a neurohormonal response, causing stress hormones to be released, leading to falls and other adverse health events. Some data suggest that inflammation – a potential indicator of physical stress – could lead to a loss of muscle mass and impaired physical function. Or it could be that sudden emotions, triggered by a stressful event, could impact balance or visual attention, leading to a fall.

The study does have some limitations: because the recall of stressful life events and fall were self-reported, they could be susceptible to error. Secondly, self-reported events may not be equally stressful to all participants, and no data were available to estimate participants' resiliency.

Dr Fink concluded: "Further studies are needed to confirm our findings and to investigate the mechanism underlying this association. Additional studies may explore whether clinical screening of older men with recent stressful life events for fall reduction interventions will reduce falls."

More information: 'Association of stressful life events with incident falls and fractures in older men: the Osteoporotic Fractures in Men (MrOS) Study' by Howard A. Fink, Michael A. Kuskowski, Lynn M. Marshall Age and Ageing,DOI: 10.1093/ageing/aft117

Provided by Oxford University Press

Better hygiene in wealthy nations may increase Alzheimer's risk

New research has found a "very significant" relationship between a nation's wealth and hygiene and the Alzheimer's "burden" on its population. High-income, highly industrialised countries with large urban areas and better hygiene exhibit much higher rates of Alzheimer's.

08 sept 2013--Using 'age-standardised'* data - which predict Alzheimer's rates if all countries had the same population birth rate, life expectancy and age structure—the study found strong correlations between national sanitation levels and Alzheimer's.

This latest study adds further weight to the "hygiene hypothesis" in relation to Alzheimer's: that sanitised environments in developed nations result in far less exposure to a diverse range of bacteria, viruses and other microorganisms—which might actually cause the immune system to develop poorly, exposing the brain to the inflammation associated with Alzheimer's disease, say the researchers.

"The 'hygiene hypothesis', which suggests a relationship between cleaner environments and a higher risk of certain allergies and autoimmune diseases, is well— established. We believe we can now add Alzheimer's to this list of diseases," said Dr Molly Fox, lead author of the study and Gates Cambridge Alumna, who conducted the research at Cambridge's Biological Anthropology division.

"There are important implications for forecasting future global disease burden, especially in developing countries as they increase in sanitation."

The researchers tested whether "pathogen prevalence" can explain the levels of variation in Alzheimer's rates across 192 countries.

After adjusting for differences in population age structures, the study found that countries with higher levels of sanitation had higher rates of Alzheimer's. For example, countries where all people have access to clean drinking water, such as the UK and France, have 9% higher Alzheimer's rates than countries where less than half have access, such as Kenya and Cambodia.

Countries that have much lower rates of infectious disease, such as Switzerland and Iceland, have 12% higher rates of Alzheimer's compared with countries with high rates of infectious disease, such as China and Ghana.

More urbanised countries exhibited higher rates of Alzheimer's, irrespective of life expectancy. Countries where more than three-quarters of the population are located in urban areas, such as the UK and Australia, exhibit 10% higher rates of Alzheimer's compared to countries where less than one-tenth of people inhabit urban areas, such as Bangladesh and Nepal.

Differences in levels of sanitation, infectious disease and urbanisation accounted respectively for 33%, 36% and 28% of the discrepancy in Alzheimer's rates between countries.

Researchers said that, although these trends had "overlapping effects", they are a good indication of a country's degree of hygiene which, when combined, account for 42.5% of the "variation" in countries' Alzheimer's disease rates—showing that countries with greater levels of hygiene have much higher Alzheimer's rates regardless of general life expectancy.

Previous research has shown that in the developed world, dementia rates doubled every 5.8 years compared with 6.7 years in low income, developing countries; and that Alzheimer's prevalence in Latin America, China and India are all lower than in Europe, and, within those regions, lower in rural compared with urban settings—supporting the new study's findings.

The results of the study are newly published by the journal Evolution, Medicine and Public Health, with these latest results coming hard on the heels of previous research led by Fox on the benefits of breastfeeding for Alzheimer's prevention.

"Exposure to microorganisms is critical for the regulation of the immune system," write the researchers, who say that say that—since increasing global urbanisation beginning at the turn of the 19th century—the populations of many of the world's wealthier nations have increasingly very little exposure to the so-called 'friendly' microbes which "stimulate" the immune system—due to "diminishing contact with animals, faeces and soil."

Aspects of modern life—antibiotics, sanitation, clean drinking water, paved roads and so on—lead to lower rates of exposure to these microorganisms that have been "omnipresent" for the "majority of human history", they say.

This lack of microbe and bacterial contact can lead to insufficient development of the white blood cells that defend the body against infection, particularly those called T-cells—the foot soldiers of the immune system that attack foreign invaders in the bloodstream.

Deficiency of anti-inflammatory ("regulatory") T-cells has links to the types of inflammation commonly found in the brain of those suffering with Alzheimer's disease, and the researchers' proposal that Alzheimer's risk is linked to the general hygiene levels of a nation's population is reinforced by their analysis of global Alzheimer's rates.

"The increase in adult life expectancy and Alzheimer's prevalence in developing countries is perhaps one of the greatest challenges of our time. Today, more than 50% of people with Alzheimer's live in the developing world, and by 2025 it is expected that this figure will rise to more than 70%," said Fox.

"A better understanding of how environmental sanitation influences Alzheimer's risk could open up avenues for both lifestyle and pharmaceutical strategies to limit Alzheimer's prevalence. An awareness of this by-product of increasing wealth and development could encourage the innovation of new strategies to protect vulnerable populations from Alzheimer's."

While childhood—when the immune system is developing—is typically considered critical to the 'hygiene hypothesis', the researchers say that regulatory T-cell numbers peak at various points in a person's life—adolescence and middle age for example—and that microorganism exposure across a lifetime may be related to Alzheimer's risk, citing previous research showing fluctuations in Alzheimer's risk in migrants.

The team used the disability-adjusted life year (DALY) rates to calculate the incidence of Alzheimer's across the countries studied. The DALY measurement is the sum of years lost due to premature mortality combined with years spent in disability – the World Health Organisation (WHO) says that one DALY can be thought of as "one lost year of 'healthy' life".

The researchers say this method is a much better measure than death rates as it "omits the effects of differential mortality rates" between developed and developing countries. The study was based on the WHO's 'Global Burden of Disease' report, which presents world dementia data for 2004.

More information: *Age-standardised data:

The process of age-standardisation presents a "single summary rate that reflects the number of events that would have been expected if the populations being compared had had identical age distribution" (WHO 2001)

The age-standardised data is calculated by adjusting the crude data for 5-year age groups by age-weights reflecting the age-distribution of the standard population. In the version of the WHO's Global Burden of Disease report we utilised, the terminal age category has been extended from the previous 85+ to 100+, which allows for better adjustment for differences in the proportion of population in older strata.

The age-adjusted and disability-adjusted life year (DALY) rates are calculated by "adjusting the crude estimates to an artificial population structure, the WHO Standard Population, that closely reflects the age and sex structure of most low and middle income countries" (WHO 2013).

The effort to construct a standard population for comparing data across populations with varied age-structures began in the 1840s, and progressed to an international scale in 1960 and was then adopted by the WHO. Statisticians have been researching and improving this process for the past five decades.

The new WHO World Standard was developed in 2000 to best reflect projections of world age-structures for the period 2000-2025. This new standard is based on the UN Population Division's assessments every two years and future projections for every five years of each country's population age-structure. This standardised procedure is widely accepted across the world, and is the basis for all relevant WHO-sponsored analyses.

Provided by University of Cambridge

Being underweight increases death risk of CAD women by two-fold

Being underweight increases the death risk of women with coronary artery disease (CAD) by 2-fold, according to research presented at the ESC Congress today by Dr Aziza Azimi from Denmark. The study suggests that underweight women with CAD should gain weight to reduce their risk of death.

07 sept 2013--Dr Azimi said: "The increasing prevalence of obesity is concerning because it is a major risk factor for cardiovascular disease, early death and other diseases like diabetes mellitus type 2, high blood pressure, and high cholesterol. To our knowledge until now the impact of weight change on risk of death in women with CAD has not been studied."

The aim of the current study was to examine the effect of weight change over time on survival in women with CAD and different body weight classes. The study included 1,685 women (average age 64 years) diagnosed with CAD based on coronary angiography during 2005-2011. Body weight was obtained from anaesthesiology and coronary angiography records. Patients were followed for 6 years.

Weight change was stratified into 3 groups: no change 

Hazard ratios (HRs) for risk of death were calculated using the normal weight group as reference. The researchers adjusted for age, smoking, diabetes, previous heart surgery, previous percutaneous coronary intervention, use of statins and antihypertensive drugs, and degree of CAD.

The researchers found that maintaining weight lowered the risk of death in obese women with CAD (HR=0.36, p=0.06 ). Weight gain and weight loss did not appear to affect their risk of CAD death compared to the normal weight group.

Dr Azimi said: "Weight maintenance decreased the risk of death in obese women with CAD. Obese women are more likely to be treated early with statins, antihypertensive or diabetes drugs, and this may reduce their risk. Weight management should be individual due to their medical condition."

In contrast, underweight women who maintained their weight significantly increased their risk of death by 2-fold (HR=2.15, p=0.03). In this group, losing weight appeared to further increase their risk by 2-fold (although the findings were not significant).

Dr Azimi said: "Weight maintenance or weight loss seems to increase the risk of death in underweight women with CAD. Our findings suggest that these women should gain weight in order to reduce their risk of death."

She concluded: "These data appear to be against the common sense that obesity is a risk factor for cardiovascular mortality as underweight has been even more strongly related to worse clinical outcome than overweight. Future investigations will be necessary to prove this new concept."

Provided by European Society of Cardiology

Training the older brain in 3-D: Video game enhances cognitive control

Participant playing NeuroRacer at home. Credit: The Gazzaley Lab

Participant playing NeuroRacer at home. Credit: The Gazzaley Lab

Scientists at UC San Francisco are reporting that they have found a way to reverse some of the negative effects of aging on the brain, using a video game designed to improve cognitive control.

06 sept 2013--The findings, published this week in Nature, show how a specially designed 3-D video game can improve cognitive performance in healthy older adults. The researchers said it provides a measure of scientific support to the burgeoning field of brain fitness, which has been criticized for lacking evidence that such training can induce lasting and meaningful changes.

In the game, which was developed by the UCSF researchers, participants race a car around a winding track while a variety of road signs pop up. Drivers are instructed to keep an eye out for a specific type of sign, while ignoring all the rest, and to press a button whenever that particular sign appears. The need to switch rapidly from driving to responding to the signs – i.e. multitasking – generates interference in the brain that undermines performance. The researchers found that this interference increases dramatically across the adult lifespan.

But after receiving just 12 hours of training on the game, spread over a month, the 60- to 85-year-old study participants improved their performance until it surpassed that of 20-somethings who played the game for the first time.

The training also improved the participants' performance in two other important cognitive areas: working memory and sustained attention. And participants maintained their skills at the video games six months after the training had ended.

"The finding is a powerful example of how plastic the older brain is," said Adam Gazzaley, MD, PhD, UCSF associate professor of neurology, physiology and psychiatry and director of the Neuroscience Imaging Center. Gazzaley co-founded the company, Akili Interactive Labs, which is developing the next generation of the video game.

Gazzaley, who has made a career out of studying how distraction affects cognitive performance, said his game, NeuroRacer, does more than any ordinary game – be it bridge, a crossword puzzle, or an off-the-shelf video game – to condition the brain. Like a good teacher, he said, NeuroRacer undermines people's natural tendency to go on automatic pilot once they've mastered a skill, and pushes them further than they think they can go.

"Normally, when you get better at something, it gets easier," he said. But with this game, "when you get better, it gets harder."

Evidence that the adult brain is capable of learning has been accumulating for more than a dozen years. A study of London taxi drivers, for example, found that their brains had changed as they learned to navigate the city's notoriously complicated streets. Nevertheless, Gazzaley said the brain's function often erodes steadily over time in many areas, with some exceptions, like wisdom.

Given this, Gazzaley said it's encouraging that even a small amount of brain training can reverse some of the age-related decline.

Gazzaley's group found evidence of a possible brain mechanism that may explain the improvements he saw in his older subjects, and why these gains transferred to other cognitive areas. Electroencephalograph (EEG) recordings point to changes in a neural network involved in cognitive control, which is necessary to pursue goals.

The scientists measured midline frontal theta – or low frequency oscillations – in the prefrontal cortex, as well as the coherence in these waves between frontal and posterior regions of the brain. As the older "drivers" became more adept at the multitasking challenges of NeuroRacer, their brains modulated this key neural network and its activity began to resemble that of young adults.

Both of these measures –midline frontal theta and theta coherence – are well established neural markers of cognitive control that have been associated with many of the processes that enable people to pursue their goals.

"We see this as evidence that the training may have improved our study participants' ability to stay in an engaged, active state for a longer period of time," said Joaquin A. Anguera, the paper's first author and a post-doc in Gazzaley's lab.

Indeed, the researchers found that the training-induced changes in this neural network predicted how well participants would do on a different test, called the Test of Variables of Attention (TOVA), which measures sustained attention.

"The amount that midline frontal theta went up was related to something that was untrained, this other measure, the TOVA," Anguera said. "It implies there's something that changed that was common to the training and to the task we tested afterwards."

Gazzaley said these findings point toward a common neural basis of cognitive control that is enhanced by the challenging and high-interference conditions of the video game, and this might explain how racing a car in 3-D could improve something as seemingly unrelated as memory.

If the finding holds, it could have wide application. Other brain disorders like ADHD, depression and dementia are also associated with deficits in cognitive control.

"Follow up studies using functional Magnetic Resonance Imaging and transcranial electrical stimulation are still needed to better understand exactly how this network is involved in the performance changes," Gazzaley said.

Other authors of the article, "Video game training enhances cognitive control in older adults," include Jacqueline Boccanfuso, Jean Rintoul, Omar Al-Hashimi, Farshid Faraji, Jacki Janowich, Erwin Kong, Yudy Larraburo, Cammie Rolle and Eric Johnston.

Gazzaley is co-founder and chief science advisor of Akili Interactive Labs, which is developing cognitive video game software as diagnostic and therapeutic tools, and has a patent pending on a game-based cognitive intervention he developed from the research presented in the paper.

Provided by University of California, San Francisco

More than one-third of populations worldwide may have low levels of vitamin D, study shows

A new systematic review published in the British Journal of Nutrition, is one of the first to focus on patterns of vitamin D status worldwide and in key population subgroups, using continuous values for 25(OH)D to improve comparisons.

05 sept 2013--Principal investigator, Dr. Kristina Hoffmann of the Mannheim Institute of Public Health (MIPH), Medical Faculty Mannheim, Heidelberg University stated, "The strength of our study is that we used strict inclusion criteria to filter and compare data, using consistent values for 25(OH)D. Although we found a high degree of variability between reports of vitamin D status at the population level, more than one-third of the studies reviewed reported mean serum 25(OH)D values below 50 nmol/l."

Low levels of vitamin D have a potentially serious impact on health, particularly on bone and muscle health. In children, vitamin D deficiency is a cause of rickets; while in adults low values are associated with osteomalacia, osteopenia, osteoporosis and risk of fracture. Emerging evidence also points to increased risk for cancer and cardiovascular diseases. Yet despite its importance to public health, data about vitamin D status at the population level are limited and studies are hampered by lack of consensus and consistency.

The study's key findings include:

• 37.3% of the studies reviewed reported mean serum 25(OH)D values below 50 nmol/l, values considered inadequate by health authorities worldwide.
• Only a limited number of studies for Latin America were available.
• Vitamin D values were higher in North America than in Europe or the Middle-East.
• Age-related differences were observed for the Asia-Pacific and Middle East regions, but not elsewhere.
• The substantial heterogeneity between the studies within each region precludes drawing conclusions on overall vitamin D status at the population level.
• There is a need for research designs which minimize potential sources of bias and thus strengthen understanding of vitamin D status in key subgroups worldwide.

International Osteoporosis Foundation (IOF) CEO Judy Stenmark noted, "Given the global increase in the number of seniors and the almost fourfold increase in hip fractures due to osteoporosis since 1990, public health officials must address the impact of inadequate vitamin D status on fracture risk and overall health in their ageing populations as well as on children and adolescents. IOF urges further research as well as public health measures that would help to improve vitamin D status in these high-risk population groups."

More information: A systematic review of vitamin D status in populations worldwide. Br J Nutr 2013. Epub ahead of print DOI: 10.1017/s0007114513001840

Provided by International Osteoporosis Foundation

Mass screening identifies untreated AF in 5% of 75-76 year olds

Stroke is the second cause of death worldwide. Atrial fibrillation is the most common clinically relevant cardiac arrhythmia in Europe, affecting approximately 1.5-2% of the general population.1 Prevalence is estimated to double in the next 50 years as the population ages.

04 sept 2013--Patients with atrial fibrillation have a five-fold increased risk of ischaemic stroke even though around 30% have no symptoms. As blood is less adequately shifted from the heart during atrial fibrillation, blood clots can form and cause large ischaemic strokes. Strokes that occur in association with atrial fibrillation are often fatal, and survivors are left more disabled and at a high risk of a recurrent stroke.

Dr Svennberg said: "There is hope, however, as oral anticoagulant medication reduces the risk of atrial fibrillation related stroke by 64-70%. But more than 50% of high-risk patients with atrial fibrillation do not receive any treatment. We are looking at an epidemic of atrial fibrillation related strokes if nothing is done to improve treatment levels."

The STROKESTOP trial is a mass screening programme of all 75-76 year olds in Stockholm County and Region Halland in Sweden. It aims to identify patients with undiagnosed atrial fibrillation and find out if oral anticoagulation(OAC) therapy reduces their risk of ischaemic stroke.

For the trial, more than 25,000 people born in 1936 and 1937 were randomised 1:1 to screening for atrial fibrillation or a control group. Screening is done at home with a handheld ECG device and takes 1 minute per day for 2 weeks. When atrial fibrillation is diagnosed, patients are offered OAC treatment. Both screening and control groups will be followed prospectively for 5 years for thromboembolic events, bleeding and mortality.

Preliminary results from STROKESTOP are presented today. A year into the trial, 6,496 (50%) of the 13,000 inhabitants in the screening arm agreed to screening for atrial fibrillation. A lower proportion of patients agreed to screening in Stockholm (49%) than in rural areas (65%). Dr Svennberg said: "We will investigate factors related to participation, in an effort to increase uptake."

More than 11% of the screening group had atrial fibrillation. Of these, previously undiagnosed atrial fibrillation was found in 192 (3%) of patients while in 129 (2%) of patients, atrial fibrillation had been diagnosed but they were not on OAC. More than 90% of the patients with undiagnosed atrial fibrillation were started on OAC.

Dr Svennberg said: "We found that 5% of patients in the screening arm had untreated atrial fibrillation. We successfully started oral anticoagulation treatment in more than 90% of the patients with newly diagnosed atrial fibrillation. This should reduce their risk of a stroke by up to 70%. We are still collecting data on patients with known atrial fibrillation but not on OAC."

Professor Mårten Rosenqvist, chair of the STROKESTOP steering committee, said: "Without appropriate treatment atrial fibrillation is a ticking bomb. We hope the STROKESTOP study will show that screening for atrial fibrillation reduces the risk of stroke. Our final results should be available by November 2018."

More information: 1 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. European Heart Journal. 2012;33:2719-3747.

2 SBU—Swedish Council on Health Technology Assessment—report 2013 "Förmaksflimmer- Förekomst och risk för stroke".

Provided by European Society of Cardiology

Women less likely to die after TAVI than men

Women are 25 percent less likely to die one year after TAVI than men, according to research presented at the ESC Congress today by Dr. Mohammad Sherif from Germany. The findings suggest that TAVI might be the preferred treatment option for elderly women with symptomatic severe aortic stenosis.

03 sept 2013--Dr Sherif said: "Earlier studies on the impact of gender on outcome after transcatheter aortic valve implantation (TAVI) have had conflicting results. A Canadian study reported in 641 consecutive patients that female sex is associated with a better long-term and short-term survival after TAVI.1 An Italian study of 305 high risk patients found no gender differences in composite safety and efficacy endpoints at 30 days and one year after TAVI."2

The current analysis examined gender differences in outcomes for 1432 consecutive patients from 27 centers who were enrolled in the German TAVI registry between January 2009 and June 2010. Women comprised 57.8% of the cohort. At baseline the average age of women was 83 years vs 80 years for men. Women had aortic valve gradients at baseline of 52 mmHg vs 45 mmHg for men (severe aortic stenosis is defined as gradients exceeding 40 mmHg).

During the TAVI procedure, 25.2% of women had vascular complications (including iliac artery dissection, and bleeding from the puncture site requiring blood transfusion) compared to 17.2% of men.

The investigators did a multivariate analysis to adjust for the effect of differences between women and men in demographic, procedural, and clinical variables on one year mortality. Figure 1 shows women's survival advantageat 12 months. Even after adjustment, female gender was an independent predictor for one-year survival after TAVI with a hazard ratio of 0.75. Dr Sherif said: "This means that women are 25% less likely to die after TAVI than men.

Dr Sherif said: "Lower levels of fibrosis in women might explain the more rapid reversal of myocardial hypertrophy after correction of aortic stenosis and might partially explain the better outcome in women compared with men.3 This might account for the time delay in the female advantage, since the reversal process takes longer than 30 days."

He added: "As a limitation for registry data, these data are observational, and therefore can only be considered to be hypothesis generating rather than causative."

Dr Sherif concluded: "Future work should focus on the effect of sex differences in outcomes for intermediate risk patients undergoing TAVI, and provide longer-term follow up for high-risk patients."

More information: 1 Humphries KH, Toggweiler S, Rodes-Cabau J, Nombela-Franco L, Dumont E, Wood DA, Willson AB, Binder RK, Freeman M, Lee MK, Gao M, Izadnegahdar M, Ye J, Cheung A, Webb JG. Sex differences in mortality after transcatheter aortic valve replacement for severe aortic stenosis. J Am Coll Cardiol. 2012;60:882-886.

2 Buchanan GL, Chieffo A, Montorfano M, Maisano F, Latib A, Godino C, Cioni M, Gullace MA, Franco A, Gerli C, Alfieri O, Colombo A. The role of sex on VARC outcomes following transcatheter aortic valve implantation with both Edwards SAPIEN and Medtronic CoreValve ReValving System® devices: the Milan registry. EuroIntervention. 2011;7(5):556-563.

3 Petrov G, Regitz-Zagrosek V, Lehmkuhl E, Krabatsch T, Dunkel A, Dandel M, Dworatzek E, Mahmoodzadeh S, Schubert C, Becher E, Hampl H, Hetzer R. Regression of myocardial hypertrophy after aortic valve replacement: faster in women? Circulation. 2010;122:S23-S28.

Provided by European Society of Cardiology

TAVI is safe alternative to redo cardiac surgery

TAVI is a safe alternative to redo cardiac surgery for failing bioprosthetic valves, according to research presented at the ESC Congress today by Dr. Spyridon Katsanos from the Netherlands. The findings suggest that transcatheter aortic valve implantation (TAVI) is a treatment alternative for inoperable elderly patients and high risk patients with failing bioprostheses.

03 sept 2013--Use of bioprosthetic heart valves has dramatically increased (from 18% in 1991 to 59% in 2003), mainly in older patients with comorbidities. This is due to the increased risk of bleeding complications associated with lifelong use of anticoagulation for mechanical prostheses.

But structural valve deterioration is one the main complications associated with bioprosthetic heart valves. In large registries including more than 300 000 patients undergoing aortic valve replacement the reoperation rate for patients receiving a bioprosthesis was 3.1% at 11-13 years of follow-up compared with 2.3% reoperation rate for recipients of an aortic mechanical prosthesis.1

Dr Katsanos said: "Reoperation for failed bioprostheses, also called redo cardiac surgery, is associated with increased rates of mortality and morbidity. Less invasive treatments have emerged such as transcatheter valve-in-valve implantation, a type of TAVI operation which is a safe therapeutic option for patients with failed bioprostheses and contraindications for surgery. But until now there has not been a direct comparison of survival between high risk patients treated with either reoperation or a TAVI operation."

The current study assessed the prognosis of patients with failed bioprosthetic aortic and mitral valves and high predicted operative risk who underwent transcatheter valve-in-valve intervention with the Edwards Sapien (23 or 26 mm) valve. They were compared with a historical cohort of patients who underwent elective redo cardiac surgery for failing mitral and aortic prostheses and failing mitral valve annuloplasty.

The TAVI group (age 80±2 years, 25% men) included 12 patients with failing aortic bioprostheses, 2 with failing mitral bioprostheses and 2 with failed mitral valve annuloplasty. The redo cardiac surgery group (age 70±1 years, 50% men) had 15 patients with failing aortic bioprostheses and 1 with failing mitral bioprostheses. The reason for valve dysfunction was stenosis in 11 patients, regurgitation in 14 patients and mixed pathology in 7 patients. Patients with endocarditis were excluded. Both groups had similar operative risk, New York Heart Association functional class, and left ventricular ejection fraction.

After a median follow up of 21 (range 7-44) months, 10 (30%) patients died. As shown in the figure, 3-year survival did not differ between patients treated with transcatheter valve-in-valve implantation and those treated with redo cardiac surgery (log-rank p=0.939).

Dr Katsanos said: "We have shown for the first time that the long term survival of high risk patients with failing bioprostheses treated with transcatheter valve-in-valve implantation is comparable to high risk patients treated with redo cardiac surgery."

He concluded: "Transcatheter valve-in-valve implantation is a minimally invasive procedure performed through transfemoral or transapical approach under fluoroscopic guidance and does not require sternotomy and cardiopulmonary bypass. Elderly patients deemed not operable and also high risk patients with failing bioprostheses may have a treatment alternative to redo cardiac surgery."

More information: 1. Schelbert EB, Vaughan-Sarrazin MS, Welke KF, Rosenthal GE. Valve type and long-term outcomes after aortic valve replacement in older patients. Heart. 2008;94(9):1181-1188.

Provided by European Society of Cardiology

TAVI feasible in bicuspid aortic valve

Transcatheter aortic valve implantation (TAVI) is feasible in patients with bicuspid aortic valve, according to research presented at ESC Congress 2013 today by Dr. Timm Bauer from Germany. The findings open up a new treatment possibility in patients with BV, which has been considered a contraindication for TAVI.

03 sept 2013--Bicuspid aortic valve (BV) is the most common congenital valvular abnormality, occurring in 1-2% of the general population. Two of the aortic valvular leaflets fuse during development resulting in a valve that is bicuspid instead of the normal tricuspid configuration. BV is associated with increased mechanical stress which predisposes to calcification and development of aortic stenosis which narrows the opening of the aortic valve.

Dr Bauer said: "TAVI is used to treat elderly high risk patients with severe aortic stenosis. Despite previous assumptions the frequency of BV is quite high even among elderly patients with symptomatic aortic stenosis."

But he added: "BV has been considered a relative contraindication to TAVI. One of the main reasons is the presumed risk for relevant aortic regurgitation, where blood leaks back through the aortic valve during ventricular diastole. However, case reports and small case series have suggested that TAVI can be successfully performed with acceptable clinical outcomes in high risk patients with BV."

The study prospectively enrolled 1,424 patients with severe aortic stenosis undergoing TAVI into the German TAVI-Registry between January 2009 and June 2010. For the present analysis patients with valve-in-valve procedures were excluded and those with BV (n=38, 2.7%) were compared to those with tricuspid aortic valve (TV) (n=1,357, 97.3%). Patient characteristics did not markedly differ and procedural success was very high in both groups.

The researchers found a higher rate of relevant aortic regurgitation (? grade 2) after TAVI among patients with BV (BV=25%, TV=14.7%; p=0.05) (see figure), whereas pacemakers were more often implanted in patients with TV (BV=16.7%, TV=35.4%; p=0.02). Dr Bauer said: "The higher rate of aortic regurgitation in BV patients was expected and is still acceptable because it did not lead to higher mortality. However, substantial improvements in the field of device technology and imaging have to be made to perform TAVI in a safer and more effective way in BV-patients."

He added: "The difference between groups in the need for a pacemaker can be partly explained by the higher implantation rate of Sapien EdwardsTM prosthesis. Maybe anatomic differences in the aortic root or left ventricular outflow tract of BV play a role, too."

The 30-day mortality was similar in both cohorts (BV=10.5%, TV=10.8%). In a Cox proportional regression analysis after adjustment for several risk factors BV was not associated with higher 1-year mortality (hazard ratio [HR]=0.64, 95% confidence interval [CI]=0.29-1.41). Dr Bauer said: "Both 30-day and 1-year mortality were not elevated in BV patients compared to patients with TV. We can therefore conclude that TAVI gave a satisfactory clinical outcome in BV patients despite their higher rate of relevant aortic regurgitation."

He concluded: "As the nature of our study is exploratory and the number of BV patients is quite low, the findings should be interpreted cautiously. However, our study opens up a new treatment possibility for selected high riskpatients with BV, who until now have received medical treatment only or conventional valve surgery. TAVI has the potential to be a safe alternative in these patients, but more studies are needed to support these findings."

Provided by European Society of Cardiology

Listening to favorite music improves endothelial function in CAD

Listening to favorite music improves endothelial function in patients with coronary artery disease, according to research presented at ESC Congress 2013 today by professor Marina Deljanin Ilic from Serbia. Music and exercise training combined produced the most benefit.

01 sept 2013--Professor Deljanin Ilic said: "In the setting of cardiovascular risk factors and cardiovascular disease the endothelium loses its normal function.1 Since endothelium derived nitric oxide is necessary to maintain an adequatevascular response, correction of endothelial dysfunction has become a goal of therapy."

She added: "Exercise training has been shown to improve endothelial function and is the cornerstone of a multifaceted programme of cardiovascular rehabilitation. However, little is known about the role of music in cardiovascular rehabilitation or the effects of listening to favourite music on endothelial function."

The current study evaluated the effects of listening to favourite music on endothelial function through changes of circulating blood markers of endothelial function: the stable end products of nitric oxide (NOx), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and xanthine oxidase (XO) in 74 patients with stable CAD.

Patients were randomised to trained (T, n=33), music and trained (MT, n=31) and music (M, n=10) groups. Patients in the T and MT groups underwent 3 weeks of supervised aerobic exercise training at a residential centre. In addition to exercise training, patients in the MT group listened to their favourite music for 30 minutes every day.

Patients in the M group received usual community care and listened to their favourite music for 30 minutes every day. Markers were measured and an exercise test performed at baseline and 3 weeks.

After 3 weeks the value of NOx increased in groups T (from 33.0±13.0 to 42.8±11.0 µmol/l, p< 0.005) and MT (from 34.5±7.1 to 49.6±12.6 µmol/l,

Professor Deljanin Ilic said: "The combination of music and exercise training led to the most improvement in endothelial function. Improvements in endothelial function were associated with significant improvements in exercise capacity."

She added: "Listening to joyful music for 30 minutes has been associated with improved endothelial function, possibly by ?-endorphin mediated activation of endothelium derived nitric oxide.2 The vascular health benefits of music may be due to endorphins or endorphin like compounds released from the brain when we hear music we like."

Professor Deljanin Ilic concluded: "Listening to favourite music alone and in addition to regular exercise training improves endothelial function and therefore may be an adjunct method in the rehabilitation of patients with CAD. There is no an 'ideal' music for everybody and patients should choose music which increases positive emotions and makes them happy or relaxed."

More information: 1 Widlansky ME, Gokce N, Keaney JF, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol. 2003;42:1149-1160.

2 Miller M, Mangano CC, Beach V, Kop WJ, Vogel RA. Divergent effects of joyful and anxiety-provoking music on endothelial vasoreactivity. Psychosom Med. 2010;72(4):354-356.

Provided by European Society of Cardiology