Treadmill performance predicts mortality

                               Treadmill (stock image). Credit: © viktoriagavril / Fotolia

Analyzing data from 58,000 heart stress tests, Johns Hopkins cardiologists report they have developed a formula that estimates one's risk of dying over a decade based on a person's ability to exercise on a treadmill at an increasing speed and incline.

Several exercise-based risk scoring systems already in use are designed to measure short-term risk of dying but do so strictly among patients with established heart disease or overt signs of cardiovascular trouble. Such scores factor in multiple variables and incorporate results from additional tests, including electrocardiograms (EKGs).

By contrast, the new algorithm, dubbed the FIT Treadmill Score and described in the March 2 issue of the journal Mayo Clinic Proceedings, can gauge long-term death risk in anyone based solely on treadmill exercise performance. The score, the research team says, could yield valuable clues about a person's health and should be calculated for the millions of patients who undergo cardiac stress testing in the United States each year.

"The notion that being in good physical shape portends lower death risk is by no means new, but we wanted to quantify that risk precisely by age, gender and fitness level, and do so with an elegantly simple equation that requires no additional fancy testing beyond the standard stress test," says lead investigator Haitham Ahmed, M.D. M.P.H., a cardiology fellow at the Johns Hopkins University School of Medicine.

In addition to age and gender, the formula factors in peak heart rate reached during intense exercise and the ability to tolerate physical exertion as measured by so-called metabolic equivalents, or METs, a gauge of how much energy the body expends during exercise. More vigorous activities require higher energy output (higher METs), better exercise tolerance and higher fitness level. An activity such as slow walking equals two METs, compared with eight for running.

"The FIT Treadmill Score is easy to calculate and costs nothing beyond the cost of the treadmill test itself," says senior study author Michael Blaha, M.D., M.P.H., director of clinical research at the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease. "We hope the score will become a mainstay in cardiologists and primary clinicians' offices as a meaningful way to illustrate risk among those who undergo cardiac stress testing and propel people with poor results to become more physically active."

Exercise stress tests -- commonly used to determine who needs invasive cardiac testing and inform treatment decisions -- measure how well the heart and lungs respond to physical exertion while a person is walking on a treadmill at progressively higher speed and elevation. The test is stopped once a person reaches the point of exhaustion or develops chest pain, dizziness or heart rhythm abnormalities. Those who have abnormal findings on their EKG tracings during exercise or who develop symptoms suggestive of abnormal heart strain during the test are referred for angiography, an invasive procedure to examine the interior of the heart's main blood vessels. Those who have normal EKG readings and no alarming symptoms while exercising are said to have "normal" results and typically do not require further testing.
However, the researchers say, the new data show varying degrees of fitness among those with "normal" stress test results that reveal telling clues about cardiac and respiratory fitness and, therefore, overall death risk over time.

"Stress test results are currently interpreted as 'either/or' but we know that heart disease is a spectrum disorder," Ahmed says. "We believe that our FIT score reflects the complex nature of cardiovascular health and can offer important insights to both clinicians and patients."
For the study, the team analyzed information on 58,020 people, ages 18 to 96, from Detroit, Michigan, who underwent standard exercise stress tests between 1991 and 2009 for evaluation of chest pain, shortness of breath, fainting or dizziness. The researchers then tracked how many of the participants within each fitness level died from any cause over the next decade. The results reveal that among people of the same age and gender, fitness level as measured by METs and peak heart rate reached during exercise were the greatest indicators of death risk. Fitness level was the single most powerful predictor of death and survival, even after researchers accounted for other important variables such as diabetes and family history of premature death -- a finding that underscores the profound importance of heart and lung fitness, the investigators say.

Scores ranged from negative 200 to positive 200, with those above 0 having lower mortality risk and those in the negative range facing highest risk of dying. Patients who scored 100 or higher had a 2 percent risk of dying over the next 10 years, while those with scores between 0 and 100 faced a 3 percent death risk over the next decade. In other words, two of 100 people of the same age and gender with a score of 100 or higher would die over the next decade, compared with three out of 100 for those with a fitness score between 0 and 100. People with scores between negative 100 and 0 had an 11 percent risk of dying in the next 10 years, while those with scores lower than negative 100 had a 38 percent risk of dying.

Published along with the study is a chart depicting death risk by age, gender and fitness level, which can be printed on placards for use in physician's offices to guide clinical advice.

For example, a 45-year-old woman with a fitness score in the bottom fifth percentile is estimated to have a 38 percent risk of dying over the next decade, compared with 2 percent for a 45-year-old woman with a top fitness score.
"We hope that illustrating risk that way could become a catalyst for patients to increase exercise and improve cardiovascular fitness," Blaha says.

Other Johns Hopkins investigators involved in the research included John McEvoy, Roger Blumenthal and Steven Jones.
Researchers from other institutions included Mouaz Al-Mallah, Clinton Brawner and Steven Keteyian of Henry Ford Hospital in Detroit and Khurram Nasir of Baptist Health Medical Group in Miami Beach, Fla.

Source: Johns Hopkins Medicine

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Breathing in diesel exhaust leads to changes 'deep under the hood'

A student participates in the study while seated in a booth.
Credit: Image courtesy of University of British Columbia

Just two hours of exposure to diesel exhaust fumes can lead to fundamental health-related changes in biology by switching some genes on, while switching others off, according to researchers at the University of British Columbia and Vancouver Coastal Health.

The study involved putting volunteers in a polycarbonate-enclosed booth -- about the size of a standard bathroom -- while breathing in diluted and aged exhaust fumes that are about equal to the air quality along a Beijing highway, or a busy port in British Columbia.

The researchers examined how such exposure affected the chemical "coating" that attaches to many parts of a person's DNA. That carbon-hydrogen coating, called methylation, can silence or dampen a gene, preventing it from producing a protein -- sometimes to a person's benefit, sometimes not. Methylation is one of several mechanisms for controlling gene expression, which is the focus of a rapidly growing field of study called epigenetics.

The study, published this month in Particle and Fibre Toxicology, found that diesel exhaust caused changes in methylation at about 2,800 different points on people's DNA, affecting about 400 genes. In some places it led to more methylation; in more cases, it decreased methylation.

How these changes in gene expression translate to health is the next step for researchers. But this study shows how vulnerable our genetic machinery can be to air pollution, and that changes are taking place even if there are no obvious symptoms.

"Usually when we look at the effects of air pollution, we measure things that are clinically obvious -- air flow, blood pressure, heart rhythm," said senior author Dr. Chris Carlsten, an associate professor in the Division of Respiratory Medicine. "But asthma, higher blood pressure or arrhythmia might just be the gradual accumulation of epigenetic changes. So we've revealed a window into how these long-term problems arise. We're looking at changes 'deep under the hood.'"

The fact that DNA methylation was affected after only two hours of exposure has positive implications, said Carlsten, the AstraZeneca Chair in Occupational and Environmental Lung Disease.

"Any time you can show something happens that quickly, it means you can probably reverse it -- either through a therapy, a change in environment, or even diet," he said.

Carlsten's team, having catalogued the changes along the entire human genome, is now sharing its data with scientists who are further exploring the function of specific genes.

Source: University of British Columbia

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Cold virus replicates better at cooler temperatures

Artist's rendering of a rhinovirus (stock illustration). Credit: © fotoliaxrender / Fotolia

The common cold virus can reproduce itself more efficiently in the cooler temperatures found inside the nose than at core body temperature, according to a new Yale-led study. This finding may confirm the popular yet contested notion that people are more likely to catch a cold in cool-weather conditions.

Researchers have long known that the most frequent cause of the common cold, the rhinovirus, replicates more readily in the slightly cooler environment of the nasal cavity than in the warmer lungs. However, the focus of prior studies has been on how body temperature influenced the virus as opposed to the immune system, said study senior author and Yale professor of immunobiology Akiko Iwasaki.

To investigate the relationship between temperature and immune response, Iwasaki and an interdisciplinary team of Yale researchers spearheaded by Ellen Foxman, a postdoctoral fellow in Iwasaki's lab, examined the cells taken from the airways of mice. They compared the immune response to rhinovirus when cells were incubated at 37 degrees Celsius, or core body temperature, and at the cooler 33 degrees Celsius. "We found that the innate immune response to the rhinovirus is impaired at the lower body temperature compared to the core body temperature," Iwasaki said.

The study also strongly suggested that the varying temperatures influenced the immune response rather than the virus itself. Researchers observed viral replication in airway cells from mice with genetic deficiencies in the immune system sensors that detect virus and in the antiviral response. They found that with these immune deficiencies, the virus was able to replicate at the higher temperature. "That proves it's not just virus intrinsic, but it's the host's response that's the major contributor," Iwasaki explained.

Although the research was conducted on mouse cells, it offers clues that may benefit people, including the roughly 20% of us who harbor rhinovirus in our noses at any given time. "In general, the lower the temperature, it seems the lower the innate immune response to viruses," noted Iwasaki. In other words, the research may give credence to the old wives' tale that people should keep warm, and even cover their noses, to avoid catching colds.

Yale researchers also hope to apply this insight into how temperature affects immune response to other conditions, such as childhood asthma. While the common cold is no more than a nuisance for many people, it can cause severe breathing problems for children with asthma, noted Foxman. Future research may probe the immune response to rhinovirus-induced asthma.

The study was published in the Proceedings of the National Academy of Sciences.

Source: Yale University

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Stick out your tongue: Tongue appearance and illness

Physicians often ask their patients to "Please stick out your tongue." The tongue can betray signs of illness, which combined with other symptoms such as a cough, fever, presence of jaundice, headache or bowel habits, can help the physician offer a diagnosis. For people in remote areas who do not have ready access to a physician, a new diagnostic system is reported in the International Journal of Biomedical Engineering and Technology that works to combine the soft inputs of described symptoms with a digital analysis of an image of the patient's tongue.

Karthik Ramamurthy of the Department of Information Technology, Rajalakshmi Engineering College, in Chennai, India, and colleagues, have trained a neural network that can take soft inputs such as standard questions about symptoms and a digitized image of the patient's tongue and offer a likely diagnosis so that professional healthcare might then be sought if needed. The digitized images of the patient's tongue reveal discoloration, engorgement, texture and other factors that might be linked to illness.

Smoothness and "beefiness" might reveal vitamin B12, iron, or folate deficiency, and anemia. Black discoloration could be indicative of fungal overgrowth in HIV patients or prolonged antibiotic use. Longitudinal furrows on the tongue are associated with syphilis. 

Ulcers may indicate the presence of Crohn's disease or colitis and various other conditions. 

The team's automated diagnostic, however, utilizes the condition of the tongue in combination with other symptoms to identify whether a patient has any of various illnesses: common cold, flu, bronchitis, streptococcal throat infection, sinusitis, allergies, asthma, pulmonary edema, food poisoning and diverticulitis.

The current system allows diagnosis of fourteen distinct conditions but the team adds that they will be able to add eye images and use those as an additional hard input for their neural network and so extend its repertoire significantly.

Source: Inderscience Publishers

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Novel approach to treating asthma: Neutralize the trigger

Current asthma treatments can alleviate wheezing, coughing and other symptoms felt by millions of Americans every year, but they don't get to the root cause of the condition. Now, for the first time, scientists are reporting a new approach to defeating asthma by targeting the trigger -- the allergen -- before it can spark an attack. They describe their new compound, which they tested on rats, in ACS' Journal of Medicinal Chemistry.

Clive Robinson and colleagues explain that to prevent many health problems, the ideal approach to treatment or prevention involves getting to the cause of a condition and targeting it directly. Asthma, which occurs when the immune system goes into overdrive affecting the airway in response to an otherwise harmless substance, has posed a challenge to this model. That's because it can be set off by different allergens or irritants. But recent studies suggest that the picture might not be as complicated as previously thought. 

Scientists have found that dust mites are one of the most important triggers of allergic asthma. So Robinson's team wanted to find a way to neutralize mite allergens.

The researchers identified a compound that binds to a major dust mite allergen and turned it into an inhalable powder. They tested it on rats and found that it significantly dampened the animals' immune response when they were exposed to a variety of allergens. This compound and other similar inhibitors could hail a new direction in asthma treatment, say the researchers.

The authors acknowledge funding from the Wellcome Trust.

Source: American Chemical Society

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Diagnosis targets in primary care are misleading, unethical, UK experts say

Last month, there was public outcry at the news that GPs in England would be paid £55 for each case of dementia diagnosed.

Now come targets for six other conditions, including diabetes coronary heart disease, asthma and depression, writes Dr Martin Brunet, a GP in Surrey. "But the data on which they are based are flawed, and the approach incentivises potentially harmful overdiagnosis," he argues.

Every practice in England has been told its diagnosis rate for each condition, estimated from practice data and the expected prevalence, he explains. The intention is to exert pressure on general practitioners to increase diagnosis rates, but he believes the principles behind such a policy need to be questioned.

Brunet argues that applying error prone national prevalence data to an individual practice is problematic. Although attempts are made to account for local demographics, practices may be under pressure to "improve" diagnosis rates that are far better than the data would suggest, he warns.

He also questions the ethical implications for individual patients of unnecessary tests and treatments that "could do more harm than good" and divert resources away from people with symptoms.

Targets in healthcare always threaten to undermine trust in the doctor-patient relationship, says Brunet. "For this reason patients need to trust that the doctor will act solely in their best interests, unencumbered by competing interests."

"NHS England needs to hear the clear message from doctors and patients that setting targets for diagnosis is problematic, unscientific, and unethical," he argues. "Instead, it needs to trust doctors and their patients to know when to seek a diagnosis."

Source: BMJ-British Medical Journal

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