Wood Street Clinic Blog

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A closer look at heart cell connectors could catch "hidden" rhythm disorders in the future

Diseased hearts may be thrown out of rhythm by structural differences - now visible for the first time - in protein groups that connect heart muscle cells, according to the authors of a study to be published in the journal Nature Communications.

By combining powerful imaging techniques and mathematical models, a research team led by NYU Langone Medical Center was able to reconstruct for the first time detailed, 3D images in mice of intercalated discs, protein structures that connect heart muscle cells in working groups. These discs pass on both the electrical signals and the pumping force needed for the heart to beat normally.

The study found that the proteins that do these two jobs occur together in clusters. Conversely, instances where these proteins are farther apart than normal, even by billionths of a meter, may represent a newfound spatial signature of electrical malfunction.

"Our new images could someday help physicians and genetic counselors more accurately identify people at risk before they develop potentially life-threatening arrhythmias, electrical disorders that throw off the heart's rhythm," says senior study investigator Mario Delmar, MD, PhD, the Patricia and Robert Martinsen Professor of Cardiology in the Department of Medicine's Leon H. Charney Division of Cardiology at NYU Langone. His long-term goal is to develop a simple blood test that could detect dangerous disc protein structures as part of mass screening.

Presently, many arrhythmias go undiagnosed. Such conditions cause no symptoms in some, while others may be prone to fainting. In rare cases, arrhythmias can be fatal when they cause the heart to stop beating. And while electrical defects can be detected by an electrocardiogram (EKG), most people do not undergo such tests unless there is a known pattern of risk in their family.

"Assessing risk for arrhythmia based on real-time, structural analysis instead of guesswork based on heredity would represent a major advance," says Delmar.

"We used innovative combinations of imaging techniques to visualize previously unseen aspects of the discs," said Eli Rothenberg, PhD, an assistant professor at NYU Langone and corresponding author of the paper along with Delmar. "Focused ion beam-scanning electron microscopy, for instance, helped us to create 3D images at nanometer resolution, which is down to one-billionth of a meter."

Closeness of Molecules Matters

Past studies have shown that intercalated discs consist partly of cadherins, proteins that anchor one cell to the next so they can pass on combined pumping force (adhesion). Also within the discs are protein channels that, upon receiving the right signal, let charged sodium particles flow through them. This flow serves as a switch that triggers heart muscle cell contraction (excitability).

Going into the current study, it was thought that adhesion and excitability were carried out by separate groups of disc molecules. But, mounting data argue that they work together. Specifically, Delmar and his colleagues revealed the existence in the discs of distinct clusters of both the adhesion molecule N-Cadherin and a protein, Nav 1.5, which is linked to sodium ion channels.

The authors speculate that the clusters identified by the study are the sites of "crosstalk" between the contractile and electrical machinery in heart muscle. Their experiments revealed, for instance, that the ability of the discs to pass on electrical signals may also equip them to more strongly adhere to each other. This would extend the study implications to heart failure, say the authors, if structural problems in discs can be tied to lower adherence, less ability to pass on force, and a weaker heartbeat.

Most promising, the researchers say, is that their discovery of the proximity of adhesion and excitability complexes may represent a new way to measure disease risk through imaging, especially in cases where disease-causing genetic changes (mutations) can be linked to differences in protein spacing. Study results showed that about 60 percent of the N-cadherin in the intercalated discs of study mice was clustered within 100 nanometers of Nav 1.5.

Rothenberg says images of the proteins - tagged with a fluorescent dye to make them light up - showed "a highly organized distribution." Nano-scale images revealed groups of 50 to 60 sodium channels arranged along the borders between cells and their intercalated discs where N-cadherin and Nav. 1.5 were concentrated. Similar clustering had been seen before in nerve cells, but never in heart muscle.

"The closeness of the proteins is probably essential to coordinating the electrical properties of the heartbeat," says Rothenberg.

As the next step, the team plans experiments with human heart cells to see if intercalated disc malformations can be linked to arrhythmias.

Funding for the study, which took four years to complete, was provided by National Heart, Lung and Blood Institute (NHLBI) grant RO1 HL106632 and by National Institute of General Medical Sciences (NIGMS) grants RO1 GM57691, RO1 GM110385, RO1 GM108119; and R21 CA187612. Both NHLBI and NIGMS are part of the National Institutes of Health.

Other researchers at NYU Langone involved in this study were Alejandra Leo-Macias, PhD; Esperanza Agullo-Pascual, PhD; Sara Keegan, PhD; Xianming Lin, PhD; Fengxia Liang, PhD; and David Fenyo, PhD, who provided the mathematical modeling needed to analyze the data. Additional research support was provided by Jose Sanchez-Alonso, PhD; Yuri Korchev, PhD; and Julia Gorelik, PhD, at the Imperial College in London, United Kingdom.

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Keep exercising, say heart experts

If you were about to put your feet up after hearing the latest rumors that exercise is bad for you, think again. A new clinical perspective from the Journal of the American College of Cardiology confirms that most people in developed countries should be more concerned with the lack of exercise in their lives than by the potential harm exercise can cause.
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Any amount and type of exercise is better than none.

There is ample evidence that regular physical activity reduces the risk of death from cardiovascular disease (CVD).

As obesity and related morbidity spiral out of control, participation in athletics and endurance sports has approximately doubled in the last 10 years. In 2012-2013, 7.7 million students participated in high school programs, and in 2014, there was a record number of nearly 42 million American runners and joggers.

Endurance sports draw older athletes, with a record 47% of marathon finishers aged 40 years or over in 2013.

It can end in disaster, however. One study reports a 0.75 fatality rate per 100,000 marathon finishers in the period 2000-2009. These were 28 people, 6 women and 22 men, with a median age of 41.5 years, half of them under 45 years.

Myocardial infarction/atherosclerotic heart disease caused 93% of deaths in those 45 years and older, and the most common cause overall was cardiac arrest.

Exercise does not have to be a marathon

Worrying, maybe, but marathon running is a far cry from federal guidelines recommending that most people should exercise for 150 minutes per week at moderate intensity or vigorously for 75 minutes per week, a target that only half of Americans meet.

A few limited but highly publicized studies have further discouraged would-be participants by suggesting that high volumes of aerobic exercise may be as bad for cardiovascular outcomes as no exercise at all.

In the current report, the American College of Cardiology (ACC) Sports and Exercise Cardiology Council examined recent research on the volume and intensity of aerobic exercise required for favorable cardiovascular health. They also looked at whether there is a threshold of exercise that increases CVD risk.

The Council conclude that small amounts of physical activity, including standing, are associated with a lower risk of CVD; more exercise reduces the risk even further.

Mortality risk in different populations is significantly reduced by moderate and vigorous intensity exercise, even in amounts lower than those recommended by the 2008 Physical Activity Guideline. Higher levels of moderate-intensity exercise reduces CVD mortality.

Is too much exercise risky for the heart?

While these benefits do level out at a certain point, there is no evidence for an upper limit to exercise-induced health benefits.

Any amount of exercise, whether moderate or vigorous, reduces both all-cause and cardiovascular disease mortality risk, compared with no exercise.

The Council believe it is worth investigating the possibility that too much exercise training could be harmful, but research results show that even for very active, life-long endurance athletes, the benefits of exercise training outweigh the risks.

Dr. Michael Scott Emery, co-chair of the ACC Sports and Exercise Cardiology Council, says:

"The public media has embraced the idea that exercise may harm the heart and disseminated this message, thereby diverting attention away from the benefits of exercise as a potent intervention for the primary and secondary prevention of heart disease."

For CVD patients, exercise can save lives, but one study showed that only 62% of heart attack patients were referred to cardiac rehabilitation when discharged from the hospital. Of those, just 23% attended more than one rehab session and only 5.4% completed more than 36 sessions.

Emery hopes that clinicians will be prompted to recommend low and moderate exercise training for most patients.

He also calls for initiatives to promote public health through exercise for all ages, because physical activity modulates behavior from childhood into adulthood.

Dr. Valentin Fuster, PhD, editor-in-chief of JACC comments, "The greatest benefit is to simply exercise, regardless of the intensity, while the danger is twofold: to not exercise at all or to exercise intensely without due preparation."

Medical News Today recently reported that exercise during childhood may lead to healthier gut flora, improving the chances of better brain and metabolic health in the future.

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New biomarkers for improved treatment of severe heart and lung disease

New blood biomarkers reflecting vasoreactivity in lung blood vessels of patients with heart- and lung disease, can lead to simplified diagnostics and better evaluation of treatment for patients with the condition pulmonary arterial hypertension (PAH). This according to a doctoral dissertation at Umeå University in Sweden.

"We have discovered that the biomarkers that we have investigated have a particularly high diagnostic value in PAH, by comparing with heart failure and healthy individuals. These biomarkers have the potential to be used as a routine diagnostic strategy and in the evaluation of PAH patients. Since the levels of these markers in the blood are reflecting the clinical efficacy of PAH specific medical treatment, there is good hope that they soon can be used routinely to measure treatment response. The results are so far based on around 20 PAH patients, which means that more research is necessary on larger patient groups," says Anna Sandqvist, doctoral student at the Department of Pharmacology and Clinical Neuroscience and author of the dissertation.

PAH is an unusual heart- and lung disease that first and foremost affects the finest branches of the arteries in the lungs. The arteries are thickened and become stiff, the blood flow is reduced which leads to hypertension - increased blood pressure - and hypoxia of the pulmonary arteries - a deprivation of adequate oxygen supply. Both heart and lung functions are affected and many patients develop right heart failure. PAH is a very serious condition which, at present, has a poorer prognosis than many cancers and there are only a few appropriate methods for treatment and evaluation.

Today, PAH patients are treated with medications that dilate the blood vessels and, hence, reduce the pulmonary artery pressure. Anna Sandqvist has studied a new drug to treat this disease called vardenafil. Vardenafil belongs to the same group of pharmaceuticals as Viagra and can be used both in diagnostics and in the treatment of PAH.

"Vardenafil has a fast onset and powerful effect on the blood vessels of the lungs. But if vardenafil is used in combination with the endothelin receptor antagonist bosentan - another pharmaceutical often used by patients with PAH - the effect of treatment can be hampered and lead to the need of increasing the dosage of vardenafil. Therapeutic drug monitoring may thus become necessary to check the pharmaceutical concentrations in the blood in order to optimise the dosage," says Anna Sandqvist.

For any corrections of factual information, or to contact our editorial team, please see our contact page.

Please note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms of use.

Copyright Medical News Today: Excluding email/sharing services explicitly offered on this website, material published on Medical News Today may not be reproduced, or distributed without the prior written permission of Medilexicon International Ltd. Please contact us for further details.

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Regular exercise critical for heart health and longevity

The majority of citizens in developed countries should not be concerned by potential harm from exercise but rather by the lack of exercise in their lives, according to a clinical perspective published in the Journal of the American College of Cardiology from the ACC Sports and Exercise Cardiology Leadership Council. According to the council, small amounts of physical activity, including standing, are associated with a lower risk of cardiovascular disease, but more exercise leads to even greater reduction in risk of death from cardiovascular disease.

"The evidence with regard to exercise continues to unfold and educate the cardiovascular clinical community," said JACC Editor-in-Chief Valentin Fuster, M.D., Ph.D. "The greatest benefit is to simply exercise, regardless of the intensity, while the danger is two-fold: to not exercise at all or to exercise intensely, without due preparation."

Studies have shown that regular physical activity reduces a person's risk of death from cardiovascular disease; however, only half of U.S. adults meet the federally recommended guidelines of 150 minutes per week of moderate intensity exercise or 75 minutes per week of vigorous intensity exercise.

In this report, the American College of Cardiology Sports and Exercise Cardiology Council examined recent research on the volume and intensity of aerobic exercise required for favorable cardiovascular health. With the rise in participation in endurance races over the past three decades, they also address the question of whether or not there is an amount of exercise that increases cardiovascular disease risk.

The council found that moderate and vigorous intensity exercise in amounts lower than the 2008 Physical Activity Guideline recommendations still significantly lower mortality risk in different populations around the globe. Increasing the amount of moderate intensity exercise a person engages in results in increased reductions in cardiovascular disease mortality; however, the reductions in cardiovascular mortality benefits from vigorous intensity exercise do level out at a certain point.

There is no evidence for an upper limit to exercise-induced health benefits and all amounts of both moderate and vigorous intensity exercise result in a reduction of both all-cause and cardiovascular disease mortality compared to physical inactivity.

While controversial, a few limited studies have raised the concern that high volumes of aerobic exercise may be as bad for cardiovascular outcomes as no exercise at all. According to the council, the possibility that too much exercise training could be harmful is worthy of investigation, but research results show that even for the very active, life-long endurance athletes, the benefits of exercise training outweigh the risks.

"The public media has embraced the idea that exercise may harm the heart and disseminated this message, thereby diverting attention away from the benefits of exercise as a potent intervention for the primary and secondary prevention of heart disease," said Michael Scott Emery, M.D., co-chair of the ACC Sports and Exercise Cardiology Council.

For cardiovascular disease patients, exercise can save lives, but one study showed that only 62 percent of heart attack patients were referred to cardiac rehabilitation at hospital discharge. Of those, just 23 percent attended more than one rehab session and only 5.4 percent completed more than 36 sessions.

"The available evidence should prompt clinicians to recommend strongly low and moderate exercise training for the majority of our patients," Emery said. "Equally important are initiatives to promote population health at large through physical activity across the life span, as it modulates behavior from childhood into adult life."

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High-rise residences raise risk of deadly heart attack

People who experience a cardiac arrest on the third floor or above of a high-rise building have lower survival rates; above the 16th floor, their chances of survival are "negligible," according to research published in the Canadian Medical Association Journal.
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The ambulance may arrive on time, but elevator delays pose new dangers.

As the high-rise population grows, the number of emergency calls to such dwellings is increasing, presenting 911 responders with unique challenges.

Building access issues, elevator delays and extended distance from the responding vehicle to the patient can all cause delays in the initiation of resuscitation.

In Toronto, Canada, high-rise residences are now home to 40% of over-65s, a population at high risk for a number of serious medical conditions, including cardiac arrest.

In North America, more than 400,000 out-of-hospital cardiac arrests occur annually. Despite efforts to improve resuscitation care, survival to hospital discharge in most communities remains below 10%.

Rapid defibrillation and high-quality cardiopulmonary resuscitation (CPR) are essential for survival. For each 1-minute delay to defibrillation, the chance of survival drops by 7-10%.

The higher the floor, the lower the chance of survival

Previous studies have measured response time between the call to 911 and arrival of an emergency vehicle on scene, but not the time required to make patient contact once there. This can take more than 4 minutes, or up to 28% of the total time from the 911 call to patient contact.

Reasons for delays include additional elevator stops in 18.6% of high-rise residential calls, adding 54 seconds per stop to the interval from arrival on scene to patient contact. Access barriers delayed 33.9% of paramedic calls, and 67.6% of calls required an entry code. Poor signage impeded 82.6% of calls, and inability to fit the ambulance stretcher into the elevator hindered 67.9% of cases.

Ian Drennan and coauthors looked into the relationship between floor of patient contact and survival after cardiac arrest in residential buildings in Toronto, focusing on the time from arrival of the vehicle to patient contact.

Of 8,216 cardiac arrest patients in private residences who were treated by 911-initiated first responders, 3.8% survived to be discharged from the hospital; the further the patient's location from the ground floor, the lower the survival rate.

Of the 5,998 (73%) patients living below the third floor, 252, or 4.2%, survived. On or above the third floor, only 48, or 2.6%, of the 1,844 patients survived. Above the 16th floor, only 0.9%, or 2 out of 216, survived; and above the 25th floor, none of the 30 who had arrests survived.

The use of automated external defibrillators (AED) was "very low."

Drennan comments:

"As the number of high-rise buildings continues to increase and as population density rises in major urban centers, it is important to determine the effect of delays to patient care in high-rise buildings on survival after cardiac arrest."

As more people take up residence at or above the third floor, the time from arrival on scene to initial patient contact will become more significant.

New interventions needed to shorten cardiac arrest response time

The researchers call for interventions aimed at shortening response times to treatment of cardiac arrest in high-rise buildings, and they outline several solutions to improve time to patient contact.

Suggestions include giving 911-initiated first responders sole access to elevators for emergency service without public interference - as during a fire - as well as emergency alerts to building staff before the arrival of first responders and better placement of defibrillators to increase bystander use.

In a linked comment, Associate Prof. Marcus Eng Hock Ong, of Singapore General Hospital, and coauthors suggest CPR/AED training for residents of high-rise apartments, a national online registry of public-access defibrillators linked to first-responder applications and using smartphones to activate volunteer first responders for patients with cardiac arrest.

Ong notes that Singapore has a multipronged approach to these situations, including a large public campaign to enroll residents' committees as first responders and to train 1 million people over the next 5 years.

Medical News Today has previously reported that bystander CPR can save lives.

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One-hour diagnosis of heart attack possible with troponin T test from Roche

Novel strategy shortens time to heart attack diagnosis drastically, enabling faster start of treatment of patients and better use of healthcare resources.

Results from the TRAPID-AMI1 clinical study have been published online by the Annals of Emergency Medicine2, confirming a novel approach for a more rapid diagnosis of heart attack in patients with acute chest pain. The strategy is based on the cardiac troponin T high-sensitivity test from Roche and reduces the observation time needed to rule-in or rule-out a heart attack from 3-6 hours to just 1 hour. It is well established that a fast and reliable diagnosis of heart attack is critical because every hour of delay from the onset of symptoms to treatment increases the mortality risk3.

"Thanks to this new approach, we can now shorten the time to heart attack diagnosis for millions of patients presenting in emergency rooms with acute chest pain all over the world," says Christian Mueller, professor of cardiology at the University of Basel, Switzerland, one of the study's principal investigators. "Patients no longer have to wait for three or more hours in the emergency department, not knowing whether they have an acute, life-threatening disease or if their chest pain is caused by other reasons."

Every minute counts

A heart attack, or acute myocardial infarction (AMI), is a common cardiac event in which the blood supply to an area of the heart muscle is interrupted, causing the muscle cells to die. Prompt treatment is essential as every 30 minutes of delay increases the relative risk of mortality by 7.5 % in patients with AMI3. Patients with chest pain and other symptoms suggestive of AMI account for approximately 10-20% of all emergency room consultations and every 43 seconds, someone in the United States will have a heart attack4.

Troponin is a heart muscle protein that is released into the blood stream during a heart attack. A limitation of the earlier generations of blood tests was the time required to detect the troponin release, sometimes requiring up to six hours with less sensitive troponin tests. The mortality rate of heart attacks is highest within hours of onset, so an early diagnosis and initiation of treatment greatly impacts outcome and potentially saves lives.

The European Society of Cardiology adopted this accelerated diagnostic concept at their annual meeting held in London (UK) in August 2015. Their new clinical practice guidelines (2015 ESC NSTEMI) now support the 1-hour diagnostic algorithm with high-sensitive troponin testing validated in the TRAPID-AMI study5.

"Results of the TRAPID-AMI study once again demonstrate how diagnostics can influence clinical practice to contribute to better patient outcomes," says Roland Diggelmann, Chief Operating Officer of Roche Diagnostics. "At Roche, we continuously invest in clinical studies to foster innovation and to advance healthcare. We provide physicians and patients around the world with diagnostic tests and solutions that improve health and save lives."

More about the TRAPID-AMI study

TRAPID-AMI is a prospective observational study supported by Roche and investigated more than 1,200 patients with acute chest pain during 2011-2014. The study was conducted in twelve institutions from nine countries and three continents, led by Professors Christian Mueller, University of Basel (Switzerland), and Bertil Lindahl, University of Uppsala (Sweden). It is the first clinical trial validating a short diagnostic procedure constructed from two blood tests taken from the patient one hour apart in early chest pain patients (i.e. with a pain onset of maximum 6 hours since hospital entry). This new approach was proposed in the earlier APACE trial on patients with later presentation6. The TRAPID-AMI study results demonstrate that the new diagnostic procedure shortens the time to diagnose heart attack to one hour from three hours or more, enabling healthcare professionals to treat the majority of patients much earlier as recommended in the new guidelines (2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation)5.

More about the cardiac troponin T high-sensitivity test from Roche

The Elecsys cardiac Troponin T high-sensitivity (cTnT-hs) test from Roche detects cardiac troponin which is the preferred biomarker for the diagnosis of heart attack in clinical practice. In combination with an electrocardiogram (ECG), it has become the gold standard for the diagnosis of heart attack. The high sensitivity of the Roche cTnT-hs assay in conjunction with this novel procedure significantly accelerates "rule-in" and "rule-out" decision-making, thereby maximising the potential for effective treatment. At the same time, the faster decision-making may help to better manage the emergency room workload and related costs for healthcare systems.

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UTSW researchers find a small protein that plays a big role in heart muscle contraction

Researchers at UT Southwestern Medical Center have identified a previously unrecognized small protein in cells of the human heart that plays a key role in heart muscle contraction. The protein is made from an RNA that was previously believed to be a blank or non-coding RNA, suggesting there may be many other small 'non-coding' segments that play important biological roles.

Significantly, the findings published yesterday in Science offer a potential new target for developing therapeutics to boost the strength of cardiac muscle contractions in patients with heart failure, a chronic condition in which the heart pumps too weakly to supply adequate oxygen to the body.

The new protein, which the researchers have named dwarf open reading frame (DWORF), comprises just 34 amino acids, making it the third smallest protein known to be encoded in the mouse genome. By comparison, an average-sized protein is 10 times larger, including about 350 amino acids. DWORF is also encoded in the human genome.

The DWORF protein stimulates a calcium-ion pump that controls muscle contraction. As DWORF increases, the heart pumps with more force.

"There's a brake in the heart that controls pumping, and DWORF shuts off the brake, which has the effect of making heart muscle pump more vigorously," said senior author Dr. Eric Olson, Chairman of the Molecular Biology, and Director of the Hamon Center for Regenerative Science and Medicine at UT Southwestern.

The researchers also found DWORF in some skeletal muscle, namely slow-twitch skeletal muscle fibers, the type of muscle fiber that allows a person to run marathons.

DWORF was found among a class of RNA transcripts that had been dismissed by scientists as non-coding RNA, sometimes colloquially called "junk" RNA. Emerging evidence, however, such as the discovery of DWORF, indicates that many small proteins with bioactive properties are hidden among these regions of the genome that are thought to be non-coding and, due to their small size, have evaded detection by scientists.

"Although small and non-enzymatic themselves, peptides like DWORF have the ability to regulate the function of much larger molecular complexes, analogous to the way that a tiny rudder determines the direction of a much larger ship," said Dr. Catherine Makarewich, a postdoctoral fellow in Dr. Olson's lab and a co-lead author of the study.

"Elucidating the full catalog of small proteins like DWORF could provide significant new insight into how the molecular machinery of the cell is regulated," added Benjamin Nelson, a student in UT Southwestern's Medical Scientist Training Program and co-lead author of the study.

"We dipped into the RNA 'junk' pile and came up with a hidden treasure," said Dr. Rhonda Bassel-Duby, Professor of Molecular Biology and a study author.

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Broken sleep raises risk of stroke

Elderly people who sleep poorly and awaken frequently are more likely to have hardened blood vessels or oxygen-starved tissue in the brain, according to a report published in the journal Stroke.
[Brain arteriolosclerosis]
Sleep fragmentation may affect brain arteries and tissues.
Image credit: American Heart Association

As people age, they experience new sleep patterns. Insomnia creeps in and falling asleep takes longer. Sleep fragmentation, when sleep is interrupted by repeated awakenings or arousals, can also be a problem.

Changes that occur in circadian rhythms, the body clock that coordinates timing of bodily functions, including sleep, can cause older people to become sleepier in the early evening and to wake earlier in the morning.

Sleep problems can stem from an underlying medical or psychiatric condition, but they are also a risk factor for further health issues, including cardiovascular disease.

Poor sleep quality has been linked with more severe arteriolosclerosis in older people's brains and of higher levels of oxygen-starved brain tissue, or infarcts. These factors increase the risk of stroke and cognitive impairment.

In the current study, researchers wanted to see if there was an association between sleep fragmentation and detailed microscopic measures of blood vessel damage and infarcts in autopsied brain tissue from the same individuals.

The team, led by Dr. Andrew Lim, an assistant professor of neurology at the University of Toronto, Canada, examined autopsied brains of 315 people, of whom 70% were women; the average age was 90 years.

Participants had undergone at least 1 full week of around-the-clock monitoring for rest or activity, from which sleep quality and circadian rhythms were quantified. Sleep fragmentation caused sleep to be disrupted on average almost seven times each hour.

In all, 29% of the patients had suffered a stroke, while 61% had signs of moderate to severe damage to their blood vessels in the brain.

Greater sleep fragmentation was associated with a 27% higher chance of having severe arteriolosclerosis. For every additional two arousals per hour of sleep, there was a 30% higher chance of having visible signs of oxygen deprivation in the brain.

Other cardiovascular risk factors, such as body mass index (BMI), smoking history, diabetes, hypertension and other medical conditions such as Alzheimer's disease, pain, depression or heart failure were all adjusted for.

Dr. Lim says:

"The forms of brain injury that we observed are important because they may not only contribute to the risk of stroke but also to chronic progressive cognitive and motor impairment. However, there are several ways to view these findings: sleep fragmentation may impair the circulation of blood to the brain, poor circulation of blood to the brain may cause sleep fragmentation, or both may be caused by another underlying risk factor."

The findings suggest that sleep monitoring could help to identify seniors at risk of stroke, but further study is needed to clarify whether brain blood vessel damage is a consequence or a cause of sleep fragmentation.

The role of specific contributors to sleep fragmentation such as sleep apnea and the underlying biological mechanisms are also unclear.

Medical News Today recently reported on research suggesting that people who lack sleep also have a tendency to eat or drink more while doing another activity, such as watching television.

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Researchers discover key pathway involved in blood vessel occlusion

Researchers have made a breakthrough in understanding blood vessel occlusion by discovering a novel pathway involved in this process.

The findings, which appear in the journal Blood, may lead to new treatments for clotting associated with atherosclerosis, cancer, heart attacks and strokes.

Clotting (thrombosis) is an important function of blood to prevent excessive bleeding, but it can become inappropriately activated during a stroke or heart attack. Earlier studies led by these same researchers identified that a protein called lysyl oxidase (LOX) is increased in certain blood cancers that have a high risk of clotting. However, the mechanism through which increased LOX leads to clotting was unknown until now.

In an experimental model that increased LOX activity in platelets (blood cells involved in clotting), researchers found that the time needed to form a blood clot after injury to the blood vessels was reduced. These platelets were more likely to form a clot and researchers pinpointed the specific receptor on the platelets affected by the oxidation activity of LOX. This receptor is responsible for platelet adhesion to proteins (collagen) in blood vessels.

"By using interdisciplinary approaches, we were able to extend discovery of basic mechanisms to in vivo studies" explains corresponding author Katya Ravid, DSc, PhD, professor of medicine and biochemistry at Boston University School of Medicine. Post-doctoral fellow, Dr. Shinobu Matsuuras is the study's first author.

This study has implications for various other diseases, such as vascular restenosis (blood vessel narrowing) and chronic kidney disease, in which there are high levels of LOX and increased blood clotting related complications.

For any corrections of factual information, or to contact our editorial team, please see our contact page.

Please note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms of use.

Copyright Medical News Today: Excluding email/sharing services explicitly offered on this website, material published on Medical News Today may not be reproduced, or distributed without the prior written permission of Medilexicon International Ltd. Please contact us for further details.

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Studying 'inflamm-aging': monocytes, cytokines, and susceptibility to pneumonia

The chronic state of low-level inflammation seen in many elderly individuals (sometimes called "inflamm-aging"), is associated with diseases such as cardiovascular disease and dementia, as well as susceptibility to infections, especially pneumonia. A study published in PLOS Pathogens reveals a crucial role of monocytes in the immune system changes that occur with age, and may help explain why older people are more susceptible to pneumonia.

Acute inflammation is part of a healthy immune response to infection or tissue injury. Chronic inflammation - ongoing heightened activity of the immune system - on the other hand, has been linked to many diseases, including asthma, diabetes, and heart disease. In the aging immune system, healthy responses are weaker, and chronic inflammation is common.

Dawn Bowdish, from McMaster University in Hamilton, Canada, and colleagues, are interested in how the immune system ages. In this study, they focus on monocytes, immune cells that are central to the process of inflammation. Monocytes multiply and mature in the bone marrow and circulate in the blood stream. They are recruited to sites of injury or infection and there turn into macrophages (literally "large eaters") that ingest pathogens, infected cells, or cellular debris. Monocytes are also potent producers of pro-inflammatory cytokines, small molecules that promote an inflammatory immune response.

Comparing younger and older mice, the researchers found that the latter have higher numbers of monocytes both in the bone marrow and in the blood. They also saw higher levels of TNF and IL-6, two pro-inflammatory cytokines, in blood from older mice and blood from older human donors. Studying mouse monocytes in more detail, the researchers found that the increase in TNF levels that occurs with age causes premature release of immature monocytes from the bone marrow into the blood stream. When stimulated with bacterial products, these immature monocytes themselves produce more inflammatory cytokines, thus further increasing levels in the blood.

The researchers then infected younger and older mice with the bacteria Streptococcus pneumoniae, which causes so-called pneumococcal pneumonia. They found that, although the older mice had higher numbers of monocytes in the blood and at the sites of infection, their monocytes were not able to clear the bacteria and successfully fight the infection. However, when the researchers used drugs or mouse mutations that reduced the number of monocytes or removed TNF, they were able to restore antibacterial immunity in aged mice.

The researchers conclude that "monocytes both contribute to age-associated inflammation and are impaired by chronic exposure to the inflammatory cytokine TNF, which ultimately impairs their anti-pneumococcal function." They go on to suggest that "lowering levels of TNF may be an effective strategy in improving host defense against S. pneumoniae in older adults", and that, "although it may be counterintuitive to limit inflammatory responses during a bacterial infection, [some existing] clinical observations and our animal model indicate that anti-bacterial strategies need to be tailored to the age of the host".

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Very small reductions in kidney function linked with heart disease

Study proves for the first time that having Chronic Kidney Disease can directly damage the heart.

Very small reductions in kidney function are directly linked to subtle heart and blood vessel damage, according to new research from scientists in Birmingham funded by the British Heart Foundation (BHF). This shows for the first time that the heart damage seen in people with Chronic Kidney Disease (CKD) is a direct result of their reduced kidney function.

The study, published in the journal Hypertension, looked at healthy people who had chosen to donate a kidney to see if it resulted in any adverse changes in their heart and blood vessels after donation.

The researchers found that, even in very healthy people, a small reduction in kidney function is associated with an enlarged left-side of the heart, which makes the heart stiffer and impairs its ability to contract. This shows the clear link between reductions in kidney function and cardiovascular disease.

Dr William Moody, a BHF Research Fellow at Queen Elizabeth Hospital and the University of Birmingham, who worked on the study said: "It should be noted that the effects on the kidney donors were very small and no studies of people who have donated a kidney have shown a cardiovascular risk that is higher than that of the general population."

The results could, however, have significant consequences for people suffering with CKD. In England in 2008/09 there were over 1.5 million people registered with CKD, though it is expected that the actual number is much larger than this1. People with CKD have impaired cardiac function to the extent that this is often the cause of premature death, although the mechanism is not clear. By demonstrating that in otherwise healthy people there is small but measurable heart and blood vessel damage following kidney donation, the researchers have shown that in patients with CKD, poor kidney function has a direct adverse effect on heart function.

For one year the researchers tracked 68 kidney donors and 56 similar adults who had not donated a kidney. The adverse changes following donation included an enlarged left-side of the heart (increased left ventricular mass), increased stiffness of the aorta, the main artery providing blood to the body, and reduced heart function. However, these effects were extremely small and at an individual level the extra risk associated with the changes is very small.

Past large studies of patients with kidney disease have shown that a worse kidney function increases likelihood of an increased left ventricular mass, which is a strong predictor of risk for cardiovascular death.

A major research effort is now needed to understand what the risk is and find measures to reduce it in patients with CKD, to prevent premature death.

This research was also funded by NIHR/Wellcome Clinical Research Facility and Queen Elizabeth Hospital Birmingham Charity.

Dr William Moody, a BHF Research Fellow at the University of Birmingham and the author of the paper said: "Early stage kidney disease is a public health problem because it is common and carries an increased risk of heart and circulatory disease. A major research effort is needed to understand this risk and to find measures to prevent this damage.

"For now, people with blood tests showing slightly reduced kidney function should certainly consider discussing heart disease risk with their doctors and consider how best to reduce this."

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation said: "By studying healthy kidney donors, this Birmingham team supported by BHF funding have been able to show convincingly for the first time that loss of kidney function has direct adverse effects on the heart, unrelated to changes in blood pressure.

"While the adverse effects in the kidney donors are small, the study suggests strongly that identification of the mechanisms involved could provide new avenues to reduce the progressive impairment of heart function seen in patients with chronic kidney disease. However it is important to note that these findings should not put anyone off donating a kidney, as those individuals are highly selected as healthy subjects and effects of kidney donation will still not even get them to an 'average' risk level".

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NHS Health Check study estimates 2,500 heart attacks and strokes prevented over 5 years

The first major evaluation of the NHS Health Check in England has found that the programme is effectively identifying people at risk of developing a major cardiovascular incident such as heart attack or stroke, and is estimated over first five years to have prevented 2,500 cases from treatment following the check, as well as helping diagnose commonly linked conditions, including type 2 diabetes, high blood pressure and chronic kidney disease.

The study, led by Queen Mary University of London, also found that those from the most deprived areas and black and minority ethnic groups, who are at greatest risk of cardiovascular disease, are more likely to attend an NHS Health Check. This makes a positive step towards tackling health inequalities in England.

The NHS Health Check programme is the first in the world to tackle prevention of heart attacks and strokes by offering a free check to every adult aged 40-74 years. It provides a personal review of the behavioural factors, such as harmful drinking and obesity, that might increase the risk of developing a heart attack or stroke and offers professional advice on lifestyle change and treatment to reduce the risk. It also identifies any new or undiagnosed serious conditions such as hypertension, diabetes and chronic kidney disease.

The study is based on robust data from 655 GP practices with 1.7 million eligible people in the nationally representative QResearch database. In addition to the 2,500 people avoiding a major cardiovascular incident, the programme has also successfully identified:

a new case of hypertension in every 27 appointments; a new case of diabetes in every 110 appointments; a new case of chronic kidney disease in every 265 appointments; 14% of attendees referred to lifestyle interventions due to obesity, smoking, alcohol or blood pressure compared to just 6% of those who were referred through standard care; Six times more people with high alcohol consumption than those who do not attend, offering brief advice and support.

However, the number of eligible people having an NHS Health Check still needs to increase for the programme to reach its full potential. The most recent annual data from Public Health England shows that about 48 per cent of all eligible people attend when invited. PHE is continuing to work with local authorities to help them deliver the programme more effectively and increase the numbers taking up their NHS Health Check.

The study also shows that there is still room for improvement. The latest evidence suggests the programme is most effective at targeting the older end of the eligible population (those aged over 60) and more work is needed to encourage uptake among the younger age group (aged 40- 60). However, as cardiovascular risk increases with age, this evidence suggests that the programme is effective in identifying and providing an NHS Health Check for those with the highest risk and not just the 'worried well'.

Study lead Dr John Robson from Queen Mary University of London said:

"The NHS Health Check programme is the first of its kind anywhere in the world and our study demonstrates a modest but successful start. We estimate that the programme could help identify 44,000 new cases of hypertension, 10,000 new cases of diabetes and 4,500 new cases of kidney disease in England every year. In the first five years of the programme, an estimated 2,500 people were also prevented from having a stroke or heart attack through treatments following their NHS Health Check.

"Uptake of the programme during the study period showed year-on-year improvement, but much still needs to be done as there is considerable scope for even better coverage."

Professor John Newton, Chief Knowledge Officer, Public Health England said:

"It's good to see the clear initial successes highlighted by this comprehensive and robust study of the NHS Health Check programme in its early stages. The evidence shows that the programme is working and working well for its target group, effectively reaching black and minority ethnic groups and people from deprived areas, who are most at risk of their condition being missed or diagnosed too late."

"While this Study shows a positive start and, the numbers attending their NHS Health Check significantly up in the past few years, there is still more to be done to improve numbers and ensure those that need help get referrals for follow up treatment - which ultimately saves lives."

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Experts recommend immediate treatment for severe primary adrenal insufficiency symptoms

Endocrine Society publishes Clinical Practice Guideline on condition known as Addison's disease.

The Endocrine Society has issued a Clinical Practice Guideline (CPG) on diagnosis and treatment of primary adrenal insufficiency, a condition commonly known as Addison's disease that occurs when the body produces too little of the hormone cortisol.

The CPG, entitled "Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline," was published online and will appear in the February 2016 print issue of the Journal of Clinical Endocrinology & Metabolism (JCEM), a publication of the Endocrine Society.

Primary adrenal insufficiency is a rare, potentially life-threatening condition that occurs when the adrenal glands located on top of the kidneys do not work properly. The adrenal glands produce cortisol, a hormone essential for the body's response to stress, maintaining blood pressure and cardiovascular function, keeping the immune system in check, and converting fat, carbohydrates and proteins into energy. When an individual develops primary adrenal insufficiency, they may experience symptoms such as weight loss, fatigue, muscle weakness, decreased appetite, nausea, vomiting and diarrhea.

"Diagnosing primary adrenal insufficiency remains challenging because many of the symptoms are associated with a variety of health conditions," said Stefan R. Bornstein, MD, PhD, of the Universitätsklinikum in Dresden, Germany, and King's College in London, U.K., and chair of the task force that authored the guideline. "Postponing treatment of more severe symptoms raises the risk of death. Severe symptoms need to be treated immediately, even if a test still needs to be conducted to confirm the diagnosis."

The Endocrine Society recommends that acutely ill patients who have unexplained symptoms undergo diagnostic testing to rule out primary adrenal insufficiency. Those who have severe symptoms of the condition or adrenal crisis should undergo immediate treatment with medication until diagnostic test results are available. Health care providers should conduct a corticotropin stimulation test to confirm the diagnosis when the patient's condition allows.

Other recommendations from the CPG include:

Patients should undergo a blood test to measure levels of adrenocorticotropic hormone (ACTH) - the hormone that signals the adrenal glands to produce cortisol - to establish a primary adrenal insufficiency diagnosis. As part of the diagnostic process, patients should have blood tests to measure the levels of the hormones renin and aldosterone. This test determines if a person has a deficiency of the hormones used to regulate the balance of salt and water in the body. Patients who have a confirmed diagnosis of primary adrenal insufficiency should undergo glucocorticoid replacement therapy - typically with hydrocortisone (cortisol), the glucocorticoid hormone naturally produced by the adrenal glands. People who have primary adrenal insufficiency and a confirmed aldosterone deficiency should undergo replacement therapy - typically with the synthetic hormone fludrocortisone - to maintain the body's salt and water balance. Anyone receiving this therapy should be monitored by testing blood electrolyte levels and checking for symptoms like salt craving, light-headedness, blood pressure changes and swelling of the legs and feet.

For any corrections of factual information, or to contact our editorial team, please see our contact page.

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The evidence for saturated fat and sugar related to coronary heart disease

Evaluation of evidence suggests sugar consumption plays greater role in heart disease than saturated fat.

Atherosclerotic Coronary Heart Disease (CHD) is responsible for one in every six deaths in the United States as well as being the leading cause of death throughout the developed world. Healthcare professionals have for many years sought to limit and control CHD by focusing on prevention and, from a dietary perspective, on limiting saturated fats.

In an article published in the journal Progress in Cardiovascular Diseases, Saint Luke's Mid America Heart Institute cardiovascular research scientist and James J. DiNicolantonio, PharmD, and James H. O'Keefe, MD, examined the question of whether that focus may be misplaced and ask does sugar have a greater impact on coronary heart disease than saturated fat?

The theory of dietary saturated fats as the principal promoter of elevated serum cholesterol and heart disease stems from research beginning in the 1950's by an American scientist Ancel Keys. It was this theory which was embraced by the American Heart Association and the US federal government in the 1960s and 70s. However, at the same time of Keys research, a British physiologist John Yudkin argued that sugar intake was more closely related to incidence of and mortality from CHD.

Both Yudkin and Keys were able to support their theories through observational studies in large part because people eat foods, not isolated food constituents. Dietary sources of saturated fat are also often dietary sources of sugar and people who eat lots of sugar often also eat lots of saturated fat.

Along with co-author, Sean C. Lucan, MD, MPH, MS, from the Albert Einstein College of Medicine, DiNicolantonio and O'Keefe evaluated the evidence to date linking saturated fats and sugars to CHD, considering basic science, epidemiology, and clinical trial data related to CHD risk, CHD events, and CHD mortality. The authors concluded that sugar consumption, particularly in the form of refined added sugars, are a greater contributor to CHD than saturated fats.

"While the original studies upon which the longstanding guidelines were based were largely observational," said DiNicolantonio, "We now have more than a half century of data as well as increased understanding of how nutrition impacts the body and specifically coronary heart disease."

The metabolic aspects of saturated fatty acids (SFAs) are complex but existing research suggests that certain SFAs may actually confer measurable benefits for lipid profiles and CHD risk. For instance, some SFAs increase high-density lipoprotein cholesterol (HDL), which is often referred to as the "good cholesterol" as this lipoprotein is associated with a reduced risk of CHD

Replacing saturated fats, or any other component, from one's diet almost inevitably means replacing it with something else. When carbohydrates, particularly refined carbohydrates like sugar, replace saturated fats, which can have a negative impact on lipid profiles (HDL tends to fall and triglycerides tend to rise).

As stated earlier, people don't eat isolated fatty acids - they eat foods that are a mix of various fatty acids and other food constituents. While high intakes from processed meats may increase risk of CHD, higher intakes from dairy sources of saturated fat may not only pose no risk but actually decrease risk.

Consuming a diet high in sugar for just a few weeks has been shown to cause numerous abnormalities found in patients with CHD, such as high total cholesterol, triglycerides, LDL, oxidized LDL, uric acid, insulin resistance and abnormal glucose tolerance, low HDL, and altered platelet function. The overall effect of consuming a diet high in sugar on these numerous health markers is likely more detrimental to overall health compared to increased consumption of saturated fat, which can increase LDL but at the same time raise HDL.

Added fructose - generally in the form of sucrose (table sugar) or high fructose corn syrup (HFCS) in processed foods and beverages seems especially potent for producing harm. Consuming these sugars can lead to resistance in leptin, which is a key hormone in the maintenance of normal body weight. The overconsumption of added fructose undoubtedly increases the risk for obesity, which is also a risk factor for CHD.

Excess fructose also markedly increases the risk for non-alcoholic fatty liver disease (NAFLD) - the most common liver disease in the US and a strong independent risk factor for CHD. The association between NAFLD and CHD is stronger than the link between CHD and smoking, hypertension, diabetes, male gender, high cholesterol or metabolic syndrome.

Sugars occurring naturally in fruits and vegetables pose no increased risk for CHD. The problem is refined sugars - with ultraprocessed foods being of greatest concern. Products with added sugars represent 75% of all packaged foods and beverages in the US and most commonly contain sucrose or HFCS, which seem to raise CHD risk even more than other sugars such as glucose.

A diet high in sugar has also been found to promote prediabetes and diabetes. And patients with both of these conditions have a much greater risk for CHD compared to normal healthy patients, particularly a severe narrowing of the left main coronary artery.

Ultra-processed foods also tend to be sources of saturated fats but the harms associated with eating these products may have nothing to do with the fat and everything to do with processed foods themselves. Therefore, best advice is to avoid processed foods rather than to simply avoid SFAs as avoiding SFAs might direct people away from foods that are not only completely benign but actually beneficial (such as dairy foods) but also steer people towards foods that may be harmful - i.e. low-fat, ultra-processed, with huge amounts of hidden added sugars.

"After a thorough analysis of the evidence it seems appropriate to recommend dietary guidelines shift focus away from recommendations to reduce saturated fat and towards recommendations to avoid added sugars," said Dr DiNicolantonio. "Most importantly recommendations should support the eating of whole foods whenever possible and the avoidance of ultra-processed food."

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SCAI releases expert consensus for cardio-oncology patients treated in cardiac catheterization labs

The Society for Cardiovascular Angiography and Interventions (SCAI) has released an expert consensus statement providing cardiologists, oncologists and internal medicine physicians guidance for treating patients facing concomitant cardiovascular disease and cancer. The document, "SCAI Expert Consensus Statement: Evaluation, Management, and Special Considerations of Cardio-Oncology Patients in the Cardiac Catherization Laboratory," was released in Catheterization and Cardiovascular Interventions (CCI), and is endorsed by the Cardiological Society of India (CSI) and Sociedad Latino Americana de Cardiologia Intervencionista (SOLACI). The paper aims to increase the competency of cardiovascular professionals providing care to cancer patients.

Advances in cancer therapy have resulted in steady decline in cancer-related mortality since the 1990s. According to the Centers for Disease Control and Prevention, there are approximately 14.5 million cancer survivors in the United States, and this number is expected to increase to 20 million in 2020. In view of these trends, the need for invasive evaluation and management in the cardiac catherization laboratory for such patients has increased.

"Little data exists as cancer patients have been excluded from national percutaneous coronary interventions (PCI) registries and from most randomized trials involving PCI," said Cezar A. Iliescu, MD, FSCAI, lead author of the document and director of the Cardiac Catheterization Laboratory at MD Anderson Cancer Center in Houston, Texas. "Therefore, SCAI commissioned a consensus group to define the landscape and provide recommendations based on the available published medical literature and the expertise of operators with accumulated experience in the cardiac catheterization of cancer patients."

Cancer is associated with a hypercoagulable state which increases the risk of acute thrombotic events. Cancer therapies can cause significant injury to the vasculature, resulting in angina, acute coronary syndromes, arrhythmias and heart failure, even independently from a direct myocardial effect.

The document highlights the review of the mechanisms of vascular toxicities in cancer patients (radiation or chemotherapy induced), and covers several other aspects of cardiovascular care such as screening and cardio-protection, as well as PCI in patients with thrombocytopenia and anemia, fractional flow reserve, intravascular ultrasound and optical coherence tomography for complex intravascular assessment and deferring stenting, if possible. The paper also includes non-coronary interventional procedures in cancer patients like endomyocardial biopsy and pericardiocentesis, as well as aortic valvuloplasty and transcatheter aortic valve implantation.

Cardio-oncology is expected to have continued growth in the coming years. Several healthcare institutions have founded onco-cardiology/cardio-oncology departments, along with fellowship training programs focusing on the cardiology subspecialty.

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Atherosclerosis is Alzheimer's disease of blood vessels, study suggests

Protein builds up as immune cells attempt to counteract plaque formation.

In atherosclerosis, plaque builds up on the inner walls of arteries that deliver blood to the body. Studying mice and tissue samples from the arteries of patients, researchers at Washington University School of Medicine​ in St. Louis suggest this accumulation is driven, at least in part, by processes similar to the plaque formation implicated in brain diseases such as Alzheimer's and Parkinson's.

The study is published in the journal Science Signaling.

A look behind the scenes in the process of plaque accumulating in arteries, the new study is the first to show that another buildup is taking place. Immune cells attempting to counteract plaque formation begin to accumulate misshapen proteins. This buildup of protein junk inside the cells interferes with their ability to do their jobs.

Protein buildup is widely studied in the brain - accumulation of proteins such as amyloid beta and tau are hallmarks of Alzheimer's, Parkinson's and other degenerative neurological disorders. But until now, the process of misshapen protein buildup within cells has not been implicated in atherosclerosis.

"In an attempt to fix the damage characteristic of atherosclerosis, immune cells called macrophages go into the lining of the arteries," said senior author Babak Razani, MD, PhD, assistant professor of medicine. "The macrophage is like a firefighter going into a burning building. But in this case, the firefighter is overcome by the conditions. So another firefighter goes in to save the first and is likewise overcome. And another goes in, and the process continues to build on itself and worsen."

The researchers showed that this protein buildup inside macrophages results from problems with the waste-disposal functions of the cell. They identified a protein called p62 that is responsible for sequestering waste and delivering it to cellular incinerators called lysosomes. To mimic atherosclerosis, the researchers exposed the cells to types of fats known to lead to the condition. The researchers noted that during atherosclerosis, the macrophages' incinerators become dysfunctional. And when cells stop being able to dispose of waste, p62 builds up. In a surprise finding, when p62 is missing and no longer gathers the waste in one place, atherosclerosis in mice becomes even worse.

Razani and his colleagues, including the study's first author, Ismail Sergin, PhD, a research assistant, also found these protein aggregates and high amounts of p62 in atherosclerotic plaque samples taken from patients, suggesting these processes are at work in people with plaque building up in the arteries.

"That p62 sequesters waste in brain cells was known, and its buildup is a marker for a dysfunctional waste-disposal system," Razani said. "But this is the first evidence that its function in macrophages is playing a role in atherosclerosis."

The study demonstrates that p62's role in gathering up the misfolded proteins is protective against atherosclerosis, even if the cell can't actually dispose of the waste it gathers.

"If p62 is missing, the proteins don't aggregate," Razani said. "It's tempting to think this might be good for the cell, but we showed this is actually worse. It causes more damage than if the waste were corralled into a large 'trash bin.' You can imagine a situation where lots of trash is being generated and see that it would be better to keep it all in one place, rather than have it strewn across the floor. You might have difficulty removing the trash to the dumpster, but at least it's contained."

In atherosclerosis, and perhaps in the brain disorders characterized by protein accumulation, such evidence suggests it would be better to focus on ways to fix the cells' waste-disposal system for getting rid of the large protein aggregates, rather than on ways to stop the aggregates from forming.

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A century after Endurance, Shackleton diagnosed with 'hole in the heart'

On the 100th anniversary of the Endurance expedition to Antarctica led by Sir Ernest Shackleton, doctors writing in the Journal of the Royal Society of Medicine believe the inspirational explorer may have had the congenital defect commonly known as a 'hole in the heart'. Shackleton was capable of severe exertion and made the first crossing of the mountains and glaciers of South Georgia without any health problems. During other expeditions, however, he alarmed his companions with repeated attacks of breathlessness and weakness.

Historians have pondered the cause of Shackleton's physical breakdowns. Inspired by his own experience of crossing South Georgia in a party led by mountaineer Stephen Venables, retired anaesthetist Dr Ian Calder, with consultant cardiologist Dr Jan Till, made use of material held in the Scott Polar Research Institute in Cambridge to diagnose an atrial septal defect (hole in the heart).

"The evidence rests in diary entries made by Dr Eric Marshall, the medical officer of Shackleton's second expedition to the Antarctic in 1907-9," said Dr Calder. "The detection and treatment of an atrial septal defect is now reasonably straightforward, but was not available to Shackleton."

The authors believe that Shackleton knew he had something wrong with his heart because he avoided being examined by doctors who might have tried to prevent him going to Antarctica.

Dr Calder comments: "Some may feel that Sir Ernest was irresponsible in undertaking the leadership of Antarctic expeditions if he suspected a problem, but to paraphrase Dr Johnson, there is seldom a shortage of prudent people, whilst the great things are done by those who are prepared to take a risk."

Shackleton died of a heart attack in 1922, a few hours after arriving in South Georgia at the beginning of his fourth expedition. He was 47 years of age.

For any corrections of factual information, or to contact our editorial team, please see our contact page.

Please note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms of use.

Copyright Medical News Today: Excluding email/sharing services explicitly offered on this website, material published on Medical News Today may not be reproduced, or distributed without the prior written permission of Medilexicon International Ltd. Please contact us for further details.

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Women, men with heart failure both benefit from implanted defibrillators

Women with heart failure benefit from implantable cardiac defibrillators as much as men, according to new research in Circulation: Heart Failure, an American Heart Association journal.

"Despite current guidelines recommending that health practitioners consider adding these devices to standard heart failure treatments in both women and men, women with heart failure have been less likely to receive defibrillators. These new data reinforce the existing gender-neutral guidelines," said Emily Zeitler, M.D., lead author of the study and a cardiology and research fellow at the Duke Clinical Research Institute in Durham, North Carolina.

An implantable cardiac defibrillator (ICD) is a small, battery-powered device placed under the skin of the chest to deliver an electrical shock to restore a normal heartbeat if it detects a dangerously abnormal heart rhythm. Patients with heart failure, a condition in which the heart's pumping ability is weakened, are at increased risk to develop dangerous heart rhythms. Previously, randomized controlled trials showed that patients with heart failure live significantly longer if they have an ICD implanted preventatively - before an abnormal heart rhythm occurs. However, because the trials enrolled relatively few women, whether women benefited to the same extent was still an open question.

Using data submitted to Medicare from 264 hospitals included in the Get With the Guidelines-Heart Failure registry, the researchers compared survival in heart failure patients with preventive ICDs or prescribed one (430 women; 859 men) versus matched patients with very similar characteristics but no ICDs. All patients had a reduced ability to pump blood out of the heart. The researchers found:

After 3 years, 40.2 percent of women with ICDs had died, compared with 48.7 percent of women without devices. After 3 years, 42.9 percent of men with ICDs had died, compared with 52.9 percent of men without devices. With an ICD, the risk of death was more than 20 percent lower in both men and women after about 3 years.

"Currently, many eligible patients with heart failure are not referred to physicians who can implant the devices. If you have heart failure, ask your doctor whether you might benefit from an ICD in addition to your other therapy," Zeitler said.

Although patients were carefully matched in age, severity of illness, and other treatments being used, this type of study does not have the power of a trial that randomly assigns some patients to receive the devices. However, because the value of ICDs has already been demonstrated, it would be ethically difficult to initiate a trial that denies the treatment to some patients.

"I would encourage patients and providers to enthusiastically pursue good research as participants and enrollers. When we don't equitably enroll women or other important groups in trials, we can be left with less clear answers on how to treat heart disease," Zeitler said.

Co-authors are Anne S. Hellkamp, M.S.; Phillip A. Schulte, Ph.D.; Gregg C. Fonarow, M.D.; Adrian F. Hernandez, M.D., M.H.S.; Eric D. Peterson, M.D., M.P.H.; Gillian D. Sanders, Ph.D.; Clyde W. Yancy, M.D.; and Sana M. Al-Khatib, M.D., M.H.S. Author disclosures are on the manuscript.

The Agency for Healthcare Research and Quality funded the study.

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Sedentary behavior linked to poor health in adults with severe obesity, independent of exercise

Sedentary behavior is associated with poor cardiovascular health and diabetes in adults with severe obesity, independent of how much exercise they perform, a University of Pittsburgh Graduate School of Public Health-led study showed for the first time.

The finding, published online in the journal Preventive Medicine, could be used to design and test programs for adults with severe obesity that emphasize reducing time spent sitting, rather than immediately working toward increased moderate- to vigorous-intensity physical activity or exercise, such as brisk walking. In the U.S., 15 percent of adults have severe obesity, placing them at high risk of cardiovascular and metabolic disease, and premature mortality.

"Adults with severe obesity often have difficultly following national guidelines to participate in at least 30 minutes per day of moderate- to vigorous-intensity physical activity for health benefits," said lead author Wendy C. King, Ph.D., associate professor in the Department of Epidemiology at Pitt Public Health. "Our findings suggest that replacing sedentary behavior, like watching television or sitting at the computer, with low-intensity physical activities, such as light housework or going for a casual stroll, may improve cardiometabolic health in this population."

In addition, Dr. King and her colleagues determined that defining "sedentary time" as 10 minutes or more without walking yielded stronger associations between sedentary behavior and cardiometabolic health compared to allowing sedentary time to be as short as one minute, which has been the norm in the field.

"This is important because accurate assessment of sedentary behavior is crucial to being able to evaluate if and how this behavior is related to health outcomes. If our estimate of sedentary behavior is poor, we may not detect true associations," said Dr. King.

She and her colleagues followed 927 patients participating in the Longitudinal Assessment of Bariatric Surgery-2 , a prospective study of patients undergoing weight-loss surgery at one of 10 different hospitals across the U.S. For a one-week period before surgery, the research team measured the participants' activity - or lack of activity - using monitors that tracked the number of steps taken each minute.

For every hour per day participants spent in sedentary bouts of at least 10 minutes, their odds of having diabetes increased by 15 percent, metabolic syndrome by 12 percent and elevated blood pressure by 14 percent, and their waist circumference was a half inch larger, after adjusting for their sex, age, household income, smoking status, alcohol use, depressive symptoms, body mass index (BMI) and time spent in moderate- to vigorous-intensity physical activity.

"These findings indicate the importance of investigating sedentary behavior as a distinct health risk behavior, not simply lack of moderate- to vigorous-intensity physical activity, among adults with severe obesity," said Dr. King. "This ultimately may inform physical activity guidelines for this special population."

Future research is needed to determine whether replacing sedentary behavior with low-intensity physical activity is an effective approach to preventing and managing cardiovascular and metabolic diseases in adults with severe obesity, and evaluate strategies to help this population make such lifestyle changes.

Additional investigators on this research are Jia-Yuh Chen, M.S., Anita P. Courcoulas, M.D., M.P.H., Steven H. Belle, Ph.D., M.Sc.Hyg., all of Pitt; James E. Mitchell, M.D., and Brian Cook, Ph.D., both of the Neuropsychiatric Research Institute; Bruce M. Wolfe, M.D., of the Oregon Health & Science University; Emma J. Patterson, M.D., of the Legacy Good Samaritan Weight Management Institute in Portland, Ore.; William B. Inabet, M.D., of Mount Sinai Hospital in New York; Gregory F. Dakin, M.D., of Weill Cornell Medical College; David R. Flum, M.D., M.P.H., of the University of Washington.

This clinical study was a cooperative agreement funded by the National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Disease, Grant number DCC -U01 DK066557; Columbia - U01-DK66667 (in collaboration with Cornell University Medical Center CTRC, Grant UL1-RR024996); University of Washington - U01-DK66568 (in collaboration with CTRC, Grant M01RR-00037); Neuropsychiatric Research Institute - U01-DK66471; East Carolina University - U01-DK66526; UPMC - U01-DK66585 (in collaboration with CTRC, Grant UL1-RR024153); and Oregon Health & Science University - U01-DK66555.

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Brain's immune cells key to maintaining blood-brain barrier

New research shows that the cells responsible for protecting the brain from infection and inflammation are also responsible for repairing the system of defenses that separates the brain from the rest of the body. These findings have significant clinical implications because certain cardiovascular drugs could possibly impede the brain's ability to repair itself after a stroke or other injury.

"This study shows that the resident immune cells of the central nervous system play a critical and previously unappreciated role in maintaining the integrity of the blood-brain barrier," said Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) and lead author of the study. "When this barrier is breached it must be rapidly repaired in order to maintain the health of the brain and aid in recovery after an injury - a process that could be impaired by drugs that are intended to prevent this damage in the first place."

The brain is essentially an independent and separate ecosystem. It possesses a dedicated system of defenses against infection and recently Nedergaard and her colleagues demonstrated that the brain also maintains its own unique process of removing waste. Movement in and out of the brain is tightly controlled through a complex system of gateways and controls that are collectively referred to as the blood-brain barrier (BBB).

When the BBB is breached the brain becomes vulnerable to infection and injury. It is, therefore, imperative that the openings in the BBB are resealed, and quickly. This most frequently occurs during a stroke, which triggers inflammation that can cause the BBB to break down.

The new study, which was published in the Proceedings of the National Academy of Sciences, reveals that the brain's immune system, specifically cells called microglia, play a central role in the process of repairing damage to the BBB.

Microglia serve as the brain's "first responders" and are present throughout the brain and spinal cord. These cells are constantly monitoring their environment, and can be switched on or activated to perform different functions such as control inflammation, destroy pathogens, clean up the debris from dead or damaged cells, and seal off the site of an injury.

Performing experiments in mice, Nedergaard and her colleagues observed that when small holes where made in the BBB, nearby microglia were rapidly mobilized and set about repairing the breach. In most instances, the integrity of the BBB was restored within 10 to 30 minutes.

The team identified a receptor called P2RYX12 that was responsible for activating the microglia and directing them to the site of the damage. This finding is significant because the same receptor is also present on platelets and is one of the targets of blood thinning drugs such as Plavix.

These drugs are given to individuals at risk of heart attack and stroke and helps prevent platelets from binding together to form blood clots that, when they make their way to the brain, can block the flow of blood and trigger a stroke. However, because these drugs also suppress P2RYX12 receptors in microglia, they could potentially impair the ability of the brain to carry out repairs to the BBB once a stroke occurs.

Nedergaard and her team are currently investigating the impact of P2RYX12-blocking drugs on microglia function in the brain.

"Our concern is that while certain types of blood thinning drugs may do a great job preventing strokes, they could have the unintended consequence of making them worse or hindering recovery once they occur," said Nedergaard.

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