New blood test detects stroke and heart attack risk in lupus patients with no CVD symptoms

The results of a study presented at the Annual European Congress of Rheumatology (EULAR) 2017 press conference have shown that a specific biomarker detected in the blood of lupus patients with no symptoms of cardiovascular disease (CVD), thought to be at low risk of CVD based on traditional risk factors, is associated with the presence of atherosclerosis .

Overall, the risk of having fatty deposits (plaques) in the carotid arteries that deliver blood to the brain due to atherosclerosis was increased by a factor of 8 times in those lupus patients who had a biomarker known as High Sensitivity Cardiac Troponin T (HS-cTnT) in their blood.

Premature CVD is much more common in young premenopausal women with lupus than healthy women of a similar age. With the increased life expectancy of lupus patients due to improved therapy, CVD has emerged as a significant threat to their health. CVD is a major cause of death and ill-health in lupus patients. Using traditional risk factors as the ‘Framingham score’ has previously underestimated the risk of CVD in this population.

“The results of our study raise the possibility that this easily measured biomarker could be introduced into clinical practice as a more reliable way of evaluating CVD risk in lupus patients,” said lead author Dr. Karim Sacre, from the Bichat Hospital, Paris, France. “This in turn will enable more effective primary prevention measures such as treating abnormally raised blood lipids to be implemented,” he added.

Using vascular ultrasound, 23 out of 63 (36.5%) consecutive lupus patients were found to have signs of carotid plaques compared to only 2 out of 18 (11.1%) of a control group. None of these patients nor the controls had symptoms of CVD and they all had a low Framingham risk factor score. Only age (p=0.006) and lupus disease status (p=0.017) were independently associated with the presence of carotid plaques.

The percentage of lupus patients with carotid plaques who had a detectable HS-cTnT was 87%; only 42.5% of lupus patients without plaques had a detectable blood level of HS-cTnT (p<0.001). Conversely, 54.5% of lupus patients with a detectable HS-cTnT, but only 11.5% with an undetectable HS-cTnT had a carotid plaque (p<0.001).

“Before introducing this new biomarker into clinical practice, we are conducting further research to confirm our findings on a larger cohort of patients, with a longer follow up period, analysing not only carotid plaques, but also the occurrence of major cardiovascular events,” Dr. Sacre concluded.

Lupus (Systemic Lupus Erythematosus) is a genetically complex chronic relapsing immune mediated rheumatic disease characterised by inflammation that may affect different tissues, including the skin, joint linings, lungs, kidneys and other organs. Lupus predominately affects women, occurring 10 times more often than in men, and frequently starting at child-bearing age. The disease is highly variable in the way it may present, and in its outcome among individuals and across different ancestral groups.

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Mind over muscles: How the brain hinders individual muscle control

The key to balance is, in part, the ability to overpower your mind. Your brain possesses what some researchers call “common drive.” It wants to activate and relax all muscles in synchrony, including the opposing ones. It’s probably why you find yourself swaying while trying to balance on one leg. When you start to teeter, your mind drives all the muscles to stiffen at the same time. The problem: This drive contains muscle oscillations, which cause you to sway again and continue the process.

All muscles typically have slight oscillations at the same time — less than three per second or three Hz — when they’re used. This is the common motor drive.

This common drive may also be a reason why stroke survivors have trouble keeping their hands from becoming rigid and shaking. Only when you control both sets of muscles individually, or overcome this common drive, the rigidity and wobbling may stop.

Georgia Institute of Technology researchers wanted to learn why some people are better than others at controlling joint stiffness by co-contracting opposing muscles to overcome this common drive. They also wanted to know if that skill could be taught. If so, it could lead to more effective rehabilitation exercises for stroke survivors or people with Parkinson’s disease.

In a new study, the researchers set up an experiment for healthy young adults. They were tasked with flexing their bicep muscles and maintaining that activation at a designated level while also extending their triceps and keeping them steady at a different level. By wearing EMG sensors, the researchers were able to determine who was more effective in steady co-contraction.

“The opposing muscles fought against each other to maintain different activation levels,” said Minoru Shinohara, an associate professor in the School of Biological Sciences at Georgia Tech. “It wasn’t easy. Some participants were actually sweating after just 30 seconds, struggling to keep both muscles activated and consistent at different levels.”

The people who were worst at the experiment were unable to reduce the synchronized oscillations from both muscles. They rose and fell at the same time.

“In contrast, better performers were able to dissociate the signal to both muscles and control them individually,” said Shinohara. “They overcame the mind’s willingness to send synchronized signals across muscles. They activated individually to better control both.”

The next part of the experiment was to see if the healthy adults could train their muscles to more easily overcome the common drive. A third of the participants were trained for dissociated co-contraction — to flex and contract both muscles simultaneously but at different levels, back and forth, for an hour. Others worked on one muscle for a while, then switched to the other. The third group rested for 60 minutes.

Afterward, everyone did the first test again. The improvement was the same across groups. Those who did nothing for an hour were just as successful (or not) as those who practiced, simply due to familiarization with the test.

“If you practice anything specific for an hour, you’re likely to see specific improvement,” said Shinohara. “But there were no specific improvements with the dissociation practice. This means that the common drive is deeply embedded into the mind. It would take a long time for healthy adults to efficiently dissociate their muscles.”

And that may partially explain why stroke survivors are slow to see any improvement after extensive rehab.

“If healthy adults have trouble controlling their muscles individually, we shouldn’t be surprised that those who always struggle to control their muscles would have an even more difficult experience. An hour isn’t enough, which isn’t too surprising. But it’s important that people don’t give up if it takes a while to progress.”

The paper, “Slow intermuscular oscillations are associated with cocontraction steadiness,” is currently published ahead of print in the journal Medicine & Science in Sports & Exercise.

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A SMARTer way to discover new stroke treatments

A sequential multiple assignment randomized (SMART) trial allows researchers to test two hypotheses at once.

The new trial method is being used in clinical trials across the industry.

“SMART trials allow you to get to two questions at once and can potentially be more efficient,” says William Meurer, M.D., associate professor of emergency medicine and neurology at Michigan Medicine and a member of the Michigan Center for Integrative Research in Critical Care. “You may find answers you wouldn’t normally find using a normal trial design.”

Meurer is the lead author on a study published in the Journal of Stroke and Cerebrovascular Diseases that investigated if the trial design could be used specifically to study stroke treatment.

“In stroke, we are often treating the patient with a tissue plasminogen activator drug upfront to dissolve a blood clot in the brain,” Meurer says. “Sometimes, that blood clot doesn’t dissolve. What do you do next?”

This question led the research team to a SMART trial design, says Meurer, also a member of the U-M Institute for Healthcare Policy and Innovation.

Researchers wanted to know two things: “If there’s a new treatment better than tPA, and if there’s something new we can do at that second step, if tPA doesn’t dissolve the clot,” he says.

Designing the trial

Meurer and colleagues conducted a numerical simulation to evaluate the study design. The simulation included two initial reperfusion strategies, alteplase versus a new pharmacologic regimen, and two rescue therapies, the current best endovascular approach versus rescue pharmacotherapy.

“Because we were testing these multiple treatment options, we knew there could be a range of possible outcomes,” Meurer says. “For example, we cite in the paper that rescue pharmacotherapy may only be effective if linked with the alteplase initial reperfusion treatment. Our main outcome of the simulated trial was to find the proportion of true-positive and false-positive trials given the scenario.”

The research team analyzed, in sample sizes of 2,000, 1,500 and 700, the overall probabilities of success for individuals following each treatment pathway:

    • – lytic A, respond

– lytic A, no response, catheterization lab

– lytic A, no response, new medication

– lytic B, respond

– lytic B, no response, catheterization lab

– lytic B, no response, new medication.

In addition, they simulated probabilities for three trial phases. This assumed a new treatment would work 50 percent of the time, and the old treatment would work 40 percent of the time, with the goal to determine how many of the clinical trials actually got the right answer based on the above simulated truth. This determined how accurate that sort of clinical trial would be in detecting an important treatment effect, and how often the trial might give a false positive result.

After probing the results, the researchers say their simulation demonstrated that a SMART trial design was effective for testing sequential treatments for acute stroke.

“The SMART simulation allowed us to find differences in dynamic treatment regimens, and tailored sequences of treatments and treatment interactions, instead of just treatments at a single stage,” Meurer says.

“Mainly, this new design allowed us to learn a couple of things at once: how well a treatment worked for the first phase of stroke, and how often an additional treatment worked in those who did not respond to the first treatment. Uniquely, some initial treatments might look the same, but may increase the number of patients who respond to the second stage treatment.

“Current clinical trial processes would not allow this result because we wouldn’t change from one first stage treatment to another if they were working similarly, and thus we would never know that we would help people because the new first stage treatment would make the second stage treatment more effective.”

SMART trials are not unusual in clinical trials overall, he adds, noting that they just have not been used specifically to study stroke treatments.

“We proved this type of consolidated approach to research in a randomized way is unique and a good way to learn more about what new treatments might work for stroke patients,” he says.

It could also potentially save time and resources.

“Clinical trials are costly and it can be challenging to find participants,” Meurer says. “A SMART trial could potentially be more efficient. In stroke care, most trials focus on the first decision made in treatment, whereas this type of trial allows treatment decisions to be made at two different times to see how they could benefit from each other.”

Is educational attainment associated with lifetime risk of cardiovascular disease?

Men and women with the lowest education level had higher lifetime risks of cardiovascular disease than those with the highest education level, according to a new study published by JAMA Internal Medicine.

One of the most important socioeconomic factors contributing to cardiovascular disease (CVD) is educational inequality. Calculating the lifetime risk of CVD according to educational levels is one way to convey the importance of educational attainment.

Yasuhiko Kubota, M.D., of the University of Minnesota, Minneapolis, and coauthors evaluated the association between educational attainment and CVD risk by estimating lifetime risks of CVD (coronary heart disease, heart failure and stroke) in a large biracial study. The authors also assessed how other socioeconomic factors (income, occupation and parental education) were related to the association between educational attainment and lifetime CVD risk.

The study included 13,948 white and African-American participants who were followed from 1987 through 2013, were 45 to 64 years old, and free of CVD at baseline from four communities in the United States (Washington County in Maryland; Forsyth County in North Carolina; Jackson, Miss.; and the suburbs of Minneapolis, Minn.). The authors documented 4,512 CVD events and 2,401 non-CVD deaths.

In men, lifetime CVD risks from ages 45 through 85 ranged 59 percent for those with a grade school education to 42 percent for those with a graduate/professional school education. In women, lifetime CVD risks ranged from almost 51 percent for those with a grade school education to 28 percent for those with the highest level of educational attainment with graduate/professional school, according to the results. In addition, educational attainment was “inversely associated” (more education associated with lower risk) with CVD regardless of other important socioeconomic factors including family income, occupation or parental education level.

The authors caution that lifetime risks of CVD should be interpreted carefully because they could be influenced by other CVD risk factors. “Even with such a proviso, our estimates of lifetime risk can help in elucidating the association between education and CVD risk,” the article notes.

“More than 1 in 2 individuals with less than high school education had a CVD event during his or her lifetime. Educational attainment was inversely associated with the lifetime risk of CVD, regardless of other important socioeconomic characteristics. Our findings emphasize the need for further efforts to reduce CVD inequalities related to educational disparities,” the article concludes.

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Robotic device developed to help stroke survivors recover

A recent study, affiliated with UNIST has introduced a new robotic tool for assessments of muscle overactivity and movement dysfunction in stroke survivors. Their robotic-assisted rehabilitation therapy, combined with standard rehabilitation, is expected to improve the mobility of patients surviving a stroke.

This breakthrough research has been led by Professor Sang Hoon Kang of Mechanical, Aerospace and Nuclear Engineering at UNIST in collaboration with Professor Pyung-Hun Chang of DGIST and Dr. Kyungbin Park of Samsung Electronics Co. Ltd.

In their study, published in the May issue of the journal, IEEE Transactions on Neural Systems and Rehabilitation Engineering, Professor Kang and his team developed a rehabilitation robotic system that quantitatively measures the 3 degree-of-freedom (DOF) impedance of human forearm and wrist in minutes.

Using their impedance estimation device, entitled the distal internal model based impedance control (dIMBIC)-based method, the team was able to accurately characterize the 3 DOF forearm and wrist impedance, including inertia, damping, and stiffness, for the first time.

Stroke, known as a leading cause of long-term disability, is a sudden loss of brain function, caused by the interruption of blood flow to the brain or the rupture of a blood vessels in the brain and an estimated 150,000 people die from it, each year. As a consequence of stroke, stroke survivors are often left with muscle overactivity, including spasticity. Spasticity is a muscle control disorder that is characterized by tight or stiff muscles and an inability to control those muscles. It is often manifested by increased stretch reflex activity and mechanical joint resistance.

“The dIMBIC-based method can be used to assist in the quantitative and objective evaluation of neurological disorders, like stroke,” says Professor Kang. “Findings from this study will open a new chapter in robot-assisted rehabilitation in the workplace accident rehabilitation hospitals, as well as in nursing homes and assisted living facilities.”

The research team expects that, in the long run, the proposed 3 DOF impedance estimation may promote wrist and forearm motor control studies and complement the diagnosis of the alteration in wrist and forearm resistance post-stroke by providing objective impedance values including cross-coupled terms.

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Is cirrhosis associated with increased risk of stroke?

Cirrhosis was associated with increased risk of stroke, especially hemorrhagic, in a study that included a representative sample of more than 1.6 million Medicare beneficiaries, according to an article published by JAMA Neurology.

Neal S. Parikh, M.D., of Weill Cornell Medicine and New York-Presbyterian Hospital, New York, and coauthors used inpatient and outpatient Medicare claims data from 2008 through 2014 for a random sample of Medicare beneficiaries older than 66.

Of more than 1.6 million Medicare beneficiaries, 15,586 patients (1.0 percent) had cirrhosis and during an average of about four years of follow-up, 77,268 patients were hospitalized with a stroke. The incidence of stroke was 2.17 percent per year in patients with cirrhosis and 1.11 percent per year in patients without cirrhosis. Patients with cirrhosis had a higher risk of stroke, especially hemorrhagic, according to the results.

The authors acknowledge multiple possible explanations for the association between cirrhosis and increased risk of stroke, including mixed coagulopathy (impaired clotting), that patients’ underlying vascular risk factors may be heightened by cirrhosis and the underlying causes of cirrhosis (alcohol abuse, hepatitis C infection and metabolic disease) also may contribute to stroke risk. The study notes limitations, including ascertaining vascular risk factors may be incomplete.

“In a nationally representative sample of elderly patients with vascular risk factors, cirrhosis was associated with an increased risk of stroke, particularly hemorrhagic stroke.

Additional investigation into the epidemiology and pathophysiology of this association may yield opportunities for stroke risk reduction and prevention,” the article concludes.

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New piece found in inflammatory disease puzzle

Inflammation is the process by which the body responds to injury or infection but when this process becomes out of control it can cause disease. Monash Biomedicine Discovery Institute (BDI) researchers, in collaboration with the Monash Institute of Pharmaceutical Sciences (MIPS), have shed light on a key aspect of the process. Their findings may help guide the development of new treatments of inflammatory diseases such as atherosclerosis, which can lead to heart attack or stroke, and type 2 diabetes.

Published today in the journal Science Signaling, the research reveals how certain proteins cause the white blood cells that play a central role in inflammatory responses to behave in different ways. White blood cells are beneficial in helping to eliminate invading microorganisms or repair damaged tissue, but they can prolong the response and damage healthy tissues, leading to disease.

The proteins, called chemokines, are secreted into blood vessels and activate chemokine receptors embedded in the outer membranes of the white blood cells. While it was previously thought that this occurred like an on-off switch, the scientists found that the chemokine receptor can behave more like a ‘dimmer switch’ with one chemokine giving a strong signal and another giving a weaker signal. They found that different responses can be caused by different chemokines activating the same receptor.

This explained for the first time the mechanism by which white blood cells produced varying responses: a strong short-lived response (acute inflammation) or a steady, longer-lived response (chronic inflammation).

“Until now, we did not understand how this was possible,” said co-lead author Associate Professor Martin Stone.

“Our work has identified the specific features of chemokines and receptors that are involved in their inflammatory activity,” Associate Professor Stone said.

“The ultimate goal is to develop anti-inflammatory drugs that target these molecules,” he said.

The findings, which Associate Professor Stone presented at an international conference on cell signalling last week, will have wide implications as the proteins involved are essential to all inflammatory diseases.

Associate Professor Stone, who heads a laboratory in the Infection and Immunity Program at the Monash BDI collaborated closely with co-lead author Dr Meritxell Canals from MIPS. First author was PhD student Mrs Zil E. Huma.

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How neural stem cells can become blood vessels

The Neural Mother Cell Physiopathology Research Group of the University of Seville and the Seville Institute of Biomedicine (IBiS) have just published a scientific article in the review Cell Reports, in which they show that mother cells from the adult carotid body can transform into blood vessels, as well as into neurons. The work has mainly been carried out by the post-doctoral researcher Valentina Annese, as a member of the group.

This discovery could have important repercussions on the advance in treatment of diseases as different as paediatric tumours and Parkinson’s. “We believe that the ability to produce blood vessels from neural stems cells could directly affect the growth of certain types of tumours on the infant population,” said the project’s main researcher, Ricardo Pardal.

The carotid body is a small structure of nerve tissue situated at the fork of the carotid artery. Its function is to act as a chemoreceptor in the blood. It monitors oxygen pressure in the blood and plays a role in the regulation of breathing.

The plasticity of adult mother cells, or the somatic mother cells, to cross boundaries and to differ in unrelated cell types has been a subject of debate in the last decade. The stem cells that come from the neural crest (NCSCs) show notable plasticity during their development, but it is not known if adult NCSCs maintain this plasticity.

In this sense, “we describe that the adult stem cells from the carotid body taken from the neural crest (CBSCs) are capable of experiencing endothelial differentiation, as well as their already described role in neurogenesis, contributing to both neurogenic and angiogenic processes that take place in the organ during acclimation to hypoxia. In addition, the conversion of CBSCs into blood vessels is dependent on the hypoxia-inducible factor (HIF) and is sensitive to vascular cytokines released in hypoxia, such as erythropoietin. Our data highlights a notable physiological plasticity in an adult population of stem cells specifically from tissue, and they could have an impact on the use of those cells for cellular therapy,” Pardal added.

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Clot removal therapy effective outside six-hour window for some stroke patients

Results of a randomized controlled trial show that endovascular treatment (ET) to remove a stroke-causing blood clot in the brain is effective in some patients even when performed within 6 to 24 hours after a stroke. Current guidelines for acute stroke treatment endorse clot removal only when performed within six hours of a stroke. The findings are presented today at the European Stroke Organisation Conference 2017 in Prague.

“This still means that you need to be rushed to the hospital as soon as possible after a stroke has occurred because the mantra “time is brain” still holds. However, our study shows that even if treated outside the time window, patients will have significantly reduced disability with clot removal,” said Tudor Jovin, M.D., director, UPMC Stroke Institute, and professor of neurology and neurosurgery at the University of Pittsburgh, who co-led the trial.

The trial sets a new selection paradigm based on physiology, showing for the first time that looking at patients fulfilling certain imaging and clinical criteria, physiological state of the brain is a much better approach to determining whether patients will benefit from endovascular therapy as opposed to adhering to strict time windows, noted co-principal investigator Raul Nogueira, M.D., professor of neurology, neurosurgery and radiology at Emory University School of Medicine, and director of neuroendovascular service and neurocritical care service at Marcus Stroke & Neuroscience Center, Grady Memorial Hospital.

In the study, researchers randomly assigned stroke victims who arrived at the hospital outside the six-hour time window to either receive endovascular therapy or receive only standard medical therapy.

Brain imaging and clinical information (neurological deficit) was used to identify and enroll patients who had a small area of irreversibly damaged brain and a significantly larger brain tissue area that was imminently threatened by loss of blood supply, but still alive — a criterion known as clinical core mismatch.

The results showed that almost half of the patients (48.6 percent) receiving endovascular therapy had a good outcome at 90 days after treatment — defined as the patients being independent in activities of daily living — showed clinical benefit while only 13.1 percent showed benefit in the group that received clot-busting drugs alone. There was no difference in mortality between the two groups.

The researchers planned to enroll 500 patients over the course of the study period. However, an intermediate review of the treatment effectiveness before enrollment was completed led the independent Data Safety Monitoring Board overseeing the study to recommend early termination of the trial after it was demonstrated that ET provided significant clinical benefit in the selected patients.

The multi-center international study known as the DAWN trial included trial locations in the United States, Spain, France, Australia and Canada. The trial was sponsored by Stryker Corporation, which manufactures the clot removal devices used in the study.

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Higher levels of biomarker linked to increased stroke risk for women

Women with elevated levels of a protein in their blood may be at a higher risk of ischemic stroke, according to a study published in the May 10, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology. The new research comes in time for Stroke Awareness Month in May.

The study found that an elevated level of beta-2 microglobulin, a protein found on the surface of many cells, was linked to an increased risk of ischemic stroke among women. The most common type of stroke, ischemic stroke occurs when the blood supply to the brain is blocked. The protein may also be a marker for inflammation.

“Recent studies have found associations between beta-2 microglobulin and heart disease,” said study author Pamela Rist, ScD, of Brigham and Women’s Hospital and Harvard Medical School in Boston and a member of the American Academy of Neurology. “However, less is known about the association between beta-2 microglobulin and ischemic stroke.”

Researchers looked at women with an average age of 61 enrolled in the Nurses’ Health Study who provided blood samples between 1989 and 1990 and who had no history of stroke or cancer. Participants were asked to complete questionnaires about their lifestyle and medical history every two years.

To learn more about beta-2 microglobulin and any possible link to stroke, researchers measured the protein levels in 473 study participants who later had an ischemic stroke as well as 473 participants of the same age who did not have a stroke. They were also matched based on other factors that could affect stroke risk, such as whether they smoked or used hormone treatments. The strokes occurred an average of nine years after the start of the study.

Researchers found that participants who later had an ischemic stroke had higher levels of beta-2 microglobulin than those who did not have a stroke. The average level of the protein was 1.86 milligrams per liter in those who had ischemic strokes, compared to 1.80 mg/L in those who did not have a stroke.

The researchers divided the participants into four groups based on their levels of the protein. Those in the highest quarter of beta-2 microglobulin levels were 56 percent more likely to have a stroke than those in the bottom quarter. In the top quarter, 163 of the 283 women had strokes, compared to 106 of the 227 women in the bottom quarter.

The results were adjusted for other factors that could affect stroke risk, such as physical activity, high blood pressure and diabetes.

Rist said that limitations of the study are that it was conducted mainly among white women and that it could not examine any changes in protein levels.

“Given the high rate of disability from stroke, it is important to identify people who may be at higher risk of this disease. This protein could be a marker that might help us in the fight against stroke,” said Rist. “Further studies are needed to determine if beta-2 microglobulin levels can be modified through lifestyle changes.”

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Helistroke service: Flying the physician to the stroke patient works

Flying a stroke specialist by helicopter to a nearby stroke patient for emergency care is feasible, saves money and, most importantly, gets critical care to patients faster than transporting the patient to a hospital first, according to a single-patient, proof-of-concept study by a Johns Hopkins Medicine research team.

Although the study was not designed to show whether “helistroke service” would improve outcomes for patients, previous research has amply demonstrated that stroke victims do best when they are treated as quickly as possible — ideally in 100 minutes or less.

A report of the findings, published in the Journal of Neurointerventional Surgery on May 3, details what is believed to be the first test of transporting a physician by helicopter to perform a standard intervention for a stroke.

“With the development of effective treatments, the most limiting factor to treating acute stroke is infrastructure — we have to keep evolving our systems to get therapy to as many appropriate patients as possible,” says Ferdinand K. Hui, M.D., associate professor of radiology and radiological science at the Johns Hopkins University School of Medicine. Hui, the report’s first author, is the physician who was transported via helicopter for the study.

In the traditional model of care, people experiencing an acute ischemic stroke (a cutoff of blood supply in a blood vessel to the brain) are taken to a hospital with a specialized center capable of performing a minimally invasive therapy in which a physician inserts a catheter into the groin and threads it up through blood vessels to the blood clot in the brain causing the stroke. Once the catheter is in place, the physician delivers drugs that break up the clot.

Patient transport time, however, can be significant and, in many cases, stroke victims are first taken to a nearby community hospital, then transported to the specialized center, often further delaying time to treatment and lowering the odds of recovery or reduced disability.

In a recent study analyzing the results of a global, multicenter trial, data show a 91 percent probability of favorable stroke outcome if patients’ blood flow was restored within 150 minutes of stroke. The next 60 minutes of delay, researchers found, resulted in a 10 percent reduction of good outcome. An additional 60 minutes resulted in an additional 20 percent reduction of good outcome. For the best chance of a favorable outcome, preintervention time was calculated to be less than 100 minutes.

To test the feasibility of a physician-to-patient model that could potentially improve outcomes for a time-sensitive procedure, investigators designed a study to fly Hui by Johns Hopkins Lifeline from Baltimore to a National Institutes of Health Stroke Center at Suburban Hospital in Washington, D.C. — 39.4 miles away — to treat a stroke victim. Suburban, part of the Johns Hopkins Health System, has radiologists and the necessary equipment to image blood vessels but no neurointerventional experts on hand to provide immediate, catheter-based treatment.

A patient was eligible for treatment in the pilot study if he or she had a large vessel blockage and a National Institutes of Health Stroke Scale rating greater than eight, which is considered a severe stroke. The stroke scale is a 15-item neurologic examination used to evaluate the potential damage of stroke as soon as possible after it occurs.

In January 2017, such a patient was identified at Suburban at 11:12 a.m. Scans to view the patient’s blood vessels and brain tissue were initiated at 11:46 a.m. and completed at 11:58 a.m.

Hui, who was at The Johns Hopkins Hospital in Baltimore, was alerted at 12:07 p.m. Johns Hopkins Lifeline, which provides critical care transportation, was called at 12:13 p.m. Weather clearance for helicopter takeoff was obtained at 12:24 p.m., and the helicopter flight from The Johns Hopkins Hospital to Suburban Hospital took 19 minutes.

Hui inserted the catheter into the patient at 1:07 p.m. and completed treatment at 1:41 p.m. Total time between decision-to-treat and groin puncture was 43 minutes, and between decision-to-treat and groin closure was 77 minutes. These times are comparable with time to treatment in one institution without transfer. The patient received tissue Plasminogen Activator, a clot-dissolving drug, and improved clinically.

Hui says the helistroke service model not only has the potential to reduce transport time and improve patient outcomes, but also could expand ideal standards of care to rural and other populations, where specialized care is limited.

“Up until now, the model has been that the ‘right place’ was a central location, like a tertiary facility such as The Johns Hopkins Hospital,” says Jim Scheulen, M.B.A., chief administrative officer of emergency medicine at The Johns Hopkins Hospital. “But what we have demonstrated here is that bringing the right resources in the right time to the patient may actually be a better approach than always moving the patient.”

Hui cautions that the helistroke service is not always the right or best choice: weather restrictions, specialist availability and transportation costs limit the use of the model. But flying a specialist to a patient may also eliminate some costs of nursing care, monitoring equipment, and the costs of ambulance services to one or more hospitals, as well as potentially fewer days of hospitalization and rehabilitation for stroke patients, he says.

Although costs vary among regions and hospital networks, the cost of transferring a physician in this case was roughly 20 percent ($2,000-$3,000) of the average patient helicopter transfer cost ($6,500-$8,000) for the hospital network.

microRNA reduces stroke risk

The most common cause for the narrowing of the carotid artery and thus the major risk factor for strokes is atherosclerosis, where so-called plaques build up on the vessel walls. If a plaque ruptures, blood clots can form that either further occlude the site that is already narrowed, or are carried away by the blood flow, which could lead to vascular occlusion at a different site. If this happens in the carotid artery, it could lead to a stroke. How easily a plaque ruptures depends on how thick the tissue layer surrounding its core is. The thicker this so-called fibrous cap, the more stable and thus more harmless the vessel deposit.

New trend: Stabilizing instead of reducing

“New imaging procedures enable us to detect dangerous plaques with increasing precision; but the therapies currently available for removing these unstable plaques and thus preventing a stroke entail a certain amount of risk that the plaques will rupture during the procedure,” explains Mägdefessel. “This is why these therapies are not used on individuals with a narrowed carotid artery who have so far not experienced any symptoms.” In an experimental manner, microRNA-210 provides the opportunity to alleviate such dangerous, unstable plaques. It stabilizes the fibrous cap so that it cannot rupture as easily. “Traditionally, physicians try to reduce the size of the deposits in the vessels in order to widen the narrowed sites. Yet for narrowed carotid arteries, the notion of stabilizing the plaques is becoming ever more prevalent. Unlike in the coronary vessels, in the carotid artery plaques rupturing is more dangerous than the narrowing.”

Tiny regulators

Mägdefessel and his team compared material from patients with stable and unstable deposits in the carotid artery. They particularly focused on microRNAs. These molecules are involved in the gene regulation in about 60 percent of mammals’ genes. They can prevent gene information that has already been read from being translated into proteins, and have become a focus of biomedical research as active ingredients and starting points for new therapies in recent years.

Mägdefessel and his team discovered that microRNA-210 was reduced the most in the blood samples of patients with unstable plaques. These were blood samples that were obtained locally near the vessel deposits. Further examinations showed that microRNA-210 is primarily present in the fibrous caps of plaques and that it inhibits the expression of the APC gene. As a consequence, fewer smooth muscle cells die in the fibrous cap and it becomes more stable. Moreover, the animal model could show that fewer plaques rupture when microRNA-210 is additionally administered.

Local application is crucial

The scientists are currently researching how microRNA-210 can be applied locally. The risk of adverse events in other organs is much too high if microRNA modulators are administered systemically. In particular, the main concern with microRNA-210 is that tumour cells that are possibly already in existence will multiply, because the expression of APC is inhibited. This is because APC is a tumour suppressor gene which inhibits the growth of tumours in the healthy body. In order to avoid such so-called off-target effects, the researchers are currently testing coated stents or balloons that are inserted directly into the carotid artery in pigs. “For this step, we also rely on the collaboration with companies that, for example, develop soft balloons that cause little friction and thus make the procedure safer,” says Mägdefessel. “Only thus will our results reach patients as effective therapies.”

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Stroke prevention may also reduce dementia

Ontario’s stroke prevention strategy appears to have had an unexpected, beneficial side effect: a reduction also in the incidence of dementia among older seniors.

A new paper by researchers at Western University, Lawson Health Research Institute and the Institute for Clinical Evaluative Sciences (ICES) shows there’s been a decade-long drop in new diagnoses of both stroke and dementia in the most at-risk group — those who are 80 or older.

“Some have said we’re on the cusp of an epidemic of dementia as the population ages,” said study author Joshua Cerasuolo, a PhD candidate in epidemiology and biostatistics at Western’s Schulich School of Medicine and Dentistry. “What this data suggests is that by successfully fighting off the risks of stroke — with a healthy diet, exercise, a tobacco-free life and high blood-pressure medication where needed — we can also curtail the incidence of some dementias.

“The take-home message is that we can prevent some dementias by preventing stroke,” Cerasuolo said.

Published in the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, this is the first study that has looked at the demographics of both stroke and dementia across Ontario since the province pioneered Canada’s first stroke prevention strategy in 2000. That strategy includes more health centres able to manage stroke, more community and physician supports, better use of hypertensive mediation and well-promoted lifestyle changes to reduce risks. Five provinces have stroke strategies and five do not.

“With lifestyle changes, we can reduce our risks of both stroke and some dementias. That’s a pretty powerful one-two punch,” said Dr. Vladimir Hachinski a clinical neuroscientist at Western’s Schulich School of Medicine and Dentistry, a Lawson Health Research Institute scientist and neurologist at London Health Sciences Centre. He is a world pioneer in stroke research and a co-supervisor of the research paper.

Hachinski said more research needs to take place to understand the specific relationships between stroke and dementia but this work suggests there are policy implications where stroke and dementia work can intersect.

“We have systems in place for stroke prevention and our hypothesis is that any studies looking at stroke prevention should also investigate dementia prevention,” Hachinski said. “It’s a good-news story for Ontario and it could be a good-news story elsewhere.”

Most strokes are caused by the restriction or constriction of blood flow to the brain. Vascular dementia also develops as blood supply to the brain is reduced.

Hachinski said someone who has had a stroke is twice as likely to develop dementia. Someone who has had a diagnosis of stroke has also likely had several prior “silent” strokes that may have affected a patient’s cognitive abilities.

The data mining took place using information from ICES, based in Toronto.

Specifically, it shows that the incidence of new stroke diagnosis among highest-risk group, people aged 80-plus, dropped by 37.9 per cent in a span of a little more than a decade. During the same timeframe, the incidence of dementia diagnoses in that age group fell by 15.4 per cent.

“As clinicians and researchers, we are still trying to get a handle on how to reduce a person’s chances of dementia late in life. Some we can’t influence — yet — but here is a pretty clear indication that we can take specific definitive steps to reduce our chances of dementia related to vascular disease,” Hachinski said.

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Materials provided by University of Western Ontario. Note: Content may be edited for style and length.

Unemployment associated with 50% higher risk of death in heart failure patients

Not being employed linked with greater likelihood of death than history of diabetes or stroke.

Unemployment is associated with a 50% higher risk of death in patients with heart failure, according to research presented today at Heart Failure 2017 and the 4th World Congress on Acute Heart Failure. The observational study in more than 20,000 heart failure patients found that not being employed was linked with a greater likelihood of death than history of diabetes or stroke.

“The ability to hold a job brings valuable information on wellbeing and performance status,” said lead author Dr Rasmus Roerth, a physician at Copenhagen University Hospital, Denmark. “And workforce exclusion has been associated with increased risk of depression, mental health problems and even suicide.”

“In younger patients with heart failure, employment status could be a potential predictor of morbidity and mortality,” he continued. “If that was the case, employment status could help to risk stratify young heart failure patients and identify those needing more intensive rehabilitation.”

This study compared the risks of all-cause death and recurrent heart failure hospitalisation in patients with heart failure, according to whether they were employed at baseline or not. Using the unique personal identification number assigned to all residents in Denmark, individual data was linked from nationwide registries on hospitalisation, prescribed medication, education level, public welfare payments, and death.

The study included all patients of working age (18 to 60 years) with a first hospitalisation for heart failure in Denmark between 1997 and 2012. Of the 21 455 patients with a first hospitalisation for heart failure, 11 880 (55%) were part of the workforce at baseline.

During an average follow-up of 1005 days, 16% of employed and 31% of unemployed patients died, while 40% of employed and 42% of unemployed patients were rehospitalised for heart failure.

After adjusting for age, sex, education level and comorbidities, heart failure patients unemployed at baseline had a 50% increased risk of death and 12% increased risk of rehospitalisation for heart failure compared to those who were employed. Not being part of the workforce was associated with a higher likelihood of death than history of diabetes or stroke.

Dr Roerth said: “We found that heart failure patients out of the workforce at baseline had a higher risk of death. Not being part of the workforce was associated with a risk of death comparable to that of having diabetes or stroke. Those without a job also had an increased risk of recurrent heart failure hospitalisation.”

Dr Roerth said the exact mechanism on how employment status may affect mortality is complex and most likely multifactorial. “The ability to work can be seen as a measure of performance status and be interpreted as whether patients meet the physical requirements of a full time job or not,” he said.

But he added: “Employment status is more than just a physical measurement as it also has an influence on quality of life, and has been shown to be important for mental health and wellbeing. Thus, both from a physical and psychological point of view it makes sense to include employment status in the evaluation of young heart failure patients’ prognosis.”

Dr Roerth said it was perhaps not surprising that employment status has importance for prognosis. “But the observation that employment status is associated with an increased risk of death comparable to that of many other comorbidities such as diabetes and stroke is notable,” he said.

In terms of implications of the findings, Dr Roerth said workforce exclusion could be used to identify heart failure patients at risk of poor outcomes and that efforts to get patients back into work might be beneficial.

He said: “It could be highly valuable to assess employment status and actually think of workforce exclusion as a prognostic marker in line with suffering from serious chronic diseases. Knowledge on why workforce exclusion has happened for the individual patient might lead to ideas on how it can be prevented — for example with more intensive rehabilitation, physical activity, psychological treatment, or a different job.”

First systemic evidence for safety of tPA in stroke patients with sickle cell disease

Adult patients with sickle cell disease (SCD) who experience a stroke caused by a clot (i.e., ischemic strokes or IS) can be treated safely with tissue plasminogen activator (tPA) if they qualify, report investigators at the Medical University of South Carolina (MUSC) and elsewhere in the March 2017 issue of Stroke.

Tissue plasminogen activator (tPA), which has been the established therapy for treating IS since 1996, speeds up the body’s ability to dissolve clots, thus improving blood flow to the brain. When administered in the requisite time window, tPA can help prevent some of the disability associated with IS.

The use of tPA in SCD patients is not well established, although it has never been contraindicated. Stroke has a different pathophysiology in those with SCD — it is caused by the enhanced adhesion of the red blood cells to the endothelium. People with SCD also have an increased risk of intracranial hemorrhage, an uncommon but potentially fatal complication of tPA.

For the study reported in Stroke, researchers at MUSC, including lead author Robert J. Adams, M.D., Distinguished Professor of Neurology and Director of the South Carolina Center for Economic Excellence in Stroke, Julie Kanter, M.D., a hematologist specializing in the care of patients with SCD who also serves as Director of Sickle Cell Research, and Shelly D. Ozark, M.D., Assistant Professor of Neurology, teamed up with researchers at other universities to analyze in-hospital data compiled by the quality improvement program Get With The Guidelines — Stroke on 2,016,652 stroke patients seen at 1952 participating US hospitals between January 2008 and March 2015.

They identified 832 patients with SCD and 3325 age-, sex- and race-matched controls and found no statistically significant differences between the two cohorts in the rate of tPA use (8.2 percent for SCD patients vs 9.4 percent for non-SCD patients), the timeliness of its administration (door-to-needle time, 73 minutes for SCD patients vs. 79 minutes for non-SCD patients) or the rate of in-hospital complications. Of patients receiving tPA, 4.9 percent of those with SCD experienced intracerebral hemorrhage vs. 3.2 percent of those without SCD, a difference that was not statistically significant but still bears watching. The overall rate of complications (6.6 percent for SCD patients and 6.0 percent for non-SCD patients), in-hospital mortality (odds ratio of 1.21 for SCD patients 1.21) and length of stay above four days (odds ratio of 1.15 for SCD patients) also did not differ significantly between the two cohorts.

“Having sickle cell disease did not adversely affect any of the indicators we measured,” says Adams. “People with sickle cell disease and an acute stroke who would otherwise qualify for tPA did not have worse outcomes than stroke patients who did not have sickle cell disease.”

Although additional studies are needed to track the intracranial hemorrhage rate, these findings suggest that tPA is safe in patients with SCD and could potentially be used as a complementary therapy to rapid and complete red blood cell exchange, the current guideline-recommended frontline therapy for IS in patients with SCD. These patients would be best served by a care team including both a hematologist and a neurologist.

“These findings suggest that a future randomized trial that compares using red-blood cell exchange alone versus combination therapy with tPA and red-blood cell exchange should be undertaken to evaluate the outcomes of IS in patients with sickle cell disease,” says Kanter.

“This is a great example of the power of the large Get With The Guidelines — Stroke database, which allows us to better understand the best care for relatively small, unique populations that are difficult to study individually,” says Edward C. Jauch, M.D., Director of the Division of Emergency Medicine at MUSC and lead author on the 2013 AHA/ASA Acute Ischemic Stroke Guidelines.

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Materials provided by Medical University of South Carolina. Note: Content may be edited for style and length.