Posted on Insomnia

Insomnia tied to a greater risk of heart attack, especially in women

People who suffer from insomnia were 69% more likely to have a heart attack compared to those who didn’t have the sleep disorder during an average nine years of follow-up, according to new research being presented at the American College of Cardiology’s Annual Scientific Session Together With the World Congress of Cardiology. In addition, when looking at sleep duration as an objective measure of insomnia, researchers found that people who clocked five or fewer hours of sleep a night had the greatest risk of experiencing a heart attack. People with both diabetes and insomnia had a twofold likelihood of having a heart attack.

“Insomnia is the most common sleep disorder, but in many ways it’s no longer just an illness, it’s more of a life choice. We just don’t prioritize sleep as much as we should,” said Yomna E. Dean, a medical student at Alexandria University in Alexandria, Egypt, and author of the study. “Our study showed that people with insomnia are more likely to have a heart attack regardless of age, and heart attacks occurred more often in women with insomnia.”

Dean and her research team are hopeful that the current study will help draw attention to the role that sleep disorders may play in heart health. Insomnia may include trouble falling asleep, staying asleep or getting good quality sleep. Growing in prevalence, insomnia is estimated to affect 10% to 30% of American adults, affecting women more than men. While studies have linked insomnia to cardiovascular and metabolic diseases, this analysis is the largest to date.

“Based on our pooled data, insomnia should be considered a risk factor for developing a heart attack, and we need to do a better job of educating people about how dangerous [lack of good sleep] can be,” Dean said.

For their analysis, the researchers conducted a systematic review of the literature that yielded 1,226 studies—of these, nine studies originating from the U.S., United Kingdom, Norway, Germany, Taiwan and China were selected for inclusion. All told, data for 1,184,256 adults (43% of whom were women) were assessed. The average age was 52 years and 13% (153,881) had insomnia, which was defined based on ICD diagnostic codes or by the presence of any of these three symptoms: difficulty falling asleep, difficulty staying asleep or waking early and not being able to get back to sleep. People with obstructive sleep apnea were not included. Most patients (96%) did not have a prior history of heart attack. Heart attacks occurred in 2,406 of those who had insomnia and 12,398 of those in the non-insomnia group.

Based on the pooled data, there was a statistically significant association between insomnia and having a heart attack after controlling for other factors that could make a heart attack more likely such as age, gender, comorbidities and smoking. This association between insomnia and heart attack remained significant across all subgroups of patients, including younger and older age (<65 and >65), follow-up duration (more or less than five years), male and female sex, and common comorbidities (diabetes, high blood pressure or cholesterol).

“Not surprisingly, people with insomnia who also had high blood pressure, cholesterol or diabetes had an even higher risk of having a heart attack than those who didn’t,” Dean said. “People with diabetes who also have insomnia had a twofold likelihood of having a heart attack.”

Moreover, people who reported five or less hours of sleep a night were 1.38 and 1.56 times more likely to experience a heart attack compared with those who slept six and seven to eight hours a night, respectively. Dean said there was no difference in the risk of heart attack between those getting five or less or nine or more hours of sleep a night, which supports findings from previous studies that have shown that getting too little or too much sleep can be harmful to heart health. Dean and her team found that patients who slept six hours had a lower risk of heart attack compared with those who slept nine hours.

In a separate analysis, the researchers sought to determine whether individual insomnia symptoms are associated with a higher risk of heart attack. Disorders of initiating and maintaining sleep—that is, trouble falling or staying asleep—were also tied to a 13% increased likelihood of heart attack compared with people without these symptoms.

Non-restorative sleep and daytime dysfunction, however, were not associated with heart attack, suggesting that those who only complain of feeling unrefreshed upon waking up without any lack of sleep aren’t at an increased risk of heart attacks, Dean said.

Based on the findings, Dean said it is important that people prioritize sleep so they get seven to eight hours of quality sleep a night.

“Practice good sleep hygiene; the room should be dark, quiet and on the cooler side, and put away devices. Do something that is calming to wind down, and if you have tried all these things and still can’t sleep or are sleeping less than five hours, talk with your doctor.”

The study had some limitations, including that most of the studies assessed relied on participants self-reporting on sleep behaviors using questionnaires, although heart attacks were validated by medical reports.

Posted on Lupus

Pathway uncovered for greatest lupus genetic risk factor, study shows

Study identifies human microRNAs linked to type 2 diabetes

Researchers at Michigan Medicine have uncovered the molecular mechanism that drives the disease-causing effects of the most common genetic risk factor for lupus, a study suggests.

Systemic lupus erythematosus is a common, incurable autoimmune disease that affects millions of individuals worldwide, with a particularly high prevalence among women. A genetic variant, called HLA-DRB1*03:01, is the greatest risk factor for the condition, which involves inflammation in many vital organs, and can lead to severe disability and death.

In a study recently published in Communications biology (a Nature Portfolio journal), investigators found that a protein coded by that HLA variant triggers a cascade of molecular and cellular effects that can cause the inflammatory symptoms seen in lupus patients.

“For the first time, we have found the enigmatic mechanism that genetically predisposes people to the worst effects of the most typical form of lupus,” said Joseph Holoshitz, M.D., senior author of the paper and professor of internal medicine and rheumatology at University of Michigan Medical School. “The findings could potentially facilitate the discovery of safe, simple and effective treatments for SLE by targeting this new pathway.”

The results support a novel theory how genetic variants of the kind of HLA-DRB1*03:01 can lead to autoimmune diseases independent of antigen presentation, the traditionally studied mechanism, which has been long proposed but, so far, not directly proven.

“We have identified a chain of events in cell culture, as well as a mouse model of the disease, that demonstrate how the abnormalities that can cause lupus develop from the first effect of the risk gene, to signaling, all the way to immune abnormalities and clinical manifestations of lupus,” said Bruna Miglioranza Scavuzzi, Ph.D., first author of the paper and a postdoctoral research fellow in the Division of Rheumatology at the University of Michigan Medical School.

The findings of this study are reminiscent of previous findings in rheumatoid arthritis, another HLA-associated disease, that have paved the way for the development of small molecules to effectively treat arthritis in mice, Holoshitz says.

“Human trials in RA with those compounds are being carried out, and I hope that our novel findings will lead to similar efforts to ease the burden of millions of lupus patients as well.” he said.

Posted on Pain Management

Hypnosis, meditation, and prayer: which is most helpful for pain management?

The research study involved the participation of 232 healthy adults
The research study involved the participation of 232 healthy adults


Researchers compared the immediate effects of hypnosis, mindfulness meditation, and Christian prayer on pain intensity and tolerance. The results suggested that a single session of hypnosis and mindfulness meditation, but not prayer, may be useful for managing acute pain, with hypnosis being slightly more useful.

Who never felt pain? Probably a tiny number of people. Pain is a common human experience, and its acute state can have negative impacts on several health domains, including sleep quality, cardiovascular and immune function, and psychological well-being.

In addition to being almost universal, pain is also a complex experience influenced by biological, psychological, and social factors. So adequate pain management requires more than biological treatments alone, such as analgesic medications.

There are then several approaches that focus on the biopsychosocial factors that influence pain, including psychosocial, complementary, and integrative approaches. Previous studies confirm the usefulness of hypnosis, mindfulness meditation, and prayer as useful practices in the self-management of chronic pain in adults. However, their effects on acute pain have been less investigated and there has not yet been any study that has compared the immediate effects of these three approaches on the experience of acute pain.

It was in this context that, with the support of the BIAL Foundation, the research team led by Alexandra Ferreira-Valente resorted to the heart rate variability and other measures to compare the immediate effects of hypnosis, mindfulness meditation, and Christian prayer on pain intensity, pain tolerance, and stress. The results of the study are described in the article “Immediate Effects of Hypnosis, Mindfulness Meditation, and Prayer on Cold Pressor Outcomes: A Four-Arm Parallel Experimental Study”, published in the Journal of Pain Research in December 2022.

The study took place at the facilities of the Psychology Laboratory of the William James Center for Research at Ispa – Instituto Universitário in Lisbon, involving the participation of 232 healthy adults. Pain was induced in the participants by wrapping the forearm and hand in a cold compress (Cold Pressor Arm Wrap – CPAW) for up to 5 minutes at the most and assessing their pain tolerance, the intensity of pain, as well as heart rate variability, as a physiological marker of stress. After a rest period, participants listened to a 20-minute recording of guided hypnosis, or mindfulness meditation, or suggesting a Christian prayer, or reading a natural history book (control condition) depending on the group they were randomly assigned to. After this session, the participants underwent a second session of CPAW, during which they listened to up to 5 minutes of the recording and their cardiac function was monitored.

The results obtained by researchers from the William James Center for Research – Ispa (Portugal), Universidade Católica Portuguesa (Portugal), University of Washington (USA), Young Harris College (USA), and University of Queensland (Australia) suggest that single brief session of hypnosis and mindfulness meditation, but not Ignatian Christian prayer based on biblical meditation, may be useful for acute pain self-management, with hypnosis being the slightly superior option.

According to Alexandra Ferreira-Valente, team coordinator, “in the future, researchers should compare the effects of different types of prayer and examine the predictors and moderators of the effects of hypnosis and mindfulness on the experience of acute pain”.

Posted on Multiple Sclerosis

‘Usual suspect’ lesions appear not to cause most severe disability in Multiple Sclerosis patients

‘Usual suspect’ lesions appear not to cause most severe disability in Multiple Sclerosis patients
‘Usual suspect’ lesions appear not to cause most severe disability in Multiple Sclerosis patients


Brain lesions — areas of brain tissue that show damage from injury or disease — are the biomarker most widely used to determine multiple sclerosis disease progression. But an innovative new study led by the University at Buffalo strongly suggests that the volume of white matter lesions is neither proportional to nor indicative of the degree of severe disability in patients.

The results were reported in a poster session on Feb. 23 at the Americas Committee for Treatment and Research of Multiple Sclerosis (ACTRIMS) annual meeting in San Diego.

The study compared two sets of 53 MS patients, ages 30-80, who had the same gender and disease duration but vast and measurable differences in the extent of their physical and cognitive disabilities.

Lesions are not a major driver of disability progression

“The absence of material differences in white matter brain lesion burden means this is not a significant driver of severe disability progression, even though many MS disease-modifying treatments are focused on slowing accumulation of white matter lesions,” said Robert Zivadinov, MD, PhD, principal investigator, professor in the Department of Neurology and director of UB’s Buffalo Neuroimaging Analysis Center and the Center for Biomedical Imaging in UB’s Clinical and Translational Science Institute.

The results are from a first-of-its-kind study led by UB that has begun to investigate why a small percentage of people with MS quickly become severely disabled while the disease progresses much more slowly in others.

The individuals in the severely disabled cohort are residents of The Boston Home in Dorchester, Massachusetts, a specialized residential facility for individuals with advanced progressive neurological disorders, including MS.

Each of them was then matched with a Buffalo-based “twin” of the same age, sex and disease duration but who experienced far less cognitive and physical disability.

Called Comprehensive Assessment of Severely Affected – Multiple Sclerosis, or CASA-MS, the investigator-initiated, privately funded UB study is focused on identifying biomarkers and cognitive differences among people whose MS disability has become severe compared to others whose disease progresses slowly. More information about how the UB team decided to compare these two populations is available in this news release.

The question of what distinguishes people with severe MS from those who respond well to therapies and continue to live nearly normal lives for decades after diagnosis has confounded patients, caregivers and clinicians for too long, said Zivadinov.

“We couldn’t know what the CASA-MS study would show, because no one has done this research previously,” he said. “What we know now is that the differences between the two groups we studied are striking, and striking in ways that may surprise many of us in this field. I am confident these findings open new doors for both people with severe disabilities, as well as the promise of new insights for the millions more who worry where their disease may take them.”

Despite many available treatments for MS, a subgroup of patients, about 5-10% of the 2.8 million people with MS worldwide, will develop rapid and progressive, and ultimately severe disability at a relatively young age.

More gray matter loss

It is widely accepted that MS is characterized by the formation of brain white matter lesions. Yet in this study participants with severe MS disability showed significantly more gray matter loss in the cortex and thalamus compared to their less-disabled “twin.” Surprisingly, the loss of whole brain volume was comparable among both groups.

While lesion load in both groups was not materially different, the study revealed other important distinctions between the groups in brain scans and cognitive tests. Severely affected people exhibited lower efficiency in thalamic structural connectivity, meaning they demonstrated lower structural connectivity of the associated brain networks than their less-disabled counterparts.

The study also concluded that members of the severely affected cohort showed more pronounced atrophy of the medulla oblongata — the connection between the brainstem and the spinal cord — which Zivadinov said serves, in this study, as a proxy for spinal cord atrophy.

“These findings suggest that severely disabled MS patients suffer from spinal cord atrophy, an irreversible state of degeneration or loss of spinal cord substance,” he said.

The severely disabled group also showed more advanced loss of neurons. This was revealed by collaborating scientists at the University of Basel, Switzerland led by Jens Kuhle, MD, PhD, professor of neurology, who used special blood-based techniques to study the extent of axonal damage.

Patient-centered approach

The idea to compare two groups of MS patients differentiated by the severity of their disability started with Larry Montani, chair of the BNAC Advisory Council, whose sister, Mary Jo, was a resident at The Boston Home. He urged Zivadinov and members of his research team to travel to Boston and meet the residents.

“You could see the wheels turning as soon as Dr. Zivadinov and his team met the residents of The Boston Home,” recalled Montani. “Dr. Zivadinov’s focus on the patient is what made this possible. His patient-centered approach leads to research that is highly relevant, validated and pursued with an urgency to find answers that offer hope. The CASA-MS study breaks new ground in all these ways for people like my sister, whose vibrant minds and gracious hearts are trapped in a severely disabled body.”

According to co-principal investigator Ralph H. Benedict, PhD, professor of neurology in the Jacobs School and a collaborator on the study, CASA-MS points to the value of new hypotheses and research focused on a better understanding of people with severe MS disability.  

“Clinical trials exploring disease progression are likely to emerge from this unusual examination of this rarely studied population,” said Benedict. “There is so much more to learn, and I can’t imagine a more deserving community of ready and willing study participants.”

Bianca Weinstock-Guttman, MD, SUNY Distinguished Professor in the Department of Neurology in the Jacobs School and co-principal investigator, noted that the study strongly suggests significant opportunities for more sophisticated MRI scanning.

“This study showed that novel 7T and PET scanning — techniques deployed specifically for this severely disabled patient population — may provide a better understanding of the pathophysiology of severe MS,” she said.

Boston Home chief executive officer Christine Reilly said: “For most of these incredible volunteers, participation in this study took extraordinary effort and patience, but they never hesitated. What we found so touching and revealing was that so many of the participants from each cohort wanted very much to meet their ‘twin’ — the person from the other cohort of the same age, sex and disease duration — whose MS experience is so dramatically different. The sheer humanity of that desire to connect is truly amazing.”

Posted on Patient Talk

Clinical trials often overlook people with disabilities.

Sample of recent cardiovascular trials shows sparse reporting and frequent exclusion
Sample of recent cardiovascular trials shows sparse reporting and frequent exclusion

Disabilities were underreported in clinical trial data and commonly used as a basis for exclusion from trial participation in an analysis of 80 recent trials involving cardiovascular outcomes, according to a study being presented at the American College of Cardiology’s Annual Scientific Session Together With the World Congress of Cardiology.

Reports estimate that over half of people with heart disease have one or more disabilities related to cognition, mobility, vision, independent living, self-care or hearing as defined by the Centers for Disease Control and Prevention (CDC). However, the new study found that 38% of clinical trials listed a disability among their exclusion criteria and only 8% of trials reported disability status as part of their baseline data. Researchers said these gaps in both inclusion and reporting suggest clinical trial designers are missing an opportunity to ensure studies adequately represent the patient populations they intend to benefit.

“We were surprised that there was this lack of reporting for disabilities, simply because doing so is CDC guideline recommended, and it would be a valuable data point for clinicians,” said Roy Lan, MD, an internal medicine resident at Stanford University and the study’s lead author. “I hope our study can jump-start an effort to increase reporting of disabilities, both in baseline patient demographics and also outcomes.”

The study is the first to specifically examine reporting and inclusion of people with disabilities within cardiovascular clinical trials. Across all 80 trials, only six included data on disabilities in published baseline participant characteristics, an omission that may be due to a lack of data collection, a lack of data reporting or both.

“There is an abundance of literature within cardiovascular trials on race, ethnicity and gender, but people with disabilities are another population that can be vulnerable,” Lan said. “As we become more advanced in targeting therapies to different population groups, this is one that we really can’t forget and need to serve well. If we aren’t even reporting disabilities in clinical trials, how can we best serve and take care of these patients?”

Researchers analyzed the 20 most recently published clinical trials in each of four major areas: atrial fibrillation, coronary artery disease, hypertension and diabetes. Only trials for which full published data were available were included in the sample, and all studies were published between 2014 and 2022. The researchers assessed disabilities reporting and exclusion criteria based on each trial’s published data as well as records from the clinical trials database (ClinicalTrials.gov).

Overall, 38% of the trials listed at least one type of disability among their exclusion criteria. Of the different types of trials, disabilities were cited in exclusion criteria most often in hypertension trials (55%) and least often in diabetes trials (15%).

Disabilities related to cognition or psychiatric issues (such as Alzheimer’s disease or other forms of dementia) were the most common type of excluded disability with one-third of trials citing this in the exclusion criteria. Between 3%-8% of trials excluded disabilities related to mobility, vision, independent living, self-care or hearing. Although the CDC provides specific criteria for defining six categories of disability, researchers noted that many clinical trials established their own definitions of disability, potentially leading to greater exclusion and making it difficult to compare results across studies.

Future studies could help to elucidate why people with certain types of disabilities are often excluded from clinical trial participation and guide efforts to design trials that are more inclusive, researchers said. They suggest it would also be useful to more routinely include information about disability status in clinical trial data, as well as capture the degree of disability at baseline to allow researchers to track any changes over the course of the trial.

In a separate study being presented at the meeting, researchers found that people with intellectual disabilities (limitations in the ability to learn at an expected level and function in daily life) who were hospitalized for acute coronary syndrome were significantly less likely to receive coronary angiography or revascularization and more likely to die in the hospital than people without intellectual disabilities. The findings point to a need to address disability-related disparities in patient care in addition to clinical trial design and practice. The trial, “Outcomes of Acute Coronary Syndrome in Patients with Intellectual Disabilities: Insights from the National Inpatient Sample,” will be simultaneously published in Cardiovascular Revascularization Medicine.