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Tag: Heart

  • Combining clot busters and blood thinners shows no advantage for people with ischemic strokes

    Combining clot busters and blood thinners shows no advantage for people with ischemic strokes

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    Giving blood thinners in addition to clot-busting medications to people with ischemic strokes (clot-caused strokes) did not improve their outcomes 90 days later, according to preliminary late-breaking science presented today at the American Stroke Association’s International Stroke Conference 2024. The meeting, held in person in Phoenix, Feb. 7 – 9, 2024, is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

    These results are from the MOST (Multi-Arm Optimization of Stroke Thrombolysis) trial. MOST is a 57-center U.S. trial that was halted after an independent data and safety board analyzed results on the first 500 patients out of a planned 1,200 participants and determined it highly unlikely that a benefit would be found if the research was completed. The study was looking for improvement in functional outcomes at 90 days.

    When we began the trial, we believed the medications would improve outcomes, so we were surprised with the negative results. However, we designed the trial to allow us to efficiently answer the question for two blood-thinning medications in one trial. We have definitely done that and are pleased with the ability to answer this question.”

    Opeolu M. Adeoye, M.D., M.S., lead author of the study and BJC HealthCare Distinguished Professor of Emergency Medicine and chair of the department of emergency medicine at Washington University School of Medicine in St. Louis, Missouri

    “A lot of our approaches in stroke treatment were learned from how we treat heart attacks. In previous trials, we first tested to make sure these medications were safe for use in stroke and then launched MOST to confirm their safety and test whether they would work to improve functional outcomes and reduce disability after stroke,” Adeoye said.

    The MOST trial enrolled adults with ischemic stroke severe enough that rehabilitation would likely be needed. All participants received a standard clot-busting medication to dissolve the clot (thrombolysis) within three hours of stroke onset. Participants were then randomized to one of three groups for additional treatment: one group received the blood thinner argatroban within 75 minutes of the clot-busting medication, followed by a 12-hour infusion of argatroban. A second group received an initial dose of the blood thinner eptifibatide within 75 minutes of the clot-busting medication, followed by a 2-hour infusion of eptifibatide and a 10-hour infusion of saline placebo. The control group received a clot buster and a placebo treatment (a 12-hour infusion of intravenous saline solution containing neither of the blood-thinning medications).

    The primary outcome was the study participant’s level of physical function at 90 days after ischemic stroke. Physical function levels were assessed using the modified Rankin score, or mRS, a 6-point disability scale. The videotaped assessment was judged by an independent neurologist reviewer who was not aware of which treatment patients had received. The mRS score was translated into a utility-weighted mRS, using validated ratings of functional outcomes by patients and physicians, resulting in a 0 to 10-point scale in which a higher score means a greater benefit from the treatment. The interim analysis was planned at the start of the study and scheduled to take place after 500 patients were enrolled. In addition, a data safety and monitoring board (DSMB) reviewed safety data after every 30 patients enrolled, looking particularly for occurrences of bleeding in the brain.

    In the 514 patients enrolled prior to the trial being halted by the DSMB in July 2023, the analysis found:

    • The two blood thinners used did not significantly increase the risk of bleeding into the brain.
    • However, neither of the two blood thinners improved outcomes in the stroke survivors. On the 0 to 10 utility-weighted mRS scale, patients receiving placebo averaged 6.8, those receiving argatroban averaged 5.2, and those receiving eptifibatide averaged 6.3. (Types of disability will vary, however, people with a utility-weighted mRS scale of 6 are expected to have difficulty performing activities of daily living without assistance or support.)

    Study details and background:

    • The three-arm study was conducted at 57 hospitals in the United States between October 2019 and July 2023.
    • Participants all had ischemic (clot-caused) stroke that rated a 6 or higher on the National Institutes of Health Stroke Severity Scale and considered a moderately severe stroke.
    • 514 adults were enrolled in the trial before it was halted; participants were an average age of 68; about 50% were women; and about 25% identified as Black adults.
    • Participants were treated within three hours after the onset of stroke symptoms (or the last time seen well) using the standard-of-care approach of thrombolysis (delivering clot-busting medications to dissolve the clot).
    • In addition, 44% of the patients across all three groups were treated with interventional removal of their clots called thrombectomy.
    • At the time of enrollment, participants were randomized to receive a blood thinner or placebo within 75 minutes of thrombolysis: 59 received argatroban; 228 received eptifibatide; and 227 received placebo.
    • The primary safety measure was the occurrence of bleeding in the brain (symptomatic intracranial hemorrhage) within 36 hours of receiving one of the two blood thinners. Safety measures were analyzed by the study’s DSMB after every 30 patients were enrolled.

    Medical professionals providing care were aware of whether a blood thinner or placebo were given to each patient. However, neither the patients nor the professionals rating patient outcomes were aware of which patients in any group had received a blood thinner or placebo.

    “In addition, we were not able to address the possible benefit of giving these or similar blood thinners directly into an artery in the area of the stroke, rather than giving the medications systemically through a vein, as done in this trial,” Adeoye said.

    For patients undergoing thrombectomy (mechanical removal of a stroke-causing clot), studies are underway to determine whether delivering blood thinners into the affected artery may improve outcomes.

    The study was conducted at National Institutes of Health StrokeNet sites. StrokeNet was created to conduct small and large clinical trials and research studies to advance acute stroke treatment, stroke prevention and recovery and rehabilitation after a stroke across the lifespan. Other principal investigators were Andrew D. Barreto, M.D., M.S.; Joseph P. Broderick, M.D.; Colin P. Derdeyn, M.D.; Jordan Elm, Ph.D.; and James C. Grotta, M.D. The full list of authors and their disclosures are listed in the abstract.

    All study authors reported funding from the National Institute of Neurological Disorders and Stroke, a division of the National Institutes of Health.

    Source:

    American Heart Association

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  • Chewing tobacco linked to higher stroke and cancer risk, study finds

    Chewing tobacco linked to higher stroke and cancer risk, study finds

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    In a recent study in the journal Nature Communications, researchers systematically reviewed and synthesized the literature on the health risks associated with chewing tobacco. Their results indicate that people who chew tobacco are significantly more likely to suffer from strokes and several cancers.

    While chewing tobacco is not as prevalent as smoking cigarettes, estimates suggest that more than 270 million people use smokeless tobacco products, of whom the majority live in India and Bangladesh. Smoking has declined since the 1990s, while the popularity of chewing tobacco appears to have increased, including among women.

    The health risks of chewing tobacco are less understood compared to the almost universal consensus on the harms caused by cigarettes and other forms of smoking. However, smokeless tobacco is thought to be a carcinogen.

    Study: Health effects associated with chewing tobacco: a Burden of Proof study. Image Credit: bildfokus.se / ShutterstockStudy: Health effects associated with chewing tobacco: a Burden of Proof study. Image Credit: bildfokus.se / Shutterstock

    About the study

    In this study, researchers conducted a systematic review and meta-analysis across three scientific databases (Global Index Medicus, Web of Science, and PubMed) to analyze relationships between chewing tobacco and stroke, ischemic heart disease, and five types of cancer of the neck and head.

    The search included publications regardless of their language and papers published from 1970 onwards. They used meta-regressions and Bayesian methods to estimate a measure of pooled relative risk and then obtained an effect size for each health outcome. Of the literature obtained from the search, 4,480 were excluded, and 111 were included in the analysis.

    Findings

    Three studies conducted in Bangladesh and India included data on chewing tobacco and stroke; the meta-analysis suggested that conservatively, using smoking tobacco products increased the risk of stroke by 16%. This association is classified as a ‘weak’ relationship. However, these findings were robust to various validations; no publication or covariate bias was detected.

    Eight studies examined associations between smokeless tobacco and ischemic heart disease, most of which were conducted in Bangladesh, India, and the United States. The meta-analysis found no evidence that chewing tobacco significantly changed ischemic heart disease risk; again, researchers found no evidence of publication bias or covariate bias.

    For esophageal cancer, 22 studies were identified; analysis suggested that using chewing tobacco significantly increased the risk of cancer by 2% conservatively. However, a meta-analytic approach yielded a higher estimate of a 2.14-fold increase in esophageal cancer risk. Smoking status, sex, and age were adjusted for in the final analysis, and no publication bias was detected.

    A total of 70 studies examined associations between smokeless tobacco products and cancers of the lip and oral cavity. The analysis incorporated numerous sources of uncertainty and found a relative risk factor of 3.64, and the association was characterized as weak; the risk of developing these forms of cancer increased when the sample was restricted to studies conducted in Asian countries.

    The effect size for laryngeal cancer was estimated from 24 studies. Researchers found that evidence regarding this outcome was weak after accounting for sources of uncertainty, while the relative risk factor was 2.66. However, for a single study, the relationship between smokeless tobacco and laryngeal cancer was significantly higher.

    17 studies were included for nasopharyngeal cancer, and weak evidence of a relationship with a relative risk measure of 2.50 was seen. Age and sex were included in the model after covariate selection, and no evidence of publication bias was found.

    The outcome included in the meta-analysis was other cancers of the pharynx; data for this model was obtained from 31 studies. The relative risk factor was 2.33, and the association was characterized as weak. However, using a subset of the data, a higher risk measure of 4.38 was found, showing a stronger association.

    Conclusions

    The study had various strengths, including reducing the impact of geographical variation. Of the seven health outcomes included, six showed at least weak evidence of increased risk faced by smokeless tobacco users; the only outcome for which no evidence was found was ischemic heart disease. The highest risks were of stroke and esophageal cancer, with a conservative estimate suggesting an increase in incidence of 2-16%.

    An important conclusion was that while chewing tobacco is considered a carcinogen, the literature predominantly examined its relationship with lip, oral cavity, and esophageal cancer, highlighting the need for more high-quality studies on associations with other cancers of the head and neck. Specifically, nasopharyngeal and laryngeal cancer should also merit careful observation in the future, as should stroke.

    Limitations of the study included the variety of smokeless tobacco products, exposure definitions, and geographical settings. The approach followed in this study was also not able to estimate dose-response relationships. However, these findings can be used by public health workers to better counsel clients on harms associated with smoking tobacco products and advocate for more effective public health policies, while they may also be of interest to community awareness campaigns.

    Journal reference:

    • Health effects associated with chewing tobacco: A Burden of Proof study. Gil, G.F., Anderson, J.A., Aravkin, A., Bhangdia, K., Carr, S., Dai, X., Flor, L.S., Hay, S.I., Matthew, M.J., McLaughlin, S.A., Mullany, E.C., Murray, C.J.L., O’Connell, E.M., Okereke, C., Sorensen, R.J.D., Whisnant, J., Zheng, P., Gakidou, E. Nature Communications (2024). 10.1038/s41467-024-45074-9, https://www.nature.com/articles/s41467-024-45074-9

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  • Eleven stroke researchers to be recognized during the 2024 International Stroke Conference

    Eleven stroke researchers to be recognized during the 2024 International Stroke Conference

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    Eleven scientists leading the way in stroke research will be recognized during the American Stroke Association’s International Stroke Conference 2024 for their exceptional professional achievements. The meeting will be held in Phoenix, Feb. 7-9, and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

    The illustrious group of awardees includes four groundbreaking scientists who have devoted their careers to stroke research and six scientists will be recognized for their notable new research. The awards include the Ralph L. Sacco Outstanding Stroke Research Mentor Award, which honors Ralph L. Sacco, M.D., M.S., FAHA, a past president of the American Heart Association and American Stroke Association, who passed away in January 2023.

    The 2024 honorees are:

    • Bernadette Boden-Albala, M.P.H., Dr.P.H., University of California, Irvine, who will receive the Edgar J. Kenton III Lecture Award.

    • Steven Warach, M.D., Ph.D., Dell Medical School at The University of Texas at Austin, who will receive the David G. Sherman Lecture Award.

    • James F. Meschia, M.D., FAHA, Mayo Clinic in Jacksonville, Florida, who will be honored with the William M. Feinberg Award for Excellence in Clinical Stroke.

    • Marc I. Chimowitz, M.B., Ch.B., Medical University of South Carolina, who will receive the Ralph L. Sacco Outstanding Stroke Research Mentor Award.

    • Louise D. McCullough, M.D., P.H.D., McGovern Medical School at UTHealth Houston, who will be awarded the Thomas Willis Lecture Award.

    • ·Takuma Maeda, M.D., Ph.D., Barrow Neurological Institute in Phoenix, who will receive the Mordecai Y.T. Globus New Investigator Award, for a research abstract.

    • Raed Joundi, M.D., D.Phil., McMaster University in Hamilton, Ontario, Canada, who will receive the Vascular Cognitive Impairment Award for research being presented at the meeting.

    • Oriana Sanchez, M.D., University of Texas, Houston, who will receive this year’s Robert G. Siekert New Investigator Award in Stroke for a research abstract.

    • ·Mohammed Abdelsaid, R.P.H., Ph.D., Mercer University School of Medicine, Savannah, Georgia, who will receive the Stroke Basic Science Award for a research abstract.

    • Shumei Man, M.D., Ph.D., FAHA, Cleveland Clinic in Ohio, who will receive the Stroke Care in Emergency Medicine Award for research being presented at the meeting.

    • Susan Linder, P.T., D.P.T., Ph.D., Cleveland Clinic in Ohio, who will be awarded the Stroke Rehabilitation Award for a research abstract.

    Bernadette Boden-Albala, M.P.H., Dr.P.H., the winner of the Edgar J. Kenton III Lecture Award, is the director and founding dean of the University of California, Irvine’s Program in Public Health and future School of Population and Public Health. With more than two decades of research experience, Boden-Albala is an internationally recognized expert in the social epidemiology of chronic disease whose research has focused on eliminating health disparities through defining and intervening on social support, structural and institutional barriers to optimal health. Her areas of expertise include community-based participatory research, health equity, stroke and cardiometabolic health disparities. She has led numerous large, multi-site studies utilizing community-based participatory research methods in urban and rural communities across the United States and globally, as well as large community health assessment, evaluation, capacity building and workforce training projects. The Edgar J. Kenton III Lecture Award recognizes lifetime contributions to the investigation, management, mentorship and community service in the field of racial and ethnic stroke disparities or related disciplines. Boden-Abala will present her Edgar J. Kenton III lecture, “A Roadmap for Health Equity: Understanding the Importance of Community-Engaged Research,” at 10:18 a.m. MT, Tuesday, Feb. 6.

    Steven Warach, M.D., Ph.D., the recipient of the David G. Sherman Lecture Award, is a professor of neurology at Dell Medical School at The University of Texas at Austin, where he is executive director of the Seton Dell Medical School Stroke Institute and also serves as the regional stroke director for Ascension Texas. Warach is known for his seminal contributions in magnetic resonance imaging of stroke. He earned his Ph.D. in psychology-neuroscience from Michigan State University and M.D. from Harvard Medical School, where he completed his neurology residency. The Sherman Award honors David G. Sherman, M.D., a prominent stroke physician and an internationally recognized leader and researcher in stroke prevention and treatment. The award recognizes lifetime contributions to the investigation, management, mentorship and community service in the stroke field. Warach will present his lecture, “Improving Stroke Diagnosis and Treatment: A Journey Toward the End of Time,“ at 11:32 a.m. MT, Wednesday, Feb. 7.

    James F. Meschia, M.D., FAHA, the awardee of the William M. Feinberg Award for Excellence in Clinical Stroke, is professor of neurology and chair emeritus of the department of neurology at Mayo Clinic in Jacksonville, Florida. Meschia is certified by the American Board of Psychiatry and Neurology (ABPN) in neurology and vascular neurology. Meschia is a pioneer in the study of inherited risk factors for ischemic stroke and has had a longstanding commitment to providing the latest evidence for carotid revascularization as a means for stroke prevention. He was the inaugural medical director of the first Joint Commission-certified stroke center within the Mayo Clinic Foundation, and he has authored or co-authored over four hundred peer-reviewed publications. The William M. Feinberg Award for Excellence in Clinical Stroke is named for the prominent stroke clinician-researcher and American Heart Association volunteer who contributed to a more comprehensive understanding of the causes of stroke. The award recognizes significant contributions to the investigation and management of clinical research in stroke. Meschia’s lecture, “Asymptomatic Carotid Stenosis: Current and Future Considerations,” will be presented at 11:03 a.m. MT, Thursday, Feb. 8.

    Marc I. Chimowitz, M.B., Ch.B., the recipient of the Ralph L. Sacco Outstanding Stroke Research Mentor Award is professor emeritus of neurology at the Medical University of South Carolina in Charleston, South Carolina. His main career interests are in improving treatments for patients with intracranial arterial atherosclerosis and helping to mentor the next generation of clinical and translational scientists.The Ralph L. Sacco Outstanding Stroke Research Mentor Award recognizes outstanding achievements in mentoring future generations of stroke researchers in the field of cerebrovascular disease. Chimowitz will present his lecture, “Mentoring Clinical Stroke Researchers in Challenging Times,” at 11:34 a.m. MT, Thursday, Feb. 8.

    Louise D. McCullough, M.D., P.H.D., FAHA, the winner of the Thomas Willis Lecture Award, is the Roy M. and Phyllis Gough Huffington Distinguished Chair of Neurology at McGovern Medical School; chief of neurology at Memorial Hermann Hospital-Texas Medical Center and co-director of UTHealth Neurosciences, all in Houston. McCullough is a physician-scientist and a practicing vascular neurologist with clinical expertise in sex/gender disparities, the microbiome, stroke and aging, and acute stroke treatments. A renowned investigator, she is well recognized for her work in cerebral vascular disease and is known for her research identifying sex differences in cell death pathways during stroke, which have now been shown to be a major factor in the response to ischemic insult. The Thomas Willis Award recognizes contributions to the investigation and management of stroke basic science. McCullough’s lecture, “Aging, Sex, and Stroke: The Three Amigos of Brain Misadventures,” will be presented at 11:03 a.m. MT, Friday, Feb. 9.

    Takuma Maeda, M.D., Ph.D., the Mordecai Y.T. Globus New Investigator Award in Stroke awardee, is a postdoctoral fellow at Barrow Aneurysm & AVM Research Center (BARRC) at the Barrow Neurological Institute in Phoenix. This award recognizes Globus’ major contributions to research in cerebrovascular disease and his outstanding contributions to the elucidation of the role of neurotransmitters in ischemia and trauma; the interactions among multiple neurotransmitters; mechanisms of hypothermic neuroprotection; and the role of oxygen radical mechanisms and nitric oxide in brain injury. Maeda’s award-winning presentation, Abstract 15, “Pharmacological Activation of Efferocytosis Prevents Intracranial Aneurysm Rupture,” will be presented at 7:30 a.m. MT, Wednesday, Feb. 7.

    Raed Joundi, M.D., D.Phil., is the Vascular Cognitive Impairment Award recipient. He is an assistant professor at McMaster University, an adjunct scientist at the Institute for Clinical Evaluative Sciences (ICES) and an investigator at the Population Health Research Institute, a joint institute of McMaster University and Hamilton Health Sciences, all in Hamilton, Ontario, Canada. The Vascular Cognitive Impairment Award encourages investigators to undertake or continue research or clinical work in the field of vascular cognitive impairment and submit an abstract to the International Stroke Conference. Joundi’ s award-winning presentation, Abstract 67, “Risk and Time-Course of Post-Stroke Dementia: A Population-Wide Cohort Study, 2002-2022,” will be presented at 7:30 a.m. MT, Thursday, Feb. 8.

    Oriana Sanchez, M.D, the winner of the Robert G. Siekert New Investigator Award in Stroke, is currently completing a vascular neurology fellowship in the department of neurology at the University of Texas in Houston. The Siekert New Investigator Award in Stroke recognizes Robert G. Siekert, M.D., who was the founding chairman of the American Heart Association’s International Conference on Stroke and Cerebral Circulation, now known as the International Stroke Conference. The award encourages new investigators to undertake or continue stroke-related research. Sanchez’s award-winning presentation, Abstract 1, “Overcoming Clinical Trial Enrollment Challenges by Monitoring EMS Radio Transmissions: Pre-Hospital Screening of Acute Ischemic Stroke Patients,” will be presented at 7:30 a.m. MT, Wednesday, Feb. 7.

    Mohammed Abdelsaid, R.P.H., Ph.D., the recipient of the Stroke Basic Science Award, is an assistant professor at Mercer University School of Medicine in Savannah, Georgia. The Stroke Basic Science Award recognizes outstanding basic or translational science that is laboratory-based. Abdelsaid’s winning presentation, Abstract 17, “SARS-CoV-2 Spike Protein Exacerbates Thromboembolic Cerebrovascular Complications in Humanized ACE2 Mouse Model,” will be presented at 7:54 a.m. MT, Wednesday, Feb. 7.

    Shumei Man M.D., Ph.D., FAHA, the Stroke Care in Emergency Medicine Award awardee, is a neurologist at the Cleveland Clinic and stroke center director of Cleveland Clinic Fairview Hospital in Ohio. The Stroke Care in Emergency Medicine Award encourages investigators to undertake or continue research in the emergent phase of acute stroke treatment and submit an abstract to the International Stroke Conference. Man’s winning presentation, Abstract 43, “Race-Ethnic Specific Trends in Stroke Thrombolysis Care Metrics in Relation to U.S. Target: Stroke Nationwide Quality Improvement Program 2003-2021,” will be presented at 2:00 p.m. MT, Wednesday, Feb. 7.

    Susan Linder P.T., D.P.T., Ph.D., the Stroke Rehabilitation Award recipient, is director of clinical research for the department of physical medicine and rehabilitation at the Cleveland Clinic in Ohio. The Stroke Rehabilitation Award encourages investigators to undertake or continue research and/or clinical work in the field of stroke rehabilitation. Linder’s winning presentation, Abstract TMP28, “Forced-Rate Aerobic Cycling Enhances Motor Recovery in Persons With Chronic Stroke: A Randomized Clinical Trial,” will be presented at 6:15 p.m. MT, Thursday, Feb. 8.

    Source:

    American Heart Association

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  • Scientists decode how tiny mutations can derail development

    Scientists decode how tiny mutations can derail development

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    Our genomes provide the instructions for proper growth and development. Millions of genomic switches, known as enhancers, control the location and timing of gene expression, which in turn ensures the correct proteins are made in the right cells at the right time throughout our lives. New research from University of California San Diego Assistant Professor Emma Farley’s lab shows how we can now predict which single base-pair changes to the DNA within our genomes will alter these instructions and disrupt development, causing extra digits and hearts.

    We now have genome sequences for over half a million people and counting. These genomes hold the key to how each of us comes to be and the promise of attaining precision medicine tailored to an individual’s own genetic makeup. Yet we cannot take full advantage of these datasets since we don’t understand a critical aspect of the genome: enhancers, which act as switches to control when and where our genes are expressed as proteins. Most genetic variants or mutations that cause disease lie within these enhancers. A central challenge has been to determine which sequence changes within enhancers matter and which do not. Thus far, pinpointing such causal enhancer variants has been akin to searching for a needle in a haystack.

    Publishing in the journal Nature, the Farley lab has addressed this challenge by achieving the ability to predict which changes to enhancers would cause changes in gene expression across thousands of enhancers and cell types. This ability to predict causal enhancer variants is rooted in a deep understanding of how enhancers function. The researchers showed that enhancers activate gene expression by binding proteins known as transcription factors very weakly. Adhering to this rule ensures enhancers activate gene expression, and thus protein production, at the right level, place and time. The Farley lab found that single-letter changes to our genome that strengthen the interaction of an enhancer with a transcription factor cause enhancers to switch on gene expression inappropriately and make proteins at the wrong level, time and/or place. Therefore, these single-letter changes to the enhancer DNA within our genome have dramatic effects on the genetic instructions, leading to extra fingers in mice and humans.

    The Farley lab identified three human families in which such mutations cause extra fingers and was able to predict which mutations would lead to even more fingers and more severe limb defects. Their ability to predict which enhancer variants will alter genomic instructions is not limited to limbs and generalizes to thousands of enhancers across cell types and species. In a complementary study published in Developmental Cell, the Farley lab showed that within marine animals known as sea squirts, single-letter changes that make heart enhancers stronger led to the development of a second beating heart.

    Pinpointing enhancer variants that alter the instructions for development encoded in a genome is key for seizing the full potential of genomic data for improving human health and obtaining the goals of precision medicine. Across thousands of enhancers, the Farley lab found that searching for DNA base-pair changes that make enhancers stronger enabled (up to) a seven-fold increase in their ability to find causal enhancer variants.

    Our study illustrates a key vulnerability in our genomes: single base-pair changes that make transcription factors bind to an enhancer even slightly stronger can cause developmental defects. Taking advantage of this knowledge will allow us to better predict which enhancer variants underlie disease in order to harness the full potential of our genomes for better human health.”


    Emma Farley, Faculty Member, Departments of Medicine (School of Medicine) and Molecular Biology (School of Biological Sciences), University of California San Diego 

    Farley is a recipient of the New Innovator Award and National Science Foundation CAREER Award, which funded this work. For the Nature paper, the first authors of this work are two UC San Diego graduate students, Fabian Lim (Biological Sciences) and Joe Solvason (Bioinformatics and Systems Biology), and postdoctoral scholar Genevieve Ryan. They were supported by Farley lab members: Sophia Le, Granton Jindal, Paige Steffen and Simran Jandu.

    The Developmental Cell paper was authored by postdoc Granton Jindal, graduate students Alexis Bantle (Biological Sciences) and Joe Solvason (Bioinformatics and Systems Biology), Jessica Grudzien, Agnieszka D’Antonio-Chronowska, Fabian Lim, Sophia Le, Benjamin Song, Michelle Ragsac, Adam Klie, Reid Larsen Kelly Frazer and Emma Farley.

    The research was funded by National Institutes of Health (DP2HG010013, T32HL007444, T32GM127235, T32GM133351, T32GM008666 and U01HL107442), National Science Foundation (2239957, CMMI1728497), American Heart Association (18POST34030077), UC San Diego Chancellor’s Research Excellence Scholars Program and California Institute for Regenerative Medicine (CIRM GC1R-06673-B).

    Source:

    University of California – San Diego

    Journal reference:

    Lim, F., et al. (2024). Affinity-optimizing enhancer variants disrupt development. Nature. doi.org/10.1038/s41586-023-06922-8.

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  • Bariatric surgery more effective in controlling hypertension rates in obese patients

    Bariatric surgery more effective in controlling hypertension rates in obese patients

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    Bariatric surgery is more effective in controlling hypertension rates, or high blood pressure, in people with obesity and uncontrolled high blood pressure compared to blood pressure medication alone, according to a study published today in the Journal of the American College of Cardiology. People who underwent bariatric surgery had lower BMI and were on fewer medications after five years while maintaining normal blood pressure levels than those who only used antihypertensive medications.

    According to the CDC, the U.S. obesity and hypertension rates in adults are 41.9% and 45.4%, respectively. Obesity is a known risk factor for cardiovascular disease and a major contributor to high blood pressure, which can make a person more susceptible to heart attack, stroke and heart failure, among other risks.

    In clinical practice, obesity is an overlooked condition. As a consequence, there is a frequent failure in approaching obesity as a crucial step for mitigating the risk of important cardiovascular risk factors including hypertension.”


    Carlos Aurelio Schiavon, MD, FACS, lead author of the study and a surgeon specializing in bariatric surgery at Heart Hospital (hcor) and BP Hospital in Sao Paulo

    Researchers in this study looked at the impact of treating obesity to lower high blood pressure. While there are new medications to treat obesity, long-term adherence to medication can be challenging. This study looks at bariatric surgery as a better long-term solution to control obesity and, as a result, high blood pressure.

    The GATEWAY trial included 100 people (76% of which were female) who had a body mass index (BMI) of around 36.9Kg/m2. All participants had hypertension and were using at least two medications. People with previous cardiovascular events and poorly controlled Type 2 diabetes were excluded. Subjects were assigned to either Roux-en-Y gastric bypass with medical therapy or medial therapy alone and the primary outcome was reduction of at least 30% antihypertensive medications while maintaining blood pressure levels less than 140/90 mmHg at five years.

    At five years, BMI was 28.01 Kg/m2 for those who received bariatric surgery and 36.40 Kg/m2 for those on medical therapy alone. People who had bariatric surgery had an 80.7% reduction in the number of medications they were taking compared to a 13.7% reduction in those only using medical therapy. Hypertension remission, defined as controlled blood pressure without medications, was 46.9% in those who underwent bariatric surgery compared to 2.4% in those on medical therapy alone.

    “Our results underscore the importance of approaching obesity in reducing hypertension rates,” Schiavon said.

    Limitations of the study include that it was a single-center, open-label study with a small sample size and there was loss of follow up in some patients.

    In an accompanying editorial comment, Michael Hall, MD, MSc, professor and chair of the Department of Medicine at the University of Mississippi Medical Center, said the study provides important long-term data on the benefits of gastric bypass on weight loss and blood pressure control, but questions remain.

    “Further studies assessing the threshold for bariatric surgery in people with obesity, optimal timing of bariatric surgery in obese people with cardiometabolic diseases, type of bariatric surgery and comparative studies of obesity pharmacotherapies and bariatric surgery are needed to clarify the optimal treatment pathways for this common and growing disease,” he said.

    Source:

    American College of Cardiology

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  • New weight loss drug may be an effective strategy for preventing or treating high blood pressure

    New weight loss drug may be an effective strategy for preventing or treating high blood pressure

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    The new weight loss medication tirzepatide significantly lowered the systolic blood pressure (the top number in a blood pressure reading) for nearly 500 adults with obesity who took the medication for about eight months, according to new research published today in Hypertension, an American Heart Association journal.

    Systolic blood pressure, or the top number in the blood pressure reading, is a stronger predictor for cardiovascular death than diastolic, or bottom number, blood pressure. According to the American Heart Association’s 2024 Heart Disease and Stroke Statistics, more than 122 million adults in the United States, or 47% of adults have hypertension, and nearly 42% of adults have obesity.

    Tirzepatide works by mimicking two metabolic hormones in the body: it acts as a glucagon-like peptide-1 (GLP-1) receptor agonist and also as a glucose dependent insulinotropic polypeptide (GIP) receptor agonist. These hormones stimulate insulin secretion and sensitivity after a person eats. Together, they have been found so far to help regulate the body’s blood sugar levels, slow down digestion and reduce appetite, which makes a person feel more full and eat less, leading to weight loss. In contrast, semaglutide has only the GLP-1 hormone; it does not contain a GIP receptor agonist.

    In 2022, the Food and Drug Administration approved tirzepatide for prescription as a treatment for Type 2 diabetes. In late 2023, the FDA also approved it for chronic weight management for people with obesity (body mass index of 30 kg/m2 or higher) or overweight (body mass index of 27-29 kg/m2) and at least one weight-related health condition, such as high blood pressure, Type 2 diabetes or high cholesterol.

     “Our findings indicate treating obesity with the weight loss medication tirzepatide may be an effective strategy for preventing or treating high blood pressure,” said lead study author James A. de Lemos, M.D., FAHA, the Kern Wildenthal, M.D., Ph.D., distinguished chair of cardiology and a professor of medicine at UT Southwestern Medical Center in Dallas. “Although tirzepatide has been studied as a weight loss medication, the blood pressure reduction in our patients in this study was impressive. While it is not known if the impact on blood pressure was due to the medication or the participants’ weight loss, the lower blood pressure measures seen with tirzepatide rivaled what is seen for many hypertension medications.”

    The current research was a planned sub-study including 600 of the participants from the SURMOUNT-1 weight loss study to determine if there was an effect on blood pressure. The sub-study was designed to assess the effects of tirzepatide on blood pressure levels as measured by 24-hour ambulatory blood pressure monitoring in people with obesity but without Type 2 diabetes.

    Participants received either a placebo or a dose of tirzepatide in one of three strengths (5 mg, 10 mg or 15 mg). About one-third of participants reported they had high blood pressure at the beginning of the study and were taking one or more hypertension medications. When the sub-study began, all of the participants had blood pressure levels that were less than 140/90 mm Hg, and if they used blood pressure medications, they were required to have been taking their blood pressure medications for at least three months. The sub-study included participants who had hypertension and who had normal blood pressure.

    The study was conducted from December 2019 to April 2022, and the participant results after 36 weeks of taking tirzepatide indicate:

    • For participants taking 5 mg of tirzepatide, there was an average reduction in systolic blood pressure of 7.4 mm Hg.

    • For participants taking 10 mg of tirzepatide, there was an average reduction in systolic blood pressure of 10.6 mmHg.

    • For participants taking 15 mg of tirzepatide, there was an average reduction in systolic blood pressure of 8.0 mm Hg.

    • The blood-pressure lowering effects of tirzepatide were evident in blood pressure measures taken during both the day and night. Nighttime systolic blood pressure is a stronger predictor for cardiovascular death and all-cause death than daytime blood pressure readings.

    The reductions in systolic blood pressure were consistent across subgroups of participants in the study who were categorized by additional factors, including age, sex, body mass index and hypertension-related risk factors.

    Study background and details:

    • SURMOUNT-1 was a randomized study on the effect of increasing doses of tirzepatide on weight loss. It found that in participants with overweight or obesity (body mass index (BMI) ≥27 kg/m2), once-weekly injections of 5 mg, 10 mg or 15 mg of tirzepatide led to mean weight reductions of 15%, 19.5% and 20.9%, respectively, compared to placebo.

    • The sub-study included 600 adults from SURMOUNT-1: 155 participants received placebo; 145 were taking tirzepatide 5 mg; 152 were taking tirzepatide 10 mg; and 148 were taking tirzepatide 15 mg.

    • Blood pressure measurements were available and analyzed for 494 participants who valid ambulatory blood pressure monitoring data at the beginning of the study and at week 36.

    • Only the study participants with at least 70% valid readings on ambulatory monitoring and a minimum of 20 daytime and seven nighttime readings were included in the data analyses. This was 494 out of 600 initial participants.

    • 69% of study participants self-identified as female, and 31% self-identified as male. 66.8% self-identified as white adults, 11.8% self-identified as Black adults and 25% self-identified as Hispanic ethnicity.

    • The average age of the participants was 45.5 years, and their average BMI was 37.4 kg/m2, which meets the criteria for obesity (obesity is BMI≥30). People with obesity have an increased risk of high blood pressure, heart disease, stroke and Type 2 diabetes, as well as other health conditions.

    • Ambulatory blood pressure monitoring used in this study included blood pressure measurements every 30 minutes during the day and every hour at night, providing a more comprehensive assessment of blood pressure than in office or daily home blood pressure measurements. For ambulatory blood pressure monitoring, study participants wore a blood pressure monitoring device for a 24- to 27-hour period that measured blood pressure throughout waking and sleeping hours. Ambulatory blood pressure monitoring was conducted when participants first began taking tirzepatide at the start of the study and after 36 weeks of being enrolled in the study.

    The 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults classifies hypertension, or high blood pressure, as having top and bottom blood pressure measures greater than or equal to 130/80 mm Hg. 

    Study limitations include that it was only conducted in a subset of the original 2,539 SURMOUNT-1 participants; the ambulatory blood pressure monitoring was only measured at two points in the study -; baseline and at 36 weeks; and measurements were only taken once per hour at night to minimize the burden on study participants. In addition, changes in food intake and 24-hour urine sodium excretion were not assessed, meaning the contribution of dietary modifications including salt intake or other changes that may help to reduce blood pressure are unknown and cannot be estimated.

    “Overall, these data are encouraging that novel weight-loss medications are effective at reducing body weight and they are also effective at improving many of the cardiometabolic complications of obesity including hypertension, Type 2 diabetes and dyslipidemia, among others. While the impact of each of these beneficial effects is individually important, many of these obesity-related complications act synergistically to increase the risk of cardiovascular disease. Thus, strategies that mitigate multiple obesity-related complications may reduce the risk of cardiovascular events,” said Michael E. Hall, M.D., M.S., FAHA, chair of the writing group for the Association’s 2021 scientific statement on weight-loss strategies for prevention and treatment of hypertension and chair of the department of medicine at the University of Mississippi Medical Center in Jackson, Mississippi.

    Additional studies will be necessary to determine the long-term impact on cardiovascular events such as heart attack and heart failure. Also, studies are needed to investigate what happens to blood pressure when medications like tirzepatide are discontinued – does the blood pressure rebound and go back up, or does it remain lowered?”


    Michael E. Hall, M.D., M.S., FAHA, chair of the writing group

    Co-authors and disclosures are listed in the manuscript. The study was funded by Eli Lilly and Company, the manufacturer of tirzepatide.

    Source:

    American Heart Association

    Journal reference:

    de Lemos, J. A., et al. (2024) Tirzepatide Reduces 24-Hour Ambulatory Blood Pressure in Adults With Body Mass Index ≥27 kg/m2: SURMOUNT-1 Ambulatory Blood Pressure Monitoring Substudy. Hypertension. doi.org/10.1161/HYPERTENSIONAHA.123.22022.

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  • UVA scientists develop new approach to machine learning for identifying heart drug

    UVA scientists develop new approach to machine learning for identifying heart drug

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    University of Virginia scientists have developed a new approach to machine learning – a form of artificial intelligence – to identify drugs that help minimize harmful scarring after a heart attack or other injuries.

    UVA scientists develop new approach to machine learning for identifying heart drug

    Jeff Saucerman, PhD. Image Credit: University of Virginia

    The new machine-learning tool has already found a promising candidate to help prevent harmful heart scarring in a way distinct from previous drugs. The UVA researchers say their cutting-edge computer model has the potential to predict and explain the effects of drugs for other diseases as well.

    “Many common diseases such as heart disease, metabolic disease and cancer are complex and hard to treat,” said researcher Anders R. Nelson, PhD, a computational biologist and former student in the lab of UVA’s Jeffrey J. Saucerman, PhD. “Machine learning helps us reduce this complexity, identify the most important factors that contribute to disease and better understand how drugs can modify diseased cells.”

    On its own, machine learning helps us to identify cell signatures produced by drugs. Bridging machine learning with human learning helped us not only predict drugs against fibrosis [scarring] but also explain how they work. This knowledge is needed to design clinical trials and identify potential side effects.”

    Jeffrey J. Saucerman, PhD., UVA’s Department of Biomedical Engineering, a joint program of the School of Medicine and School of Engineering

    The power of combining human learning and machine learning

    Saucerman and his team combined a computer model based on decades of human knowledge with machine learning to better understand how drugs affect cells called fibroblasts. These cells help repair the heart after injury by producing collagen and contract the wound. But they can also cause harmful scarring, called fibrosis, as part of the repair process. Saucerman and his team wanted to see if a selection of promising drugs would give doctors more ability to prevent scarring and, ultimately, improve patient outcomes.

    Previous attempts to identify drugs targeting fibroblasts have focused only on selected aspects of fibroblast behavior, and how these drugs work often remains unclear. This knowledge gap has been a major challenge in developing targeted treatments for heart fibrosis. So Saucerman and his colleagues developed a new approach called “logic-based mechanistic machine learning” that not only predicts drugs but also predicts how they affect fibroblast behaviors.

    They began by looking at the effect of 13 promising drugs on human fibroblasts, then used that data to train the machine learning model to predict the drugs’ effects on the cells and how they behave. The model was able to predict a new explanation of how the drug pirfenidone, already approved by the federal Food and Drug Administration for idiopathic pulmonary fibrosis, suppresses contractile fibers inside the fibroblast that stiffen the heart. The model also predicted how another type of contractile fiber could be targeted by the experimental Src inhibitor WH4023, which they experimentally validated with human cardiac fibroblasts.

    Additional research is needed to verify the drugs work as intended in animal models and human patients, but the UVA researchers say their research suggests mechanistic machine learning represents a powerful tool for scientists seeking to discover biological cause-and-effect. The new findings, they say, speak to the great potential the technology holds to advance the development of new treatments – not just for heart injury but for many diseases.

    “We’re looking forward to testing whether pirfenidone and WH4023 also suppress the fibroblast contraction of scars in preclinical animal models,” Saucerman said. “We hope this provides an example of how machine learning and human learning can work together to not only discover but also understand how new drugs work.”

    Findings published

    The researchers have published their findings in the scientific journal PNAS, the Proceedings of the National Academy of Sciences. The research team consisted of Nelson, Steven L. Christiansen, Kristen M. Naegle and Saucerman. The scientists have no financial interests in the work.

    The research was supported by the National Institutes of Health, grants HL137755, HL007284, HL160665, HL162925 and 1S10OD021723-01A1.

    Source:

    University of Virginia Health System

    Journal reference:

    Nelson, A. R., et al. (2024). Logic-based mechanistic machine learning on high-content images reveals how drugs differentially regulate cardiac fibroblasts. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2303513121.

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  • A study on the evolving tides of romantic love

    A study on the evolving tides of romantic love

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    In a recent article published in the journal Humanities & Social Communications, researchers reviewed trends in recent research and avenues for future studies on the subject of romantic love and relationships. Their findings have implications for the formulation of policies that can promote stronger familial ties and, thus, a more solid and resilient social fabric.

    Review: A decade of love: mapping the landscape of romantic love research through bibliometric analysis. Image created with the assistance of DALL·E 3

    Review: A decade of love: mapping the landscape of romantic love research through bibliometric analysis. Image created with the assistance of DALL·E 3

    Background

    Romantic love has been defined as an intense longing for union with another person. The presence of love leads to the transition from the initial stages of a relationship to the communication and satisfaction of a committed partnership. 

    Despite the power of love, however, romantic relationships are shorter than ever, and nearly half of first marriages now end in divorce in the United States. Commitment is no longer a significant factor in relationships, and expectations and experiences of love also appear to be changing.

    Love is a unique and enigmatic phenomenon that has captivated not just the great poets but also neuroscientists, psychologists, sociologists, and biologists. This has led to a wide array of scholarly work on the subject, covering numerous disciplinary domains and examining not just the positive emotions that love evokes but also the negative behaviors that it can engender.

    Bibliometric analysis, which provides quantitative insights into scientific, technological, and academic work, offers a way to summarize and synthesize the depth and breadth of this vast literature.

    About the study

    The Web of Science database was used to identify relevant literature published between 2013 and 2022 using a keyword search. Included studies were written in English; early access articles, conference proceedings, book chapters, retracted publications, and data papers were excluded.

    On applying these criteria, 6858 papers were included in the analysis, which involved generating and interpreting informative and intuitive visual maps as well as evolutionary and co-occurrence analysis based on themes and trends identified from the literature.

    Findings

    Since 2013, annual publications and citation counts have shown an upward trend, with a 90-fold surge to 2022. More researchers are focusing on this topic, suggesting that these numbers might rise faster in the coming years. More than 15,000 researchers from 104 countries contributed to these papers.

    Network analysis identified the most influential authors and collaborators in this group; the most productive writer published 74 articles. The trend showed high levels of collaboration between authors from around the world. However, dissemination of research was higher in high-income countries, which has implications for well-being.

    The 6,858 publications were published in 1,251 journals, with the top 10 publications accounting for nearly one-fourth of all articles. Journals from the United States accounted for half of all publications, while the United Kingdom published 40%. China was the most prolific of the developing countries, with 328 publications.

    While some papers were published in journals with an impact factor (IF) of nearly 8.5, there were indications that studies on romantic love might have difficulty getting accepted to high-IF publications (the average IF was 4.070). Psychology journals accounted for 66% of publications, but other disciplines included psychiatry, sociology, women’s studies, and economics.

    Keyword analysis suggested that between 2020 and 2022, the phrases ‘conflict resolution,’ ‘social relationships,’ and ‘same-sex’ peaked in popularity. Non-heterosexual relationships have often been stigmatized, but emerging research shows how destigmatization can lead to less risky sexual behaviors and higher emotional well-being.

    An increase in focus on conflict resolution may promote healthier relationship outcomes; in this regard, computer-mediated conflict resolution has shown promise. Studies on social relationships have focused on racial issues and brain scans to examine the neurobiological foundations of love. In recent years, studies have shown that peer victimization and dating violence are becoming more common in younger age groups and that online dating can lead to increases in depression.

    Over time, the authors noticed a shift from an idealized view of love to a more realistic one. Open fields of inquiry include teen dating, intimate partner violence, sexual abuse, and attachment insecurity, with a focus on the interconnected cluster of romantic relationships, gender, and attachment. For example, there were clear indicators that male adolescents are more likely to be perpetrators of dating or intimate partner violence.

    Conclusions

    The findings from this study included trends in research, identified the historical trajectory that scholarship has taken, and assessed fruitful avenues for future exploration. The results are also relevant in terms of identifying interventions – for example, adolescent males can be targeted to reduce the incidence of dating violence. Future studies can expand this research question to databases beyond the Web of Science and include publications written in other languages as well as grey literature (conference papers, working papers, and other publications.

    Journal reference:

    • A decade of love: mapping the landscape of romantic love research through bibliometric analysis. Han, Y., Luo, Y., Chen, Z., Gao, N., Song, Y., Liu, S. Humanities & Social Communications (2024), DOI – 10.1057/s41599-024-02665-7, https://www.nature.com/articles/s41599-024-02665-7

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  • Stroke and neck artery tear increase heart attack risk in the first year

    Stroke and neck artery tear increase heart attack risk in the first year

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    Heart attack risk almost doubles in the first year after a stroke or when combined with a tear in a neck artery wall, however, a tear without a stroke does not seem to raise heart attack risk, according to preliminary research to be presented at the American Stroke Association’s International Stroke Conference 2024. The meeting will be held in Phoenix, Feb. 7-9, and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

    Our findings may aid physicians in assessing and managing cardiovascular risk after these events.”

    Liqi Shu, M.D., clinical fellow in neurology, Warren Alpert Medical School of Brown University in Providence, Rhode Island

    Aortic dissection is a tear in the wall of the aorta, the large artery that receives blood directly from the heart, and is known to increase heart attack risk. Tears in the walls of the carotid or vertebral arteries, which extend out from the aorta and carry blood through the neck to the brain, are called carotid or vertebral artery dissections. These dissections can result in stroke, and stroke is known to be associated with heart attack. It was unclear whether carotid or vertebral artery dissection itself increases heart attack risk prior to this study.

    The researchers analyzed health information for more than 800,000 adults (average age of 63 years; 62% women) hospitalized in New York (between 2011 and 2017) or Florida (between 2011-2019). The patients with no history of recent major head or neck trauma were separated into four groups based on diagnoses: acute ischemic stroke; cervical artery dissection; both; or a reference group of patients with transient ischemic attack known as a “warning stroke,” temporary loss of short-term memory (transient global amnesia) or migraine.

    After adjusting for heart attack risk factors, the study found:

    • Patients who had carotid or vertebral artery dissection without stroke had the same risk of having a heart attack within a year as those in the reference group.
    • Patients with stroke, either with or without carotid or vertebral artery dissection, were almost twice as likely to have a heart attack within a year, in comparison to patients in the reference group.

    “Before, it was just a guess, but now we know that carotid or vertebral artery dissection not causing a stroke does not raise the risk of a heart attack, and it makes sense that clinicians should focus predominantly on stroke prevention in this subgroup of patients,” Shu said.

    Study background:

    • Participants with a recent history of major head or neck trauma were excluded. Head or neck trauma may lead to traumatic carotid dissection, which is different from this study’s focus on spontaneous dissection.
    • The analysis controlled for several heart attack risk factors, including age, Type 1 or Type 2 diabetes, heart failure, coronary artery disease, high cholesterol and high blood pressure.
    • Almost 20,000 of the participants experienced a heart attack within one year of their initial hospitalization, and the risk of heart attack was compared among the diagnostic groups.
    • Among the study group of 823,634 participants, 65.4% were white, 16.2% were Black or African American, and 12.2% were Hispanic or Latino adults. 

    While this study is based on hospitalization data only in New York and Florida, it’s important to note that these states collectively represent a substantial portion of the U.S. population, accounting for over 10% of the total. These two states also provide a good representation of diverse demographic groups, adding strength to the findings. However, caution should still be exercised when generalizing these results to people living in other geographic areas. In addition, this retrospective analysis (looks back in time to analyze data) might not have accounted for all factors influencing heart attack risk such as medication usage, which was not included in the databases.

    According to the American Heart Association’s Heart Disease and Stroke Statistics 2024 Update, stroke accounted for approximately 1 of every 21 deaths in the United States in 2021.

    Source:

    American Heart Association

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  • Most stroke survivors can safely take two types of common antidepressants

    Most stroke survivors can safely take two types of common antidepressants

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    Most stroke survivors were able to safely take two types of common antidepressants, according to a preliminary study to be presented at the American Stroke Association’s International Stroke Conference 2024. The meeting will be held in Phoenix, Feb. 7-9, and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

    Among people with ischemic (clot-caused) stroke, those who began taking an antidepressant known as an SSRI (selective serotonin reuptake inhibitor) and/or an SNRI (serotonin and norepinephrine reuptake inhibitor) for the common conditions of post-stroke depression and anxiety, did not have an increased risk of hemorrhagic (bleeds) stroke or other serious bleeding. This included people taking anticoagulation medications. There was, however, an increased risk of hemorrhagic stroke among stroke patients taking two anti-platelet medications, also called dual anti-platelet therapy or DAPT.

    Mental health conditions, such as depression and anxiety, are very common yet treatable conditions that may develop after a stroke. Our results should reassure clinicians that for most stroke survivors, it is safe to prescribe SSRI and/or SNRI antidepressants early after stroke to treat post-stroke depression and anxiety, which may help optimize their patients’ recovery. However, caution is needed when considering the risk-benefit profile for stroke patients receiving dual anti-platelet therapy because we did find an increased risk of bleeding among this group.”


    Kent P. Simmonds, D.O., Ph.D., study lead author, third-year physical medicine and rehabilitation resident, University of Texas Southwestern Medical Center in Dallas

    According to the American Heart Association’s Heart Disease and Stroke Statistics 2024 Update, when considered separately from other cardiovascular diseases, stroke ranks fifth among all causes of death, behind diseases of the heart, cancer, COVID-19 and unintentional injuries/accidents. Approximately one-third of stroke survivors develop poststroke depression. If left untreated, depression may affect quality of life and reduce the chances for optimal poststroke recovery such as returning to their usual daily living activities without assistance.

    The most common classes of antidepressants are SSRIs or SNRIs, and they are widely used and effective for treating anxiety and depression. However, they may not be prescribed at all or early enough after a stroke, when the risk of depression or anxiety is particularly high, due to concerns that they may increase the risk of a hemorrhagic stroke or other serious types of bleeding.

    Researchers looked at the frequency of serious bleeding among hundreds of thousands of stroke survivors who took different types of SSRI and/or SNRI antidepressants (such as sertraline, fluoxetine, citalopram, venlalfaxine). Serious bleeding was defined as bleeding in the brain, digestive tract; and shock, which occurs when bleeding prevents blood from reaching the body’s tissues.

    Researchers also investigated serious bleeding among stroke survivors who took antidepressants combined with different types of blood-thinning medications that are used to prevent future blood clots. These blood-thinning medications may include either anticoagulants or antiplatelet medications. Anticoagulants are prescribed as a single medication and include medications such as warfarin, apixaban and rivaroxaban. Antiplatelet medications may be prescribed as either a single medication (commonly aspirin) or two types of antiplatelet medications can be used in dual antiplatelet therapy. DAPT includes aspirin plus another antiplatelet medication called a P2Y12 inhibitor (such as clopidogrel, prasugrel or ticagrelor).

    The study found:

    • SSRI and SNRIs were generally safe to start during the important early stages of recovery as patients taking these medications were not more likely to develop serious bleeding compared to stroke survivors who did not take an antidepressant. This included ischemic stroke patients who are also taking anti-coagulation therapy.

    • An increased risk of serious bleeding occurred when SSRIs or SNRIs were taken in combination with DAPT treatments (aspirin and blood thinners). However, the overall risk remained low as serious bleeding events were rare.

    • Among ischemic stroke patients on antidepressant medications, there was a 15% increase in the risk of serious bleeding when taking medications from classes such as mirtazapine, bupropion and tricyclics compared to SSRI/SNRIs.

    “Maximizing rehabilitation early after a stroke is essential because recovery is somewhat time-dependent, and most functional gains occur during the first few months after a stroke,” Simmonds said. “Fortunately, dual antiplatelet therapy is often administered for 14, 30 or 90 days, so, when indicated, clinicians may not need to withhold antidepressant medications for prolonged periods of time. Future research should investigate the risk of bleeding associated with the use of anti-depressant and anxiety medications among patients with hemorrhagic or bleeding stroke.”

    According to a 2022 American Heart Association scientific statement, social isolation and loneliness are associated with about a 30% increased risk of heart attack or stroke, or death from either. “Depression may lead to social isolation, and social isolation may increase the likelihood of experiencing depression. The current study helps answer safety issues around the use of antidepressants for treatment of mental health issues that may develop after a stroke,” said Crystal Wiley Cené, M.D., M.P.H., FAHA, chair of the writing group for the Association’s scientific statement, and a professor of clinical medicine and chief administrative officer for health equity, diversity and inclusion at the University of California San Diego Health. Dr. Cené was not involved in this study.

    Study details and design:

    • The retrospective study included electronic medical records data from 666,150 ischemic stroke patients from over 70 large health care centers in the United States: 35,631 were taking SSRI/SNRI antidepressant medication, and 23,241 were taking other antidepressants; however, most (607,278) were not taking any antidepressant.

    • Patients were treated at 70 health care centers over 20 years.

    • Patients were identified from electronic medical records for 2003 through 2023.

    The study had some limitations. Researchers used statistical methods to adjust for differences among the groups that may not have accounted for all the important differences among the groups. The study also did not account for the dosage, duration, or number of antidepressants taken by participants, which may have affected the results.

    Source:

    American Heart Association

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