Tag: Heart

  • Cardiovascular health variances in women’s lifespan

    Cardiovascular health variances in women’s lifespan

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    Women’s cardiovascular disease risks and outcomes differ throughout the lifespan from those of men, according to a collection of studies devoted to cardiovascular medicine research focused on women of all ages, published today in a special “spotlight” issue of the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association.

    Cardiovascular disease kills more women than all forms of cancer combined. Among females 20 years and older, nearly 45% are living with some form of cardiovascular disease, and less than 50% of women entering pregnancy in the U.S. have good heart health. In addition, more than half of deaths from high blood pressure are in women. Yet, women make up only 38% of participants in cardiovascular disease clinical trials, according to the American Heart Association.

    The special Go Red for Women issue of the Journal, in recognition of American Heart Month, features studies that reveal insights such as: how diet may affect the high preeclampsia risk in pregnant Hispanic/Latina women; how women were less likely than men to receive bystander CPR and automated external defibrillator (AED) treatment, as well as survive the first 30 days post-hospitalization after out-of-hospital cardiac arrest; and how rehospitalization rates differ in women with heart failure and obstructive sleep apnea. In yet another study featured, researchers report that while the incidence of intracerebral hemorrhage (bleeding within the brain), the second most common stroke type, was lower in women, women were more likely to die one year after a stroke than men.

    Below are highlights of some of the manuscripts in this issue,

    • Prospective Associations of Accelerometer-measured Machine-learned Sedentary Behavior with Mortality among Older Women: The OPACH Study

    Steve Nguyen, Ph.D., et al.; University of California, San Diego, La Jolla, California

    This team studied sedentary behavior patterns in nearly 6,000 older women (average age 79 years) to determine the impact of sitting time on death from cardiovascular disease and all causes. Using a measurement tool powered by machine learning to accurately classify sitting time, researchers found those who sat more than 11.6 total hours a day and had longer bouts of uninterrupted sitting had a 57% higher risk of death from all causes and a 78% increased risk of death from cardiovascular disease. This was compared to women who sat less than 9.3 hours a day. The increased risk of death was consistent regardless of age, body mass index, physical functioning, cardiovascular disease risk factors, physical activity intensity and race/ethnicity. Reducing overall sedentary behavior and uninterrupted sitting time would likely have large public health benefits in an aging society, according to researchers.

    • Sex Differences in the Relationship between Schizophrenia and the Development of Cardiovascular Disease

    Hidehiro Kaneko, M.D., Ph.D., et al.; University of Tokyo, Tokyo, Japan

    Researchers studied cardiovascular disease risk in people with schizophrenia, a serious psychotic disorder and one of the top 15 leading causes of disability worldwide. Schizophrenia results in severe, chronic mental illness characterized by disturbances in perception, thought and behavior. The study found a strong association between schizophrenia and risk of developing cardiovascular disease in adults, but particularly in women. This higher risk in women may be related to hormonal changes during pregnancy and menopause, or reports that women are more sedentary than men. Nevertheless, the findings point to the need for health care professionals to take a thorough and gender-focused approach to cardiovascular disease prevention due to the notable role schizophrenia seems to play in cardiovascular disease. The researchers suggest that it’s crucial to promote physical activity, especially among women with schizophrenia, as inactivity may have increased the risk in female participants in this study. Healthcare providers should routinely screen and treat schizophrenia as part of standard clinical practice, with special attention to women, authors wrote.

    • Maternal Dietary Patterns During Pregnancy Are Linked to Hypertensive Disorders of Pregnancy Among a Predominantly Low-Income US Hispanic/Latina Pregnancy Cohort

    Luis E. Maldonado, Ph.D., M.P.H., et al.; Keck School of Medicine, University of Southern California

    In a study of more than 400 predominantly low-income, pregnant Hispanic/Latina women in Los Angeles, researchers found that a diet characterized by higher intakes of solid fats, refined grains and cheese was strongly associated with greater odds of having had a hypertensive disorder of pregnancy including preeclampsia during pregnancy.

    Other papers in the spotlight issue include:

    • Association of Sex With Cardiovascular Outcomes in Heart Failure Patients With Obstructive or Central Sleep Apnea -; Jian Zhang, M.D., Ph.D., et al.; Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    • Pregnancy History at 40 Years of Age as a Marker of Cardiovascular Risk -; Liv G. Kvalvik, M.D., Ph.D., et al.; University of Bergen, Bergen, Norway
    • Sex Differences in the Epidemiology of Intracerebral Hemorrhage Over 10 Years in a Population-Based Stroke Registry -; Simona Sacco, M.D., et al.; University of L’Aquila, L’Aquila, Italy
    • Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease: Insights From the ISCHEMIA Trial -; Harmony R. Reynolds, M.D., FAHA, et al.; NYU Grossman School of Medicine, New York City
    • Sex Differences in Receipt of Bystander CPR Considering Neighborhood Racial and Ethnic Composition -; Audrey L. Blewer, Ph.D., M.P.H., et al.; Duke University, Durham, North Carolina
    • Hypertension in Pregnancy among Immigrant and Swedish Women – A Cohort Study of All Pregnant Women in Sweden -; Axel C. Carlsson, Ph.D., et al.; Karolinska Institutet, Huddinge, Sweden
    • Sex Differences In Out-of-Hospital Cardiac Arrest Survival Trends -; R. L. A. Smits, et al.; Amsterdam University Medical Center, Amsterdam, The Netherlands;
    • Posttraumatic Stress Disorder is Associated With Elevated Risk of Incident Stroke and Transient Ischemic Attack in Women Veterans -; Ramin Ebrahimi, M.D., et al.; University of California, Los Angeles; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles; and
    • Sex differences in Outcomes of Acute Myocardial Injury After Stroke -; Michela Rosso, M.D., et al.; University of Pennsylvania, Philadelphia.

    Source:

    Journal reference:

    Mujahid, M. S. & Peterson, P. N., (2024) JAHA Go Red for Women Spotlight on Women and Cardiovascular Disease and Stroke. Journal of the American Heart Association. doi.org/10.1161/JAHA.124.035104.

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  • Mayo Clinic study finds minimal impact of daylight saving time on heart health

    Mayo Clinic study finds minimal impact of daylight saving time on heart health

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    A recent Mayo Clinic study examining the effects of daylight saving time (DST) on heart health suggests that the impact is likely minimal.

    In the nationwide study, researchers applied an advanced statistical model to look for any connections between DST and serious cardiovascular problems, including heart attacks and strokes. The study looked at 36,116,951 adults aged 18 and up across most U.S. states. (Arizona and Hawaii were excluded since these states do not observe DST.)

    Researchers focused on the week directly after the spring and fall DST transition, when clocks are set either an hour forward or backward.

    We looked at five years across the U.S., and what we found is that it’s unlikely that there is a clinically meaningful difference in cardiovascular health due to daylight saving time.”


    Benjamin Satterfield, M.D., Ph.D., cardiovascular diseases fellow and lead author of the study

    Researchers found 74,722 adverse cardiovascular events occurred throughout the study during the spring and fall DST transition. An adverse cardiovascular event was documented when a person was hospitalized with a primary diagnosis of a heart attack, stroke, cardiogenic shock or cardiac arrest.

    “These cardiovascular events are common health conditions, so this led to the question of whether this is more than would be expected if this had not followed the daylight saving time transition,” says Dr. Satterfield. 

    The observance of daylight saving time varies around the world. Countries that move clocks forward or back one hour may do so on different dates, and some do not observe daylight saving time at all.

    In the Mayo Clinic study, the Monday and Friday following the spring DST transition showed a statistically slight increase in the rates of cardiovascular events -; but when looking at all the data, researchers did not see the rise as clinically significant, he said.

    Researchers note that the time change practice was intended to align social and work activities with daylight hours and to conserve energy using less artificial lighting. They underscore that making changes to the DST system out of concern for heart health is unnecessary.

    When decisions are made about whether to abolish daylight saving time, there is no need to take concerns regarding heart health into account.”


    Bernard J. Gersh, M.B., Ch.B., D.Phil., cardiologist and senior author of the study

    Dr. Gersh and Dr. Satterfield note that the debate over DST includes other aspects of health. For example, Dr. Satterfield said researchers are exploring DST’s effect on mental health and its effect on the rates of motor vehicle accidents.

    Source:

    Journal reference:

    Satterfield, B. A., et al. (2024). Daylight Saving Time Practice and the Rate of Adverse Cardiovascular Events in the United States: A Probabilistic Assessment in a Large Nationwide Study. Mayo Clinic Proceedings: Innovations, Quality & Outcomes. doi.org/10.1016/j.mayocpiqo.2023.12.006.

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  • Spirulina shows promise in battling heart disease and diabetes

    Spirulina shows promise in battling heart disease and diabetes

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    In a recent study published in the journal Nutrients, a team of Italian researchers reviewed clinical and experimental findings from recent studies to understand the therapeutic contributions of Spirulina, also called blue-green cyanobacteria, in managing cardiovascular disease and its risk factors.

    Study: Beneficial Effects of Spirulina Supplementation in the Management of Cardiovascular Diseases. Image Credit: baibaz / ShutterstockStudy: Beneficial Effects of Spirulina Supplementation in the Management of Cardiovascular Diseases. Image Credit: baibaz / Shutterstock

    Background

    Although Spirulina has recently gained popularity as a ‘superfood’ because of its high nutritional content, the use of microalga in diet dates back to the ancient times of the Aztecs in Mexico. Spirulina is also known as blue-green cyanobacteria and are microscopic, photosynthesizing, filamentous microalgae of the genus Arthrospira, with A. plantensis and A. maxima being the two species most commonly used for their therapeutic and nutritional value.

    They grow in the tropics, in alkaline lakes with high bicarbonate and carbonate salt concentrations, although they have been known to survive in extremely cold temperatures. Spirulina is considered a ‘superfood’ because 60% to 70% of its dry weight is composed of protein, while it is also abundant in minerals, vitamins, carbohydrates, phycocyanin, carotenes, and fatty acids. As a nutraceutical, it has been added to various types of foods, including sports supplements and baby foods, while the pharmaceutical industry has popularized it in the form of capsules, dehydrated powders, and tablets.

    Therapeutic effects of Spirulina

    Research indicates that Spirulina exhibits a wide range of therapeutic effects such as anti-inflammatory, antidiabetic, antioxidant, hypolipidemic, and neuroprotective properties. The antioxidant properties are attributed mainly to the pigments phycocyanin, β-carotene, diatoxanthin, and diadinoxanthin found in Spirulina.

    Given its hypolipidemic and antioxidant properties, supplementation with Spirulina could be beneficial in lowering the risk of cardiovascular disease. Furthermore, diabetes, along with dyslipidemia and hypertension, is one of the risk factors for cardiovascular disease. Therefore, the present review examined how the cumulative health benefits of Spirulina could lower the overall risk of cardiovascular disease, which continues to be one of the major causes of mortality across the globe.

    Beneficial effects of Spirulina in CVDs.Beneficial effects of Spirulina in CVDs.

    Spirulina and hypertension

    The impact of Spirulina in lowering the risk of hypertension and stroke has been studied extensively in clinical trials, and the findings from these studies have shown that daily consumption of Spirulina, even added to foods such as salad dressing, significantly reduced the diastolic and systolic blood pressure.

    Consumption of Spirulina in the form of nutraceutical tablets also showed similar hypotensive results. Furthermore, animal studies using hypertensive rat models have shown that the high silicon content of Spirulina could be responsible for improving the elasticity of the arterial walls, along with angiotensin-converting enzyme-inhibiting properties that result in hypotensive effects.

    Antidiabetic effects of Spirulina

    Diabetes mellitus increases the risk of cardiovascular events such as heart failure, myocardial infarction, stroke, and peripheral vascular disease due to the micro- and macrovascular consequences of hyperglycemia. Cellular membrane integrity is also impacted by hyperglycemia, causing the peripheral tissues and liver to become insulin-resistant, increasing the generation of reactive oxygen species.

    In comparison to metformin, which is the standard treatment for hyperglycemia during diabetes, supplementation with Spirulina is believed to not only lower the levels of circulating glucose but also have a positive impact on lipid metabolism, which is linked to diabetes. The hypoglycemic and hypolipidemic properties of Spirulina are believed to have a cumulative effect in decreasing the risk of cardiovascular disease.

    The review discussed various clinical trials and studies using animal models of diabetes mellitus that have investigated the hypoglycemic properties of Spirulina and compared its efficacy in lowering blood sugar levels with that of metformin.

    While the mechanism through which Spirulina impacts blood glucose levels is not yet fully understood, the researchers believe that it could be influencing the secretion of insulin from the β-cells in the islets of Langerhans in the pancreas or further downstream, facilitating the transport of glucose from blood to all the peripheral tissue.

    Hyperlipidemia and Spirulina

    Spirulina has also demonstrated hypolipidemic properties by lowering the concentrations of low-density-lipoprotein cholesterol and triglycerides in the plasma while increasing the levels of high-density lipoprotein cholesterol, with the beneficial effects not being dose-dependent or toxic at high concentrations.

    Studies in animal models and overweight or obese human participants have reported significant benefits of Spirulina supplementation in lowering triglyceride levels, either as food additives or as nutraceutical pills or tablets. Spirulina was also found to be beneficial as an adjunct therapy to metformin in overweight diabetes patients.

    Conclusions

    Overall, this comprehensive review reported that consumption of Spirulina, either as an additive to regular foods or as a nutraceutical supplement, had numerous potential benefits, such as hypoglycemic, antioxidant, and hypolipidemic effects. However, the dosage and timing of Spirulina supplementation need to be standardized for optimal benefits in lowering the risk of cardiovascular disease.

    In conclusion, based on these data, more rigorous studies should be planned in the future aiming to address these critical questions, putting the foundations for developing a common guideline on “how and when” to use Spirulina.

    Journal reference:

    • Prete, V., Abate, A. C., Pietro, D., Lucia, D., Vecchione, C., & Carrizzo, A. (2024). Beneficial Effects of Spirulina Supplementation in the Management of Cardiovascular Diseases. Nutrients, 16(5). DOI: 10.3390/nu16050642, https://www.mdpi.com/2072-6643/16/5/642

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  • Flavonol-rich diet linked to lower mortality and disease risk, study shows

    Flavonol-rich diet linked to lower mortality and disease risk, study shows

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    In a recent prospective cohort study published in the journal Scientific Reports, researchers investigated the association between flavonol intake and cause-specific and all-cause mortality risk in adults in the United States. They found that an elevated dietary intake of flavonol is associated with a lower risk of all-cause mortality as well as Alzheimer’s disease (AD), cancer, and cardiovascular disease (CVD)-related mortality risk.

    Study: Flavonol-rich diet linked to lower mortality and disease risk, study shows. Image Credit: sematadesign / ShutterstockStudy: Flavonol-rich diet linked to lower mortality and disease risk, study shows. Image Credit: sematadesign / Shutterstock

    Background

    Flavonoids are biologically active polyphenolic compounds found in various plant-based foods. Among the six subclasses of flavonoids, flavonols are the most prevalent and active. Primary flavonols like quercetin, kaempferol, myricetin, and isorhamnetin are abundant in tea, onions, and berries. The consumption of flavonoids is known to potentially enhance endothelial function, maintain nitric oxide status, and influence biological processes relevant to lipid metabolism, platelet function, inflammation, oxidative stress, and blood pressure. Additionally, flavonoids are also known to exhibit anti-tumor effects by targeting key molecules and pathways, leading to apoptosis and inhibiting cell growth and metastasis.

    However, the relationship between flavonol intake and mortality risk has not been studied thoroughly so far. Therefore, using data from the National Health and Nutrition Examination Survey (NHANES) database, researchers in the present study explored the relationship between flavonol intake (total flavonol, kaempferol, myricetin, isorhamnetin, and quercetin), all-cause mortality risk, and cause-specific mortality risk (AD, CVD, cancer, and diabetes mellitus (DM)).

    About the study

    The study included 11,679 individuals aged≥ 20 who completed questionnaires, in-person assessments, and laboratory tests. The exclusion criteria were lack of flavonol intake and missing basic and demographic information. Flavonol intake data for the present study were derived from the US Department of Agriculture Survey Food and Beverage Flavonoid Values database (2003–2004). Detailed dietary interviews were conducted to capture information on foods and beverages consumed in the preceding 24 hours. The precise amounts of total flavonols were estimated in various foods, and the daily flavonol intake of participants was calculated.

    For mortality analysis, data from the National Death Index file and the 2019 Public Access Link mortality dataset were used. Mortality was categorized by causes such as cancer, CVD, DM, AD, and other causes, as per the International Statistical Classification of Diseases and Related Health Problems 10 (ICD-10) codes. Follow-up was conducted from the interview date to either the date of death or the study’s conclusion on December 31, 2019. Participants were stratified based on sociodemographic variables, including age, sex, race/ethnicity, marital status, education level, poverty ratio, alcohol consumption, body mass index (BMI), disease history, and the presence of various health conditions. Statistical analysis involved the use of Cox regression, Fine and Gray competing risks regression models, hazard ratios (HR), chi-square tests, and sensitivity analyses.

    Results and discussion

    Participants with the highest total flavonol intake tended to be male, younger, Non-Hispanic White, married, educated, above the poverty line, alcohol consumers, with BMI 18.5–30.0 kg/m2 and had a history of DM, hypertension, hyperlipidemia, congestive heart failure, coronary heart disease, angina, heart attack, and stroke. Increasing total flavonol intake showed a declining trend in all-cause mortality as well as AD, cancer, and CVD-specific mortality (p < 0.05 for all). Similar decreasing trends were observed for isorhamnetin, kaempferol, and quercetin intakes across various mortality categories, while myricetin intake exhibited a decreasing trend in AD mortality.

    While higher age was associated with a significant increase in all-cause mortality, female gender was found to be significantly linked to a lower risk of all-cause mortality. Conversely, a history of diseases was significantly associated with a higher risk of all-cause mortality.

    Further, higher total flavonol intake, particularly isorhamnetin, kaempferol, myricetin, and quercetin, was found to be associated with a reduced risk of all-cause and mortality owing to AD, CVD, cancer, and other causes. However, no correlation was found between flavonol intake and DM-specific mortality (p>0.05). The findings from the subgroup and sensitivity analyses aligned with the study’s main findings.

    Although the study is strengthened by its use of a multiple confounder-adjusted competing risks model to address competing risks of death, the study is limited by missing flavonol intake data, potential lack of generalizability, lack of data on primary food sources and dietary patterns, and the lack of exclusion of micronutrient supplement intake.

    Conclusion

    In conclusion, the present study establishes an association between dietary flavonol intake and overall mortality as well as cancer, AD, and CVD-specific mortality risk in US adults. The findings suggest that flavonol intake could be employed as an independent and reliable predictor of disease survival, offering patients the potential for health- and risk-management through dietary modifications.

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  • Understanding obesity’s effects on liver metabolism

    Understanding obesity’s effects on liver metabolism

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    Your liver plays a vital role in your metabolism, the biological process which converts food into energy. We know that being overweight can negatively affect metabolic activity, but not exactly how. To better understand this, researchers compared the livers of mice which were a typical weight with mice which were obese. They were surprised to find that biological regulation of metabolic activity, after a period of feasting and fasting, was reversed between them. In typical mice, allosteric regulation (the process which controls metabolism) was inhibited during feeding and activated when fasting. However, in obese mice, allosteric regulation increased during feeding and decreased when fasting. Investigating the reasons behind this reversed biological behavior could help health professionals understand how obesity affects the body and the development of disease.

    The World Obesity Federation (WOF) estimates that by 2035, over 4 billion people will be overweight or living with obesity. This may lead to a rise in obesity-related health conditions, such as heart disease, nonalcoholic fatty liver disease and Type 2 diabetes. Identifying the causes and effects of obesity, which is now understood to be a complex disease, is key for physicians looking to provide support and help people stay healthy.

    One known way that obesity can affect health is by impacting metabolism, the process by which our bodies take in, store and use energy from our food. Certain organs play key roles in this process, notably the liver. Not only is food processed there to provide energy, but it is one of the places where useful products at the end of the metabolic process are stored until we need them. To better understand the effects of obesity on the liver, researchers compared the livers of typical mice and obese mice after periods of feeding and fasting.

    The team carried out trans-omics analysis, an approach where they gathered data on five sets of biological processes (multi-omics). They then combined these layers of data with information from biological databases to create a trans-omic network. This gave them an overview of how the different layers interacted. “

    We constructed a trans-omic network of metabolic reactions in the livers of mice that could feed freely. We then compared this with data we had previously gathered from mice that had fasted for 16 hours. While enzyme and allosteric regulation which controls metabolism was suppressed in typical mice during feeding, we were surprised to find that the reverse occurred in obese mice and that this activity increased.”

    Professor Shinya Kuroda, Graduate School of Science, University of Tokyo

    When we eat, our liver builds up stores of energy which is then released as needed, a system known as metabolic homeostasis. However, the researchers saw that in obese mice this equilibrium became dysregulated, i.e., normal function was disrupted, indicating a potential breakdown of the system. This could lead to metabolic disorders such as tiredness, lack of energy and decreased appetite. By contrast, they saw that transcriptional regulation, a process which regulates metabolism and controls cell activity at a genetic level, did not change much between feeding and fasting. This means that, compared to allosteric regulation, it is more stable and less affected by what we eat.

    The team noted that what they observed may not only be evidence of disruption within the liver alone, but a change to broader metabolic cycles throughout the body. “Obesity is a metabolic disease, so to understand it, it is important to construct a trans-omic network with metabolome (the complete set of small-molecule chemicals) at its center,” said Kuroda. “We are interested not only in the liver, but also how the products of metabolic reactions circulate between liver and muscle through the blood in obese mice, which is what we will be working on now.”

    Source:

    Journal reference:

    Bai, Y., et al. (2024) Trans-omic analysis reveals opposite metabolic dysregulation between feeding and fasting in liver associated with obesity. iScience. doi.org/10.1016/j.isci.2024.109121.

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  • Novel insights into pathologies of diabetic cardiomyopathy, hippocampal neurotoxicity, and Alzheimer’s

    Novel insights into pathologies of diabetic cardiomyopathy, hippocampal neurotoxicity, and Alzheimer’s

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    DCM is the leading cause of heart failure in patients with chronic diabetes. However, the underlying mechanisms of DCM are poorly understood, and treatment options are limited. Another mystery is the regulation of cytochrome P450 enzymes (CYPs) in the central nervous system. Moreover, the link between the gut microbiome, microbiota-derived metabolites, and the progression of AD remains unknown. In the December issue of JPA, three articles provide insights into the pathologies of DCM, hippocampal neurotoxicity, and AD, providing a comprehensive exploration of these interconnected diseases.

    In the first study, researchers used mass spectrometry imaging (MSI), a technique combining the specificity of mass spectrometry (MS) with spatial imaging information, to map region-specific metabolites in the rat heart. Their findings, available online on 17 August 2023, were published in Volume 13, Issue 12 of the journal in December 2023. The team developed DCM mouse models to visualize region-specific metabolites, and analyze the effect of ferulic acid, an anti-myocardial injury drug. They used optimized ambient air-flow-assisted desorption electrospray ionization (AFADESI)-MSI to detect maximum number of metabolites and used matrix-assisted laser desorption ionization (MALDI)-MSI to increase coverage and resolution. MSI analyses of frozen rat heart tissue sections revealed heterogenous metabolic activity and region-specific distribution of the metabolites. Blood biochemical analyses showed decreased levels of glucose, HbA1c, triglycerides, and alanine aminotransferase in response to a high dose of ferulic acid for 20 weeks. “Our novel method unveiled metabolic changes in DCM rat hearts and is the first to explore alterations and spatial distribution of endogenous metabolites in the diabetic heart,” say corresponding authors Dr. Zeper Abliz and Dr. Zhonghua Wang.

    The second study, available online on 25 July 2023, aimed to understand the regulation of CYPs in the hippocampus in response to antiepileptic drug, phenytoin (PHT). PHT causes neuronal damage and cognitive impairment, leading to increased expression of CYP-mediated testosterone metabolism. The study found that pregnenolone 16α-carbonitrile (PCN), a pregnane X receptor (PXR) agonist, relieved PHT-induced neuronal side effects. Surprisingly, PCN increased hepatic CYP expression but decreased hippocampal CYP3A11 and CYP2B10 expression. The hippocampal CYP suppression by PCN was independent of PXR but associated with the activation of glucocorticoid receptor signaling pathway. Corresponding authors Hui Wang and Dan Xu conclude, “We propose glucocorticoids as a potential therapeutic strategy for mitigating the neuronal side effects of PHT. Within the coming 5 to 10 years, this research holds the potential to drive substantial progress in the field of PCN, potentially revolutionizing our understanding of PCN’s mechanisms within the body.

    The third study, available online on 28 July 2023, attempted to demonstrate the link between gut microbiome and AD progression. It found that gut dysbiosis in transgenic AD mice increased the levels of trimethylamine N-oxide (TMAO), which activated the CDK5/STAT3 pathway in the brain, leading to enhanced cognitive impairment. Fecal microbiota transplantation from non-transgenic mice mitigated neuronal inflammation. “The involving microbiota-gut-brain axis mechanisms underlying AD pathology may afford a new perspective on the novel targets for AD treatment,” explain corresponding authors Dr. Yan-Fang Xian and Dr. Zhi-Xiu Lin.

    Overall, these studies pave the way for further research and improved treatment strategies.

    Source:

    Journal references:

    • Liu, Y., et al. (2023). Integrated mass spectrometry imaging reveals spatial-metabolic alteration in diabetic cardiomyopathy and the intervention effects of ferulic acid. Journal of Pharmaceutical Analysis. doi.org/10.1016/j.jpha.2023.08.011.
    • Zhang, S., et al. (2023). Pregnenolone 16α-carbonitrile negatively regulates hippocampal cytochrome P450 enzymes and ameliorates phenytoin-induced hippocampal neurotoxicity. Journal of Pharmaceutical Analysis. doi.org/10.1016/j.jpha.2023.07.013.
    • Qu, C., et al. (2023). Gut dysbiosis aggravates cognitive deficits, amyloid pathology and lipid metabolism dysregulation in a transgenic mouse model of Alzheimer’s disease. Journal of Pharmaceutical Analysis. doi.org/10.1016/j.jpha.2023.07.014.

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  • Horse sedative use among humans spreads in deadly mixture of ‘tranq’ and fentanyl

    Horse sedative use among humans spreads in deadly mixture of ‘tranq’ and fentanyl

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    Andrew McClave Jr. loved to lift weights. The 6-foot-4-inch bartender resembled a bodybuilder and once posed for a photo flexing his muscles with former pro wrestler Hulk Hogan.

    “He was extremely dedicated to it,” said his father, Andrew McClave Sr., “to the point where it was almost like he missed his medication if he didn’t go.”

    But the hobby took its toll. According to a police report, a friend told the Treasure Island Police Department that McClave, 36, suffered from back problems and took unprescribed pills to reduce the pain.

    In late 2022, the friend discovered McClave in bed. He had no pulse. A medical examiner determined he had a fatal amount of fentanyl, cocaine, and xylazine, a veterinary tranquilizer used to sedate horses, in his system, an autopsy report said. Heart disease was listed as a contributing factor.

    McClave is among more than 260 people across Florida who died in one year from accidental overdoses involving xylazine, according to a Tampa Bay Times analysis of medical examiner data from 2022, the first year state officials began tracking the substance. Numbers for 2023 haven’t been published.

    The death toll reflects xylazine’s spread into the nation’s illicit drug supply. Federal regulators approved the tranquilizer for animals in the early 1970s and it’s used to sedate horses for procedures like oral exams and colic treatment, said Todd Holbrook, an equine medicine specialist at the University of Florida. Reports of people using xylazine emerged in Philadelphia, then the drug spread south and west.

    What’s not clear is exactly what role the sedative plays in overdose deaths, because the Florida data shows no one fatally overdosed on xylazine alone. The painkiller fentanyl was partly to blame in all but two cases in which the veterinary drug was included as a cause of death, according to the Times analysis. Cocaine or alcohol played roles in the cases in which fentanyl was not involved.

    Fentanyl is generally the “800-pound gorilla,” according to Lewis Nelson, chair of the emergency medicine department at Rutgers New Jersey Medical School, and xylazine may increase the risk of overdose, though not substantially.

    But xylazine appears to complicate the response to opioid overdoses when they do happen and makes it harder to save people. Xylazine can slow breathing to dangerous levels, according to federal health officials, and it doesn’t respond to the overdose reversal drug naloxone, often known by the brand name Narcan. Part of the problem is that many people may not know they are taking the horse tranquilizer when they use other drugs, so they aren’t aware of the additional risks.

    Lawmakers in Tallahassee made xylazine a Schedule 1 drug like heroin or ecstasy in 2016, and several other states including Pennsylvania, Ohio, and West Virginia have taken action to classify it as a scheduled substance, too. But it’s not prohibited at the federal level. Legislation pending in Congress would criminalize illicit xylazine use nationwide.

    The White House in April designated the combination of fentanyl and xylazine, often called “tranq dope,” as an emerging drug threat. A study of 20 states and Washington, D.C., found that overdose deaths attributed to both illicit fentanyl and xylazine exploded from January 2019 to June 2022, jumping from 12 a month to 188.

    “We really need to continue to be proactive,” said Amanda Bonham-Lovett, program director of a syringe exchange in St. Petersburg, “and not wait until this is a bigger issue.”

    ‘A good business model’

    There are few definitive answers about why xylazine use has spread — and its impact on people who consume it.

    The U.S. Drug Enforcement Administration in September said the tranquilizer is entering the country in several ways, including from China and in fentanyl brought across the southwestern border. The Florida attorney general’s office is prosecuting an Orange County drug trafficking case that involves xylazine from a New Jersey supplier.

    Bonham-Lovett, who runs IDEA Exchange Pinellas, the county’s anonymous needle exchange, said some local residents who use drugs are not seeking out xylazine — and don’t know they’re consuming it.

    One theory is that dealers are mixing xylazine into fentanyl because it’s cheap and also affects the brain, Nelson said.

    “It’s conceivable that if you add a psychoactive agent to the fentanyl, you can put less fentanyl in and still get the same kick,” he said. “It’s a good business model.”

    In Florida, men accounted for three-quarters of fatal overdoses involving xylazine, according to the Times analysis. Almost 80% of those who died were white. The median age was 42.

    Counties on Florida’s eastern coast saw the highest death tolls. Duval County topped the list with 46 overdoses. Tampa Bay recorded 19 fatalities.

    Cocaine was also a cause in more than 80 cases, including McClave’s, the Times found. The DEA in 2018 warned of cocaine laced with fentanyl in Florida.

    In McClave’s case, Treasure Island police found what appeared to be marijuana and a small plastic bag with white residue in his room, according to a police report. His family still questions how he took the powerful drugs and is grappling with his death.

    He was an avid fisherman, catching snook and grouper in the Gulf of Mexico, said his sister, Ashley McClave. He dreamed of being a charter boat captain.

    “I feel like I’ve lost everything,” his sister said. “My son won’t be able to learn how to fish from his uncle.”

    Mysterious wounds

    Another vexing challenge for health officials is the link between chronic xylazine use and open wounds.

    The wounds are showing up across Tampa Bay, needle exchange leaders said. The telltale sign is blackened, crusty tissue, Bonham-Lovett said. Though the injuries may start small — the size of a dime — they can grow and “take over someone’s whole limb,” she said.

    Even those who snort fentanyl, instead of injecting it, can develop them. The phenomenon is unexplained, Nelson said, and is not seen in animals.

    IDEA Exchange Pinellas has recorded at least 10 cases since opening last February, Bonham-Lovett said, and has a successful treatment plan. Staffers wash the wounds with soap and water, then dress them.

    One person required hospitalization partly due to xylazine’s effects, Bonham-Lovett said. A 31-year-old St. Petersburg woman, who asked not to be named due to concerns over her safety and the stigma of drug use, said she was admitted to St. Anthony’s Hospital in 2023. The woman, who said she uses fentanyl daily, had a years-long staph infection resistant to some antibiotics, and a wound recently spread across half her thigh.

    The woman hadn’t heard of xylazine until IDEA Exchange Pinellas told her about the drug. She’s thankful she found out in time to get care.

    “I probably would have lost my leg,” she said.




    Kaiser Health NewsThis article was reprinted from khn.org, a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

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  • Reevaluating the role of direct oral anticoagulants in cardiovascular treatment

    Reevaluating the role of direct oral anticoagulants in cardiovascular treatment

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    Direct oral anticoagulants (DOACs) are a common treatment for patients with a wide variety of cardiovascular conditions. DOACs are the preferred treatment over vitamin K antagonists (VKAs) for many patients with atrial fibrillation or venous thromboembolism, since the latter would have a higher risk of intracranial bleeding and more complex dosing routine. However, new research suggests that DOACs should not be the first line of treatment for every patient who need to treat or prevent blood clots.

    A systematic overview from researchers at Brigham and Women’s Hospital, a founding member of Mass General Brigham, discusses the efficacy of DOACs compared to other treatment methods. This review utilized data from randomized controlled trials to compare DOACs with other treatment methods for various cardiovascular conditions. Although there is merit to using DOACs in many common conditions, the manuscript provides a robust summary of clinical trials indicating that DOACs fare worse in patients with mechanical heart valves, thrombotic antiphospholipid syndrome, atrial fibrillation associated with rheumatic heart disease, and patients with embolic stroke of unclear source. The authors also highlight clinical scenarios in which there is uncertainty, with a look toward future for better evidence generation.

    The results we reviewed here have significant implications for optimizing anticoagulation therapy and improving patient outcomes in clinical practice. There is a critical need for further research regarding why DOACs are less efficacious or safe than the standard of care in certain scenarios.”


    Behnood Bikdeli, MD, MS, of the Brigham’s Heart and Vascular Center

    Source:

    Journal reference:

    Bejjani, A., et al. (2024). When Direct Oral Anticoagulants Should Not Be Standard Treatment. Journal of the American College of Cardiology. doi.org/10.1016/j.jacc.2023.10.038.

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  • Genetic variants influence blood pressure from early in life

    Genetic variants influence blood pressure from early in life

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    Certain genes associated with hypertension affect blood pressure from early in life, and they increase the risk of cardiovascular disease as you get older. However, you can do something about it.

    We are talking about really small differences, so small that they may fall within what is considered normal blood pressure. The problem is that they tend to last your whole life.” 


    Karsten Øvretveit, PhD Candidate at the Norwegian University of Science and Technology’s (NTNU) Department of Public Health and Nursing

    He is one of the researchers behind a new study that has looked at the relationship between gene variants and blood pressure in the population.

    The study shows that high blood pressure occurs in all age groups and that it is related to hereditary factors.

    “We found that genetic factors affect blood pressure from the first years of childhood and throughout your entire life,” says Øvretveit.

    Genetic data from large population studies

    High blood pressure is the main cause of heart attacks and strokes, and cardiovascular disease is the second most common cause of death in Norway, accounting for 23 per cent of all deaths in 2022.

    The direct medical cause of high blood pressure is unknown in many cases, but research shows that our genes play a signifcant role.

    “Lifestyle diseases are often caused by a combination of heredity and environment. Diseases are often the result of not only one, but very many genetic variants,” says Øvretveit.

    In order to find out how much a person is at risk of high blood pressure, researchers have used genetic data from large population studies. This has helped them develop a genetic risk score, which indicates how much your exact genetic makeup puts you at risk.

    Developing genetic risk scores

    Put very simply, a certain value is placed on each gene variant, which reflects the extent to which it can affect blood pressure. The variants are then “weighted”, i.e. some genes weigh more heavily than others, and the genetic risk score is then the sum of the genetic effects.

    “This is how people who are particularly at risk can be identified, and measures can be taken at an early stage before the condition is expressed.

    By keeping their blood pressure alow level, people with a high genetic risk score can achieve a lower risk of disease than people diagnosed with high blood pressure who we consider genetically protected,” says Øvretveit.

    To study the significance of the genetic risk, the researchers have used health data from participants in the HUNT Study from Trøndelag and from the British ‘Children of the 90s’ study. The latter includes health data from nearly 14,000 children from the time they were born until they were in their twenties. The Health Survey in Trøndelag (HUNT) is a large, Norwegian population-based health survey that includes health information and biological material from the inhabitants of Trøndelag. Since the first collection round in 1984, 250,000 people from Trondheim have participated.

    By comparing the blood pressure of the children who had the highest genetic risk with the children who were lowest on the scale, the researchers were able to see how the average blood pressure in the first group was higher from as early as the age of three. The difference lasted throughout their childhood and became more pronounced in adulthood.

    Difference increases with age

    “Although the differences in blood pressure are not very large, the time component is important. If your blood pressure is slightly elevated over many years, it will affect how prone you are to cardiovascular disease and kidney disease,” says Øvretveit.

    When the researchers compared the risk scores and health data of the HUNT Study participants, they saw that the differences in blood pressure between the participants with the highest and those with the lowest risk persisted throughout their whole lives.

    “We have been able to follow the same people from when they were around 37 until they were approximately 70 years old. We found that the differences persisted and resulted in various disease risks, where the differences in disease were quite large.”

    The researchers also found more positive results: if measures are taken, such as lifestyle changes and medications, the risk of disease can be significantly reduced.

    “By keeping their blood pressure at a low level, people with a high genetic risk score can achieve a lower risk of disease than people diagnosed with high blood pressure who we consider genetically protected. It seems that controlling your blood pressure matters more than genetics,” says Øvretveit.

    Large population studies provide good data

    As a basis for the study, Øvretveit and colleagues have used findings from the largest genetic study on blood pressure currently available, which includes data from over a million people. Øvretveit believes the study shows the possibilities that lie in genetic data from large population studies.

    “I don’t think you should start measuring blood pressure in every single child, but the type of data we have used in this study can be used in the future not only to prevent disease, but also to address the risk factors associated with a disease,” says Øvretveit.

    Is it a problem that Europeans are overrepresented in population studies?

    “Yes, it is, but we are now actively working on developing genetic risk scores that are adapted to other populations, and that can be used across many different populations,” says Øvretveit.

    To date, the researchers have identified around 1500 gene variants that have a clear connection with blood pressure, but the biological effect that many of these genes have on blood pressure is not known. In order to find a reliable method, the researchers had to identify high-risk combinations of gene variants and combinations that posed a lower risk through a process of trial and error. 

    “A common method for creating a risk score for genetic disease is to include only those gene variants that are known to have a strong connection with the disease,” says Øvretveit.

    But there are other methods such as including gene variants that produce effects we are more uncertain about. As a result, we get a lot more data in the calculation. 

    “Complex blood pressure traits may be affected by far more gene variants than we have identified so far. The methods we have developed allow this to be taken into account, but we also have to keep in mind that the individual effects of these variants are small,” says Øvretveit.

    The method that gave the most accurate risk score included over a million gene variants.

    “But there are far more that have a known connection with high blood pressure,” says Øvretveit.

    Source:

    Journal reference:

    Øvretveit, K., et al. (2023). Polygenic risk scores associate with blood pressure traits across the lifespan. European Journal of Preventive Cardiology. doi.org/10.1093/eurjpc/zwad365.

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  • Understanding how stress accelerates cancer spread

    Understanding how stress accelerates cancer spread

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    Stress is inevitable. But too much of it can be terrible for our health. Chronic stress can increase our risk for heart disease and strokes. It may also help cancer spread. How this works has remained a mystery-;a challenge for cancer care.

    Xue-Yan He, a former postdoc in Cold Spring Harbor Laboratory (CSHL) Adjunct Professor Mikala Egeblad’s lab, says, “Stress is something we cannot really avoid in cancer patients. You can imagine if you are diagnosed, you cannot stop thinking about the disease or insurance or family. So it is very important to understand how stress works on us.”

    Now, He and Egeblad may have reached a breakthrough in understanding exactly that. Working with CSHL Professor Linda Van Aelst, they discovered that stress causes certain white blood cells called neutrophils to form sticky web-like structures that make body tissues more susceptible to metastasis. The finding could point to new treatment strategies that stop cancer’s spread before it starts.

    The team arrived at their discovery by mimicking chronic stress in mice with cancer. They first removed tumors that had been growing in mice’s breasts and spreading cancer cells to their lungs. Next, they exposed the mice to stress. What He observed was shocking. 

    She saw this scary increase in metastatic lesions in these animals. It was up to a fourfold increase in metastasis.” 

    Mikala Egeblad, Adjunct Professor, CSHL

    The team found that stress hormones called glucocorticoids acted on the neutrophils. These “stressed” neutrophils formed spider-web-like structures called NETs (neutrophil extracellular traps). NETs form when neutrophils expel DNA. Normally, they can defend us against invading microorganisms. However, in cancer, NETs create a metastasis-friendly environment.

    To confirm that stress triggers NET formation, leading to increased metastasis, He performed three tests. First, she removed neutrophils from the mice using antibodies. Next, she injected a NET-destroying drug into the animals. Lastly, she used mice whose neutrophils couldn’t respond to glucocorticoids. Each test achieved similar results. “The stressed mice no longer developed more metastasis,” He says.

    Notably, the team found that chronic stress caused NET formation to modify lung tissue even in mice without cancer. “It’s almost preparing your tissue for getting cancer,” Egeblad explains.

    To Van Aelst, the implication, though startling, is clear. “Reducing stress should be a component of cancer treatment and prevention,” she says.

    The team also speculates that future drugs preventing NET formation could benefit patients whose cancer hasn’t yet metastasized. Such new treatments could slow or stop cancer’s spread, offering much-needed relief.

    Source:

    Journal reference:

    He, X.-Y., et al. (2024). Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment. Cancer Cell. doi.org/10.1016/j.ccell.2024.01.013.

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