Publisher Health

Getting good sleep can play a role in supporting your heart and overall health—and maybe even how long you live—according to new research being presented at the American College of Cardiology’s Annual Scientific Session Together With the World Congress of Cardiology. The study found that young people who have more beneficial sleep habits are incrementally less likely to die early. Moreover, the data suggest that about 8% of deaths from any cause could be attributed to poor sleep patterns.
“We saw a clear dose-response relationship, so the more beneficial factors someone has in terms of having higher quality of sleep, they also have a stepwise lowering of all cause and cardiovascular mortality,” said Frank Qian, MD, an internal medicine resident physician at Beth Israel Deaconess
Medical Center, clinical fellow in medicine at Harvard Medical School and co-author of the study. “I think these findings emphasize that just getting enough hours of sleep isn’t sufficient. You really have to have restful sleep and not have much trouble falling and staying asleep.”
For their analysis, Qian and team included data from 172,321 people (average age 50 and 54% women) who participated in the National Health Interview Survey between 2013 and 2018. This survey is fielded each year by the Centers for Disease Control and Prevention (CDC) and the National Center for Health Statistics to help gauge the health of the U.S. population and includes questions about sleep and sleep habits. Qian said this is the first study to his knowledge to use a nationally representative population to look at how several sleep behaviors, and not just sleep duration, might influence life expectancy.
About two-thirds of study participants self-reported as being White, 14.5% Hispanic, 12.6% Black and 5.5% Asian. Because researchers were able to link participants to the National Death Index records (through December 31, 2019), they could examine the association between individual and combined sleep factors and all-cause and cause-specific mortality. Participants were followed for a median of 4.3 years during which time 8,681 individuals died. Of these deaths, 2,610 deaths (30%) were from cardiovascular disease, 2,052 (24%) were from cancer and 4,019 (46%) were due to other causes.
Researchers assessed ?ve different factors of quality sleep using a low-risk sleep score they created based on answers collected as part of the survey. Factors included: 1) ideal sleep duration of seven to eight hours a night; 2) difficulty falling asleep no more than two times a week; 3) trouble staying asleep no more than two times a week; 4) not using any sleep medication; and 5) feeling well rested after waking up at least five days a week. Each factor was assigned zero or one point for each, for a maximum of five points, which indicated the highest quality sleep.

“If people have all these ideal sleep behaviors, they are more likely to live longer,” Qian said. “So, if we can improve sleep overall, and identifying sleep disorders is especially important, we may be able to prevent some of this premature mortality.”
For the analysis, researchers controlled for other factors that may have heightened the risk of dying, including lower socioeconomic status, smoking and alcohol consumption and other medical conditions. Compared to individuals who had zero to one favorable sleep factors, those who had all five were 30% less likely to die for any reason, 21% less likely to die from cardiovascular disease, 19% less likely to die from cancer, and 40% less likely to die of causes other than heart disease or cancer. Qian said these other deaths are likely due to accidents, infections or neurodegenerative diseases, such as dementia and Parkinson’s disease, but more research is needed.
Among men and women who reported having all five quality sleep measures (a score of five), life expectancy was 4.7 years greater for men and 2.4 years greater for women compared with those who had none or only one of the five favorable elements of low-risk sleep. More research is needed to determine why men with all five low-risk sleep factors had double the increase in life expectancy compared with women who had the same quality sleep.
“Even from a young age, if people can develop these good sleep habits of getting enough sleep, making sure they are sleeping without too many distractions and have good sleep hygiene overall, it can greatly benefit their overall long-term health,” Qian said, adding that for the present analysis they estimated gains in life expectancy starting at age 30, but the model can be used to predict gains at older ages too. “It’s important for younger people to understand that a lot of health behaviors are cumulative over time. Just like we like to say, ‘it’s never too late to exercise or stop smoking,’ it’s also never too early. And we should be talking about and assessing sleep more often.”
These sleep habits can be easily asked about during clinical encounters, and the researchers hope patients and clinicians will start talking about sleep as part of their overall health assessment and disease management planning.  
One limitation of the study is that sleep habits were self-reported and not objectively measured or verified. In addition, no information was available about the types of sleep aid or medicine used or how often or long participants used them. Future research is needed to understand how these gains in life expectancy might continue as people age, as well as further explore the sex differences that were observed.

Previous studies have shown that getting too little or too much sleep can negatively affect the heart. It’s also been widely reported that sleep apnea, a sleep disorder that causes someone to pause or stop breathing while asleep, can lead to a number of heart conditions, including high blood pressure, atrial fibrillation and heart attacks.
Qian will present the study, “Low-risk Sleep Patterns, Mortality, and Life Expectancy at Age 30 Years: A Prospective Study of 172,321 U.S. Adults,” on Monday, March 6, at 12:45 p.m. CT / 18:45 UTC in Prevention and Health Promotion Moderated Poster Theater 10, Hall F.
ACC.23/WCC will take place March 4-6, 2023, in New Orleans, bringing together cardiologists and cardiovascular specialists from around the world to share the newest discoveries in treatment and prevention. Follow @ACCinTouch, @ACCMediaCenter and #ACC23/#WCCardio for the latest news from the meeting.
The American College of Cardiology (ACC) is the global leader in transforming cardiovascular care and improving heart health for all. As the preeminent source of professional medical education for the entire cardiovascular care team since 1949, ACC credentials cardiovascular professionals in over 140 countries who meet stringent qualifications and leads in the formation of health policy, standards and guidelines. Through its world-renowned family of JACC Journals, NCDR registries, ACC Accreditation Services, global network of Member Sections, CardioSmart patient resources and more, the College is committed to ensuring a world where science, knowledge and innovation optimize patient care and outcomes. Learn more at ACC.org,###
Media Contacts Nicole Napoli Thy-Ann Nguyen 202.669.1465 703.638.2938 nnapoli@acc.org thyann.nguyen@curastrategies.com

Adverse childhood experiences in mothers can affect their children’s mental and physical health, as researchers from Charité – Universitätsmedizin Berlin now report in the journal The Lancet Public Health. The study found that maltreatment during a mother’s childhood is associated with a higher risk of health problems such as asthma, autism, and depression in the next generation. Early intervention to support affected mothers might help to counter this effect.
Maltreatment during childhood is an especially serious risk factor for health problems in the exposed individual, as it brings a host of lifelong consequences. Among the impacts are physical, mental, behavioral, and social ramifications that can continue through pregnancy and parenthood. As a result, adverse experiences during the parents’ childhood can affect their own children’s development and health.
Higher risk of asthma, ADHD, autism, and depression
In the newly published study, a team of researchers headed by Dr. Claudia Buss, a professor at the Institute of Medical Psychology at Charité, shows that health problems are more common in children of mothers who experienced maltreatment themselves as children. The researchers define maltreatment as physical, emotional, or sexual abuse or neglect by a parent or guardian leading to physical or emotional harm or the threat of harm to a child. They analyzed data on more than 4,300 American mothers and their children from 21 long-term cohorts. Mothers reported on their childhood experiences and provided information on health diagnoses in their biological children up to the age of 18, or this information was collected during visits conducted as part of the study. This valuable trove of data extending across two generations of the same family allowed researchers to identify meaningful connections.
They found that children of mothers who reported adverse experiences were at higher risk of asthma, attention-deficit/hyperactivity disorder (ADHD), and autism. These children also have a higher incidence of symptoms and behaviors associated with depression and anxiety disorders, which are known as “internalizing” disorders. Daughters of mothers in this group are also at higher risk of obesity than their sons. “All of these connections are independent of whether the mother has the same diagnosis,” explains Buss, the study’s lead author. “That suggests that the risk of that particular health problem is not being transmitted genetically.”
First study to cover multiple health outcomes
Researchers have not yet fully decoded the exact mechanisms by which the risk is passed on to the next generation. There are indications that adverse childhood experiences could affect maternal biology during pregnancy, as for example stress hormones. This can affect fetal development in a way that the offspring become more vulnerable for impaired health. There is evidence that biological changes like these are more pronounced in mothers who have developed mental health problems, such as depression, as a consequence of their traumatic experiences. If the mother’s mental health is affected by her childhood experiences, this may also impact on how she interacts with her child once it is born, which is likely to be just as important a factor in these multigenerational effects.

“To our knowledge, this is the first study to examine multiple health problems at once in relation to early trauma in mothers in a large, sociodemographically and ethnically diverse sample. That has been done primarily for individual diseases in the past,” explains Dr. Nora Moog, also from the Institute of Medical Psychology at Charité and first author of the publication. In keeping with this approach, the researchers showed that children of mothers exposed to early trauma are at greater likelihood of developing multiple physical and mental health problems. The risk is also greater the more serious the mother’s childhood experiences were. “At the same time, I should stress that our findings do not mean that all children of mothers with adverse childhood experiences automatically end up with health problems,” Buss says, providing context for the group’s findings. “The risk is elevated, but it doesn’t necessarily lead to a specific health problem.”
Early identification and support for those affected
“I assume that appropriate support for mothers who suffer from the consequences of childhood maltreatment can have a positive effect on their health and well-being and that of their children. That means it’s very important to identify these mothers and children early on,” Buss points out. One way to do this would be to have doctors address parents’ own childhood experiences during prenatal or pediatric checkups and provide information on how to contact various support programs or counseling services. This kind of early intervention could help two generations: the parent, who experienced maltreatment and may be suffering from health consequences; and the child, who could be prevented from developing health problems.
Developing new, targeted therapeutic measures will depend on better understanding the exact mechanisms by which the elevated risk of health problems is passed on to the next generation. The research team is currently working on that. The researchers also plan to conduct follow-up studies to investigate which children remain resilient, meaning they do not suffer consequences beyond one generation: What makes them, their mothers, and their social environment different? Beyond that, the father’s childhood experiences have received relatively little attention so far, but there are indications that these experiences can also be passed on to the next generation, albeit in some cases by different mechanisms than those involved in mother-child transmission. The researchers plan to explore these research questions in further detail in future projects as well.
About the study
The international team of researchers analyzed the data of 4,337 American mothers from 21 long-term cohorts with an eye to the mothers’ childhood experiences. They also examined information on health diagnoses in the mothers’ biological children up to the age of 18. The cohort data were provided by a research program named Environmental influences on Child Health Outcomes (ECHO). ECHO encompasses 69 cohorts in the United States. It is supported by the National Institutes of Health (NIH). Dr. Claudia Buss, a professor at the Institute of Medical Psychology at Charité and adjunct professor at the Department of Pediatrics at the University of California Irvine, led the study. She is a principal investigator of a research group within the ECHO consortium and has furthermore received a Starting Grant from the European Research Council (ERC) and funding from the German Research Foundation (DFG) and the German Federal Ministry of Education and Research (BMBF).

A research group at Uppsala University has developed a simple and effective artificial blood-brain barrier model that can be used to determine how well antibody-based therapies can enter the brain. Today animal experimentation is the most common method for testing an antibody’s function and the new model could reduce the need for animal testing.
Protein-based biopharmaceuticals or biologics, such as antibodies, are promising therapeutic tools to specifically target clumps of protein found in neurodegenerative diseases such as Alzheimer’s disease and Parkinson Disease. However, the blood-brain barrier (BBB) provides a significant hurdle when trying to deliver biologics to areas of the brain to stop these large molecules causing disease.
Greta Hultqvist’s research group at Uppsala University has recently published an article in Molecular Pharmaceutics highlighting the development of an artificial BBB model that can be used to determine how well antibody-based therapies can enter the brain.
One of the most effective ways of delivering large antibodies into the brain is to piggyback existing pathways within the body that are designed to deliver essential molecules. Antibodies can be re-designed to essentially trick the BBB into thinking the antibody needs to enter the brain via an existing pathway. Animal experimentation is the most common method for testing whether an antibody can penetrate the BBB. However, aside from the cost in terms of time and money, there is an ethical requirement to reduce the amount of animal experiments. The artificial BBB model developed by the Hultqvist group can now instead be used to validate the antibody’s ability to cross the BBB.
“There are many different cell culture-based BBB models published, but most try to mimic the complex functions of the BBB, making them harder to work with when compared to the artificial BBB model we have developed that primarily focuses on studying how biologics are transported,” says Jamie Morrison, lecturer at the Department of Pharmacy at Uppsala University.
“Our goal was to develop a robust and simple mouse cell culture model system, where multiple antibodies could be tested in a relatively short period of time. Our results show a clear distinction between antibodies that are able to cross the BBB and those that cannot. Our findings from the new model have been validated in mice,” says Morrison.
The research group has also developed a new in-house designed antibody that has been shown to have a better uptake into the brain compared to traditional antibodies. The new antibody was tested using the artificial BBB model and later confirmed in mice studies. The new antibody was presented in Journal of Neuroscience.
“We validated the results using the artificial BBB model multiple times, but it was still somewhat surprising to see just how well the results mimicked what we saw when conducting brain uptake studies in mice using our antibody. It was exciting to see a significant improvement in brain uptake using the new antibody format,” says Nicole Metzendorf, researcher at the Department of Pharmacy at Uppsala University and first author on the antibody study.
Even though the artificial BBB model is new, it has already become ingrained in many of the new research projects within the research group.
“The assay will no doubt enhance the pre-clinical development of methods to deliver large antibody-based biologics across the BBB and into the brain, providing hope to those suffering from neurodegenerative disorders,” says Morrison.

UVA Health scientists have discovered an unknown contributor to harmful blood vessel growth in the eye that could lead to new treatments for blinding macular degeneration and other common causes of vision loss.
UVA’s Jayakrishna Ambati, MD, and Shao-bin Wang, PhD, and their colleagues have identified a new target to prevent the formation of abnormal tangles of blood vessels associated with eye conditions such as neovascular age-related macular degeneration, proliferative diabetic retinopathy and ischemic retinal vein occlusion.
“Our study has opened up the possibility of mitigating aberrant blood vessel growth in eye diseases by targeting the epigenetic machinery,” said Ambati, the founding director of UVA’s Center for Advanced Vision Science and a member of the University of Virginia School of Medicine’s Department of Ophthalmology. “Through local targeting of the epigenetic regulator, we have gained a deeper understanding of how ocular immune cells can cause a loss of control over blood vessel growth under the retina. This approach also offers a new direction for the development of more effective, cost-efficient and accessible interventions, thereby avoiding issues such as drug resistance, which is a growing concern with conventional anti-VEGF therapies used in clinical treatments.”
Understanding Vision Loss
Scientists have known that abnormal vessel overgrowth in the eye is fueled by excessive amounts of a substance called “vascular endothelial growth factor-A,” or VEGF, that plays an important role in blood vessel formation. There are now treatments available that target VEGF to prevent vessel overgrowth, and they often provide dramatic benefits at first. Unfortunately, these benefits can fade with time. That leaves doctors in need of better treatments to help preserve patients’ eyesight.
Ambati and Wang’s new research identifies a key protein that determines VEGF levels. Blocking this protein in lab mice reduced their VEGF levels significantly, and it did so in a targeted way, without unwanted side effects. The scientists noted, for example, that they observed no toxic effects on the retina, the light-sensing portion of the eye where the vessel overgrowth occurs. “This fat mass and obesity-associated (FTO) protein was previously shown to be correlated with obesity in humans. Unexpectedly, we found it also play important roles in regulating ocular neovascularization through an epigenetic mechanism,” Ambati said. “This exciting discovery finally answers a longstanding question about how ocular immune cells, such as macrophages, contribute to abnormal blood vessel growth under the retina. This question was first investigated by our team 20 years ago, and we’re thrilled to have found an answer.”
In addition to identifying a promising target for the development of new treatments for vision loss, the discovery sheds important light on the fundamental mechanisms responsible for the blood vessel overgrowth that robs millions of people of their sight. Neurovascular age-related macular degeneration alone affects more than 200 million people worldwide. While much more research and testing will be needed before the new finding could be translated into a treatment, the UVA scientists are excited about the potential of the discovery.
“Current strategies for treating ocular neovascular disorders, which primarily focus on regulating the protein levels of VEGF, are not perfect. Therefore, it is imperative to identify more targetable candidates to develop alternative therapies,” Wang said. “We are hopeful that our study will pave the way for the development of new treatments, ultimately reducing the burden of neovascular-related illnesses.”

Scientists who study the origins and evolution of the plague have examined hundreds of ancient human teeth from Denmark, seeking to address longstanding questions about its arrival, persistence and spread within Scandinavia.
In the first longitudinal study of its kind, focusing on a single region for 800 years (between 1000-1800AD), researchers reconstructed Yersinia pestis genomes, the bacterium responsible for the plague, and showed that it was reintroduced into the Danish population from other parts of Europe again and again, perhaps via human movement, with devastating effects.
The historical samples were taken from nearly 300 individuals located at 13 different archaeological sites throughout the country.
“We know that plague outbreaks across Europe continued in waves for approximately 500 years, but very little about its spread throughout Denmark is documented in historical archives,” says Ravneet Sidhu, one of the study’s lead authors and a graduate student at McMaster’s Ancient DNA Centre, where the analysis was conducted.
The McMaster researchers, working with a team of historians and bioarchaeologists in Denmark and Manitoba, performed an in-depth examination of the relatedness and differences between the different strains of plague that were present in Denmark during this time.
They reconstructed and sequenced the genomes of Y. pestis, using fragments teased from ancient teeth, which can preserve traces of blood-borne infection for centuries. They compared the plague genomes to one another and to their modern-day relatives.

Researchers found positive plague samples in 13 individuals who had lived and died over a period of three centuries.
Nine of those samples provided enough genetic information to draw evolutionary conclusions about the plague’s persistence in Denmark. The results create a picture of urban and rural populations hammered by relentless waves of plague.
“The high frequency of Y. pestis reintroduction to Danish communities is consistent with the assumption that most deaths in the period were due to newly introduced pathogens. This association between pathogen introduction and mortality illuminates essential aspects of the demographic evolution, not only in Denmark but across the whole European continent,” says Jesper L. Boldsen, the skeletal collection curator and paleodemographer at ADBOU, University of Southern Denmark.
The analysis, reported today in the journal Current Biology, revealed that the Danish Y. pestis sequences were interspersed with medieval and early modern strains from other European countries, including the Baltic region and Russia, rather than coming from a single domestic cluster that re-emerged from natural reservoirs over the centuries.
“The evidence for plague in Denmark, both historical and archaeological, has been far more sparse than in some other regions, such as England and Italy. This study identified plague for the first time from medieval Denmark, therefore enabling us to connect the experience in Denmark to disease patterns elsewhere,” said Julia Gamble a co-author on the study and assistant professor of anthropology at the University of Manitoba.

In striking detail, researchers describe the earliest known appearance of Y. pestis in Denmark in the town of Ribe dating back to 1333 during the Black Death, its appearance in rural areas such Tirup — where there is no surviving historical evidence — and its disappearance by 1649.
Most places it hit in Denmark were port cities, but one of the last outbreaks struck a small rural site in the centre of the country with no access to water, suggesting importation via land.
Plague is a disease of rodents, but clearly the results suggest human-facilitated movement of plague, either via rodents travelling with humans or via other vectors, such as lice, on them.
“The results reveal new connections between past and present experiences of plague, and add to our understanding of the distribution, patterns and virulence of re-emerging diseases,” says Hendrik Poinar, senior author of the paper, director of the McMaster Ancient DNA Centre and an investigator with the Michael G. DeGroote Institute for Infectious Disease Research.
“We can use this study and the methods we employed for the study of future pandemics,” he says.

Gestational diabetes and preeclampsia may be linked to slower biological development in infants, according to a new study led by USC.
The research, published today in JAMA Network Open, found that newborns exposed to these two pregnancy complications were biologically younger than their chronologic gestational age. The infants’ biological or “epigenetic” age is based on molecular markers in their cells.
The results raise intriguing questions about how common pregnancy complications may affect infants and health outcomes later in childhood. Could they create developmental delays? Could some exposures advance biological age prematurely, even in the womb? What about stressors such as exposures to environmental pollution?
“In aging research, if your epigenetic ‘clock’ shows an older age than your chronological age — due to exposures to various stressors — that’s viewed as bad, as putting people at increased risks for illness,” said corresponding author Carrie Breton, a professor of population and public health sciences at the Keck School of Medicine of USC. “We wondered how far back we could take this concept; could we take it to the womb?
“In this case we found the opposite — pregnancy complications led to babies with a younger biological age. This raises a ton of questions about the impact later in life. This is a fairly new metric and very little is known about it.”
For the study, researchers collected DNA samples from 1,801 newborns from 12 cohorts across the U.S. The participants were born between 1998 and 2008 to mothers who had preeclampsia, gestational diabetes or hypertension during pregnancies and compared to pregnancies without any of these complications.
The researchers used these samples to evaluate each infant’s epigenetic age. They then compared the epigenetic age to the infant’s chronological age at birth, measured in pregnancy weeks.
The researchers found that babies who were exposed to preeclampsia or gestational diabetes while they were developing in the womb were biologically younger than babies without the exposures, indicating that these exposures may have slowed down the babies’ biological development. The difference was more noticeable in female babies compared to male babies. Exposure to hypertension didn’t have a measurable impact.
“In the future, we plan to continue our research with a larger sample of participants and investigate whether these biological changes detected at birth are linked to health outcomes later in childhood,” said Breton. “If so, doctors and researchers could use that knowledge to develop targeted interventions that can reduce the adverse effects of preeclampsia and gestational diabetes on children’s health.”
In addition to Breton, other authors of the study are Elizabeth Vang, Sahra Mohazzab-Hosseinian, Zhongzheng Niu and Daniel Weisenberger of the Keck School; Christine Ladd-Acosta, Xingyu Gao, Meredith Palmore, Ashley Song and Heather Volk of Johns Hopkins University; Emily Barrett of Rutgers University; Catherine Bulka, Rebecca Fry and Michael O’Shea of the University of North Carolina at Chapel Hill; Nicole Bush of the University of California, San Francisco; Andres Cardenas of the University of California, Berkeley; Dana Dabelea of the University of Colorado; Anne Dunlop, Anna Knight, Elizabeth Kennedy and Alicia Smith of Emory University; Jaclyn Goodrich of the University of Michigan; Julie Herbstman of Columbia University; Marie-France Hivert of Harvard University; Linda Kahn and Leonardo Trasande of New York University; Margaret Karagas of Dartmouth College; Andréanne Morin of the University of Chicago; Douglas Ruden of Wayne State University; Rebecca Schmidt of the University of California, Davis; and Eliot Spindel of Oregon Health & Science University.
The research was supported by the Environmental influences on Child Health Outcomes Program (ECHO) at the National Institutes of Health.