Researchers identified genes and biological pathways linked to immune regulation, metabolism, and circadian rhythm in people who reduced their hypertension after eight-week relaxation response training.

BOSTON – High blood pressure – or hypertension – is a major risk factor for heart attack and stroke that affects as many as 100 million Americans and 1 billion people worldwide. Decades of research have demonstrated that the relaxation response – the physiological and psychological opposite of the well-known fight-or-flight stress response that can be achieved through relaxation techniques like yoga or mediation – can reduce blood pressure in people with hypertension. Exactly how these interventions act on the body to lower blood pressure remains unclear.

A new study led by investigators at Beth Israel Deaconess Medical Center (BIDMC), Massachusetts General Hospital (MGH), and the Benson-Henry Institute for Mind Body Medicine at MGH identified the genes associated with the body’s response to relaxation techniques and sheds light on the molecular mechanisms by which these interventions may work to lower blood pressure. The findings were published today in the Journal of Alternative and Complementary Medicine.  Read the study here.

“Traditionally, hypertension is treated with pharmacologic therapy, but not all patients respond to drug therapy, and many experience treatment-limiting side effects,” said co-senior author Randall Zusman, MD, Director of the Division of Hypertension at MGH. “In these patients, alternative strategies are invaluable. In this study, we found that the relaxation response can successfully help reduce blood pressure in hypertensive patients who are not taking medication.”

Towia Libermann, PhD, Director of the Genomics, Proteomics, Bioinformatics, and Systems Biology Center at BIDMC said, “To our knowledge, this is the first study to test such a mind-body intervention for a population of unmedicated adults with carefully documented, persistent hypertension, and this is the first study to identify gene expression changes specifically associated with the impact of a mind-body intervention on hypertension. Our results provide new insights into how integrative medicine – especially mind-body approaches – influences blood pressure control at the molecular level.”

First described more than four decades ago by Herbert Benson, MD, Director Emeritus of the Benson Henry Institute and a co-author of the current study, the relaxation response is characterized by a set of measurable changes to the body, including decreased respiration rate and heart rate, all of which can be induced by mind-body techniques including meditation and yoga. Long-term relaxation response practice has been associated with increased brain cortical thickness and specific changes in gene expression.

In this study, Libermann, Zusman and colleagues enrolled 58 people with Stage 1 essential hypertension – defined as having a systolic (top number) blood pressure between 140-159mm Hg and diastolic (bottom number) between 90-104mm Hg. Participants were either not taking medications to control their blood pressure or had tapered off them for five weeks prior to the outset of the study. Participants also filled out standardized questionnaires about stress, depression and anxiety.

Over the next eight weeks, participants attended eight weekly training sessions at which they were guided through mind-body interventions designed to elicit the relaxation response – including diaphragmatic breathing, mantra repetition and mindfulness meditation –while passively ignoring intrusive thoughts. Participants were also given an audio CD that guided them through the same sequence for use at home once a day.

After the eight weeks of training, patients filled out the same stress, depression and anxiety questionnaires and had blood drawn for gene expression testing along with blood pressure measurement. Overall, 13 of the 24 participants who completed the eight-week intervention experienced a clinically relevant drop in blood pressure – that is, specific reductions in both systolic and diastolic blood pressure readings that moved participants below 140/90 mm Hg, the clinical definition of stage 1 hypertension.

Patients who demonstrated significant reductions in both systolic and diastolic blood pressure – enough so that their blood pressure was below the definition of Stage I essential hypertension – were classified as “responders.” Those whose blood pressure still fell within the definition of Stage I hypertension – and those who did not see reduction in both numbers – were classified as “non-responders.”

When Libermann and colleagues ran gene expression analyses comparing blood samples from the two groups, they found that specific gene expression changes had occurred in the responders over the course of the eight-week relaxation response intervention that were not observed in the non-responders. Specifically, among responders the expression of 1,771 genes differed between the baseline blood tests and those taken after the eight weeks of relaxation response practice. Further, Libermann and colleagues determined that the reduction in blood pressure was correlated with genes linked to immune regulatory pathways, metabolism and glucose metabolism, cardiovascular system development and circadian rhythm.

“Interactive network analysis of the gene signature identified several molecules, particularly immune system-linked genes, as critical molecules for blood pressure reduction,” said first author Manoj Bhasin, PhD, Co-Director of the Genomics, Proteomics, Bioinformatics, and Systems Biology Center at BIDMC.

“Our results suggest that the relaxation response reduced blood pressure – at least in part – by altering expression of genes in a select set of biological pathways,” co-first author John Denninger, MD, PhD, Director of Research at the Benson-Henry Institute, noted. “Importantly, the changes in gene expression associated with this drop in blood pressure are consistent with the physical changes in blood pressure and and inflammatory markers that one would anticipate and hope to observe in patients successfully treated for hypertension.”

​ In addition to Zusman and Libermann, investigators included co-first author Manoj Bhasin and Marie Joseph of Beth Israel Deaconess Medical Center; co-first author John Denninger, Jeffrey Huffman, Halsey Niles, Emma Chad-Friedman, Roberta Goldman, Beverly Buczynski Kelley, Barbara Mahoney, Gregory Fricchione and Herbert Benson of Massachusetts General Hospital and Benson-Henry Institute for Mind Body Medicine at MGH; and Jeffery Dusek of Abbott Northwestern Hospital, Institute for Health and Healing.

This study was funded by a grant from the Centers for Disease Control and Prevention (R01 DP000339).

About Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding.

BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.

Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $900 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, genomic medicine, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2017 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of “America’s Best Hospitals.”

 

The Benson-Henry Institute for Mind Body Medicine in the Department of Psychiatry at MGH was established in 2006 to improve the clinical care of MGH patients through the application of mind body integrative medicine approaches and to improve our understanding of the mechanisms involved through basic and clinical research.

In celebration of International Yoga Day, the Benson-Henry Institute for Mind Body Medicine at MGH is pleased to invite the entire community to hear Jeffery Dusek, PhD present “Kripalu’s RISE: A Yoga-Based Mindfulness Program for Healthcare Professionals, Educators and Frontline Professionals.”  This presentation will be held Thursday, June 21^st from 1 PM to 2:15 PM in the MGH Ether Dome.

Since its inception in 2015, the International Day of Yoga has served as an opportunity to study and celebrate the physical, mental and spiritual practice of yoga.  In Massachusetts, the celebration precedes the 3^rd International Conference on Integrative Medicine: Role of Yoga and Ayurveda in Cancer and Palliative Care, which will be held June 22-24, 20198 at the Joseph Martin Conference Center at Harvard Medical School.

Dr. Dusek, the Chief Research Officer at Kripalu Center for Yoga & Health in Stockbridge, MA, will discuss the ways in which mindfulness and yoga practices can help healthcare providers balance life and work.  Dr. Dusek has been a longtime research collaborator with the Benson-Henry Institute for Mind Body Medicine (BHI) at Massachusetts General Hospital, is a recent appointee of MGH’s Department of Psychiatry.

Download the flier

The holidays can be the best of times and the worst of times, but we can manage our response to stress and find joy in small things to build resiliency. BHI’s John Denninger, MD, PhD, has some ideas for how to make the holidays a little lighter and brighter for those who may be feeling stressed, lonely or overwhelmed during this second pandemic holiday season.

By focusing our intentions on the following, Dr. Denninger says, we can reframe our thoughts and bring positivity to a stressful season or event: optimism, flexibility, social connection, creativity and kindness, and mindfulness.

 

Optimism

Focusing on optimism in an intentional way is a good way to reduce pandemic-related stress.

“We should be reminding ourselves that things are likely to continue to improve,” Dr. Denninger says. “We can expect the best, while preparing for the worst and build a sense of empowerment by doing our part to lessen the impact of the pandemic: getting vaccinated, wearing masks, limiting our exposure and, when we gather together, doing so in small groups and in safe, ventilated spaces.”

Gratitude is another important thing factor.

“Gratitude has been shown to be helpful in maintaining mood and preventing depression. Although it may seem like a difficult time to generate gratitude—with everyone weary from all we’ve been through—it is a time to focus on how grateful we are for what we’ve come through, what we’ve survived.”

Dr. Denninger recommends keeping a gratitude diary—on paper, on your phone or other device, or just as a daily reflection.  Bringing to mind one to three things, people, or activities we appreciate each day can be a wonderful way to maintain gratitude and build a positive outlook.

 

Flexibility

Flexibility in the face of adversity is a trait we can all benefit from cultivating.

“You may be thinking, ‘Here we are—even in highly vaccinated Massachusetts—and we’re still seeing an upswing in infection rates!’ Practicing flexible thinking will help us see that this doesn’t mean we can’t celebrate with friends and family, but just have to think about shifting things a little: having smaller gatherings, making sure all are vaccinated—and preferably boosted—and paying to attention to what local COVID rates are.”

Recognize that we can’t control the pandemic, just our response to it.

“Practice acceptance. Acceptance is not saying that you like the situation—it’s just coming to a point where you can admit, ‘This is the reality, I have to deal with it,” and then figure out where to go from there,” Dr. Denninger says.

“We’ve all had things we’ve needed to accept—things beyond our control—and we’ve all experienced the peace that comes from accepting a situation as opposed to just being angry or hurt by it.  We are in the midst of a pandemic, and, sure, the holidays are going to be somewhat different. But they can still be joyous.”

 

Social Connection

Many people report feeling isolated or lonely at the holidays, and even more so during the pandemic.

“One thing is to take stock of who you give support to and who you get support from—both now and in the past. Especially during this holiday season it may be a good time to reach out to people you think may need your support or to those who have no one to spend the holidays with and may be feeling lonely,” Dr. Denninger says.

And it doesn’t just have to be to individuals; we can reach out (even virtually) through religious organizations, support groups, clubs and peer-led organizations like Alcoholics Anonymous, all of which can be wonderful ways to connect.

It’s also a good idea to gather with others who love the things you do: if you are an art lover, go to a museum. You’ll find others who share your passion. Like music? Try a concert (but wear a mask). Even if you’re going to something by yourself, it can be a way to feel connected to the people around you when you’re sharing in things you all enjoy.

“Human beings are social creatures, and if we feel that our connection to our family or work group has been damaged, there are many others who are looking for similar connections. It can feel difficult to reach out, but we often find that that difficulty is easily overcome. Especially at the holidays, and during a pandemic.”

 

Creativity & Kindness

Kids are great at expressing creativity, but somewhere along the line many adults stop finding time to be “makers.”  Find time pick up an old knitting project, get back to your woodworking tools, get out some pencils and find some time to draw or color.  Dr. Denninger and his family like to make gingerbread houses during the holidays.

“it’s not about the finished product, it’s about finding time to do something you enjoy.”

People draw satisfaction and purpose from helping others; so, while you’re being creative, you can bake some cookies for a neighbor and drop them off.  Take the extra food in your cupboards to the local pantry, donate toys or coats to those less fortunate.

“We can improve our own outlook by knowing we are useful and helpful to those around us.  Think of who in your life could use a little boost, and find a way to make that happen—whether it’s going through old photos and sending them to a friend or shoveling an elderly relative’s driveway, there are plenty of things we can do to make ourselves and those around us feel valued and seen.”

 

Taking a Mindful Moment

If something is stressful, stop, breathe, reflect, and choose:

• Stop for a moment
• Take time to do some mindful breathing or a longer guided meditation
• Reflect on how you want to proceed in the face of the stressor
• Choose a path forward.

“We’re all in the same boat together.  One could view that as something to be despairing about, but it’s also an opportunity for us to come together,” Dr. Denninger says.  “The holidays are a potential time for unity and wouldn’t it be nice if we were all working together toward unity and compassion?”