Can a different approach improve evaluation and treatment for women with heart disease?
Can a program to lower stress reduce insomnia and associated life-threatening diseases for Black women?
Can an understanding of biological sex, chronic pain, and opioid use improve treatments for opioid use disorder?
This last year has delivered difficult but important lessons. These are lessons about how sex, gender, race, and ethnicity influence the development and health outcomes of disease. As well as the increasing prevalence of certain disorders. With these three new studies, we are taking the next necessary steps toward understanding conditions that continue to have a devastating effect on women. And particularly on women of color.
Investigating a Method for Improving the Diagnosis of Heart Disease in Women
Dr. Samit Shah is using this year’s Wendy U. and Thomas C. Naratil Pioneer Award to study women with ischemic heart disease. Ischemia, or reduced flow of blood to the heart, is often caused by a blocked artery. This results in chest pain and other well-recognized symptoms of a heart attack. But many women with reduced blood flow to the heart do not show “typical” symptoms. In a catheterization procedure, when specialists thread a long thin tube through blood vessels to the heart, these women often do not have blocked arteries or cholesterol build-up that that is usually associated with heart disease. This study is focusing on women with reduced blood flow to the heart who do not have significant blockages in the blood vessels. The focus of this work will be to improve the diagnostic value of invasive heart catheterizations so we can better assess all forms of heart disease in women.
Under the current standard for diagnosis of ischemic heart disease, women receive the same evaluation performed on men. This invasive procedure is known as coronary angiography. It uses contrast dye and X-rays designed to detect cholesterol build-up, called plaque. This plaque blocks blood flow supplying oxygen to the heart. But about 50 percent of women who suffer from ischemic heart disease do not have significant coronary artery disease with such plaque buildup. Instead, these women might experience a problem with the small blood vessels or spasms that can suddenly narrow an artery. Routine coronary angiography cannot help to diagnose such conditions.
“With the current diagnostic standard, symptomatic women may be told that there is nothing wrong or that they should feel reassured that there isn’t a more serious problem,” said Shah, an interventional cardiologist at Yale School of Medicine. “But these patients suffer from a poor prognosis with persistent symptoms. Better understanding of the underlying disease process would set the foundation for improved patient communication and the development of targeted therapies.”
Technological advances now allow cardiologists to safely and effectively diagnose abnormalities in the functioning of the heart that often drive symptoms of heart disease in women. But these tests are not widely used because they need increased time and expertise. And providers are not sure if extra testing is better than trial and error with different medications.
Dr. Shah’s team is studying 100 women over two years undergoing coronary angiography at Yale New Haven Hospital. They are testing the real-world diagnostic benefit of validated, but not-widely used physiological tests. They are seeking to determine coronary artery pressure and flow for women with ischemia but who show no evidence of obstructive coronary artery disease. They are comparing the outcomes with women receiving standard care for the same diagnosis. The researchers are also comparing the patients’ experiences using structured interviews. The patients answer questions about their perception of their illness. Other questions cover the patients’ ability to control symptoms, quality of life, lifestyle modification, and medication changes.
Building on work begun by Dr. Erica Spatz’s WHRY-funded research, Dr. Shah is also leading efforts to develop a multi-center registry of women with ischemia but no evidence of obstructive coronary artery disease. He is creating a guide for future research and a tool for cardiologists to categorize, diagnose, and treat such patients more accurately.
A Therapy for Clinically Significant Sleep Disruption Common in Black Women
About 30 percent of adults in the United States suffer from insomnia. This is a condition that can include difficulty initiating or maintaining sleep, early awakening, and impaired daytime functioning. Effects can include anxiety, moodiness, and fatigue. Other possible effects include irritability, poor work performance, headaches, and upset stomach. The condition is generally undertreated and more common in women than men.
Black women in the United States have an especially high prevalence of significant insomnia. For example, Black women report shorter total sleep time, take longer to fall asleep, wake more often, and spend more time in bed awake than White women. This is true even after controlling for socioeconomic status. Psychological stressors contributing to sleep difficulty are often reported to be rooted in the sociocultural intersection of race and gender. They can be compounded by socioeconomic strains. This stress can result in sleep deficiency observed in studies through objective sleep measurements and that produces potentially damaging physical responses.
The current recommended treatment for insomnia is cognitive behavioral therapy (CBT-I). But about 60 percent of people undergoing CBT-I continue to experience insomnia following completion of the therapy.
With a grant from WHRY, Dr. Soohyun Nam is studying the effectiveness of a mindfulness-based therapy for insomnia (MBTI) designed to target the causes of sleep difficulty specifically for Black women. Dr. Nam has spent nine years developing relationships with the community in the Greater New Haven area. This has included meetings to elicit input on potential sleep interventions. The meetings produced positive reactions for the feasibility and likely reception of MBTI.
“To date, no published intervention research including MBTI has targeted Black women’s insomnia,” said Nam, Associate Professor of Nursing at Yale School of Nursing. “With our strong community support and promising findings from our previous studies, we believe we can fill a need for an intervention to reduce psychological stress to improve sleep in Black women.”
The mindfulness-based intervention that Dr. Nam is using is an evidence-based management program. It has been shown to be effective across a variety of health conditions. In applying it to insomnia, Dr. Nam’s team is seeking to address the psychological stress that Black women experience. They are doing this by cultivating non-judgement, self-compassion, and present-focused awareness. The researchers are collecting data on the feasibility and acceptability of MBTI to reduce stress, improve sleep, and reduce health risks associated with insomnia. The goal is to launch a full-scale trial to support wide adoption of the intervention in conjunction with community partners.
Opioids, Pain, and the Brain
Two million Americans suffer from chronic pain, 70 percent of whom are women.
Even though the country has been understandably preoccupied with the coronavirus pandemic, we remain in the midst of an epidemic of opioid use, addiction, and overdose deaths — which increased by 29 percent over the last year. This represents the greatest number of overdose deaths since the opioid epidemic began. The degree to which overdose rates are rising is greater among women. Women are more likely to become exposed to opioids as a function of seeking medical care for acute or chronic pain. After exposure, women are more likely to become addicted.
But women remain underrepresented in research on this subject. And most research studying pain focuses on different areas of the brain than the research on addiction. As a result, headway has not been made in understanding the intersection of pain, analgesia, and opioid use. And no studies to date have explored the influence of sex.
With a WHRY grant, Dr. Sarah Yip is launching the first-ever adequately sized study of these interactions with an emphasis on women. She is using a recently developed assessment technique called connectome-based modeling. The connectome provides a "wiring diagram” of all the brain’s neural connections at the same time. This allows simultaneous examination of pain and addiction-based circuitry capable of producing unique and highly valuable insights.
“Using this new technique, we are able to produce what you might call a neural fingerprint,” said Yip, Assistant Professor of Psychiatry and Director of the Yale Imaging and Psychopharmacology Lab. “With this approach, we can discover pathways in the brain involved in the sensation of pain and pain relief through opioids. In this way, we can take a critical first step toward understanding individual patterns of brain organization between and among females and males to better treat chronic pain and avoid addiction.”
Working with co-project leader, Dr. Sarah Lichenstein, Dr. Yip’s team is using magnetic resonance imaging (MRI) to scan women and men. They are following them over six months to collect data. The data includes their experience of pain, severity of any opioid use, and any co-occurring disorders. The researchers will use the connectome’s state-of-the-art methods to analyze the neuroimaging data and describe how pain and opioids interact. They will also identify potential neural markers that might predict outcomes for people with opioid use disorder (OUD). This work builds on collaborations with Drs. Declan Barry, Marc Potenza, and Kathleen Carroll. In part, the work could guide development of improved, sex-specific treatments for people with OUD.
“Despite our country’s long and ongoing struggle with opioid addiction, we still do not understand enough about how the brain responds to pain and opioids,” Yip said. “By using the connectome to study this interaction at the same time, we can seek ways to relieve pain that account for the dangers of opioids and the neurological differences between how women and men experience pain."
Women's Health Research at Yale's Pilot Project Program
The Pilot Project Program is made possible by The Rice Family Foundation, The Werth Family Foundation, the Community Foundation for Greater New Haven, and the Maximilian E. and Marion O. Hoffman Foundation.
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