Although cardiovascular disease is a leading cause of death for women, they remain underrepresented in clinical trials for common heart conditions. These findings, by investigators in the Smidt Heart Institute at Cedars-Sinai, were presented at the 2025 European Society of Cardiology Congress in Madrid.

“Numbers don’t lie,” said Martha Gulati, MD, director of Preventive Cardiology in the Smidt Heart Institute and senior author of the paper. “We hope that keeping track of male-to-female participant ratios will motivate researchers to design trials that reflect the real-world population.”

Gulati presented the findings in an oral abstract at the European Society of Cardiology Congress. The results were simultaneously published in JAMA Network Open.

Gulati and colleagues reviewed data from 1,079 cardiovascular clinical trials registered on ClinicalTrials.gov from 2017 to 2023. Women accounted for 41% of the study participants. Investigators found the proportion of women included in clinical trials for certain conditions was much lower than the proportion of women who have these conditions.

The team applied a ratio called the participation-to-prevalence ratio (PPR) to capture whether the percentage of women in a clinical trial reflected how common the condition is among women. The participation-to-prevalence ratios for women were lowest for trials of coronary heart disease, acute coronary syndrome and stroke. Research on obesity and pulmonary hypertension had much higher female participation.

Investigators also found that younger women, ages 19 to 55, were more likely to participate in clinical trials than women 61 or older, and that women tended to enroll in trials studying lifestyle interventions and not trials studying procedures.

“Some studies might stop enrolling once they reach a certain number of people,” Gulati said. “It would be more equitable to continue enrolling until the number of women in the study reflects the proportion of women with that condition.”

The authors also recommend researchers improve outreach efforts to female patients.

“Although we’ve made progress, critical gaps persist,” said study co-author Susan Cheng, MD, MPH, the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science in the Smidt Heart Institute. “It’s important to ensure that what we learn from research can be applied to women, who represent more than half of the world’s population.”

Frederick Berro Rivera, MD, is first author of the study. Other authors include John Vincent Magalong, MD; Nathan Ross B. Bantayan, BSc; Nicole Tesoro, MD; Mark Jason Milan, MD; Vikramjit Purewal, DO; Polyn Luz S. Pine, MD, MBA; Chieh-Mei Tsai, MD; Ann Marie Navar, MD, PhD; Sharon L. Mulvagh, MD; James Januzzi, MD; C. Michael Gibson, MD; Anuradha Lala-Trindade, MD; Kyla Lara-Breitinger, MD; and Mayra Guerrero, MD.

Funding: This work was supported by contracts from the National Heart, Lung, and Blood Institutes, General Clinical Research Center, National Center for Advancing Translational Sciences, Department of Defense, Gustavus and Louis Pfeiffer Research Foundation, Women’s Guild of Cedars-Sinai Medical Center, Ladies Hospital Aid Society of Western Pennsylvania, QMED, Edythe L. Broad and the Constance Austin Women’s Heart Research Fellowships (Cedars-Sinai Medical Center), Barbra Streisand Women’s Cardiovascular Research and Education Program (Cedars-Sinai Medical Center), Society for Women’s Health Research, Linda Joy Pollin Women’s Heart Health Program, Erika Glazer Women’s Heart Health Project, Adelson Family Foundation (Cedars-Sinai Medical Center), Robert A. Winn Diversity in Clinical Trials Career Development Award, and the Anita Dann Friedman Endowment in Women’s Cardiovascular Medicine & Research.

Read more on the Cedars-Sinai Blog: Why Diversity Matters in Clinical Trials

Exercises that work the muscles help build bone mass, improve balance, reduce joint stiffness, lower blood pressure and boost metabolism.

Gulati told the Los Angeles Times strength training can include lifting weights as well as yoga, Pilates, Tai Chi and using the body’s own weight—doing pushups, lunges and planks—to build muscle.

Using resistance bands is another way to increase resistance over time, she said, explaining that “it may not feel like you’re lifting a heavy weight, but they are tough. Even people with joint problems can do that.”

Gulati told the Los Angeles Times building muscle mass is especially important for older adults because muscle loss occurs naturally with aging and increases rapidly after 60.

“Falls can be catastrophic as we age and building our muscle mass is really important,” she said. “It’s not about becoming a bodybuilder, it’s about preserving your health. Just to be healthy and strong is a beautiful thing.”

Strength training also can reduce the risk of death from cardiovascular disease in women, according to a recent study Gulati led.

She told the Los Angeles Times older adults should discuss weight training with their doctor—especially if they are new to it, haven’t exercised recently or have a heart condition.

Click here to read the complete article from the Los Angeles Times.

Gulati, the study’s co-lead author, told TIME that because women usually have less muscle mass than men, the same amount of exercise can be just as or more impactful.

“For me, the news to women is: a little goes a long way,” Gulati said.

Gulati, the Anita Dann Friedman Chair in Women’s Cardiovascular Medicine and Research, told TIME that men should not feel discouraged by the study’s findings.

“Our pitch should be the same to men and women: something is better than nothing,” Gulati said. “Sit less and move more.”

In an interview with ABCNews.com, Cheng, the study’s senior author, said the results were “exciting and positive, especially for the really busy women out there who are juggling a lot of responsibilities both at work and at home.”

Cheng, who holds the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science, told CNN.com that exercising is a choice, but the benefits can be significant. 

“The irony is that exercise is free,” Cheng said. “The catch, of course, is that exercise takes work.”

Click here to read the complete article from TIME, here to read the complete article on ABCNews.com and here to read the complete article on CNN.com.

The findings, published in the Journal of the American College of Cardiology (JACC), show that women can exercise less often than men, yet receive greater cardiovascular gains.   

“Women have historically and statistically lagged behind men in engaging in meaningful exercise,” said Martha Gulati, MD, director of Preventive Cardiology in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai, the Anita Dann Friedman Chair in Women's Cardiovascular Medicine and Research and co-lead author of the study. “The beauty of this study is learning that women can get more out of each minute of moderate to vigorous activity than men do. It’s an incentivizing notion that we hope women will take to heart.”

Investigators analyzed data from 412,413 U.S. adults utilizing the National Health Interview Survey database. Participants between the time frame of 1997 to 2019—55% of whom were female—provided survey data on leisure-time physical activity. Investigators examined gender-specific outcomes in relation to frequency, duration, intensity and type of physical activity.

“For all adults engaging in any regular physical activity, compared to being inactive, mortality risk was expectedly lower,” said Susan Cheng, MD, MPH, the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science, director of the Institute for Research on Healthy Aging in the Department of Cardiology in the Smidt Heart Institute, and senior author of the study. “Intriguingly, though, mortality risk was reduced by 24% in women and 15% in men.”

The research team then studied moderate to vigorous aerobic physical activity, such as brisk walking or cycling, and found that men reached their maximal survival benefit from doing this level of exercise for about five hours per week, whereas women achieved the same degree of survival benefit from exercising just under about 2 1/2 hours per week.

Similarly, when it came to muscle-strengthening activity, such as weightlifting or core body exercises, men reached their peak benefit from doing three sessions per week and women gained the same amount of benefit from about one session per week.

Cheng said that women had even greater gains if they engaged in more than 2 1/2 hours per week of moderate to vigorous aerobic activity, or in two or more sessions per week of muscle-strengthening activities. The investigators note their findings help to translate a longstanding recognition of sex-specific physiology seen in the exercise lab to a now-expanded view of sex differences in exercise-related clinical outcomes.

With all types of exercise and variables accounted for, Gulati says there’s power in recommendations based on the study’s findings. 

“Men get a maximal survival benefit when performing 300 minutes of moderate to vigorous activity per week, whereas women get the same benefit from 140 minutes per week,” Gulati said. “Nonetheless, women continue to get further benefit for up to 300 minutes a week.”

Christine M. Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute and the Lee and Harold Kapelovitz Distinguished Chair in Cardiology, says concrete, novel studies like this don’t happen often.

“I am hopeful that this pioneering research will motivate women who are not currently engaged in regular physical activity to understand that they are in a position to gain tremendous benefit for each increment of regular exercise they are able to invest in their longer-term health,” said Albert, professor of Cardiology.

Other Cedars-Sinai authors include Tzu Yu Huang, MSc; Alan Kwan, MD; David Ouyang, MD; and Joseph Ebinger, MD. Other authors include Hongwei Ji, MD; Kaitlin Casaletto, PhD; Kerrie L. Moreau, PhD; and Hicham Skali, MD, MSc.

Funding: This work was supported in part by NIH grants K23HL153888, K23AG058752, R21HL156132, R01HL142983, R01HL151828, R01HL131532, R01HL143227, R01AG072475, U54AG062319, and U54AG065141, and the Erika J Glazer Family Foundation, National Key R&D Program of China (2022YFC2502800), National Natural Science Foundation of China (82103908), Shandong Provincial Natural Science Foundation (ZR2021QH014), Shuimu Scholar Program of Tsinghua University, and National Postdoctoral Innovative Talent Support Program (BX20230189).

Read more from the Cedars-Sinai Blog: High Blood Pressure: How to Recognize and Treat It

Gulati told Voice of America host Crystal Dilworth that heart disease is the leading cause of death for women, who don’t always experience the same symptoms as men. Though 90% of men and women report having chest pain or pressure before a heart attack, Gulati said women are more likely to experience three or more additional symptoms, including profound fatigue, shortness of breath, jaw pain and shoulder pain.  

Gulati, associate director of the Preventive and Rehabilitative Cardiac Center in the Smidt Heart Institute at Cedars-Sinai and the Anita Dann Friedman Chair in Women’s Cardiovascular Medicine and Research, said she and her colleagues are “finding that there’s a difference in the underlying pathophysiology of cardiovascular disease. Certain types of diseases we’re seeing more frequently in women compared with men.”

Women also account for 90% of Takotsubo cases and 60% of heart failure with preserved ejection fraction, said Merz, a professor of Cardiology and the Irwin and Sheila Allen Chair in Women’s Heart Research. She gave Dilworth examples of differences in male and female bodies, both of which can lead to heart attack. Women have proportionately smaller coronary arteries that can be too small to effectively deliver blood to the heart. Whereas men have larger arteries that are prone to clogging. Because of these differences, a heart attack in a woman won’t appear the same as in a man or require the same treatment.

Merz and Van Eyk—the Erika J. Glazer Chair in Women's Heart Health—studied blood samples collected from women with Takotsubo syndrome up to 10 years after the initial diagnosis. They compared these samples with blood collected from healthy individuals and found different protein patterns in the blood of Takotsubo patients, a lasting marker of the disease.

“What we know with Takotsubo is that if you’ve had it once, you’re at a higher risk of getting it a second time,” Van Eyk said.    

Click here and here to watch the complete segments from Voice of America. 

The medication, sold under the names Wegovy and Ozempic, belongs to a class of medications called GLP-1 agonists.

But “there’s more to them than simply weight loss,” Gulati said of these drugs, which improve fatty-acid metabolism and reduce inflammation. “This is what’s so fascinating about these drugs. They work on the brain, the pancreas, the cardiovascular system, the gastrointestinal tract,” Gulati, the Anita Dann Friedman Endowed Chair in Women’s Cardiovascular Medicine and Research, told Nature.

Early data from a clinical trial suggest that Wegovy could help patients avoid serious heart issues. The results indicate that semaglutide reduced the risk of serious cardiovascular events— including heart attack, stroke and death—by 20%.

Despite these promising results, providers have been hesitant to prescribe the drug to avoid giving hope to patients, only for them to be turned down by their insurance, said Gulati, who was not involved in the study. But physicians are eager to recommend the medication.

“It’s hard to think of other [drugs], apart from statins, that have shown such a profound effect,” Gulati told Nature.

Complete data from the trial will be presented at a conference later this year with hopes it will result in approval of the medication by the U.S. Food and Drug Administration for cardiovascular-risk reduction.

If semaglutide becomes more widely accessible, it “will be a game-changer for the clinical practice of preventive cardiology,” Gulati said.

Click here to read the complete article from Nature.

The study—published in the peer-reviewed journal Current Problems in Cardiology—also found that the Black, Hispanic, Asian and Pacific Islander patients who had both COVID-19 and an acute myocardial infarction (AMI)—the medical term for a heart attack—fared worse than their white counterparts.

“The COVID-19 pandemic had a significant impact on heart attack patients and disrupted optimal care that led to delays and changes in traditional, often lifesaving treatment approaches,” said Martha Gulati, MD, director of Preventive Cardiology in the Smidt Heart Institute and the study’s senior author. “Most importantly, we found significant racial disparities in the management of AMI in patients with concurrent COVID-19, with Black, Hispanic, Asian, and Pacific Islander patients receiving lower rates of treatment when compared to white patients.”

Gulati, the Anita Dann Friedman Endowed Chair in Women’s Cardiovascular Medicine and Research and the associate director of the Barbra Streisand Women’s Heart Center, said these findings point to the urgent need to address disparities and enhance access to care.

As investigators explain, the COVID-19 pandemic put a spotlight on gaps in cardiovascular care that already existed based on race and ethnicity. Addressing these disparities in healthcare urgently requires a multifaceted approach.

“While this study provides valuable insight, it is one piece of the puzzle,” said Christine M. Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute. “Addressing healthcare disparities, particularly during a global pandemic, requires a concerted effort from all stakeholders, including policymakers, healthcare providers, and the community at large.”

The Cedars-Sinai Newsroom sat down with Gulati to learn how the findings of this research study prompted ideas on addressing healthcare disparities and enhancing access to care:

Newsroom: Please share your recommendations on how best to address healthcare disparities and enhance access to care.

Gulati: There are four main ways to address these disparities, which include improving access; providing culturally sensitive care; addressing social determinants of health; and policy changes.

Newsroom: How might the medical field improve access?

Gulati: We must increase access to high-quality healthcare in and for underserved communities. This could include establishing more medical offices in these areas, improving transportation to healthcare facilities, and enhancing telehealth capabilities.

Newsroom: How can providers better provide culturally sensitive care?

Gulati: We must first ensure that healthcare providers are trained to provide culturally sensitive care. This includes understanding and respecting cultural differences, addressing language barriers and actively combating biases and stereotypes.

Newsroom: What are some of the ways the broader medical community can address social determinants of health?

Gulati: We must address the social determinants of health that contribute to these disparities. This includes efforts to reduce poverty, improve education, and provide safe and secure housing.

Newsroom: How can policy changes make an impact?

Gulati: Implementing policy changes to reduce systemic bias and racism in the healthcare system could involve changes to how care is funded. This might include assessing measures of quality, rewarding quality care and better identifying how resources are allocated.

DOI: https://doi.org/10.1016/j.cpcardiol.2023.101798

Additional Cedars-Sinai investigators include Amer Muhyieddeen, MD, and Susan Cheng, MD, MPH.

Read more on the Cedars-Sinai Blog: Preventing Heart Disease in Women