As legendary Emory cardiologist Nanette Wenger, MD, wrote in a 2016 American College of Cardiology article: “Although heart disease is the number one killer of women, cardiovascular disease was really thought of as a man’s disease until the last few decades.”

In the not-so-distant past, Wenger added, “Women who came into the emergency room with chest pains were told they had a stomach problem or that they were imagining the pain and had emotional problems, so they were sent home.”

Thankfully, following down the path first carved out by pioneers like Wenger, there are researchers and physicians like Viola Vaccarino, MD, PhD, who have continued to build a data-backed case for the fact that women are very much not just making things up.

Viola Vaccarino, MD, PhD

Vaccarino, the Wilton Looney Professor of Cardiovascular Research at Rollins’ Department of Epidemiology and faculty member in the Division of Cardiology, is the principal investigator of a prospective study funded by the National Institutes of Health (NIH) looking at sex differences in bodily responses to mental stress and subsequent cardiovascular events among young and middle-aged patients who survived a heart attack at Emory University. 

A resulting paper focusing on the reactivity of small vessels to stress, published earlier this month in the journal Arteriosclerosis, Thrombosis, and Vascular Biology, will be one of two articles featured in the AHA Journal’s April 2023 issue.

Samaah Sullivan, PhD, the first author of the paper, now at the University of Texas Health Science Center at Houston, was a postdoctoral fellow at Emory University working with Vaccarino when she embraced this research. With these latest findings, Sullivan, Vaccarino and their co-authors—including Emory cardiologists Puja Mehta, MD, Arshed A Quyyumi, MD, and Amit Shah, MD—are building upon a growing body of evidence that links acute mental stress with a host of adverse cardiovascular events especially among women.

Samaah Sullivan, PhD

Their work supports emerging research that the function of small vessels, also known as the microcirculation, plays a key role in ischemic heart disease (meaning decreased blood flow and oxygen to the heart muscle) among women. Vaccarino and her colleagues went into this new study with a strong hunch that mental stress makes this condition far worse. And, “in fact, that’s exactly what we found,” she said.

The women in the study experienced more tightening of their small peripheral arteries (the blood vessels that carry blood away from the heart to other parts of the body) than men did when under mental stress. Not only that, but this microvascular response to stress was also associated with adverse outcomes in women but not in men. As a result, researchers determined that the ways in which small peripheral arteries in the body respond to stress carry important risks for women.

Vaccarino said that the reasons for these differences between women and men are still unclear. But the team is working steadily toward gaining more insights.

To that end, she added, there’s a strong need for more studies and clinical trials to include more diverse samples of patients. “If we think about stress and mental health issues, a larger representation of women is essential,” Vaccarino said. “We knew that women are more likely to have these issues – stress and depression. Young and middle-aged women struggle more, and we think it's perhaps because of the hardship of everyday life they may face.”

Indeed, finding a clinical trial in the cardiovascular field that has included the same number of women as men can be challenging. “If we’re lucky, it’s normally 30%,” she said. In the case of this study, however, the participant breakdown between men and women was almost 50/50. How? By not turning people away because their symptoms were subtler or because they had other comorbidities. 

“To get participants in the study, we rigorously defined heart attacks, but didn’t exclude people because they have other health problems, which opens up a level of participation for women. That’s one thing that clinical trials should be more open to doing.”

In terms of next steps, Vaccarino said they’re planning to continue deepening their research into this area, thanks to continued funding from NIH. They have already begun enrolling men and women into a second phase of the study, which will have a larger sample size and go into more detail about the findings.

This second research phase will also expand stressful exposures “from the lab to everyday life,” and in a separate study they’ll also start looking at women and men in rural communities in four states in the southeast (not including Georgia). Eventually, Vaccarino said the goal is for these findings to help inform clinicians and the public and expand health advisories from professional organizations.

“Often stress and mental health factors are not considered in the guidance,” Vaccarino said. “And as we identify these specific mechanisms, there could be opportunities for future interventions.”

Vaccarino holds a medical degree from the University of Milan and a PhD in epidemiology from Yale University. She joined Emory in 2000 in the Division of Cardiology and was the Chair of the Department of Epidemiology at the Rollins School of Public Health between 2010 and 2018. She has directed the Emory Program in Cardiovascular Outcomes Research and Epidemiology ("EPICORE") since 2005.