Women’s bodies are different from men’s in ways that medicine is still learning. Meanwhile, their risk of serious cardiovascular events can be underestimated if their distinct risk profiles are blurred with men’s.
The latest example of important sex differences centers on the plaque burden in coronary arteries — a measure of fat and cholesterol deposits that also accounts for blood vessel size.
Women tend to have lower volumes of plaque than men, but their total plaque burden is higher because the fatty deposits take up a larger fraction of their smaller coronary arteries. Their risk for a heart attack or hospitalization for chest pain emerged when their plaque burden was lower than men’s, and their risk climbed more steeply, too, a new study published Monday in Circulation: Cardiovascular Imaging concluded.
“What stood out was that although women had lower overall plaque volumes, their risk appeared to emerge at lower plaque burden levels,” lead author Jan Brendel, a postdoctoral research fellow at the Cardiovascular Imaging Research Center at Massachusetts General Hospital and Harvard Medical School, told STAT via email. “At the same time, we also observed substantial overlap between women and men, especially at higher plaque levels. So rather than a dramatic difference, the results suggest nuanced variation in how coronary plaque relates to risk.”
The observational study looked at the coronary CT angiography scans (or CCTA) of just over 4,200 people — half women over age 50 and half men over age 45 — who made up a subset of the much larger PROMISE trial, a study of adults with stable chest pain and no history of coronary artery disease. The new analysis revealed that fewer women (55%) than men (75%) had any coronary plaque; the women also had smaller amounts.
Even so, women were just as likely as men to die from any cause over the two years they were followed. Most striking for researchers hoping to understand whether plaque carries the same prognostic meaning in women and men, the women’s heart risk rose when they had less plaque compared to men. The women’s risk of heart attack or chest pain that would send them to a hospital started at a 20% plaque burden, compared to men’s risk starting at 28%. As plaque levels climbed, risk rose more sharply for women than for men.
Just as it has been more common to measure the quantity of plaque rather than the burden of plaque in small arteries, most studies and clinical practice have focused on the obstructive plaque that, as its name suggests, blocks coronary arteries. Women are more commonly diagnosed with non-obstructive coronary artery disease than men. Despite sounding less threatening, non-obstructive heart disease is still serious: the heart’s arteries tighten, function poorly after branching into tiny vessels, or get squeezed by heart muscle.
“For so long, our management of coronary artery disease has focused on identifying obstructive coronary artery disease, but now, with the increasing use of cardiac CT angiography and new analytics regarding plaque composition, important questions regarding the implications of nonobstructive disease are being raised,” cardiologist Julie Marcus of NewYork-Presbyterian and Weill Cornell Medicine told STAT in an email. She was not involved in the study. “As we move to more advanced quantitative assessments of plaque burden, the implications of these findings are ripe for research. We know that sex differences exist in terms of coronary artery disease, and studies like this are important to better understand these differences mechanistically.”
The larger PROMISE trial discovered that most heart attacks and deaths, particularly in women, occurred in patients with non-obstructive coronary artery disease. An editorial published with the study in Circulation: Cardiovascular Imaging urged continued attention to sex-specific characteristics, singling out non-obstructive disease.
“We must prioritize our efforts to ensure each woman receives proper clinical care for coronary artery disease,” Armin Arbab-Zadeh, a cardiologist at Johns Hopkins Medicine, wrote. “A critical step towards this goal is to emphasize the importance of nonobstructive disease.”
Study author Brendel said the researchers didn’t determine the mechanism behind the sex differences they found, but possibilities include hormonal factors, differences in vascular biology, microvascular dysfunction, and inflammatory processes.
“It’s also possible that traditional risk models — largely developed in male populations — may not fully capture the biology of atherosclerosis in women,” he said. “Ultimately, integrating quantitative plaque assessment into CCTA interpretation may support more precise cardiovascular risk assessment and enable earlier, more individualized prevention strategies.”
The researchers also cited studies documenting disparities in preventive care, which can lead to women receiving fewer guideline-recommended therapies compared with men.
Marcus noted that the interplay between medical therapies and plaque progression has not been fully spelled out.
“As the authors highlight, risk of adverse outcomes appeared to emerge at lower plaque burden in women than in men, so perhaps our threshold for initiating various medical treatments should be adjusted accordingly,” she said. “The goal would be to help identify women at risk of coronary artery disease and future events earlier, so we can improve the prompt initiation of preventative medications and strategies.”
Marcus sees cardiac CT angiography emerging as a tool not just to diagnose heart disease but also to provide quantitative analyses to distinguish what coronary artery disease looks like between men and women. That would allow clinicians to interpret imaging reports, predict future risk, and understand when to start treatment, if appropriate.
“These findings are another important example of why it is imperative to recognize that cardiovascular disease can impact men and women so differently,” said cardiologist Stacey Rosen, who as president of the American Heart Association has urged greater attention to disparities. She is also senior vice president of women’s health at Northwell Health in New York City. “There is an overdue recognition of fundamental, biological differences in the way health conditions manifest in women versus men, and these differences can influence everything from risk factors to symptoms to treatment response.”
