- A new study shows that, despite having less plaque overall, females experience cardiovascular events at a similar rate to males, suggesting that they face a risk at lower levels of plaque buildup.
- In females, cardiovascular risk increased earlier and more steeply at lower plaque levels, suggesting that uniform plaque thresholds may underestimate risk in females.
- As such, the study’s findings indicate that sex-specific interpretation could improve risk assessment.
Cardiovascular diseases are the
Previous research has highlighted sex-specific differences for CAD, with females having a significantly greater risk of experiencing complications. Notably, plaque characteristics differ between males and females.
Females often have a smaller coronary artery diameter, meaning they can present with a higher total plaque burden. This describes the total amount of fatty deposits within an artery, typically expressed as the percentage of the vessel area occupied by plaque.
Now, a study published in
These findings indicate that using the same plaque thresholds for both sexes could underestimate cardiovascular risk in females.
Although previous research has shown sex-specific plaque characteristics and that females tend to have smaller overall plaque volumes, it is still unclear how these differences translate into the risk of major adverse cardiovascular events (MACE), such as heart attack, hospitalization for chest pain, or death.
To explore this question, researchers from Mass General Brigham analyzed data from nearly 4,300 stable outpatients with chest pain and no known history of CAD.
The team drew on data from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial, which included participants across 193 sites in North America.
Using coronary computed tomography angiography (CCTA), the researchers assessed total plaque volume, total plaque burden, and plaque subtype, including stable and high-risk plaques.
The researchers found that while females had a lower median total plaque volume than males, their vessel size–adjusted total plaque burden was similar.
After a median follow-up of 26 months, females and males experienced comparable rates of MACE.
Lead author Jan Brendel, MD, of the Cardiovascular Imaging Research Center (CIRC) in the Mass General Brigham Department of Radiology, was surprised at the similar MACE rates despite differences in total plaque volume:
“Yes, that was notable. Women had lower absolute plaque volumes but similar event rates.”
“Because women have smaller coronary arteries, a smaller absolute plaque volume may reflect a comparable relative disease burden, helping explain why event rates were similar despite differences in total plaque volume.”
— Jan Brendel
Kevin Shah, MD, board certified cardiologist and Program Director of Heart Failure Outreach at MemorialCare Heart & Vascular Institute at Long Beach Medical Center, who was not involved in the study, also emphasized this finding:
“This study reinforces that plaque biology and distribution matter — not just total quantity. Less plaque does not necessarily mean low risk in women.”
A key finding was that female cardiovascular risk appeared at a lower level of plaque burden. In particular, the risk of MACE increased at a total plaque burden of about 20% in females, compared with around 28% in males.
“From a clinical perspective, this suggests that modest plaque burden warrants careful attention rather than being assumed benign, particularly in women,” Brendel added.
Additionally, the pattern of risk progression also differed. In females, MACE risk rose more steeply at lower plaque levels. In contrast, males displayed a more gradual increase in risk, typically requiring a higher plaque burden before risk accelerated.
Importantly, these sex-based differences persisted even after researchers adjusted for traditional cardiovascular risk factors and imaging findings, such as the presence of high risk plaques.
Brendel notes that these findings could help to avoid underestimating cardiovascular risk in females:
“First, avoid assuming that low plaque volume equals low risk. Second, consider plaque burden – which accounts for vessel size – rather than volume alone. And third, integrate imaging findings with clinical risk factors to ensure women receive appropriate preventive evaluation and follow-up.”
The study findings indicate that current approaches to interpreting coronary plaque measurements may need refinement.
If clinicians rely on uniform thresholds for plaque burden, females could be classified as lower risk despite having a meaningful likelihood of adverse events.
Therefore, incorporating sex and potentially age into plaque interpretation could potentially improve risk prediction and help guide earlier preventive strategies.
“Currently, there are no widely established plaque burden thresholds in routine clinical practice,” Brendel highlighted.
“Our data do not justify immediate sex-specific cutoffs. Rather, they support the need for future research to develop such age- and sex-specific thresholds or reference ranges, similar to percentile-based approaches used for coronary calcium scoring,” he said.
The researchers suggest that tailoring cardiovascular risk assessment could help to reduce missed opportunities for prevention. This may be particularly true for females, who have historically been under-recognized and undertreated in cardiovascular care.
Shah shared similar sentiments on potential changes to risk thresholds:
“The data suggest that risk thresholds may not be one-size-fits-all. Women may reach clinically meaningful risk at lower plaque burdens than men.”
“Future guidelines may benefit from incorporating sex-specific interpretations, but additional validation of these findings would be important before formal changes are made. Take symptoms seriously, use imaging thoughtfully when risk is uncertain, and avoid dismissing lower plaque burdens as ‘low risk’ without considering the full clinical picture. Prevention should be individualized based on patient goals, values, and preferences.”
— Kevin Shah, MD
