• A number of lipid parameters and biomarkers predict heart disease in women better than LDL cholesterol level.
• More precision phenotyping approaches are necessary.

SCOTTSDALE, Ariz. — Certain lipid parameters and biomarkers are better predictors of heart disease in women than LDL cholesterol level, a speaker said at the American Society for Preventive Cardiology Congress on CVD Prevention.

The insight was part of the 2026 Nanette Wenger Award Lecture delivered by Samia Mora, MD, MHS, director of the Center for Lipid Metabolomics at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School. The award, named after Healio | Cardiology Today Editorial Board Member Nanette Wenger, MD, who pioneered research on sex-specific CVD risk, is given to someone who has made major contributions to women’s heart health.

Data from the Women’s Health Study published in Circulation in 2009 showed that women with high LDL cholesterol levels had a 74% increased risk for incident CVD, but women with a high number of LDL particles had a 2.51-fold increased risk, those with high apolipoprotein B particle levels had a 2.57-fold increased risk and those with a high ratio of total cholesterol to HDL cholesterol had a 2.82-fold increased risk, Mora said during the presentation.

“The total atherogenic particle burden, or the measures that represent more the particle count rather than the cholesterol per se, especially in women, were better predictors of risk,” Mora said.

That led to the determination, in a paper published in Circulation in 2014, that women with discordance — higher LDL and/or ApoB particle counts than their LDL cholesterol levels would indicate — were at increased risk for CVD compared with women with the same LDL cholesterol levels but lower LDL and/or ApoB particle counts, she said.

“There were a subset of women who were higher risk because they had higher particle count,” Mora said. “This is how the ApoB comes in, because in individuals who have similar LDL cholesterol, if the ApoB is high, then the risk is high. And that’s what the guidelines have also now moved toward identifying both for men and for women. The more atherogenic particles we have, the greater the risk.”

Despite these papers and other research that have refined women’s CVD risk, the number of women experiencing MI before age 55 years has grown in recent years, Mora said.

“The women who had the earlier-onset events ... were the women who had more premature metabolic risk factors, in particular diabetes,” Mora said, referring to a paper published in JAMA Cardiology in 2021. “The relative risk for diabetes was 10-fold for having an MI or another current event less than age 55 in women. Metabolic syndrome was the other really strong risk factor, with fivefold increased risk. Smoking was also relevant, with a threefold increased risk, but I think now the burden has turned into cardiometabolic disease being the primary driver behind this premature presentation.”

The biomarker most predictive of coronary heart disease in women younger than 55 years is lipoprotein insulin resistance, she said.

These data suggest numerous opportunities to improve prevention of heart disease in women, Mora said during the presentation.

“The good news is that if we take a life course look at a woman’s risk and identify her risk earlier, especially when she is coming in for OB/GYN or earlier care early on, we actually can build on a lot about what predicts a woman’s risk. So this life course lens is important. To reiterate Nanette’s global call to action, we need to understand the biological differences between men and women, and we need a cultural shift toward not treating women as atypical. We need more precision phenotyping approaches.”