New research from the University of Illinois Urbana-Champaign has linked multiple types of per- and polyfluoroalkyl substances (PFAS, also known as "forever chemicals") with increased risk of cardiovascular diseases in postmenopausal women. Specifically, the study reveals how PFAS chemicals interact with pro-inflammatory pathways in older women, providing potential explanations for the increased risk.

The work is published in the journal Toxicological Sciences.

"Previous research suggests PFAS exposures may play a role in the development of cardiovascular disease during the menopause transition, but the biological mechanisms were not well understood," said lead study author Alicia Arredondo Eve, a postdoctoral researcher in the Department of Food Science and Human Nutrition (FSHN) in the College of Agricultural, Consumer and Environmental Sciences (ACES) at Illinois.

"We focused on specific PFAS chemicals as well as the cardiovascular diseases that are more common in older women."

It's difficult to escape PFAS. The man-made chemicals coat nonstick pans, waterproof clothing, food wrappers, receipts, and many more items we come in contact with daily, not to mention being present in much of our water supply. Some forms—and there are thousands of chemical variants—could persist in the environment for hundreds or thousands of years, hence their "forever chemicals" moniker.

Not surprisingly, studies suggest nearly all Americans carry PFAS in their blood and other bodily tissues. But premenopausal women are a little better off. Thanks to childbirth, breastfeeding, and their monthly menstrual cycle, premenopausal women expel more PFAS than men and postmenopausal women. After menstruation stops, PFAS accumulates and can cause problems.

Scientists are still piecing together exactly what PFAS chemicals do in the body, but they appear to disrupt hormone signaling, interfering with normal reproductive and cardiovascular function. Most PFAS studies have focused on men or women during their reproductive years, but Arredondo Eve and co-author Zeynep Madak-Erdogan say postmenopausal women experience unique cardiovascular issues.

Motivated to fill the knowledge gap, the researchers analyzed data and samples from 70 postmenopausal women in Turkey. About a third of the women had been diagnosed with coronary artery disease, the world's leading form of heart disease. Another third had coronary microvascular disease, which is common in postmenopausal women. The remaining third had no sign of heart disease.

All of the samples were tested for the presence and levels of two long-chain "legacy" PFAS (no longer manufactured in the U.S.)—PFOS and PFOA—and a newer short-chain PFAS chemical known as PFBS. Next, the researchers used complex machine-learning techniques to analyze the relationships between the PFAS and various blood metabolites and proteins.

"When you have multiple factors and you want to focus on one or two, machine learning techniques are very efficient in reducing that number," said Madak-Erdogan, an associate professor in FSHN. "We found PFOS was closely associated with coronary artery disease, while PFOA was more predictive of coronary microvascular disease."