Higher concentrations of bisphenol A—a common ingredient in plastics found in products ranging from polyester to water bottles—have been linked to heart disease, according to a new follow-up study. A similar study was performed by the same team in 2008 using older data from a survey conducted by the U.S. Centers for Disease Control and Prevention (CDC).

"Our analysis of the [earlier data] was rightly treated with caution; it was the first ever report of these links," says epidemiologist Richard Melzer of the Peninsula Medical School in England, an author of both studies, the latest one published Tuesday in PLoS ONE. "Associations with heart disease were clearly present again."

Analyzing urine results collected, also by the CDC, from 2,605 U.S. subjects of all ages, the researchers found that higher levels of bisphenol A (BPA) were associated with coronary heart disease, again. Roughly 10 percent of men aged 60 or older who were among the top third in BPA concentrations developed cardiovascular disease compared with roughly 7 percent of similarly aged men with the lowest BPA concentrations, a difference that was statistically significant. "Given the obvious concern that BPA might be driving these health effects, we now need to clarify the mechanism behind these associations," Melzer says.

One possibility is offered by a 2008 study in Environmental Health Perspectives, which found that human fat tissue exposed in culture to BPA showed suppressed levels of adiponectin, a human hormone excreted by fat cells that controls sugar levels in the blood. And another study that year found BPA stored in the fat tissue of women and children in Spain.

"Decreased adiponectin, if it happens in vivo, appears to be a bad thing and could result in increased heart disease," says environmental health scientist Richard Stahlhut of the University of Rochester Medical Center, who was not involved in the research. "So this could be real if [these studies] are right."

To determine that will require further research, such as testing BPA exposure and adiponectin levels, and whether high concentrations of BPA predict subsequent onset of new disease. And there are other candidates for the mechanism behind the link. "The animal and cell work suggest a number of possibilities, including disruption of sex hormone signaling, changes in adiponectin release, oxidative damage, and direct effects on muscle cells," Melzer says. But "this new analysis shows that the trends are present repeatedly. This greatly strengthens doubts about the safety of BPA and the case for research."

BPA is a ubiquitous component in many plastics, including the form of polycarbonate used to make products such as water and baby bottles, sports equipment, medical and dental devices, and eyeglass lenses. The compound is also used to make epoxy resins that coat the insides of food and beverage cans. More than one million metric tons of the polymer is made in the U.S. alone each year. Human exposure is thought to result from eating or drinking contaminated food and beverages that have picked up BPA from plastic containers or plastic container liners. It remains unclear how long BPA lingers in the body, a topic Stahlhut has researched, finding that it can still be detected in human urine even after 24 hours of fasting.

Already, both the U.S. Environmental Protection Agency and U.S. Food and Drug Administration have undertaken new reviews of BPA safety, although the FDA has missed several deadlines for its new report. Countries such as Canada and states including Minnesota have banned BPA in products such as baby bottles because infant exposure could be more dangerous. The U.S. Department of Health and Human Services's National Toxicology Program has classified BPA as of "some concern" for "development of toxicity in fetuses, infants and children—with effects on the brain, behavior and the prostate gland," warning in a report that "the possibility that bisphenol A may alter human development cannot be dismissed."

For now, U.S. scientists with concerns about BPA recommend that anyone sharing those worries avoid using products made from it: Polycarbonate plastic can be clear or colored, and is typically marked with a "number 7" on the bottom, and canned foods such as soups can be purchased in cartons instead.

But the data in this latest study also revealed something puzzling: falling levels of BPA in urine when 2006 measurements were compared with 2004; concentrations decreased from an average of 2.49 to 1.79 nanograms per milliliter. "There don't seem to have been any changes in assay methods used by the labs at CDC Atlanta," Melzer notes. "BPA in baby's bottles has been very controversial and we speculate that manufacturers may be switching to other plastics for use involving food and beverages."

And it may be that the link between BPA and heart disease is merely correlation and not causation. "Could there be a reason why heart disease patients or diabetics or even just obesity maybe would get exposed to higher levels of BPA than the rest of us?" Stahlhut asks. "Replication is not very sexy, but it is important…. It makes it more likely that we have a real association. It doesn't address whether or not the association is causal, just that it's not as likely due to chance."