Americans knock back an estimated $2 billion a year in over-the-counter painkillers like Tylenol, Advil and Motrin, with little evident concern for their safety. That may change.

A new study suggests that these drugs may increase the risk of developing high blood pressure by as much as twofold in women who are regular users and that a "substantial proportion" of high blood pressure cases may be related to painkiller use.

"It's the first time such a decisive result has been found," said Bernard Rosner, a professor of medicine at Harvard Medical School and one of the paper's authors.

The study followed more than 80,000 middle-aged female nurses, who were asked how many times per month they took painkillers. Two years later the same nurses were asked whether they had been diagnosed with high blood pressure since the study's inception.

The results, though preliminary, are cause for concern because of the extensive use of over-the-counter painkillers in the United States. More than 70 percent of the women in the study used at least one type of painkiller in the average month.

"Given that these medications are readily available over the counter and used by a large proportion of the adult population, this association merits additional study," the researchers concluded.

Women who used acetaminophen, the active ingredient in Tylenol, for 22 days a month or more had the highest hypertension risk, estimated at twice that of non-users. And even those who used the drug as little as one to four days a month had a greater risk than non-users. Women in this category were 22 percent more likely to report high blood pressure than those who took no painkillers.

The risk for those taking NSAIDS (nonsteroidal anti-inflammatory drugs), including ibuprofen products such as Advil and Motrin and naproxen drugs such as Aleve, was similar. Heavy users -- again, those who took the drugs at least 22 days a month -- had a risk of high blood pressure 86 percent higher than those who didn't use the drug. Light users -- again, those who took the drugs only one to four days a month -- carried a 17 percent higher risk.

While aspirin is tied to other risks, including bleeding ulcers, it came off better in this study than the other pain relievers. Although aspirin appeared to raise hypertension risk somewhat, the researchers said the increase was not significant.

Despite Rosner's confidence in the study's design, he suggested additional research may be needed before the results can be generalized to other groups. The authors also noted other study shortcomings, including a lack of data on the length of painkiller use, making it impossible to tell if years of product use raised risk any more than weeks or months of use.

Officials at Johnson & Johnson, the makers of Tylenol, Motrin and St. Joseph's aspirin, said that they knew of no plausible mechanism by which acetaminophen might raise blood pressure and questioned whether other factors could have skewed the data.

-- Brian Reid