Women who regularly take acetaminophen, ibuprofen or similar painkillers have as much as double the normal risk of developing high blood pressure, Boston researchers reported yesterday.

Although many popular over-the-counter painkillers have been linked before to high blood pressure, acetaminophen, best known by the brand name Tylenol, has generally been considered relatively free of such risk.

"What is important and new in this study is that acetaminophen can raise blood pressure" just like ibuprofen, said Dr. Gregg Fonarow, a cardiologist at UCLA Medical Center who was not involved in the study. "That has not been completely appreciated."

The regular use of these drugs by millions of Americans may help explain the growing incidence of high blood pressure, or hypertension, in the United States, where one in five people suffers from the problem, a team from Brigham and Women's Hospital reported in the online edition of the journal Hypertension. High blood pressure is a major contributor to heart disease and strokes.

The Brigham and Women's team originally reported their conclusion three years ago using data from the massive Nurses' Health Study, an epidemiological study in which more than 120,000 female nurses have been followed since 1976.

At the time, critics charged they did not have enough data about actual dosages of the drugs or about complicating factors, such as headaches, which might have caused the increased risks. For example, hypertension can cause headaches, which could lead to increased use of painkillers, rather than vice versa.

The new study was designed to answer those critics, said co-author Dr. Gary Curhan of Brigham and Women's.

The study found no increased risk of hypertension from regular use of aspirin, Curhan said. But the authors do not recommend that women switch to aspirin because of its increased risk of gastrointestinal bleeding.

The study represents a second black mark against acetaminophen. Regular use of acetaminophen and related drugs triples the risk of kidney disease, and by some measures accounts for as much as 20 percent of all kidney disease requiring dialysis or transplants.

NSAIDs

The other painkillers in the study, which are among a class of drugs called NSAIDs (non-steroidal anti-inflammatory drugs), also have been found to carry other risks. The federal government recently required NSAIDs to carry stricter warning labels because of the risk for heart-related problems.

NSAIDs include ibuprofen, sold as Advil and Motrin, and naproxen, sold as Aleve. Many people had turned to those painkillers in the wake of problems with prescription drugs such as Vioxx.

Acetaminophen, aspirin and ibuprofen are the three most commonly used drugs in the United States, with total sales of well over $2 billion per year. As many as 45 million Americans take them for chronic headaches and nearly 32 million for arthritis.

Curhan, Dr. John Forman and Dr. Meir Stampfer studied 1,903 women between the ages of 51 and 77 and 3,220 women between the ages of 34 and 53. None had high blood pressure at the beginning of the study.

The women, who were members of the original Nurses' Health Study, were given supplementary questionnaires about how much of the drugs they took and why they took them.

Older women taking more than 500 milligrams of acetaminophen daily — the equivalent of one extra-strength Tylenol — were 93 percent more likely to develop hypertension than those not taking the drugs, while younger women taking the same dosage were 99 percent more likely.

For ibuprofen, older women taking at least 400 milligrams per day — two regular-strength tablets — were 78 percent more likely to have high blood pressure, while younger women were 60 percent more likely.

Absolute risk

The absolute risk of developing hypertension, however, was small in the entire group. In this study, the risk of developing high blood pressure for women who weren't taking painkillers was about 1 to 3 percent a year, researchers said.

The researchers concluded that the increase in risk was directly related to dosage, but there were not enough women in the study using higher doses to quantify their risks.

"We are by no means suggesting that women with chronic pain conditions not receive treatment for their pain," Forman said in an e-mail. "By pointing out risks associated with these drugs, more informed choices can be made by women and their clinicians."

Dr. Christie Ballantyne, a cardiologist at the Methodist DeBakey Heart Center in Houston who had no role in the study, said, "If you're taking these over-the-counter medications at high dosages on a regular basis, make sure that you report it to your doctor and you're checking your blood pressure."

As for why aspirin didn't raise risk, it might be because "aspirin has a different effect on blood vessels than NSAIDs and acetaminophen have," said Dr. Daniel Jones, dean of the school of medicine at University of Mississippi Medical Center in Jackson.