Researchers sought a connection to coffee, which does not appear to cause hypertension. More studies on soda are recommended.

ATLANTA — A 12-year study of more than 155,000 women has found an unexpected possible contributor to the national epidemic of high blood pressure: sugared and diet colas such as Pepsi and Coke.

The research by four scientists from Harvard Medical School and Harvard School of Public Health, published in today's Journal of the American Medical Association, was launched on the assumption that coffee causes high blood pressure.

To their surprise, the study cleared coffee, but pointed the finger at cola instead.

The researchers cannot offer a biological cause and effect for the connection. But after scrutinizing their data for factors such as smoking and family history that could distort their results, they are confident the connection exists.

"There was a direct and positive association between cola consumption and the risk of high blood pressure," said Dr. Wolfgang Winkelmayer of Harvard's Brigham and Women's Hospital, the lead author. "It was present in sugared cola and diet cola, and it was absolutely a surprise to us."

Coca-Cola Co. declined comment, deferring to the American Beverage Association, a trade group.

"The basis for this preliminary finding is unclear and requires further investigation," the association said in a statement. "The authors themselves acknowledge the limitations of their study and contend that more research is needed to determine if caffeinated soft drinks are causally related to an increased risk of hypertension."

Hypertension, the formal term for a persistent blood pressure reading of 140/90 or higher, is one of the most common and deadly cardiovascular conditions. More than 50 million American adults are believed to have it, putting them at increased risk of heart attacks, stroke and kidney failure.

Winkelmayer and his co-authors — Drs. Meir Stampfer, Walter Willett and Gary Curhan — set out to examine whether caffeine consumption affects blood pressure over the long term. Numerous studies have noted that blood pressure rises immediately after drinking caffeine — but none, Winkelmayer said, had observed their subjects for more than a week.

The Harvard researchers, though, had access to data that stretched over years: the Nurses Health Study, begun in 1976 with 121,700 women who were at least 30, and the Nurses Health Study II, begun in 1989 with 116,671 women who were at least 25. The studies are ongoing; every two years, the 238,371 participants give blood and other samples for tests and complete a lengthy questionnaire that includes food they have consumed recently.

Winkelmayer and colleagues examined questionnaires that 155,594 participants from both studies completed between 1990-91 and 2002-03, looking for women who entered the study with normal blood pressure but reported that they later developed hypertension. Using complex statistical programs, they looked at those women's consumption of regular colas, diet colas and regular and decaffeinated coffee and tea.

The results, Winkelmayer said, showed no causal relationship between coffee and high blood pressure. In fact, women who drank more than three cups of coffee daily were about 7 percent to 12 percent less likely to develop high blood pressure than women who drank little or no coffee.

The findings for tea were less clear, showing mixed effects depending on the participant's age.

But in both groups of women, younger and older, there was a clear correlation between cola drinking and high blood pressure.

Those who drank at least four cans of sugared cola drinks daily had a 28 percent to 44 percent increased risk of high blood pressure, compared with women who drank few or none. Diet soft drinks also increased the risk, although slightly less than the nondiet drinks.

And there was no change in risk when the researchers ran the data again to control for factors that also might influence blood pressure, including weight gain, smoking, alcohol use, family history of hypertension and consumption of sodium and chocolate.

"They did a good job; they looked at all the other factors they thought might skew or affect their data," said Dr. Laurence Sperling, director of preventive cardiology at Emory University School of Medicine, who has no connection to the research. "And they did find a consistent relationship between cola-containing beverages and risk of developing high blood pressure."

Other researchers who reviewed the study were more critical.

"These people who are drinking large amounts of soda: What are they not drinking? What are their diets like?" asked Dr. Ruth Kava, director of nutrition for the nonprofit American Council on Science and Health. "It is an interesting result, but I wouldn't want to change what I did or didn't drink based simply on this."

The authors emphasize that their study draws an association between cola and high blood pressure but provides no biological rationale. In their paper, they suggest possible avenues for exploration, including the effect of caramel coloring in all colas and high-fructose corn syrup in sugared ones.

Corn syrup might be a promising avenue, said several researchers not associated with the paper.

Studies have found that consumption of fructose — which makes up 55 percent of high-fructose corn syrup — and rates of obesity and weight-related diseases have risen in tandem over several decades. And lab animals fed large amounts of fructose commonly develop hypertension, said Dr. Steven Aldana, professor of exercise sciences at Brigham Young University .

The study published today should be viewed as a starting point for more research, the authors said.

"I would not base any recommendations on the soda findings at this point," Winkelmayer said. "The take-home message is the clearing of coffee."