C-reactive protein may presage hypertension.

A protein that shows up in inflammation may signal risk of high blood pressure, researchers report in the first large-scale trial to link the two disorders.

The compound, called C-reactive protein (CRP), has already been implicated in heart disease and stroke. In light of that, some doctors have begun routinely testing patients' blood for elevated concentrations of the compound. Many studies have indicated that low-level inflammation triggers blood vessel damage.

While CRP's role in either inflammation or heart disease is far from clear, high blood pressure is a well-recognized danger sign for heart attacks and strokes.

To investigate a link between CRP and hypertension, epidemiologist Howard D. Sesso of Harvard Medical School in Boston and his colleagues tapped into a database of 20,525 women who had donated blood samples during the early 1990s as part of a wide-ranging health study called the Women's Health Study. The women entered the study at age 45 or older with no history of high blood pressure, heart disease, stroke, or cancer. But after roughly 8 years, one-fourth of them showed high blood pressure.

The scientists measured CRP in the initial blood samples and then divided the volunteers into roughly equal-size high-, medium-, and low-CRP categories. They found that women in the low-CRP group were about 50 percent as likely to have developed hypertension during the study as were those in the high-CRP category. The report appears in the Dec. 10 Journal of the American Medical Association.

Next, the researchers set aside the data from women who smoked, were overweight, had diabetes, were using hormone therapy, or had high cholesterol. Of the 6,795 women who remained, those with low CRP at the start of the study were still only about 60 percent as likely to have developed high blood pressure as were the high-CRP women.

The study shows a "potential relationship between hypertension and inflammation," says Daniel Jones, an internist at the University of Mississippi Medical Center in Jackson. But scientists still need to determine whether inflammation can incite high blood pressure in lab animals, he says. Until then, "there are too many gaps in our knowledge" to suggest that CRP causes high blood pressure, Jones says.

The largest gap lies in the absence of a recognized biological mechanism for the link, but basic research has turned up some possibilities. For example, studies show that vessel-lining cells exposed to CRP produce abundant surface molecules that activate angiotensin, a compound that causes blood pressure to rise. Other research suggests that CRP depresses production of nitric oxide, a vessel dilator.

However, since the role of CRP in inflammation remains unclear and its link to hypertension unproved, doctors should be careful about prescribing anti-inflammatory drugs--which can have side effects--on the basis of a high CRP reading, says physician Marvin Moser of Yale University School of Medicine.