HARVARD GAZETTE ARCHIVES

JoAnn Manson is part of a nationwide team that has found a new predictor of strokes, heart attacks, and fatal heart disease. (Staff file photo Kris Snibbe/Harvard News Office)

"For years, researchers have suspected a link between elevated white blood cell count and heart attack," notes JoAnn Manson, one of the study leaders and Elizabeth F. Brigham Professor of Women's Health at Harvard Medical School. "The present study is the largest to test this association and provides the strongest evidence to date that WBC [white blood cell] count predicts the risk of heart attack."

As part of the federally supported Women's Health Initiative, investigators at medical centers all over the United States collected information on 72,242 postmenopausal women 50 to 79 years old. All were free of heart and blood vessel disease at the start of the study. During six years of follow-up, 1,626 heart disease deaths, heart attacks, and strokes occurred. Women with more than 6.7 billion white cells per liter of blood had more than double the risk of fatal heart disease than women with 4.7 billion cells per liter or lower. A count of 6.7 is considered to be in the upper range of normal, so what is "normal" may have to be redefined.

Women with the highest counts had a 40 percent higher risk of nonfatal heart attack, 46 percent higher risk of stroke, and a 50 percent greater risk of death from all causes.

These research results are independent of other risk factors such as smoking, diabetes, high blood pressure, high cholesterol, obesity, and lack of physical activity. Therefore, WBC count may identify people with a high probability of heart disease who show none of the more obvious risk factors.

Relevance for men

Asked if the same test would be as revealing for men, Manson answered, "We have every reason to believe so. Some small studies have suggested a similar link in men. There probably will be other studies to look at this link in greater depth."

Manson also believes that white blood cell counts apply to younger as well as older women. "They would apply, but women under 50 are less likely to have high counts," she says. "That's because they are less likely to have been exposed to risk factors that raise the counts and eventually lead to hardening and blockage of their arteries."

Women (or men) can take steps to keep their counts down, simply by reducing or avoiding things that tend to raise them, such as smoking, high cholesterol levels, and being overweight, Manson says. "We are also looking into the contribution of factors like high blood pressure and diabetes," she points out. "Although all these risk factors correlate with high WBC counts, the two are independent so WBC levels can be elevated in the absence of traditional factors."

No new tests need to be developed, because blood-cell levels are now measured routinely in doctors' offices. The tests identify patients with infections or check for those at risk for infections, like cancer patients undergoing chemotherapy. "Physicians may want to look closer at WBC levels when obtaining the tests for other reasons," Manson notes. "However, infections can cause a high white blood cell count that may make it appear that a patient is at high risk for heart disease when she is not. Therefore, routinely giving everyone the test to screen for heart disease is premature. More research needs to be done."

A companion test

High WBC levels signal the presence of inflammation in blood vessels, which doctors believe is involved in hardening and clogging arteries. Someday, this test might be combined with measurement of C-reactive protein (CRP), another marker for inflammation. The Women's Health Initiative study included measurements of CRP, and it turned out to be almost as good a predictor of heart disease.

"Used together, the two can provide additive and powerful information about risk," Manson comments. Women who showed high levels of both inflammation markers had seven times the risk of heart disease as those with low levels.

These results were published in the March 14 issue of the Archives of Internal Medicine. Besides Manson, the authors include Karen Margolis of the Hennepin County Medical Center in Minneapolis and colleagues at participating medical facilities in several other states.

Manson, who is also chief of the division of preventive medicine at Brigham and Women's Hospital in Boston, sums up their findings: "WBC count appears to be a very promising way to identify people at increased risk of heart disease. At this point, it may add information that physicians can use when evaluating a patient's risk factors. With additional research, it may become one of the routine screening tests for heart disease."