A simple white blood cell count could identify cardiovascular risk in older women who otherwise demonstrate no signs of disease, suggests an article in the March 14 issue of the Archives of Internal Medicine.

Increasing evidence supports a role for inflammation in the development of atherosclerosis, that is, thickening and hardening of the arteries, according to background information in the article.

Measurement of a number of different molecules involved in inflammation may be an effective way to identify and monitor patients at risk for coronary heart disease. White blood cell count is a stable, well-standardized, widely available and inexpensive measure of systemic inflammation, say the authors.

White Blood Cell Count as Independent Predictor

Karen L Margolis, M.D., M.P.H., of the Hennepin County Medical Center, Minneapolis, and colleagues used data from a total of 72,242 postmenopausal women aged 50 to 79 years who participated in the Women's Health Initiative (WHI) Observational Study (WHI-OS), to assess white blood cell (leukocyte) count as an independent predictor of cardiovascular events (for example, heart attack or stroke) and death from any cause.

Screening of test subjects included collection of personal information, medical history, information about previous history of cardiovascular (CVD) events or cancer, and blood collection at the beginning of the study. Follow-up was conducted by annual questionnaires, except in the third year, when participants visited a clinic for a follow-up exam.

"Because of its large size and broad representation of women from across the United States, this cohort provides an opportunity to determine whether the association of white blood cell count with future cardiovascular events is present in postmenopausal women and to examine the independence of this association from other known CVD risk factors and biomarkers," the authors write.

Other known CVD risk factors and biomarkers included in the analysis included age, race, ethnicity, baseline hypertension, diabetes, smoking, body mass index diet, physical activity, current use of aspirin or hormone therapy and C-reactive protein, a biomarker for inflammation.

Independent Association Demonstrated

White blood cell counts were measured at the beginning of the study, and women were divided into four levels or quartiles. The first quartile consisted of women with the lowest level of white blood cells and the fourth quartile was comprised of women with the highest level. Medical histories were taken each year for six years of follow-up. Only participants who were entirely free of clinical CVD and cancer at the beginning of the study were included in the analysis.

Women in the fourth quartile (highest WBC) had a doubled risk for coronary heart disease death compared with women in the first quartile (lowest WBC), after statistical adjustment for other risk factors, the researchers found.

"Women in the upper quartile also had a 40 percent higher risk for nonfatal myocardial infarction (heart attack), a 46 percent higher risk for stroke, and 50 percent higher risk for total mortality," the authors write. "In multivariable models adjusting for C-reactive protein, the WBC (white blood cell) count was an independent predictor of coronary heart disease risk, comparable in magnitude to C-reactive protein (CRP)," they note.

"In summary, we have demonstrated that a WBC count in the upper quartile is independently associated with cardiovascular events and death in older women after adjustment for traditional risk factors," say the authors.

"These data add to available evidence in men suggesting a similar link and suggest that the predictive role of the WBC count is independent of CRP. Cardiovascular risk categorization by inflammatory markers, including the WBC count, may identify high-risk individuals who are not currently identified by traditional risk factors; further studies are needed to assess the effectiveness of risk reduction in these patients," the authors conclude.

Ripe Area for Investigation

"Several issues must be considered when interpreting data from observational studies on new risk factors," suggests Mary Cushman, M.D., M.Sc., of the University of Vermont, Colchester, Vermont, in an editorial accompanying this study. For leukocyte (white blood cell) count automated measurement methods are well standardized and precision excellent. There is little information on the variability of leukocyte count in individuals over time, but from limited data, the within person compared with between-person variability is similar to that of cholesterol or C-reactive protein (CRP)," she points out.

"Considering the use for vascular risk assessment in practice, the cost of leukocyte count determination is lower compared with other novel vascular risk markers under current consideration," Dr. Cushman writes. "One must also consider other costs of screening. There may be benefits or even harms and hidden costs," she notes.

"In addition, it is possible that assessment of more than one inflammation-sensitive factor at the same time allows better classification of patients as to whether they have inflammation," Dr. Cushman suggests.

"It is reassuring to see continuing study of simple and well-standardized biomarkers, such as leukocyte count, and risk of vascular outcomes. Whether novel risk markers, such as leukocyte count or CRP concentration, should be added to routine vascular risk assessment in asymptomatic patients is an area of ongoing intense interest," Dr. Cushman observes.

"Improvement of the precision of 'inflammation testing' by exploring even newer biomarkers or using combinations of tests is a ripe area for investigation. The latter will probably require pooled data from multiple studies to achieve precise risk estimates that can be translated into practice," Dr. Cushman concludes.