White blood cell count may predict risk for cardiovascular events and all-cause mortality in postmenopausal women without traditional risk factors, according to an article in the March 14th issue of Archives of Internal Medicine.
The authors had considered that white blood cell count is a stable, well-standardized, widely available and inexpensive measure of systemic inflammation.

Karen L Margolis, MD, MPH, and her American 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 count as an independent predictor of cardiovascular events and death from any cause.

Women underwent screening that included collection of personal information, medical history, information about previous history of cardiovascular events or cancer, and blood collection at the beginning of the study. Follow-up was conducted by annual questionnaires, except in the third year, which featured a clinical follow-up visit.

"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 cardiovascular disease (CVD) risk factors and biomarkers," the authors wrote.

Known 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.

White blood cell counts were measured at the beginning of the study and women were divided into quartiles. 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 highest quartile had double the risk for coronary heart disease death compared with women in the lowest quartile after statistical adjustment for other risk factors.

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

In an editorial accompanying this study, Mary Cushman, MD, suggested that "several issues must be considered when interpreting data from observational studies on new risk factors. 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."

"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," Cushman wrote. "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."

"It is reassuring to see continuing study of simple and well-standardized biomarkers, such as leukocyte count, and risk of vascular outcomes," Cushman concluded. "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. 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."