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The Women’s Health Initiative Observational Study

Karen L. Margolis, MD, MPH; JoAnn E. Manson, MD, DrPH; Philip Greenland, MD; Rebecca J. Rodabough, MS; Paul F. Bray, MD; Monika Safford, MD; Richard H. Grimm, Jr, MD, PhD; Barbara V. Howard, PhD; Annlouise R. Assaf, PhD; Ross Prentice, PhD; for the Women’s Health Initiative Research Group

Arch Intern Med. 2005;165:500-508.

Background  Increasing evidence supports a role for inflammation in the atherosclerotic process. The role of the leukocyte count as an independent predictor of risk of a first cardiovascular disease (CVD) event remains uncertain. Our objective was to describe the relation between the baseline white blood cell (WBC) count and future CVD events and mortality in postmenopausal women.

Methods  In this prospective cohort study set in 40 US clinical centers, the study population comprised 72 242 postmenopausal women aged 50 to 79 years, free of CVD and cancer at baseline, enrolled in the Women’s Health Initiative Observational Study. Main outcome measures included incident fatal coronary heart disease (CHD), nonfatal myocardial infarction, stroke, and total mortality.

Results  At baseline, the mean ± SD age of the women was 63 ± 7.3 years, 84% were white, 4% had diabetes, 35% had hypertension, and 6% were current smokers. The mean WBC count was 5.8 ± 1.6x10⁹ cells/L. During a mean of 6.1 years of follow-up, there were 187 CHD deaths, 701 nonfatal myocardial infarctions, 738 strokes, and 1919 deaths from all causes. Compared with women with WBC counts inthe first quartile (2.5-4.7x10⁹ cells/L), women in the fourth quartile (6.7-15.0x10⁹ cells/L) had over a 2-fold elevated risk for CHD death (hazard ratio, 2.36; 95% confidence interval, 1.51-3.68), after multivariable adjustment for age, race, diabetes, hypertension, smoking, hypercholesterolemia, body mass index, alcohol intake, diet, physical activity, aspirin use, and hormone use. Women in the upper quartile of the WBC count also had a 40% higher risk for nonfatal myocardial infarction, a 46% higher risk for stroke, and a 50% higher risk for total mortality. In multivariable models adjusting for C-reactive protein, the WBC count was an independent predictor of CHD risk, comparable in magnitude to C-reactive protein.

Conclusions  The WBC count, a stable, well-standardized, widely available and inexpensive measure of systemic inflammation, is an independent predictor of CVD events and all-cause mortality in postmenopausal women. A WBC count greater than 6.7x10⁹ cells/L may identify high-risk individuals who are not currently identified by traditional CVD risk factors.

A complete listing of the Women’s Health Initiative Research Group is given in a box at the end of this article.Author Affiliations: Hennepin County Medical Center, Minneapolis, Minn (Drs Margolis and Grimm); Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (Dr Manson); Northwestern University, Chicago, Ill (Dr Greenland); Fred Hutchinson Cancer Research Center, Seattle, Wash (Ms Rodabough and Dr Prentice); Baylor College of Medicine, Houston, Tex (Dr Bray); University of Alabama, Birmingham (Dr Safford); Medstar Research Institute/Howard University, Washington, DC (Dr Howard); Brown University, Pawtucket, RI (Dr Assaf).

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