Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: the Women's Health Initiative Observational Study.
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 +/- 1.6 x 10(9) 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 in the first quartile (2.5-4.7 x 10(9) cells/L), women in the fourth quartile (6.7-15.0 x 10(9) 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 6.7 x 10(9) cells/L may identify high-risk individuals who are not currently identified by traditional CVD risk factors.
Margolis
Karen L
KL
Hennepin County Medical Center, and Berman Center for Outcomes and Clinical Research, 825 S. Eighth Street, Minneapolis, MN 55404, USA. margo006@umn.edu
Manson
JoAnn E
JE
Greenland
Philip
P
Rodabough
Rebecca J
RJ
Bray
Paul F
PF
Safford
Monika
M
Grimm
Richard H
RH
Howard
Barbara V
BV
Assaf
Annlouise R
AR
Prentice
Ross
R
D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D015331:Cohort Studies; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D017698:Postmenopause; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012959:Socioeconomic Factors
D002097:C-Reactive Protein