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(Circulation. 2005;111:1756-1762.)
© 2005 American Heart Association, Inc.

Coronary Heart Disease

White Blood Cell Count Predicts Reduction in Coronary Heart Disease Mortality With Pravastatin

Ralph A.H. Stewart, MD; Harvey D. White, DSc; Adrienne C. Kirby, MSc; Stephane R. Heritier, PhD; R. John Simes, MD; Paul J. Nestel, MD; Malcolm J. West, MD, PhD; David M. Colquhoun, MD; Andrew M. Tonkin, MD, for the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study Investigators

From Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand (R.A.H.S., H.D.W.); National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia (A.C.K., S.R.H., R.J.S.); Baker Medical Research Institute, Melbourne, Australia (P.J.N.); Department of Medicine, University of Queensland, Brisbane, Australia (M.J.W., D.M.C.); and Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia (A.M.T.).

Correspondence to Dr Ralph Stewart, Cardiology Department, Auckland City Hospital, Private Bag 92024, Auckland 1030, New Zealand. E-mail rstewart{at}adhb.govt.nz

Received June 1, 2004; revision received October 20, 2004; accepted October 29, 2004.

Background— Elevated serum inflammatory marker levels are associated with a greater long-term risk of cardiovascular events. Because 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) may have an antiinflammatory action, it has been suggested that patients with elevated inflammatory marker levels may have a greater reduction in cardiovascular risk with statin treatment.

Methods and Results— We evaluated the association between the white blood cell count (WBC) and coronary heart disease mortality during a mean follow-up of 6.0 years in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study, a clinical trial comparing pravastatin (40 mg/d) with a placebo in 9014 stable patients with previous myocardial infarction or unstable angina. An increase in baseline WBC was associated with greater coronary heart disease mortality in patients randomized to placebo (hazard ratio for 1x10⁹/L increase in WBC, 1.18; 95% CI, 1.12 to 1.25; P<0.001) but not pravastatin (hazard ratio, 1.02; 95% CI, 0.96 to 1.09; P=0.56; P for interaction=0.004). The numbers of coronary heart disease deaths prevented per 1000 patients treated with pravastatin were 0, 9, 30, and 38 for baseline WBC quartiles of <5.9, 6.0 to 6.9, 7.0 to 8.1, and >8.2x10⁹/L, respectively. WBC was a stronger predictor of this treatment benefit than the ratio of total to high-density lipoprotein cholesterol and a global measure of cardiac risk. There was also a greater reduction (P=0.052) in the combined incidence of cardiovascular mortality, nonfatal myocardial infarction, and stroke with pravastatin as baseline WBC increased (by quartile: 3, 41, 61, and 60 events prevented per 1000 patients treated, respectively).

Conclusions— These data support the hypothesis that individuals with evidence of inflammation may obtain a greater benefit from statin therapy.

Key Words: coronary disease • inflammation • leukocytes • mortality • statins

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