White blood cell count predicts reduction in coronary heart disease mortality with pravastatin

• Published in: Circulation (New York, N.Y.) Vol. 111; no. 14; pp. 1756 - 1762
• Main Authors: STEWART, Ralph A. H, WHITE, Harvey D, KIRBY, Adrienne C, HERITIER, Stephane R, SIMES, R. John, NESTEL, Paul J, WEST, Malcolm J, COLQUHOUN, David M, TONKIN, Andrew M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 12.04.2005
• Subjects: Aged; Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Coronary Disease - drug therapy; Coronary Disease - mortality; Coronary heart disease; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Fundamental and applied biological sciences. Psychology; Heart; Humans; Inflammation - diagnosis; Inflammation - drug therapy; Leukocyte Count; Male; Medical sciences; Middle Aged; Myocardial Infarction - prevention & control; Pravastatin - administration & dosage; Predictive Value of Tests; Prognosis; Stroke - prevention & control; Survival Rate; Vertebrates: cardiovascular system; Enzyme; Leukocyte; Mortality; Enzyme inhibitor; Cardiovascular disease; Inflammation; Statin derivative; Pravastatin; Coronary heart disease; White cell reduction; coronary disease; statins; Hydroxymethylglutaryl-CoA reductase; leukocytes; Oxidoreductases; Blood cell count; Antilipemic agent
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000160924.73417.26

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. 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 1x10(9)/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 >8.2x10(9)/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). These data support the hypothesis that individuals with evidence of inflammation may obtain a greater benefit from statin therapy.