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CLINICAL RESEARCH: CARDIOVASCULAR RISK

Which White Blood Cell Subtypes Predict Increased Cardiovascular Risk?

Benjamin D. Horne, PhD, MPH^_*, Jeffrey L. Anderson, MD, FACC^_*,,_*, Jerry M. John, MD^_*,, Aaron Weaver, MD^_*,, Tami L. Bair, BS^_*, Kurt R. Jensen, MS^_*, Dale G. Renlund, MD, FACC^_*,, Joseph B. Muhlestein, MD, FACC^_*, Intermountain Heart Collaborative (IHC) Study Group

^_* Cardiovascular Department, LDS Hospital, Salt Lake City, Utah.
University of Utah, Salt Lake City, Utah.

Manuscript received December 7, 2004; revised manuscript received January 25, 2005, accepted February 8, 2005.

^_* Reprint requests and correspondence: Dr. Jeffrey L. Anderson, LDS Hospital Cardiovascular Department, 8th Avenue and C Street, Salt Lake City, Utah 84143. (Email: jeffrey.anderson{at}ihc.com).

OBJECTIVES: We sought to determine the predictive ability of total white blood cell (WBC) count and its subtypes for risk of death or myocardial infarction (MI).

BACKGROUND: An elevated WBC count has been associated with cardiovascular risk, but which leukocyte subtypes carry this risk is uncertain.

METHODS: Consecutive patients without acute MI who were assessed angiographically for coronary artery disease (CAD) and were followed up long-term were studied. The predictive ability for death/MI of quartile (Q) 4 versus Q1 total WBC, neutrophil (N), lymphocyte (L), and monocyte (M) counts and N/L ratio were assessed using Cox regressions.

RESULTS: A total of 3,227 patients was studied. Mean age was 63 years; 63% of patients were male, and 65% had CAD. In multivariable modeling entering standard risk factors, presentation, and CAD severity, the total WBC (hazard ratio [HR] 1.4, p = 0.01) and M (HR 1.3, p < 0.02) were weaker and N (HR 1.8, p < 0.001), L (HR 0.51, p < 0.001), and N/L ratio (HR 2.2, p < 0.001) were independent predictors of death/MI. When WBC variables were entered together, N/L ratio and M were retained as independent predictors. Risk associations persisted in analyses restricted to CAD patients or including acute MI patients.

CONCLUSIONS: Total WBC count is confirmed to be an independent predictor of death/MI in patients with or at high risk for CAD, but greater predictive ability is provided by high N (Q4 >6.6 x 10³/µl) or low L counts. The greatest risk prediction is given by the N/L ratio, with Q4 versus Q1 (>4.71 versus <1.96) increasing the hazard 2.2-fold. These findings have important implications for CAD risk assessment.

Abbreviations and Acronyms   AUC = area under the curve   CAD = coronary artery disease   CHD = coronary heart disease   CI = confidence interval   CK-MB = creatine kinase-myocardial band   CRP = C-reactive protein   HR = hazard ratio   L = leukocyte   M = monocyte   MI = myocardial infarction   N = neutrophil   Q = quartile   WBC = white blood cell

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