Basophil Blood Cell Count Is Associated With Enhanced Factor II Plasma Coagulant Activity and Increased Risk of Mortality in Patients With Stable Coronary Artery Disease: Not Only Neutrophils as Prognostic Marker in Ischemic Heart Disease

Abstract

Background White blood cell count, which is inexpensive and widely available in clinical practice, has been proposed to provide prognostic information in coronary artery disease (CAD). Elevated levels of white blood cell subtypes may play different roles in atherothrombosis and predict cardiovascular outcomes. Methods and Results The association between white blood cell counts and mortality was evaluated in 823 subjects with angiographically demonstrated and clinically stable CAD in an observational-longitudinal study. The correlation among white blood cell counts and factor II plasma coagulant activity was analyzed in 750 subjects (554 CAD and 196 CAD-free) not taking anticoagulant drugs. Subjects with overt leukocytosis or leukopenia were excluded. In the longitudinal study after a median follow-up of 61 months, 160 (19.4%) subjects died, 107 (13.0%) of whom from cardiovascular causes. High levels of neutrophils, monocytes, eosinophils, and basophils were associated with an increased mortality rate. In multiadjusted Cox regression models, only neutrophils and basophils remained predictors of total and cardiovascular mortality. The associations remained significant after adjustment for traditional cardiovascular risk factors and by including D-dimer and the chemokine CXCL12 in the regression models. Neutrophils and basophils were also significant predictors of factor II plasma coagulant activity variability after adjustment for blood cell counts, age, sex, inflammatory markers, CAD diagnosis, and prothrombin G20210A polymorphism. Factor II plasma coagulant activity was similarly increased in subjects with high neutrophil and basophil counts and in carriers of the prothrombin 20210A allele. Conclusions Both high neutrophil and basophil blood counts may predict mortality in patients with clinically stable CAD and are associated with enhanced factor II plasma coagulant activity, thereby suggesting underlying prothrombotic mechanisms.

Keywords: basophils; factor II plasma coagulant activity; neutrophils; secondary prevention of coronary artery disease; white blood cell count.

Figure 1. Total (A) and cardiovascular (CV) mortality (B) in the study population (n=823) stratified on the basis of quartile distribution of neutrophil, monocyte, eosinophil, and basophil cell counts.

Lymphocyte cell count was not associated with mortality rate and is not reported in these graphs. P values were calculated by log rank for trend.

Figure 2. Total (A) and cardiovascular (CV) (B) mortality by combining high or low cell counts of neutrophils and basophils (C).

Hazard ratio (HR) with 95% CI were calculated by comparing subjects with high cell counts of both neutrophils and basophils (G4) versus those with low cell counts of both neutrophils and basophils (G1). P values were calculated by log rank for trend. HRs were estimated by sex‐ and age‐adjusted and full‐adjusted Cox regression models (by including sex, age, myocardial infarction history, smoke, diabetes mellitus, hypertension, plasma cholesterol and triglyceride, estimated glomerular filtration rate, and high‐sensitivity C‐reactive protein). B indicates basophils; and N, neutrophils.

Figure 3. Factor II plasma coagulant activity (FII:c) in subjects not taking anticoagulant drugs (n=750) stratified on the basis of quartile distribution of neutrophil (A) and basophil cell counts (B), or by combining neutrophil and basophil levels (C).

P values were calculated by ANOVA for linear trend. B indicates basophils; and N, neutrophils.

Figure 4. Factor II plasma coagulant activity (FII:c) in subjects not taking anticoagulant drugs stratified within the study sample according high/low counts of neutrophils and basophils (only subjects with concordant high or low counts of both neutrophils and basophils were considered for this analysis) and the carriership of the prothrombin G20210A polymorphism.

P values were calculated by ANOVA with polynomial contrast for linear trend and by ANOVA with Tukey post hoc comparison*.