Baseline total and specific differential white blood cell counts and 5-year all-cause mortality in community-dwelling older women

Abstract

Increasing evidence demonstrates that inflammation is associated with many pathophysiologic processes and mortality in older adults. Increase in total white blood cell (WBC) counts is recognized as an important cellular marker of systemic inflammation. However, relationships of total WBC and individual differential counts with mortality in older adults, particularly in older women, have not been adequately evaluated. To address this important question, we obtained baseline total WBC and differential counts and 5-year all-cause mortality of 624 community-dwelling women age 65–101 in the Women's Health and Aging Study cohort, excluding those with WBC counts above the normal range. Using Kaplan–Meier survival and Cox proportional hazard regression analyses, and adjusting for age, race, body mass index, smoking, and education, we identified that baseline higher total WBC, higher neutrophil, or lower lymphocyte counts were independently associated with increased mortality. No significant associations of eosinophil, monocyte, or basophil counts with mortality were observed. These results suggest that beyond acute bacterial infection, changes in counts of baseline total WBC and its specific subpopulations predict increased mortality in older women. They provide a basis for further investigation into the role of leukocytes in age-related inflammation and its associated adverse outcomes in older adults.

Introduction

A large body of evidence demonstrates that age-related inflammatory phenotype, as marked by elevated levels of interleukin-6 (IL-6) or C-reactive protein (CRP), is associated with many pathophysiologic processes and mortality in older adults (Ershler et al., 1997, Ershler and Keller, 2000; Ferrucci et al., 1999; Harris et al., 1999; Ikeda et al., 2001; Taaffe et al., 2000; Volpato et al., 2001). Increase in peripheral white blood cell (WBC) count is recognized as an important cellular marker of systemic inflammation, primarily due to acute bacterial infection. Several studies in middle-aged populations have demonstrated that high total WBC count is associated with increased risk for cardiovascular disease (CVD), decline in lung function, as well as coronary, cancer, and all-cause mortality (Grau et al., 2004; Lee et al., 2001; James et al., 1999; Chan-Yeung et al., 1988; Gillum et al., 1993; de Labry et al., 1990; Grimm et al., 1985). However, the relationships of counts of total WBC and its subpopulations with mortality in older adults, particularly in older women, have not been closely examined. In addition, total WBC count above the clinically defined normal range was not excluded in the studies cited above, leaving acute bacterial infection as a potential major contributor to all-cause mortality. Furthermore, our recent data from the Women's Health and Aging Studies (WHAS) have shown direct in vivo associations of total WBC and specific differential counts with circulating IL-6 levels, the hallmark of the age-related inflammatory phenotype (Leng et al., 2005). Hence, evaluating the relationships of total and differential WBC counts with mortality in older women, will help to advance our understanding of the role of leukocytes in the age-related inflammatory phenotype and its associated adverse health outcomes in this growing and highly vulnerable population.

This study was designed to test our hypothesis that baseline total and specific differential WBC counts are associated with increased mortality in community-dwelling older women, excluding potential effects from acute bacterial infection. In the WHAS cohort, we examined the relationships of baseline total WBC and differential (neutrophil, lymphocyte, eosinophil, monocyte, and basophil) counts with 5-year all-cause mortality in community-dwelling women aged 65 years and older.