Author(s): Neil M. Johannsen 1 , * , Damon L. Swift 1 , William D. Johnson 2 , Vishwa D. Dixit 3 , Conrad P. Earnest 1 , Steven N. Blair 4 , Timothy S. Church 1
Elevated white blood cell (WBC) count is a strong independent risk factor for coronary heart disease (CHD) morbidity and mortality -. Epidemiologic studies suggest that greater total granulocyte or neutrophil counts are the strongest predictor - accounting for an increased risk of CVD death of approximately 40% . Total WBC count is also associated with insulin sensitivity such that an increase in total WBC count is indicative of an increased risk of future type 2 diabetes mellitus , . Recently, Dixon and O'Brien  demonstrated that total WBC, and especially the neutrophil subclass, were associated with BMI and independently associated with insulin concentrations. Postmenopausal women represent a unique demographic deserving investigation because they have additional risk factors including elevated systolic blood pressure, deteriorating blood lipid profile, increasing body weight and low levels of physical activity that, together with elevated WBC counts, could result in a heightened CVD and type 2 diabetes risk , , .
Recently, we reported that fitness (inversely) and fatness (directly) are associated with total and fractionated WBC counts , . Men with low fitness and high fatness had higher total WBC, neutrophil, lymphocyte, and basophil counts compared to men with high fitness levels. While acute exercise bouts have been implicated in an augmented inflammatory state , high levels of physical activity have been linked to reduced systemic inflammation and aerobic exercise training has been shown to decrease WBC counts  and associated inflammatory biomarkers (ex. IL-6) . However, the dose of exercise necessary to improve total and fractionated WBC counts and their relationship with exercise-induced changes in adiposity, inflammatory biomarkers, and fasting glucose metabolism in postmenopausal women has not been examined. The Dose-Response to Exercise in Women Aged 45-75 yr (DREW) study provides a unique opportunity to evaluate the dose of exercise necessary to promote improvements in total WBC and WBC subfraction counts. We hypothesized that total WBC and WBC subfraction counts would be reduced to a greater extent at higher doses of exercise. We also hypothesized that the reduction in total WBC and WBC subfraction counts would be related to improvements in cardiorespiratory fitness (VO2peak ), and markers of adiposity (BMI and waist circumference), inflammatory cytokines and adipokines (IL-6, TNF-[alpha], C-reactive protein, and adiponectin), and fasting glucose metabolism (glucose, insulin, and calculated HOMA).
Study design and participants
The DREW study was approved annually by The Cooper Institute during data collection and subsequently by the Pennington Biomedical Research Center institutional review board for continued analyses. Written informed consent was obtained from all participants prior to study screening. The design and methods for the DREW study and the primary outcomes have been previously published , . Briefly, DREW was a randomized, controlled intervention designed to examine the effect of aerobic exercise dose on improvements in cardiorespiratory fitness in...