White blood cell count and incidence of hypertension in the general Japanese population: ISSA-CKD study.

OBJECTIVES: This study aimed to clarify the relationship between the white blood cell (WBC) count and hypertension in the general Japanese population. METHODS: We conducted a population-based retrospective cohort study using annual health check-up data of residents of Iki City, Nagasaki Prefecture, Japan. A total of 2935 participants without hypertension at baseline were included in the present analysis. WBC counts were classified as tertile 1 (<4700/µL), tertile 2 (4700-5999/µL), and tertile 3 (≥6000/µL). The outcome was incident hypertension (blood pressure ≥140 mmHg). Multivariable-adjusted hazard ratios and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazards model. RESULT: During an average follow-up of 4.5 years, 908 participants developed hypertension. The incidence (per 100 person-years) of hypertension increased with an elevation in the WBC count (6.3 in tertile 1, 7.0 in tertile 2, and 7.4 in tertile 3). This association was significant, even after adjustment for other risk factors, including age, sex, current smoking habits, current alcohol intake, exercise habits, obesity, elevated blood pressure, diabetes mellitus, and dyslipidemia. The hazard ratios were 1.07 for tertile 2 (95% CI 0.90-1.26) and 1.27 for tertile 3 (95% CI 1.06-1.51) compared with the reference group of tertile 1 (p = 0.009). CONCLUSION: The WBC count was associated with future development of hypertension in the general Japanese population.

Impact of genetic polymorphisms determining leukocyte/neutrophil count on chemotherapy toxicity.

Neutropenia and infection are major dose-limiting side effects of chemotherapy. The risk of initial infection and subsequent complications are directly related to the depth and duration of neutropenia. Recent genome-wide association studies identified variants in DARC and CXCL2 genes, and in ORMDL3-GSDMA-CSF3 locus on chromosome 17q21 that influence white blood cell and neutrophil counts in healthy individuals. To investigate whether polymorphisms in these loci in conjunction with chemotherapy may modulate risk of treatment complications, we analyzed 21 SNPs across these genes for an association with chemotherapy-related neutropenia and infection in 286 Caucasian children with acute lymphoblastic leukemia. After correction for multiple testing, DARC polymorphism rs3027012 in 5'-UTR was associated with higher risk of low absolute phagocyte count (APC<500 and <1000 cells per microliter, P=0.001 and P<0.0005, respectively) and hospitalization due to febrile neutropenia (P=0.002). Protective effect was instead seen for DARC rs12075 A to G substitution (P=0.004). The SNP rs3859192 in the GSDMA were associated with hospitalization due to infection (P=0.004); infection was also modulated in the additive manner by the CXCL2 rs16850408 (P=0.002). This study shows for the first time that the variations in DARC, GSDMA and CXCL2 genes may play a role in the onset of chemotherapy complications.

White blood cell count predicts the odds of kidney function decline in a Chinese community-based population.

BACKGROUND: Inflammatory processes are very important in the development of kidney disease. Nevertheless, the association between white blood cell (WBC) count and the risk of renal dysfunction has not been well-established, especially in subjects without chronic kidney disease (CKD). Our study investigated the association between WBC count and kidney function decline in a Chinese community-based population with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2. METHODS: A total of 3768 subjects who were enrolled in an atherosclerosis cohort in Beijing were included in this study. EGFRs were calculated at baseline and follow-up using the CKD-EPI formula. The outcomes of this study were renal function decline (RFD) (a drop in eGFR stage along with a decline in eGFR of 25% or exceeding 5 mL/min/1.73 m2/year), rapid eGFR decline (an annual decrease in eGFR exceeding 3 mL/min/1.73 m2), and incident CKD (eGFR <60 min/1.73 m2 at follow-up). Multivariate logistic regression models were used to evaluate the associations between WBC count and each outcome. RESULTS: On average, the subjects were 56.6 ± 8.5 years old, and 35.9% were male. Of the participants, 48.6% had hypertension and 17.4% had diabetes. The mean (SD) WBC count at baseline was 6.1 ± 1.5 × 109/L. The mean (SD) eGFR at baseline was 101.1 ± 10.6 mL/min/1.73 m2. After 2.3 years follow-up, the incidence rates of RFD, rapid eGFR decline and new CKD were 7.7, 20.9, and 0.8%, respectively. WBC count was significantly related to RFD, rapid eGFR decline and new CKD in the univariate analyses. Even after adjustment for demographic variables, comorbidities, medications and baseline eGFR, these associations remained. Moreover, similar trends in RFD were observed in nearly all subgroups stratified by each confounding variable. The increase in the odds of RFD associated with each 109/L increase in WBC count was significantly greater in subjects not undergoing treatment with lipid-lowering drugs than those not undergoing this treatment (P-interaction: 0.05). CONCLUSIONS: In conclusion, elevated WBC count served as a predictor of the odds of kidney function decline in this population, which supports the hypothesis that systemic inflammation may serve as a risk factor for CKD development.

Longitudinal study on white blood cell count and the incidence of metabolic syndrome.

OBJECTIVE: Many studies have revealed that white blood cell count (WBC) is related to insulin resistance which is a central mechanism of metabolic syndrome (MetS). However, few cohort studies have examined the role of WBC in the development of MetS. We hypothesized that WBC is associated with the future development of MetS, and investigated the longitudinal incidence of MetS in healthy workers. METHODS: WBC was measured in 5,073 workers (mean age 42.5 years) without MetS at baseline. The incidence of MetS was monitored over 7 years of follow-up, in relation to quartiles of WBC. During the follow-up, 925 participants were diagnosed as MetS. RESULTS: Incidence of MetS was increased in participants with higher WBC: the rates of incidence of MetS were 22.6, 32.9, 42.9, and 57.5 per 1,000 person-years of follow-up in the 1st, 2nd, 3rd, and 4th quartiles of WBC, respectively. After adjustments for confounding factors, the adjusted hazards ratio (95% confidence interval) for MetS was 1.00 (reference), 1.22 (0.98 to 1.51), 1.52 (1.24 to 1.87), and 1.66 (1.35 to 2.04) through the quartiles of WBC, respectively, (p <0.001). This relationship was consistent among current smokers and never smokers, and among male and female genders, respectively. CONCLUSION: WBC is useful in predicting the future development of MetS which leads to atherosclerotic diseases.

Low birth weight and markers of inflammation and endothelial activation in adulthood: the ARIC study.

BACKGROUND: To investigate the hypothesis that intrauterine growth restriction might produce a longstanding pro-inflammatory tendency, we investigated the association of low birth weight with blood levels of markers of inflammation and endothelial activation in middle-aged adults. METHODS: The ARIC Study enrolled subjects aged 45-64 years sampled from four U.S. communities. An inflammation/endothelial activation score from 0 to 6 was created, one point being given for each above-median value of white blood cell count, fibrinogen, von Willebrand factor and Factor VIII, and for each below-median value of albumin and activated partial thromboplastin time. RESULTS: Of the 9809 individuals reporting birth weight and having all inflammation/endothelial markers and covariates, 349 (3.6%) reported low birth weight (LBW). The mean (standard deviation) score was 3.5 (1.5) for those with and 3.1 (1.6) for those without LBW (p<0.001). In robust poisson regression models adjusting for gender, ethnicity, age, study center, educational level, and current drinking and smoking status and amount, those with LBW were more likely to have a high score (> or =4 points) (RR=1.16, 95% CI: 1.05-1.29). CONCLUSION: In the ARIC Study, LBW predicted greater inflammation and endothelial activation, as indicated by the higher score of blood markers, consistent with the hypothesis that early life events may result in a hyper-responsive innate immune system. Such a pro-inflammatory tendency could help explain the association of low birth weight with elements of the metabolic syndrome and ischemic heart disease.