White Blood Cell Counts as Risk Markers of Developing Metabolic Syndrome and Its Components in the Predimed Study

Background The Metabolic Syndrome (MetS) is a cluster of metabolic abnormalities that includes hyperglucemia, hypertension, dyslipidemia and central obesity, conferring an increased risk of cardiovascular disease. The white blood cell (WBC) count has been proposed as a marker for predicting cardiovascular risk. However, few prospective studies have evaluated the relationship between WBC subtypes and risk of MetS. Methods Participants were recruited from seven PREDIMED study centers. Both a baseline cross-sectional (n = 4,377) and a prospective assessment (n = 1,637) were performed. Participants with MetS at baseline were excluded from the longitudinal analysis. The median follow-up was 3.9 years. Anthropometric measurements, blood pressure, fasting glucose, lipid profile and WBC counts were assessed at baseline and yearly during the follow-up. Participants were categorized by baseline WBC and its subtype count quartiles. Adjusted logistic regression models were fitted to assess the risk of MetS and its components. Results Of the 4,377 participants, 62.6% had MetS at baseline. Compared to the participants in the lowest baseline sex-adjusted quartile of WBC counts, those in the upper quartile showed an increased risk of having MetS (OR, 2.47; 95%CI, 2.03–2.99; P-trend<0.001). This association was also observed for all WBC subtypes, except for basophils. Compared to participants in the lowest quartile, those in the top quartile of leukocyte, neutrophil and lymphocyte count had an increased risk of MetS incidence. Leukocyte and neutrophil count were found to be strongly associated with the MetS components hypertriglyceridemia and low HDL-cholesterol. Likewise, lymphocyte counts were found to be associated with the incidence of the MetS components low HDL-cholesterol and high fasting glucose. An increase in the total WBC during the follow-up was also associated with an increased risk of MetS. Conclusions Total WBC counts, and some subtypes, were positively associated with MetS as well as hypertriglyceridemia, low HDL-cholesterol and high fasting glucose, all components of MetS. Trial registration Controlled-Trials.comISRCTN35739639.

[1]  Shih-Yi Lin,et al.  Differential White Blood Cell Count and Type 2 Diabetes: Systematic Review and Meta-Analysis of Cross-Sectional and Prospective Studies , 2010, PloS one.

[2]  S. Volpato,et al.  White blood cell count is associated with some features of metabolic syndrome in a very old population. , 2001, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[3]  H. Yatsuya,et al.  Association of white blood cell count and clustered components of metabolic syndrome in Japanese men. , 2004, Circulation journal : official journal of the Japanese Circulation Society.

[4]  Dolores Corella,et al.  Effects of a Mediterranean-Style Diet on Cardiovascular Risk Factors , 2006, Annals of Internal Medicine.

[5]  L. Groop,et al.  Cardiovascular morbidity and mortality associated with the metabolic syndrome. , 2001, Diabetes care.

[6]  Yoon-Ho Choi,et al.  The Associations of Total and Differential White Blood Cell Counts with Obesity, Hypertension, Dyslipidemia and Glucose Intolerance in a Korean Population , 2008, Journal of Korean medical science.

[7]  Kenichi Watanabe,et al.  Prevalence of metabolic syndrome increases with the increase in blood levels of gamma glutamyltransferase and alanine aminotransferase in Japanese men and women. , 2009, Internal medicine.

[8]  E. Kang,et al.  The association of total and differential white blood cell count with metabolic syndrome in type 2 diabetic patients. , 2006, Diabetes research and clinical practice.

[9]  M. Graffar.  [Modern epidemiology]. , 1971, Bruxelles medical.

[10]  Peymane Adab,et al.  White blood cell count and the metabolic syndrome in older Chinese: the Guangzhou Biobank Cohort Study. , 2008, Atherosclerosis.

[11]  Paul Zimmet,et al.  The metabolic syndrome—a new worldwide definition , 2005, The Lancet.

[12]  R. Elosua,et al.  Validation of the Minnesota Leisure Time Physical Activity Questionnaire in Spanish men. The MARATHOM Investigators. , 1994, American journal of epidemiology.

[13]  W. Fiers,et al.  Stimulation of lipolysis in cultured fat cells by tumor necrosis factor, interleukin-1, and the interferons is blocked by inhibition of prostaglandin synthesis. , 1992, Endocrinology.

[14]  H. Iso,et al.  Leukocyte count is an independent predictor for risk of acute myocardial infarction in middle-aged Japanese men. , 2007, Atherosclerosis.

[15]  K. Williams,et al.  Atherosclerosis--an inflammatory disease. , 1999, The New England journal of medicine.

[16]  W. Markiewicz,et al.  Predictive value of white blood cell subtypes for long-term outcome following myocardial infarction. , 2008, Atherosclerosis.

[17]  B. Horne,et al.  Which white blood cell subtypes predict increased cardiovascular risk? , 2005, Journal of the American College of Cardiology.

[18]  Akihiko Uehara,et al.  Longitudinal study on white blood cell count and the incidence of metabolic syndrome. , 2011, Internal medicine.

[19]  E. Ortega,et al.  White blood cell count is associated with carotid and femoral atherosclerosis. , 2012, Atherosclerosis.

[20]  P. Hedberg,et al.  White blood cell counts associate more strongly to the metabolic syndrome in 75-year-old women than in men: a population based study. , 2007, Metabolic syndrome and related disorders.

[21]  A. Aljada,et al.  Contemporary Reviews in Cardiovascular Medicine Metabolic Syndrome A Comprehensive Perspective Based on Interactions Between Obesity, Diabetes, and Inflammation , 2022 .

[22]  Sander Greenland,et al.  Modern Epidemiology 3rd edition , 1986 .

[23]  Ryozo Nagai,et al.  Association between cigarette smoking, white blood cell count, and metabolic syndrome as defined by the Japanese criteria. , 2007, Internal medicine.

[24]  J. Shaw,et al.  Metabolic syndrome—a new world‐wide definition. A Consensus Statement from the International Diabetes Federation , 2006, Diabetic medicine : a journal of the British Diabetic Association.

[25]  Michael Karin,et al.  A central role for JNK in obesity and insulin resistance , 2002, Nature.

[26]  A. Cerami,et al.  Studies of endotoxin-induced decrease in lipoprotein lipase activity , 1981, The Journal of experimental medicine.

[27]  D. Carroll,et al.  Lymphocyte sub-population cell counts are associated with the metabolic syndrome and its components in the Vietnam Experience Study. , 2010, Atherosclerosis.

[28]  K. Tatara,et al.  Associations between white blood cell count and features of the metabolic syndrome in Japanese male office workers. , 2002, Industrial health.

[29]  K. Uysal,et al.  Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. , 1997, Nature.

[30]  A. Nakata,et al.  Association of lymphocyte sub-populations with clustered features of metabolic syndrome in middle-aged Japanese men. , 2004, Atherosclerosis.

[31]  R Peto,et al.  Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. , 1998, JAMA.

[32]  R. Sacco,et al.  Elevated White Blood Cell Count and Carotid Plaque Thickness: The Northern Manhattan Stroke Study , 2001, Stroke.

[33]  E. DeLong,et al.  Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. , 1988, Biometrics.

[34]  R. Klein,et al.  Relationship between white blood cell count and incident hypertension , 2004 .

[35]  K. Uysal,et al.  Protection from obesity-induced insulin resistance in mice lacking TNF-α function , 1997, Nature.

[36]  K. Chien,et al.  Peripheral differential leukocyte counts in humans vary with hyperlipidemia, smoking, and body mass index , 2001, Lipids.

[37]  D. Pei,et al.  Relationship between white blood cell count and components of metabolic syndrome among young adolescents , 2010, Acta Diabetologica.

[38]  Dolores Corella,et al.  A short screener is valid for assessing Mediterranean diet adherence among older Spanish men and women. , 2011, The Journal of nutrition.

[39]  S. Sheu,et al.  Association of peripheral total and differential leukocyte counts with metabolic syndrome and risk of ischemic cardiovascular diseases in patients with type 2 diabetes mellitus , 2007, Diabetes/metabolism research and reviews.

[40]  Dolores Corella,et al.  Cohort profile: design and methods of the PREDIMED study. , 2012, International journal of epidemiology.

[41]  Y. Aizawa,et al.  Lymphocyte count was significantly associated with hyper-LDL cholesterolemia independently of high-sensitivity C-reactive protein in apparently healthy Japanese , 2012, Heart and Vessels.

[42]  J. Beattie,et al.  Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ , 2001, Proceedings of the Nutrition Society.

[43]  M. Laakso,et al.  The metabolic syndrome predicts cardiovascular mortality: a 13-year follow-up study in elderly non-diabetic Finns. , 2007, European heart journal.

[44]  S. Srinivasan,et al.  Black-White Divergence in the Relation of White Blood Cell Count to Metabolic Syndrome in Preadolescents, Adolescents, and Young Adults: The Bogalusa Heart Study , 2010, Diabetes Care.