CORRESPONDENCE: LETTER TO THE EDITOR
White Cell Count, Mortality, and Metabolic Syndrome in the Baltimore Longitudinal Study of Aging
David S.H. Bell, MD* and
James H. O’Keefe, MD
* Southside Endocrinology, 1020 26th Street South, Room 204, Birmingham, Alabama 35205 (Email: dshbell{at}uab.edu).
Ruggiero et al. (1) have shown that higher white cell counts (WCCs) are associated with higher mortality from both cardiovascular disease and cancer. There also was a positive correlation of the WCC with body mass index and triglyceride levels and a negative correlation with physical activity. Waist circumference, waist-to-hip ratio, or high-density lipoprotein levels were not recorded in this study. We believe that if the criteria to diagnose the metabolic syndrome were available they would have explained the elevated WCC, and that the presence of the metabolic syndrome likely would have been the causal factor for both the elevated WCC and the increased mortality.
The metabolic syndrome is an inflammatory state associated with an elevated WCC caused by leucocyte infiltration of an increased mass of intraperitoneal fat. Pickup et al. (2) in 1998 provided evidence that type 2 diabetes was associated with increased concentrations of markers of the acute-phase response, including sialic acid, alpha-1 acid glycoprotein, amyloid A, C-reactive protein, and cortisol. The major cytokine involved in this inflammatory state is interleukin-6, which stimulates hepatic production of C-reactive protein (3). Recently, Tsai et al. (4) have shown that after adjustment for age, gender, and other known risk factors, the greater the number of features of the metabolic syndrome that are present, the higher were the total leukocyte, monocyte, neutrophil, and lymphocyte counts and the higher was the risk of ischemic cardiovascular disease in patients with type 2 diabetes. Similarly, Shim et al. (5) have shown that the greater the number of components of the metabolic syndrome, the more elevated was the WCC.
Although obesity, without features of the metabolic syndrome, has been shown to be associated with an increased WCC, Desai et al. (6) showed that the association of the leukocyte count with obesity is highly dependent on the presence of the metabolic syndrome. In the National Health and Nutrition Examination Survey, an elevated WCC was independently associated with insulin resistance (7).
Therefore, we believe that the association between an elevated WCC and mortality simply reflects the co-association between the metabolic syndrome and mortality. Had assessments of waist-to-hip ratio and the triglyceride-to-high-density lipoprotein ratio been available, we believe that this relationship would have been apparent.
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1. Ruggiero C, Metter EJ, Cherubini A, et al. White blood cell count and mortality in the Baltimore Longitudinal Study of Aging J Am Coll Cardiol 2007;49:1841-1850.[Abstract/Free Full Text]2. Pickup JC, Crook MA. Is type II diabetes mellitus a disease of the innate immune system Diabetologia 1998;41:1241-1248.[CrossRef][Web of Science][Medline] 3. Cseh K, Baranyi E, Winkler G. The role of cytokines of the innate and adaptive immune system in the regulation of insulin resistance Diabetologia 1999;42:497-498.[CrossRef][Web of Science][Medline] 4. Tsai JC, Sheu SH, Chiu HC, 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 Diabetes Metab Res Rev 2007;23:111-118.[CrossRef][Web of Science][Medline] 5. Shim WS, Kim HJ, Kang ES, et al. The association of total and differential white blood cell count with metabolic syndrome in type 2 diabetic patients Diabetes Res Clin Pract 2006;73:284-291.[CrossRef][Web of Science][Medline] 6. Desai MY, Dalal D, Santos RD, Carvalho JA, Nasir K, Blumenthal RS. Association of body mass index, metabolic syndrome, and leukocyte count Am J Cardiol 2006;97:835-837.[CrossRef][Web of Science][Medline] 7. Chen J, Wildman RP, Hamm LL, et al. Third National Health and Nutrition Examination SurveyAssociation between inflammation and insulin resistance in U.S. nondiabetic adults: results from the Third National Health and Nutrition Examination Survey. Diabetes Care 2004;27:2960-2965.[Abstract/Free Full Text]
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