CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Carmelinda Ruggiero, MD*,
Antonio Cherubini, MD, PhD,
Samer S. Najjar, MD and
Luigi Ferrucci, MD, PhD
* National Institute on Aging, NIA-ASTRA UNIT, 3001 S. Hanover Street, Baltimore, Maryland 21225 (Email: ruggieroc07{at}hotmail.it).
We thank Drs. Bell and O’Keefe for the interest in our study about the relationship between the white blood cell (WBC) count and mortality over the period 1958 to 2002 (1).
Drs. Bell and O’Keefe point out that the metabolic syndrome (MetS) could mediate the relationship between elevated WBC count and increased mortality shown in our study. Although we find this hypothesis interesting, we do not have adequate data to address it in the BLSA (Baltimore Longitudinal Study of Aging). Information on the components of the MetS were not systematically collected over the period 1958 to 2002, and therefore we could not explore possible secular trends for this syndrome. Although the mortality risk ratio between WBC groups was adjusted for some components of MetS, such as triglycerides, blood pressure, and diabetes status, we could not investigate the role of waist circumference, waist-to-hip ratio, or high-density lipoprotein levels. Data on waist circumference were available for a small subgroup of the BLSA study population, and high-density lipoprotein was measured starting in the mid-1980s. Other longitudinal studies exist that collected information on the MetS and may better discern whether the presence of MetS is causal in both the elevated WBC count and the increased mortality.
The finding that WBC count is nonlinearly associated with all-cause mortality and almost linearly associated with cardiovascular mortality, while there is no significant association between WBC count and cancer mortality, supports hypotheses that elevated WBC count may be part of a cluster of risk factors that predispose an individual to cardiovascular morbidity and mortality (2). However, whether this cluster corresponds to the MetS is still uncertain.
The finding that secular mortality decline is at least in part independent of WBC secular downward trend suggests that other factors, such as the changes in the treatment of inflammatory-related conditions and cardiovascular risk factors, should be considered.
Finally, the relationship between the MetS and inflammatory status is not crystal clear. There are several studies showing a cross-sectional association between MetS and WBC count, but limited evidence suggesting that the MetS may cause an increase in WBC count (3,4). On the other hand, other lines of research have shown that chronic inflammation and elevated WBC count contribute to the development of MetS. A chronic low-grade inflammation seems to be a key factor underlying the cluster of MetS components, such as atherogenetic dyslipidemia, elevated blood pressure, elevated plasma glucose (5,6), and also is a recognized risk factor for cardiovascular disease and type 2 diabetes (7). Moreover, elevated C-reactive protein (CRP) levels have been significantly associated with each component of MetS (8), and elevated levels of high-sensitivity CRP has been found to predict MetS (7). Considering that WBC count and CRP are both markers of inflammation, and that WBC by producing interleukin-6 stimulates the hepatic synthesis of CRP (10), we suggest that WBC count may be an index of the inflammatory status associated with subclinical levels of each component of MetS. We are collecting data in the BLSA that will be helpful to better clarify the relationship between WBC and the occurrence of each component of MetS in older adults. (9).
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References
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- 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]
- Daskalopoulou SS, Athyros VG, Kolovou GD, Anagnostopoulou KK, Mikhailidis DP. Definitions of metabolic syndrome: where are we now? Curr Vasc Pharmacol 2006;4:185-197.[CrossRef][Medline]
- 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][ISI][Medline]
- Lohsoonthorn V, Dhanamun B, Williams MA. Prevalence of metabolic syndrome and its relationship to white blood cell count in a population of Thai men and women receiving routine health examinations Am J Hypertens 2006;19:339-345.[CrossRef][ISI][Medline]
- Grundy SM. Metabolic syndrome: a multiplex cardiovascular risk factor J Clin Endocrinol Metab 2007;92:399-404.[Abstract/Free Full Text]
- Grundy SM. Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds J Am Coll Cardiol 2006;47:1093-1100.[Abstract/Free Full Text]
- Haffner SM. The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease Am J Cardiol 2006;97:3A-11A.[ISI][Medline]
- Dupuy AM, Jaussent I, Lacroux A, Durant R, Cristol JP, Delcourt C. Waist circumference adds to the variance in plasma C-reactive protein levels in elderly patients with metabolic syndrome Gerontology 2007;53:91-101.[CrossRef][Medline]
- 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][ISI][Medline]
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