Light-dark patterns of soluble CD40 ligand: Clinical implications

Light-dark patterns of soluble CD40 ligand: Clinical implications We have read with great interest the article by Keaney et al1 entitled “Clinical correlates, heritability, and genetic linkage of circulating CD40 ligand in the Framingham Offspring Study.” In this article, the authors examined the clinical correlates, the heritability, and genetic linkage of plasma and serum circulating soluble CD40L (sCD40L) concentration in a large ambulatory cohort. They concluded that circulating sCD40L levels were poorly associated with known cardiovascular disease risk factors, and it was modestly heritable in samples derived from either plasma or serum. Likewise, they found that the method of sample acquisition to has profound effect on sCD40L concentration, particularly the time delay between blood draw and the processing of serum. Because of this, we would like to point out an important aspect about the influence of preanalytical factors such as diurnal variation, which can play a role in determining the accuracy and clinical usefulness of sCD40L. Recently, we have demonstrated that a diurnal variation in sCD40L levels exists in ST-segment elevation myocardial infarction.2 The concentration of sCD40L was significantly higher in the light phase (09:00 hours) than that in the dark phase (02:00 hours). It indicates the need to standardize blood sampling timing in studies assessing sCD40L concentrations in patients with acute coronary syndrome. Our finding about sCD40L levels show day-night variations have important implications. Giving the diversity of diurnal variations regarding several of intrinsic properties of the cardiovascular system, extreme caution should be taken to ensure that time of day sampling issues are clearly understood when designing research protocols that involve single-point assessment of this biomarker of inflammation in both in vivo and in vitro studies.2 Performance of experiments at an inappropriate time of the day and lack of information regarding circadian changes in the concentration of the omission of suitable time controls may lead to incorrect conclusions. Such temporal considera-

tions will undoubtedly aid to reduce studies performed in different laboratories, as well as discrepancies between animal models and humans. Indeed, most clinical studies published to date have assessed subjects during the daylight hours, when the subjects are usually awake.3 Therefore, considering these findings, it is obvious that preanalytic conditions, such as diurnal variation in the sCD40L levels, are of paramount importance. Diurnal variation is an important source of heterogeneity that may bias the analysis of epidemiologic studies and coronary heart disease risk prediction in individuals.3 Am Heart J 2009;157:e3. 0002-8703/$ - see front matter doi:10.1016/j.ahj.2008.11.005

Alberto Dominguez-Rodríguez, MD, PhD Department of Cardiology

University Hospital of Canarias Tenerife, Spain E-mail: [email protected] Pedro Abreu-Gonzalez, PhD Department of Physiology

School of Medicine University of La Laguna Tenerife, Spain

References 1. Keaney Jr JF, Lipinska I, Larson MG, et al. Clinical correlates, heritability, and genetic linkage of circulating CD40 ligand in the Framingham Offspring Study. Am Heart J 2007;156:1003-1009.e1. 2. Dominguez-Rodriguez A, Abreu-Gonzalez P, Garcia-Gonzalez MJ, et al. Diurnal variation of soluble CD40 ligand in patients with acute coronary syndrome. Soluble CD40 ligand and diurnal variation. Thromb Res 2008 (Electronic Publication 2008 June 23). 3. Rudnicka AR, Rumley A, Lowe GD, et al. Diurnal, seasonal, and blood-processing patterns in levels of circulating fibrinogen, fibrin D-dimer, C-reactive protein, tissue plasminogen activator, and von Willebrand factor in a 45-year-old population. Circulation 2007; 115:996-1003.