Myeloperoxidase in the acute coronary syndrome: Equal concentrations at any time of day?

Abstract

We read the elegant review on oxidative stress biomarkers as predictors of cardiovascular disease by Strobel et al [1] with great interest. Table 2 in the article comprehensibly highlights all longitudinal studies investigating the value of myeloperoxidase (MPO) in predicting cardiovascular disease. However, wewould like to point out an important aspect about diurnal variations in MPO in patients with acute coronary syndrome (ACS). Circulating biomarkers are one such tool used for identifying better high-risk individuals and to prognosticate effectively and treat patients with disease. Recent prospective studies have consistently shown that several proinflammatory biomarkers, markers of plaque destabilization and plaque rupture may be used to predict future cardiovascular events not only in apparently healthy subjects, but also in patients with ACS [2]. In practice, preanalytical and analytical factors are important contributors to biomarker performance [3]. Preanalytical variability refers to biological variability and stability over time, whereas analytical variability relates to the performance of the test in the laboratory. It is well documented that serum biomarkers assays from different manufacturers may yield different results for the same blood specimen because of intermethod differences [4]. Moreover, it is known that serial measurements of an individual serum biomarker concentration, even when all results are obtained by a single method, they may fluctuate with higher amplitude than can be explained by the assay's analytical variation [4]. This reflects an additional component of intraindividual or within-subject variation, known as biological variation. Biological variation has also been used as a term for diurnal or circadian variation, but this is not appropriate because biological variation is a global term for several different types of random variation, whereas diurnal and circadian variation properly designates systematic, rather than random variability [5]. Based on these observations, circulating biomarkers are subject to daily variation, thus this variability must be determined and adjusted for the interpretation of the markers of inflammation in setting ACS [6]. MPO is a hemoprotein that which catalyze the conversion of chloride and hydrogen peroxide to hypochlorite. It is stored in azurophilic granules of polymorphonuclear neutrophils and macrophages and it is released into both the extracellularfluid and the general circulation during inflammation [7]. A number of methodological issues regarding the measurement of circulating MPO levels in humans may partly explain the controversial results provided the various clinical studies [8]. The cut points applied in different studies are disparate, perhaps because of different sample types and handling, leaving optimal decision limits uncertain and highlighting the need for studies of preanalytical and analytical performance [9]. Recently, we have demonstrated that a diurnal variation inMPO levels exist in ST-segment elevation myocardial infarction [10]. The concentration of MPO was significantly higher in the dark phase (02:00 h) than that in the light phase (09:00 h). It indicates the need to standardize blood sampling timing in studies assessing MPO concentrations in patients with ACS. Temporal variation is an important source of heterogeneity that may bias the analysis of epidemiologic studies and coronary artery disease risk prediction [6]. In summary, additional investigations on analytical concerns will be necessary, for better acceptance of MPO as an independent biomarker for cardiovascular risk in ACS patients. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [11].