Preanalytic conditions of the C-reactive protein are of paramount importance to use as a predictor of cardiovascular disease in clinical practice

Abstract

We read the article by Wu et al. [1] about of the intra-individual variability of high-sensitivity C-reactive protein (hsCRP) in a cohort of Chinese adults. They recruited a large population (44,140 males and 12,078 females) inwhich blood samples were obtained during morning. The authors conclude that the age and gender are factors that influenced the hsCRP level. However, in the present article we saw an additional potential limitation of the study: they have not determined the hsCRP along a 24-hour period to eliminate the possible influence of circadian rhythms. Many epidemiological studies have demonstrated that hsCRP, a biomarker of inflammation, is an important prognostic factor for the future occurrence of major cardiovascular events, both in patients with known cardiovascular disease and apparently in healthy subjects [2,3]. The 2009 National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines included and endorsed the use of hsCRP as a novel means by which to identify individuals who are at risk for vascular disease [4]. Circulating biomarkers are subject to variability arising from sampling procedures andbiologic variation, and this variabilitymust be determined and adjusted for in the interpretation of laboratory results. Diurnal variation may be an important source of heterogeneity or bias, and standardization for sampling time may be important in populationbased studies, as well as, in using these variables for additional coronary heart disease risk prediction in individuals [5–8]. The available data on diurnal variations of hsCRP levels in healthy subjects are few and controversial. We have demonstrated absence of diurnal variation of hsCRP levels, when blood samples were collected at 9:00 AM (light period) and 2:00 AM (dark period) from 70 healthy subjects [9]. Previously, Meier-Ewert and colleagues found no diurnal variation in hsCRP samples that were taken hourly from 13 healthy subjects [10]. In other study of hsCRP, D-dimer, tissue plasminogen activator, and von Willebrand factor in a middle-aged population showed diurnal variation as high as 34% in hsCRP, with maximum hsCRP levels observed at 3:00 PM. However, that study was limited in that hsCRP was measured between 9:00 AM and 10:00 PM [11]. Moreover, recently Koc and colleagues [12] demonstrated a variation of 86% of hsCRP in 30 subjects who had normal coronary arteries at 6hour intervals over 24-hour period. Wu et al. have discussed in their manuscript that the age and environmental variables, such as lipid levels, blood pressure, obesity and diabetesmellitus can contribute to the variation of hsCRP [1,13]. However, with the items mentioned above, we believe that the diurnal variation should be taken into account as a control variable in multivariate regression models. In summary, hsCRP represents the most extensively studiedproinflammatorymolecule, but additional effort is requiredon the part of the investigators to manage standardization of methodology and to determine cost-effective timing and frequency of measurements. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010;144:1–2).