C-reactive protein and endothelial dysfunction: The clinicians should have in mind diurnal variations

Abstract

We read the article by Forte et al. [1] that the increase in C-reactive protein (CRP) plasma levels across the coronary circulation is associated with a profound impairment in coronary endothelialdependent function, outlining a novel pathophysiological mechanism linking CRP to acute coronary syndrome (ACS). However, in the present article we saw an additional potential limitation of the study: the authors have not measured CRP during a 24-hour period. Clinicians have used additional tools to aid clinical assessment and to enhance their ability to identify the “vulnerable” patients at risk for cardiovasculardiseases. Circulating biomakers are one such tool used for identifying better high-risk individuals and to prognosticate effectively and treat patients with disease [2]. Circadian rhythms influence nearly every important physiologic process. The human cardiovascular system and cardiovasculardisease are influenced bycircadian rhythms. It is now evident that molecular circadian clocks play a role in the regulation of daily oscillations in cardiovascular function [3]. The existence of a circadian rhythm in the incidence of ACS suggests an association between physiological rhythms and the development of coronary events, with a peak along of day [4]. Moreover, experimental studies have shown that both immune cell number and immune functions may vary throughout the 24-hour circadian period [5]. Our group demonstrated that patients with ACS have daytime variations in serum CRP concentrations. Serum CRP values were significantly higher in the light phase (9:00 a.m.) when compared to the dark phase (2:00 a.m) [6]. In other study, Rudnicka et al. [7] described one of the largest cross-sectional studies of seasonal and diurnal fluctuations in fibrinogen, CRP, fibrin D-dimer, tissue plasminogen activator antigen, and von Willebrand factor in 9377 men and women aged 45 years. These investigators demonstrated that diurnal variations existed for these biomarkers. The amplitude of the diurnal variation for all analytes was greater than the seasonal variation. Moreover, recently Koc and colleagues describe measurements of CRP over a 24-hour cycle in 124 Turkish patients with and without coronary artery disease. They demonstrated a variation of CRP in patients with stable coronary artery disease at 6-hour intervals over a 24-hour period. Besides, they showed that the sampling time of CPR is important, because only midnight CRP measurements predicted severe coronary artery disease [8]. Several studies have shown diurnal variations in inflammatory systemic markers in patients with ACS. Diurnal variations can alter the analysis of blood-derived samples. Prior to the analysis of a blood sample, multiple steps are necessary to generate the desired specimen [9]. In summary, temporal variation is an important source of heterogeneity that may bias the analysis of epidemiologic studies and coronary artery disease risk prediction. 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).