Does C‐reactive protein represent an oxidative stress marker in cardiovascular disease?

It is well established that oxidative stress (OS) plays an important role in the pathophysiology of various cardiovascular diseases such as atherosclerosis, coronary artery disease, hypertension, heart failure, anthracycline-induced cardiomyopathy, and atrial fibrillation.1-4 In addition, most conventional risk factors for atherosclerosis such as diabetes, smoking, obesity, hypercholesterolaemia and end-stage renal disease, have all been associated with OS.2, 4 Intensive research efforts regarding antioxidant interventions are under way, in order to arrest the oxidative processes involved in these conditions, and during the past decade several novel risk factors have emerged. There is general agreement that the acute-phase reactant C-reactive protein (CRP) represents the most important of them.5 Compelling evidence is accumulating that CRP levels strongly predict major cardiovascular events, as well as cardiovascular mortality. From a pathophysiological point of view, CRP seems to reflect low-grade inflammation in atherosclerotic plaques and in expansion plaque instability. Furthermore, it has been found elevated in atrial fibrillation, particularly in the persistent form, implicating an inflammatory process in atrial electrical remodelling.3, 6 It has become apparent that inflammation is associated with antioxidant status,4 giving rise to the assumption that CRP may correlate with the occurrence of OS in cardiovascular disease. On the other hand, various oxidative metabolites can promote synthesis of proinflammatory cytokines resulting in amplification of the inflammatory cascade.4 In fact, the hypothesis that CRP correlates with OS might be of great importance, because easily determined reliable markers of OS are lacking. Obviously, the effects of antioxidant interventions in diverse disease states would be efficiently assessed. To the best of our knowledge, only a few studies have investigated the possible link between CRP and OS. Khaw and Woodhouse were the first to report a significant inverse relationship between markers of acute-phase response and serum ascorbic acid concentrations in healthy volunteers.7 Subsequently, a similar association was observed in patients with peripheral arterial disease,8 the strongest association being observed in advanced disease states. Moreover, CRP levels have been correlated with levels of lipid peroxidation products (indirect markers of OS) in dialysis patients.9 Finally, Yasunari et al recently showed that CRP directly relates to monocyte OS in hypertensive and diabetic patients.10 We believe that the role of CRP as an OS marker in cardiovascular disease deserves further study. Apart from pure antioxidants, several cardiovascular drugs appear to exhibit antioxidant capacity.11 Thus, medications such as ACE inhibitors, statins, aspirin, carvedilol and trimetazidine may serve as valuable therapeutic tools in the research of this potential association. It remains to be seen whether this pioneering idea can be put into clinical practice.