Statins and the assessment of endothelial function - reply to Lee et al.

Abstract

We agree with Lee et al. [1] that noninvasive assessment of endothelial dysfunction requires expensive and specialized equipment (ultrasound system), the presence of a trained observer and, above all, that it is observer dependent. On the other hand, it has been shown that endothelial function of coronary arteries, measured by coronary angiography – which has similar disadvantages to those of the method used in our study [2] – is an independent predictor of atherosclerosis disease progression and of the rate of cardiovascular events, independently of other coronary risk factors in patients with clinical evident coronary artery disease [3]. We may assume that the influence of all atherosclerotic risk factors is mirrored in endothelial (dys)function. Because of this, markers of endothelial dysfunction are actively being sought. Currently, the most promising areas involve the study of endothelium-dependent vasodilation and the detection of circulating markers of endothelial damage [4]. Endothelial injury may result in the release of various factors that can be detected in the circulation and therefore used as potential markers of endothelial dysfunction. Levels of E-selectin, which is expressed only on endothelial cells, were elevated in patients with dyslipidemia, and were shown to decrease after treatment with statins [5]. Proteins involved in haemostasis and synthesized by endothelial cells have been proposed as markers of endothelial dysfunction [4]. The main problem with these markers is their relatively poor specificity, which may hamper their use in diagnostic tests or for monitoring the effects of treatment. Endothelial dysfunction has also been shown in patients with increased levels of homocysteine [6]. For these reasons, we also measured fibrinolytic parameters – tissue plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor 1 (PAI-1) antigen and activity, fibrinogen, total and free tissue factor pathway inhibitor (TFPI), homocysteine and the highly sensitive C-reactive protein. In summary, cerivastatin has been shown to have no influence on the level of serum homocysteine, whilst fenofibrate increased it significantly. On the other hand, both drugs decreased serum C-reactive protein levels, with a somewhat higher decrease after cerivastatin. Cerivastatin and fenofibrate differently affected TFPI and PAI-1: cerivastatin decreased the levels of total and free TFPI antigen with no influence on PAI-1, whilst fenofibrate increased PAI-1 but did not affect TFPI. Taken together, these data provide additional information on the role of antiatherogenic mechanisms of these hypolipemic drugs. Further prospective studies, with a larger number of patients, are needed to answer the question as to whether these differences can explain the greater relative risk reduction observed in secondary prevention studies with statin [7], than with fibrate [8].