Lipid lowering and the assessment of endothelial function.

We read with interest the report by Malik et al. [1] that suggested that a continuum probably exists between endoboth atorvastatin and fenofibrate equally improved endothelial activation (from early exposure to risk factors, such thelium-dependent arterial vasoreactivity in patients with as smoking), endothelial dysfunction (resulting in thromcombined hyperlipidaemia. Interestingly, a recent study by bogenesis and atherogenesis) and finally, endothelial damˇ ˇ Sebestjen et al. [2] reported similar observations using age (with overt vascular damage and atherosclerosis). cerivastatin and fenofibrate, although the effects seemed to An alternative way to assess endothelial damage / be greater in the patients receiving the statin. Indeed, most dysfunction is perhaps by measurement of plasma markers of us now recognise that the beneficial effects of statins on that are related to the endothelium, such as von Willebrand the early cardiovascular events reduction in major clinical factor (vWf), soluble thrombomodulin or E-selectin [5]. trials may involve mechanisms that modify endothelial Indeed, vWf has been most widely used as an index of function, inflammatory responses, plaque stability, and endothelial damage in experimental studies. This molecule thrombus formation which may be unrelated, or indirectly is synthesised by and stored in endothelial cells and when related, to their lipid-lowering abilities [3]. released, it mediates platelet aggregation and adhesion to Endothelial dysfunction has been regarded as an early the vascular endothelium, which is the first step in event in atherogenesis, preceding the formation of atherosthrombus formation. It is therefore plausible that levels of clerotic plaques. An important functional consequence of vWf are more representative of the extent of endothelial endothelial damage /dysfunction is a reduced vasodilatory damage in the whole vascular system rather than segmental responses to a variety of pharmacological and physiologiarterial dysfunction which might be the case for methods cal stimuli such as reactive hyperaemia. This is most that rely on reactive local arterial vasodilatation. In fact, commonly assessed by postischaemic dilation of forearm increased levels of vWf have been found in atherosclerotic vessels, using plethysmography, or flow-mediated dilatavascular diseases and in the presence of several of its tion (FMD) of the brachial artery, using ultrasound. major risk factors (smoking, hypercholesterolaemia, hyHowever, the methods used by Malik et al. in assessing pertension, obesity and diabetes). Furthermore, treatment vascular reactivity (or ‘function’) seem particularly attracof these risk factors has been shown to lower plasma vWf tive. In their study, FMD of brachial artery measured by levels [5], and high plasma vWf levels have been shown to automatic border detection B-mode scans was compared be an independent prognostic marker of death and cardirectly with reactive hyperaemia measured by peak blood diovascular events. Moreover, plasma markers measureflow (PBF) and blood flow increase (BFI) using pulsement is relatively cheaper, easier and more readily availDoppler spectral scans. As pointed out by the authors, able, with good reproducibility and low interand intraFMD has considerably higher interand intra-observer as observer variability, when compared to observer-dependent well as intra-subject variability and thus worst reprotechniques such as FMD, PBF or BFI measurements. ducibility as compared to PBF, which reflects ‘mean’ Indeed, as a plasma marker with such advantageous vascular reactivity of a relatively large portion of arterial properties, vWf would be ideal as a screening tool in large tree and (perhaps) more representative of endothelial population-based epidemiological studies. function. However, the next question is whether a significant Nevertheless, the best way of assessing endothelial relationship exits between plasma vWf level and FMD? damage/dysfunction is uncertain. Blann and Lip [4] has Our recent pilot study on 89 hypertensive patients (78 men; mean age 64 years, S.D. 8.4; mean BP 167/91 mmHg) has suggested that such a relationship does exist *Corresponding author. Tel.: 144-121-5075-080; fax: 144-121-5544083. (Spearman’s, r520.517, P,0.001). Furthermore, using