oa Editorial [Hot topic: Current Topics on Hypolipidaemic Therapy and Cardiovascular Risk Assessment (Guest Editors: Evangelos C. Rizos and Moses S. Elisaf)]

Atherosclerotic vascular disease remains an enormous public health problem. Cardiovascular risk assessment and hypolipidaemic therapy were greatly advanced during the last 15 years. In fact, hypolipidaemic drugs are consistently among the top ten best-seller drugs worldwide. Although the progress in this field is enormous, there are topics still unresolved. Distinguished authors in the field were invited to give their perspective on current controversies in this supplemental issue of the Current Vascular Pharmacology journal. Biomarkers of kidney function include serum creatinine and more recently estimated glomerular filtration rate (eGFR). These biomarkers and microalbuminuria predict the development of cardiovascular disease (CVD) [1]. Recent analyses indicate that eGFR is a much stronger predictor of CVD than is microalbuminuria. While microalbuminuria indicates endothelial dysfunction and is associated with increased risk for CV events, its level is related more to the level of blood pressure and glycemic control than directly to the pathophysiology of atherosclerosis. Hence, microalbuminuria could be viewed as a biomarker but not as a risk factor for CVD, since risk factors must be an integral part of the disease pathophysiology. Conversely, while microalbuminuria is not of prognostic value to predict chronic kidney disease (CKD) outcomes, increases over time into the albuminuria range clearly indicate presence of kidney disease and are associated with a more rapid decline in kidney function. Kalaitzidis et al. proposes the concomitant evaluation of both biomarkers eGFR and albuminuria to assess kidney function and CVD risk thoroughly. But what happens when the beneficial effect of a treatment adversely affects a biomarker? In this respect the case of fenofibrate is interesting. In the FIELD study, a placebo-controlled study in 9795 patients with type 2 diabetes, fenofibrate over 5 years reduced non fatal cardiovascular events and microvascular events such as albuminuria, the need for laser treatment for proliferative retinopathy or maculopathy and amputations but failed to reduce fatal cardiovascular events [2]. On the other hand, fibrates and in particular fenofibrate, are known to increase homocysteine levels (Hcy), a biomarker associated with an increased risk for CVD, venous thromboembolic events (VTE) and possibly cognitive disorders and bone fractures. It seems that the actual level of a biomarker has a different meaning compared to its changes upon intervention, which seems to be the case with Hcy. The results of all randomized clinical trials reported to date indicate that a reduction of Hcy levels with vitamin B supplements does not improve CVD, recurrence of VTE and cognitive disorders in patients with mild hyperhomocysteinemia, while the increase in Hcy levels with fenofibrate was not associated with adverse cardiovascular outcomes. There is no evidence to recommend measurement of homocysteine in patients receiving a fibrate or to add vitamin B supplements to their treatment. In this issue Foucher et al. suggests that Hcy levels currently represent a risk marker rather than a risk factor, suggesting that the risk factor(s) behind Hcy are awaited to be found. When it comes to hypolidaemic therapy, we focus mainly on statin treatment and its effect on various parameters beyond cholesterol lowering. Pulse wave velocity (PWV) is a method to estimate arterial stiffness. At a given blood pressure, the stiffer the vessel, the less time it takes for the pulse wave to travel the length of the vessel. As a result, PWV is increased with stiffer less compliant arteries. Aortic PWV is considered to be the gold standard of arterial stiffness measurements. Age, blood pressure levels and diabetes mellitus are the major factors associated with increased PWV. Aortic PWV is an independent predictor of both cardiovascular and all-cause mortality in hypertensive patients, and independently predicts mortality in patients with normal renal function or end stage renal failure. By contrast, there is no unanimous opinion concerning the role of dyslipidaemia on PWV, with the majority of the studies reporting no association between lipids and PWV. Statins have been shown to improve the compliance of the vasculature. In this issue we present the available data on the effect of statin administration on arterial stiffness by measuring PWV. Nine eligible randomized controlled trials (RCTs) with 471 participants were found. The most frequent comparison was between fluvastatin against placebo, and the most extensively studied agent was also fluvastatin , while the most frequent indication for statin therapy was hyperlipidaemia (n = 6), with or without other cardiovascular risk factors. Aortic PWV was assessed in 4 studies, with significant reduction (improvement of arterial stiffness) in 2 studies, a nonsignificant change in one study and a significant increase in the other....