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div>81; P?=?0.002] and low-grade RAS (HR 2.32; P?=?0.038) was observed. Other end-points did not differ significantly between study groups. Conclusion.? Hypertensive subjects with RAS of any extent, compared with hypertensives without RAS, carry a substantially increased risk for future CV events. Therefore, even in patients with low-grade RAS, aggressive pharmacological treatment strategies should be adopted as a preventive measure. Renal artery stenosis (RAS) is the most prevalent primary disease of the renal arteries and patients with a so-called ��significant�� (��50% lumen narrowing) atherosclerotic RAS face an increased risk from cardiovascular (CV) and all-cause mortality [1, 2]. From a haemodynamic point of view, a stenosis in the renal artery is significant Pritelivir research buy when there is a demonstrable pressure gradient, as the pressure drop distal to the narrowed lumen activates renal adaptive mechanisms ultimately leading to hypertension and renal ischaemia. Almost 50?years ago, it was observed in experimental models with dogs that a significant pressure gradient is established with a stenosis of at least 50% . In the latest scientific statement on RAS from the American Heart Association, it was therefore stated that ��renal arterial lesions http://www.selleckchem.com/products/gsk2126458.html causing <50% angiographic diameter stenosis are generally not considered to be haemodynamically important�� and should therefore not translate into adverse outcome . A recent, elaborate study, however, demonstrated that haemodynamic and humoral changes already begin to take place with a distal pressure gradient of as low as 10% . Additionally, it has been established in CAL-101 sequential angiographic studies that atherosclerotic RAS is commonly a progressive disease [6, 7] and CV risk factor modification may halt or in some cases even reverse RAS [8, 9]. Thus, because of the progressive nature of atherosclerosis, the early haemodynamic and humoral changes , and most notably the accelerative proatherogenic effects of renovascular disease , one can wonder if a lower limit of 50% lumen narrowing is adequate in classifying patients as candidates for an intensified treatment approach. Based on these considerations, we initiated this long-term follow-up study in order to assess the clinical relevance originally instituted on haemodynamic grounds of the cut-off value of a 50% narrowing of the renal artery. This was done by assessing CV and renal complications and CV and all-cause mortality in subjects radiographically subdivided as having no, a low-grade (<50%) and high-grade (��50%) RAS respectively. A total of 480 consecutive hypertensive patients with clinical suspicion of RAS, who were referred to our tertiary hypertension unit from 1982 to 2002, were initially considered eligible for this study. Exclusion was performed for subjects with a follow-up of <2?years (n?=?110), subjects with a history of renal disease (i.e.