Objectives To determine whether aortic pulse wave velocity (aPWV) improves prediction of cardiovascular (CVD) events beyond conventional risk factors. Background Several studies have shown that aPWV may be a useful risk factor for predicting CVD but have been underpowered to examine whether this is true for different sub-groups. Methods We undertook a systematic review and obtained individual participant data from 16 studies. Study-specific associations of aPWV with cardiovascular outcomes were determined using Cox proportional hazard models and random effect models to estimate pooled effects. Results Of 17,635 participants, 1,785 (10%) had a cardiovascular (CVD) event. The pooled age- and sex-adjusted hazard ratio [95% CI] per SD change in loge aPWV was 1.35 [1.22, 1.50, p<0.001] for coronary heart disease (CHD), 1.54 [1.34, 1.78, p<0.001] for stroke, and 1.45 [1.30, 1.61, p<0.001) for CVD. Associations stratified by sex, diabetes and hypertension were similar, but decreased with age (1.89, 1.77, 1.36 and 1.23 for ≤50, 51–60, 61–70 and >70 years respectively, pinteraction <0.001). After adjusting for conventional risk factors, aPWV remained a predictor: CHD 1.23, [1.11, 1.35 p<0.001]; stroke 1.28, [1.16, 1.42 p<0.001]; cardiovascular events 1.30 [1.18, 1.43, p<0.001]. Reclassification indices showed the addition of aPWV improved risk prediction (13% for 10 year CVD risk for intermediate risk) for some sub-groups. Conclusions Consideration of aPWV improves model fit and reclassifies risk for future cardiovascular events in models that include standard risk factors. aPWV may enable better identification of high-risk populations who may benefit from more aggressive cardiovascular risk factor management.

To make an evidence-based evaluation of the relationship between kidney failure and cardiovascular risk, we reviewed the literature obtained from a PubMed search using pre-defined keywords related to both conditions and covering 18 years (1986 until end 2003). Eighty-five publications, covering 552 258 subjects, are summarized. All but three studies support a link between kidney dysfunction and cardiovascular risk. More importantly, the association is observed very early during the evolution of renal failure: an accelerated cardiovascular risk appears at varying glomerular filtration rate (GFR) cut-off values, which were >/=60 ml/min in at least 20 studies. Many studies lacked a clear definition of cardiovascular disease and/or used a single determination of serum creatinine or GFR as an index of kidney function, which is not necessarily corresponding to well-defined chronic kidney disease. In six studies, however, chronic kidney dysfunction and cardiovascular disease were well defined and the results of these confirm the impact of kidney dysfunction. It is concluded that there is an undeniable link between kidney dysfunction and cardiovascular risk and that the presence of even subtle kidney dysfunction should be considered as one of the conditions necessitating intensive prevention of this cardiovascular risk.

, and the results of epidemiologic and clinical studies showed that large artery damage is a major factor that contributes to the mortality of these patients (2,3). The arterial system has two distinct, interrelated functions: To deliver an adequate blood supply from the heart to peripheral tissues (i.e., the conduit function) and to dampen blood flow and pressure oscillations that are caused by intermittent ventricular ejection (i.e., the cushioning function). Conduit function depends primarily on the diameter of the arterial lumen. It is highly efficient, and its physiologic adaptability is mediated through acute arterial diameter changes, which depend in large part on the endothelium response to alterations of shear stress, a phenomenon called flow-mediated dilation (FMD) (4). Conduit function disorders result from the narrowing of the arterial lumen or the diminished ability of the artery to dilate in response to shear stress changes. The cushioning function is altered by diminished distensibility that is caused by stiffening of arterial walls. Arterial stiffening results from fibroelastic intima thickening, increased collagen accumulation, and fragmentation of elastic lamellae with secondary fibrosis and calcification of the media (5).In patients with ESRD, both aspects of arterial functions are abnormal, characterized by arterial outward remodeling (6,7), increased arterial stiffening (6,7), and decreased FMD (8,9). These anomalies are enhanced further with aging, but these age-related effects are accelerated in uremic patients, in whom they are predictive of all-cause and cardiovascular mortality (3,10). The pathogenesis of these dysfunctions is not entirely clear. Conventional risk factors, such as aging and hypertension, only partly explain arterial abnormalities in patients with ESRD. Intimal and medial arterial calcifications (AC) are frequent in patients with ESRD (11); they result in arterial stiffening and abnormal conduit function and are associated with poor outcome (12). Several mineral metabolism disorders have been associated with increased AC and cardiovascular risk, including hyperphosphatemia, hyperparathyroidism, and increased calcium-phosphate product (13). Patients with chronic kidney disease and ESRD have vitamin D deficiency that is characterized by low serum 25-hydroxyvitamin D [25(OH)D 3 ] levels (14). With the decreased capacity of 1-␣-hydroxylase to synthesize calcitriol (1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]), the serum levels of the "hormonal" form of vitamin D also are low. Results of studies on the general population indicate that poor vitamin D status, characterized by low serum 25(OH)D 3 levels, is associated with higher prevalences of chronic heart failure, hypertension, and hyperparathyroidism (15-18), all fre-

SummaryBackground and objectives Radiographic calcification and arterial stiffness each individually are predictive of outcome in dialysis patients. However, it is unknown whether combined assessment of these intermediate endpoints also provides additional predictive value.Design, setting, participants, & measurements Scoring of abdominal aortic calcification (AAC) using plain lateral abdominal x-ray and measurement of carotid-femoral pulse wave velocity (PWV) were performed in a cohort of 1084 prevalent dialysis patients recruited from 47 European dialysis centers.Results During a follow-up of 2 years, 234 deaths and 91 nonfatal cardiovascular (CV) events occurred. Compared with the lowest tertile of AAC, the risk of an event was increased by a factor 3.7 in patients with a score of 5 to 15 (middle tertile), and by a factor 8.6 in patients with scores of 16 to 24. Additionally, each 1-m/s increase in PWV was associated with a 15% higher risk. At higher AAC (scores Ն5), the effect of PWV was attenuated because of a negative PWV ϫ AAC interaction (hazard ratio [HR]: 0.895 and 0.865 for middle and upper AAC tertiles). After accounting for age, diabetes, and serum albumin, AAC and PWV remained independent predictors of outcome.Conclusions AAC and central arterial stiffness are independent predictors of mortality and nonfatal CV events in dialysis patients. The risk associated with an increased PWV is less pronounced at higher levels of calcification. Assessment of AAC and PWV is feasible in a clinical setting and both may be used for an accurate CV risk estimation in this heterogeneous population.

Background. Patients with chronic kidney disease stage 5 have a high prevalence of vascular calcification, but the specific anatomical distribution and severity of abdominal aortic calcification (AAC), in contrast to coronary calcification, is less well documented. AAC may be recorded using plain radiographs. The present report is an analysis of baseline data on AAC in patients enrolled in the CORD (Calcification Outcome in Renal Disease) study.Methods. A total of 47 centres in six European countries participated in this cross-sectional study. Inclusion criteria were age ≥18 years and duration of dialysis ≥3 months. Lateral lumbar radiography of the abdominal aorta was used to determine the overall AAC score, which is related to the severity of calcific deposits at lumbar vertebral segments L1–L4. The reliability of the method was tested by double reading of 64 radiographs (coefficient of correlation 0.9).Results. A lateral lumbar radiograph was obtained in 933 patients. Calcification (AAC score ≥ 1) was present in 81% of the patients; its severity increased significantly from L1 to L4 (P < 0.0001) and affected all of these segments in 51% of patients. Independent predictors for the presence and severity of calcification were age (odds ratio [OR] 1.103/year; P < 0.0001), duration of dialysis (OR 1.110/year; P = 0.002) and history of cardiovascular disease (OR 3.247; P < 0.0001).Conclusions. AAC detected by lateral lumbar radiograph is associated with several risk factors of uraemic calcification. This semi-quantitative method is more widely available and less expensive than the current procedures for studying calcification and could form part of a pre-transplant workup and cardiovascular risk stratification.