Background. Cross-sectional and follow-up studies on end-stage renal disease patients showed that arterial calcifications are associated with cardiovascular (CV) morbidity and are an independent predictor of all-cause and CV mortality. However, these studies did not examine the impact on prognosis according to the type of calcification, i.e. intimal vs medial. Arterial media calcification (AMC), a non-occlusive condition, affects haemodynamics differently from arterial intima calcification (AIC), which occurs in atherosclerotic plaques. The aim of this study was to investigate the prognostic value of AMC in relationship to all-cause or CV mortality for stable haemodialysis (HD) patients. Methods. We included 202 such patients in the present study. At baseline, soft-tissue native radiograms of the pelvis and the thigh were analysed for the presence and type (AMC vs AIC) of arterial calcifications. All patients underwent B-mode ultrasonography of the common carotid artery to determine the presence of atherosclerotic calcified plaques, measurement of aortic pulse wave velocity and echocardiography. Results. AIC was usually observed in older patients with a clinical history of atherosclerosis before starting HD treatment and typical risk factors associated with atherosclerotic disease. AMC was observed in young and middle-aged patients without conventional atherosclerotic risk factors. AMC was closely associated with the duration of HD and calcium–phosphate disorders, including the oral dose of elemental calcium prescribed as phosphate binder (CaCO₃). Compared to patients with AIC, patients with AMC had a longer survival, but in turn their survival was significantly shorter than that of patients without calcifications. Conclusions. AMC is a strong prognostic marker of all-cause and CV mortality in HD patients, independently of classical atherogenic factors. The principal effect of AMC on arterial function is increased arterial stiffness.

The increased effect of arterial wave reflections on central arteries like the common carotid artery seen in end-stage renal failure (ESRF) patients favors myocardial hypertrophy and oxygen consumption and alters coronary blood flow distribution. Nevertheless, the impact of wave reflection on the outcome and end points such as mortality remains to be demonstrated. One hundred eighty ESRF patients (age, 54±16 years) were monitored for 52±36 months (mean±SD). Seventy deaths, including 40 cardiovascular (CV) and 30 non-CV events, occurred. At entry, patients, in addition to standard clinical and biochemical analyses, underwent aortic pulse wave velocity measurement and determination of arterial wave reflexion by applanation tonometry on the common carotid artery that was expressed as augmentation index. Cox analyses demonstrated that predictors of all-cause and CV mortality were age, aortic pulse wave velocity, low diastolic blood pressure, preexisting CV disease, and increased augmentation index, whereas the prescription of an ACE inhibitor had a favorable effect on survival. After adjustment for all confounding factors, the risk ratio for each 10% increase in augmentation index was 1.51 (95% confidence interval, 1.23 to 1.86; P <0.0001) for all-cause mortality and 1.48 (95% confidence interval, 1.16 to 1.90; P <0.0001) for CV mortality. These results provide the first direct evidence that in ESRF patients increased effect of arterial wave reflections is an independent predictor of all-cause and CV mortality.

Arterial calcification (AC) is a common complication of end-stage renal disease (ESRD). The mechanisms responsible are complex, including disturbances of mineral metabolism and active expression of various mineral-regulating proteins. An inverse relationship between AC and bone density has been documented in uremic patients. In the study presented here, which included 58 patients with ESRD on hemodialysis (HD), bone-histomorphometry characteristics were compared with the AC scores (0 to 4) determined according to the number of arterial sites with calcifications. Patients with AC scores of 0 (no calcifications), or 1 or 2 (mild calcifications) had similar serum parathyroid hormone levels and bone histomorphometry, with larger osteoclast resorption, higher osteoclast numbers, and larger osteoblastic and double tertracycline-labeled surfaces. In contrast, patients with high AC scores (3 and 4) were characterized by lower serum parathyroid hormone, low osteoclast numbers and osteoblastic surfaces, smaller or absent double tetracycline-labeled surfaces, and high percentages of aluminum-stained surfaces. According to multivariate analysis, AC score was positively associated with age (P < 0.0001), daily dose of calcium-containing phosphate binders (P = 0.009), and bone aluminum-stained surfaces (P = 0.037), and an inverse correlation was observed with osteoblastic surfaces (P = 0.001). A high AC score is associated with bone histomorphometry suggestive of low bone activity and adynamic bone disease. These findings suggest that therapeutic interventions associated with excessive lowering of parathyroid activity (parathyroidectomy, excessive calcium or aluminum load) favor lower bone turnover and adynamic bone disease, which could influence the development and progression of AC.

In ESRD, arterial function is abnormal, characterized by decreased capacitive function (arterial stiffening) and reduced conduit function, shown by diminished flow-mediated dilation (FMD). The pathophysiology of these abnormalities is not clear, and this cross-sectional study analyzed possible relationships among arterial alterations and cardiovascular risk factors, including mineral metabolism parameters, such as serum parathormone, and vitamin D “nutritional” and “hormonal” status by measuring serum 25-hydroxyvitamin D [25(OH)D₃] and 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] levels. Aortic stiffness (pulse wave velocity), brachial artery (BA) distensibility (echotracking; n = 42), BA FMD (hand-warming; n = 37), and arterial calcification scores (echography and plain x-rays) were measured in 52 stable and uncomplicated patients who were on hemodialysis. 25(OH)D₃ and 1,25(OH)₂D₃ serum levels were low and weakly correlated (r = 0.365, P < 0.05). After adjustment for BP and age, multivariate analyses indicated that 25(OH)D₃ and 1,25(OH)₂D₃ were negatively correlated with aortic pulse wave velocity (P < 0.001) and positively correlated with BA distensibility (P < 0.01) and FMD (P < 0.001). Arterial calcification scores were not independently associated with 25(OH)D₃ and 1,25(OH)₂D₃ serum concentrations. These results suggest that nutritional vitamin D deficiency and low 1,25(OH)₂D₃ could be associated with arteriosclerosis and endothelial dysfunction in patients who have ESRD and are on hemodialysis.

Arterial pressure is a cyclic phenomenon characterized by a pressure wave oscillating around the mean blood pressure, from diastolic to systolic blood pressure, defining the pulse pressure. Aortic input impedance is a measure of the opposition of the circulation to an oscillatory flow input (stroke volume generated by heart work). Aortic input impedance integrates factors opposing LV ejection, such as peripheral resistance, viscoelastic properties and dimensions of the large central arteries, and the intensity and timing of the pressure wave reflections, associated with the opposition to LV ejection influenced by inertial forces. The two most frequently used methods of arterial stiffness are measurement of PWV and central (aortic or common carotid artery) pulse wave analysis, recorded directly at the carotid artery or indirectly in the ascending aorta from radial artery pressure curve. The arterial system is heterogenous and characterized by the existence of a stiffness gradient with progressive stiffness increase (PWV) from ascending aorta and large elastic proximal arteries to the peripheral muscular conduit arteries. Analysis of aortic or carotid pressure waveform and amplitude concerns the effect of reflected waves on pressure shape and amplitude, estimated in absolute terms, augmented pressure in millimetre of mercury, or, in relative terms, ‘augmentation index’ (Aix in percentage of pulse pressure). Finally, if the aortic PWV has the highest predictive value for prognosis, the aortic or central artery pressure waveform should be recorded and analysed in parallel with the measure of PWV to allow a deeper analysis of arterial haemodynamics.