Background. Osteoprotegerin (OPG) is a marker and regulator of arterial calcification, and it is related to cardiovascular survival in haemodialysis patients. The link between OPG and aortic stiffening-a consequence of arterial calcification-has not been previously evaluated in this population, and it is not known whether OPG-related mortality risk is mediated by arterial stiffening. Methods. At baseline, OPG and aortic pulse wave velocity (PWV) were measured in 98 chronic haemodialysis patients who were followed for a median of 24 months. The relationship between OPG and PWV was assessed by multivariate linear regression. The role of PWV in mediating OPG related cardiovascular mortality was evaluated by including both OPG and PWV in the same survival model. Results. At baseline mean (standard deviation) PWV was 11.2 (3.3) m/s and median OPG (interquartile range) was 11.1 (7.5-15.9) pmol/L. There was a strong, positive, linear relationship between PWV and lnOPG (P = 0.009, model R 2 = 0.540) independent of covariates. During follow-up 23 patients died of cardiovascular causes. In separate univariate survival models both PWV and lnOPG were related to cardiovascular mortality [hazard ratios 1.31 (1.14-1.50) and 8.96 (3.07-26.16), respectively]. When both PWV and lnOPG were entered into the same model, only lnOPG remained significantly associated with cardiovascular mortality [hazard ratio 1.11 (0.93-1.33) and 7.18 (1.89-27.25), respectively). Conclusion. In haemodialysis patients OPG is strongly related to PWV and OPG related cardiovascular mortality risk is, in part, mediated by increased PWV.Correspondence and offprint requests to: Gabor Speer,

Background: Measuring arterial stiffness (augmentation index (AI), aortic pulse wave velocity (PWV)) in hemodialysis (HD) patients has prognostic significance. To assess its validity, the new oscillometric Arteriograph device (AI_A, PWV_A) was compared to the validated PulsePen tonometer (AI_P, PWV_P). Methods: AI and PWV were measured in 98 patients with both devices before HD. Validity was evaluated by Pearson’s correlation, Bland-Altman analysis, and by assessing the prognostic value of AI and PWV to predict cardiovascular (CV) mortality over 29 months. Results: Correlation between AI_P and AI_A was significant (R = 0.527, p < 0.001). The mean difference of AI values obtained by the two devices was –20.6%, and 30% of the paired AI differences fall outside the ±1 SD boundary of the mean between-device difference. There was no significant correlation between the PWV_P and PWV_A readings (R = 0.173, p = 0.097). The average difference of PWV values by the two devices was –1.2 m/s, and 20.6% of the paired PWV differences fall outside the ±1 SD boundary. In survival analyses, only PWV_P but not PWV_A was significantly related to CV mortality. Conclusion: Lack of correlation between PWV_P and PWV_A and lack of prognostic significance of PWV_A suggest limited validity of Arteriograph to determine PWV in patients on HD.

Background and aims The aim of this study was to develop an integrated central blood pressure–aortic stiffness (ICPS) risk score to predict cardiovascular events. Methods It was a retrospective cohort study. A total of 100 chronic kidney disease (CKD) patients on conservative therapy were included. Pulse wave velocity (PWV), central systolic blood pressure (cSBP), and central pulse pressure (cPP) were measured. A score was assigned to tertiles of PWV (0–2), cPP (0–2), and cSBP (0 to the first and second and 1 to the third tertile) based on each parameter’s ability to individually predict cardiovascular outcome. The sum of these scores and three ICPS risk categories as predictors were studied. Finally, we compared discrimination of the ICPS risk categories with PWV, cSBP, and cPP. Results Adjusted for age and sex, patients in high and very high ICPS risk categories had increased cardiovascular risk (HR: 3.52, 95% CI: 1.65–7.49; HR: 7.56, 95% CI: 3.20–17.85, respectively). High and very high ICPS risk categories remained independent predictors in a model adjusted for multiple CV risk factors (HR: 4.58, 95% CI: 1.65–7.49; HR: 8.56, 95% CI: 3.09–23.76, respectively). ICPS risk categories (Harrell’s C: 0.723, 95% CI: 0.652–0.795) showed better discrimination than PWV (Harrell’s C: 0.659, 95% CI: 0.586–0.732, p = 0.028) and cSBP (Harrell’s C: 0.660, 95% CI: 0.584–0.735, p = 0.008) and there has been a tendency of significance in case of cPP (Harrell’s C: 0.691, 95% CI: 0.621–0.761, p = 0.170). Conclusion The ICPS score may clinically importantly improve the identification of CKD patients with elevated cardiovascular risk.

Aortic stiffening and aortic calcification are risk factors for cardiovascular events in hemodialysis (HD) patients, and these 2 risk factors are interrelated. Sevelamer decreases aortic calcification but its effect on aortic stiffness has not been investigated previously. Thirteen HD patients commencing sevelamer treatment and 13 matched controls were followed for 11 months. Aortic pulse wave velocity (PWV), augmentation index (AIx), and levels of inhibitors of vascular calcification (fetuin-A, matrix-GLA-protein, osteoprotegerin/RANKL) were measured at baseline and at the end of follow-up, and the differences between the groups were compared. Determinants of the changes in PWV during follow-up were assessed by multivariate linear regression. At baseline, PWV was 9.93 (2.10) m/s in sevelamer-treated patients and 9.20 (2.84) m/s in control patients (p=0.464). By the end of follow-up, PWV decreased by 0.83 (2.3) m/s in sevelamer-treated patients while it increased by 0.93 (1.88) m/s in controls (p=0.042). The direction of changes in AIx were similar, but not statistically significant. There were no significant differences in the levels of inhibitors of calcification either at baseline or during follow-up. In multivariate linear regression sevelamer treatment, diabetes, heart rate, and C-reactive protein were related to the change in PWV. These data suggest that sevelamer treatment is associated with an improvement in aortic stiffness in HD patients, but it does not seem to affect serum levels of inhibitors of vascular calcification.

PWV calculated using suprasternal notch-to-femoral distance minus suprasternal notch-to-carotid distance provides the strongest relationship to cardiovascular mortality. Longer torso weakens the predictive value of PWV, possibly due to more tortuosity of the aorta hence, more error introduced when using surface tape measurements.

Background: Our aim was to study the predictive power of integrated central blood pressure-aortic stiffness (ICPS) risk categories on cardiovascular (CV) mortality in end-stage renal disease (ESRD) patients. Methods: This is a secondary analysis of a prospective study of 91 ESRD patients on hemodialysis therapy. At baseline, pulse wave velocity (PWV), central systolic blood pressure (cSBP) and central pulse pressure (cPP) were measured and patients were followed up for CV mortality for a median 29.5 months. Based on the shape of the association of each individual ICPS parameter with the CV outcome, patients were assigned ICPS scores: one point was given, if either the cSBP value was in the 3rd, or if the PWV or cPP was in the 2nd or 3rd tertiles (ICPS range: 0-3). We then evaluated the role of ICPS risk categories (average: 0-1, high: 2, very high: 3 points) in the prediction of CV outcomes using Cox proportional hazard regression analysis and compared its discrimination (Harrell's C) to that of each of its components. Results: We found a strong dose-response association between ICPS risk categories and CV outcome (high risk HR = 2.62, 95% CI: 0.82-8.43, p for trend = 0.106; very high risk HR = 10.03, 95% CI: 1.67-60.42, p = 0.02) even after adjustment for multiple potential confounders. ICPS risk categories had a modest discrimination (C: 0.622, 95% CI: 0.525-0.719) that was significantly better than that of cSBP (dC: 0.061, 95% CI: 0.006-0.117). Conclusion: The ICPS risk categories may improve the identification of ESRD patients with high CV mortality risk. H I G H L I G H T S • Integrated evaluation of central blood pressure and stiffness (ICPS) may improve risk prediction. • ICPS risk categories were developed and tested in end-stage renal disease (ESRD). • Very high ICPS risk category is a strong predictor of cardiovascular mortality in ESRD.

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Aortic valve calcification (AVC) and carotid artery calcification (CAC) are considered to be markers of generalized atherosclerosis. However, the role of intracardiac calcification (ICC) (valvular and perivalvular calcification) is unclear. The objective of this retrospective study was to analyze the relationship between ICC and CAC, risk factors, and clinical atherosclerotic disease. Risk factors included age, sex, diabetes mellitus, hypercholesterolemia, and hypertension; clinical atherosclerosis comprised stroke, coronary artery disease, and peripheral artery disease. Between January 1, 2001, and January 1, 2004, all consecutive patients were enrolled into the study who underwent both carotid ultrasonography and transthoracic echocardiography examinations within 2 months. Patients with renal failure, substantial aortic stenosis, and carotid artery occlusion were excluded. There were 320 patients (104 men; mean +/- SEM age, 66.6 +/- 0.76 years). Positive results on carotid ultrasonography are defined as any CAC. Patients were categorized as having mild, moderate, or severe CAC. Positive results on transthoracic echocardiography were defined as any ICC; AVC was defined as mitral anulus calcification (MAC) or both. Intracardiac calcification was found in 181 patients, AVC in 51 patients, MAC in 48 patients, and calcification of both structures in 82 patients. Using multiple logistic regression analysis, ICC (odds ratio, 1.9), age (10-year periods) (odds ratio, 2.0), and the presence of peripheral artery disease (odds ratio, 1.7) were independent predictors of CAC. Carotid ultrasonography results were positive in 227 patients. For CAC, the sensitivities of AVC, MAC, both, and any ICC were 52.4%, 52.0%, 33.5%, and 71.2%, respectively, and the specificities were 84.9%, 87.1%, 92.5%, and 78.5%, respectively. The extension of ICC as 0, 1 location (AVC or MAC) , or 2 locations (AVC and MAC) was associated with the severity of CAC (P < .001, tau = 0.42). There was no difference between patients with AVC vs patients with MAC in the presence of different stages of CAC (P = .62). Intracardiac calcification (MAC or AVC) is an independent predictor of CAC as a marker of atherosclerosis, although the lack of ICC does not rule out atherosclerosis. Intracardiac calcification is related to CAC, with high specificity. The extension of ICC is related to the severity of atherosclerosis. Based on our results, antiatherothrombotic therapy should be considered in patients with ICC even before obtaining a positive carotid ultrasonography result.