József Egresits

Serum osteoprotegerin level, carotid-femoral pulse wave velocity and cardiovascular survival in haemodialysis patients

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.

The Method of Distance Measurement and Torso Length Influences the Relationship of Pulse Wave Velocity to Cardiovascular Mortality

BACKGROUND The method of estimating distance traveled by the pulse wave, used in the calculation of pulse wave velocity (PWV), is not standardized. Our objective was to assess whether different methods of distance measurement influenced the association of PWV to cardiovascular mortality in hemodialysis (HD) patients. METHODS Ninety-eight chronic HD patients had their PWV measured using three methods for distance estimation; PWV1: suprasternal notch-to-femoral site minus suprasternal notch-to-carotid site, PWV2: carotid-to-femoral site, PWV3: carotid-to-femoral site minus suprasternal notch-to-carotid site. Carotid-to-femoral distance was used to approximate torso length. Patients were followed for a median of 30 months and the association of PWV and cardiovascular mortality was assessed using survival analysis before and after stratification for torso length. RESULTS The three methods resulted in significantly different PWV values. During follow-up 50 patients died, 32 of cardiovascular causes. In log-rank tests, only tertiles of PWV1 was significantly related to outcome (P values 0.017, 0.257, 0.137, for PWV1, PWV2, and PWV3, respectively). In adjusted Cox, proportional hazards regression only PWV1 was related to cardiovascular mortality. In stratified analysis, however, among patients with below median torso length all PWV values were related to outcome, whereas in patients with above median torso length none of the PWV methods resulted in significant relationship to outcome. CONCLUSIONS 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.

Validation of arteriograph - A new oscillometric device to measure arterial stiffness in patients on maintenance hemodialysis

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 (AIA, PWVA) was compared to the validated PulsePen tonometer (AIP, PWVP). 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 AIP and AIA 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 PWVP and PWVA 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 PWVP but not PWVA was significantly related to CV mortality. Conclusion: Lack of correlation between PWVP and PWVA and lack of prognostic significance of PWVA suggest limited validity of Arteriograph to determine PWV in patients on HD.

Effect of sevelamer on aortic pulse wave velocity in patients on hemodialysis: A prospective observational study

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.

Arterial Stiffness in Hemodialysis: Which Parameter to Measure to Predict Cardiovascular Mortality?

In previous studies, different parameters of arterial stiffness were related to cardiovascular mortality in hemodialysis patients, but their relative prognostic value has not previously been evaluated in 1 cohort. Carotid-femoral pulse wave velocity (PWV), the carotid augmentation index, carotid pulse pressure (CPP) and carotid-brachial pulse pressure amplification (AMP) were measured in 98 patients before and after hemodialysis. Patients were followed for a median of 29 months (1–34) and the association of these parameters with cardiovascular mortality were assessed using log-rank tests and Cox proportional hazards regressions. During follow-up, 25 patients died of cardiovascular causes. Increasing pre- and postdialysis PWV tertiles and decreasing predialysis AMP tertiles were significantly related to cardiovascular mortality (p = 0.012 and 0.011 for PWV, respectively; < 0.001 for AMP). Neither the carotid augmentation index nor carotid pulse pressure were related to cardiovascular mortality. The adjusted hazard ratios for 1 m/s higher pre- and postdialysis PWV were 1.24 (1.07–1.44) and 1.17 (1.06–1.28), respectively. The hazard ratio for 10% lower predialysis AMP was 1.41 (1.03–1.92). When included in the same model, both predialysis PWV and AMP remained significantly associated with cardiovascular mortality. Among different stiffness parameters, PWV is consistently related to cardiovascular mortality, irrespective of the timing of measurement. Predialysis AMP seems to provide additional prognostic information.

Intracardiac calcification is a marker of generalized atherosclerosis

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, τ = 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.

The role of laser Doppler flowmetry tests, serum angiopoietin-2, asymmetric and symmetric dimethylarginine to predict outcome in chronic kidney disease.

Objective: The role of biochemical and functional markers of microvascular dysfunction to predict cardiovascular outcomes in nondialyzed chronic kidney disease (CKD) remains unclear. In this prospective cohort study, we assessed whether biochemical [serum level of angiopoietin-2 (Ang-2), asymmetric and symmetric dimethylarginin] and functional (laser Doppler flowmetry) measures of microvascular function predicted cardiovascular events, cardiovascular and all-cause mortality in CKD patients. Methods: Postocclusive reactive hyperemia area (PORHHA), acetylcholine and sodium nitroprusside-mediated flow changes were estimated by laser Doppler flowmetry, and Ang-2, asymmetric and symmetric dimethylarginin were assessed in 105 CKD patients at baseline. Multiple failure time Cox-regression analyses with backward elimination were performed to determine the predictors of the combined endpoint of cardiovascular mortality and cardiovascular events or all-cause mortality and cardiovascular events during a median of 66.6 (interquartile range 39.8–80.4) months of follow-up. Results: In univariate models lnAng-2 and lnPORHHA both predicted the cardiovascular outcome besides age, diabetes, baseline cardiovascular disease, brachial pulse pressure and log C-reactive protein. In multivariate analysis lnPORHHA [hazard ratio: 0.66 (95% confidence interval: 0.49–0.89) per ln(mU s)], age [1.03 (1.01–1.06) per year], log C-reactive protein [1.31 (1.06–1.64) per ln(mg/l)] and diabetes [3.33 (1.70–6.53)] remained significant predictors of the cardiovascular outcome, whereas lnAng-2 did not enter the model. Neither of the microvascular variables were an independent predictor of all-cause mortality and cardiovascular events. Conclusion: Among the functional and biochemical microvascular parameters PORHHA seems to improve cardiovascular risk assessment in CKD. Nevertheless the robustness of traditional risk factors seems to outweigh the role of microvascular biomarkers on all-cause mortality and cardiovascular events at this time.

INTEGRATED CENTRAL PRESSURE-STIFFNESS SCORE, A POTENTIAL NEW TOOL FOR CARDIOVASCULAR RISK STRATIFICATION: FIRST RESULTS IN CHRONIC KIDNEY DISEASE

Objective: To develop an integrated central pressure-stiffness (ICPS) score to predict cardiovascular events. Design and method: One hundred chronic kidney disease (CKD) patients on conservative therapy were included in our study. 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 to 2), cSBP (0 to 2) and cPP (0 to the first and second and 1 to the third tertile) based on each parameters ability to individually predict cardiovascular events. The sum of these scores (ICPS) and three ICPS risk categories as predictors were studied. Finally, we compared discrimination of the ICPS risk categories with that of the Framingham CVD score. Results: High (ICPS 3 to 4; n = 37) and very high risk ICPS risk categories (ICPS 5; n = 12) had an increased cardiovascular risk (HR: 4.95, 95%CI: 1.97–12.42, HR: 9.73, 95%CI: 3.06–20.23, respectively) compared to the average risk group (ICPS 0 to 2; n = 51). The very high ICPS risk category remained an independent predictor (HR: 4.87, 95%CI: 1.81–13.08) in a model further adjusted for the Framingham CVD score (HR: 1.66, 95%CI: 1.13–2.43 per 1 SD increase). When comparing discrimination of the Framingham score (Harrells C: 0.704, 95%CI: 0.625–0.784) and with ICPS added to the Framingham score (C: 0.729, 95%CI: 0.647–0–810), the difference was not significant probably due to the limited power of our study. Conclusions: The ICPS score may clinically importantly improve the identification of CKD patients with elevated cardiovascular risk, but larger studies are required.

The consequence of arterial stiffness parameters to predict the cardiovascular mortality in hemodialysis patients: a prospective cohort study

UNLABELLED Previous studies demonstrated that different parameters of arterial stiffness are related to cardiovascular mortality in hemodialysis patients. The relative prognostic value of these parameters has not previously been evaluated in one cohort. PATIENTS AND METHODS Carotid-femoral pulse wave velocity, carotid augmentation index, carotid pulse pressure and carotid-brachial pulse pressure amplification were measured in 98 patients before and after hemodialysis. Patients were followed for a median of 29 months (1-34) and the association of these parameters with cardiovascular mortality was assessed using log-rank tests and Cox proportional hazards regressions. RESULTS During follow-up, 40 patients died (mortality rate 20.7/100 patient-year), of which 25 died of cardiovascular causes. Increasing pre- and postdialysis pulse wave velocity tertiles and decreasing predialysis pulse pressure amplification tertiles were significantly related to cardiovascular mortality (p-values are 0.012 and 0.011 for pre- and postdialysis pulse wave velocity, and <0.001 and 0,321 for pre- and postdialysis pulse pressure amplification, respectively). Neither the carotid augmentation index nor carotid pulse pressure was related to cardiovascular mortality. In the Cox-regression, the adjusted hazard ratios for 1 m/s higher pre- and postdialysis pulse wave velocity were 1.24 (1.07-1.44) and 1.17 (1.06-1.28), respectively. The hazard ratio for 10% lower predialysis pulse pressure amplification was 1.41 (1.03-1.92). When included in the same model, both predialysis pulse wave velocity and pulse pressure amplification remained significantly associated with cardiovascular mortality (relative risk: 1.23 [1.07-1.42] and 1.39 [1.02-1.89]). CONCLUSION Among different stiffness parameters, pulse wave velocity is consistently related to cardiovascular mortality, irrespective of the timing of measurement. Predialysis pulse pressure amplification seems to provide additional prognostic information.

A különbözo érfali tágulékonysá gi paraméterek jelentosége a cardiovascularis mortalitás elorejelzésében hemodializált betegek között: prospektív kohorszvizsgálat

UNLABELLED Previous studies demonstrated that different parameters of arterial stiffness are related to cardiovascular mortality in hemodialysis patients. The relative prognostic value of these parameters has not previously been evaluated in one cohort. PATIENTS AND METHODS Carotid-femoral pulse wave velocity, carotid augmentation index, carotid pulse pressure and carotid-brachial pulse pressure amplification were measured in 98 patients before and after hemodialysis. Patients were followed for a median of 29 months (1-34) and the association of these parameters with cardiovascular mortality was assessed using log-rank tests and Cox proportional hazards regressions. RESULTS During follow-up, 40 patients died (mortality rate 20.7/100 patient-year), of which 25 died of cardiovascular causes. Increasing pre- and postdialysis pulse wave velocity tertiles and decreasing predialysis pulse pressure amplification tertiles were significantly related to cardiovascular mortality (p-values are 0.012 and 0.011 for pre- and postdialysis pulse wave velocity, and <0.001 and 0,321 for pre- and postdialysis pulse pressure amplification, respectively). Neither the carotid augmentation index nor carotid pulse pressure was related to cardiovascular mortality. In the Cox-regression, the adjusted hazard ratios for 1 m/s higher pre- and postdialysis pulse wave velocity were 1.24 (1.07-1.44) and 1.17 (1.06-1.28), respectively. The hazard ratio for 10% lower predialysis pulse pressure amplification was 1.41 (1.03-1.92). When included in the same model, both predialysis pulse wave velocity and pulse pressure amplification remained significantly associated with cardiovascular mortality (relative risk: 1.23 [1.07-1.42] and 1.39 [1.02-1.89]). CONCLUSION Among different stiffness parameters, pulse wave velocity is consistently related to cardiovascular mortality, irrespective of the timing of measurement. Predialysis pulse pressure amplification seems to provide additional prognostic information.