Aortic Stiffness In Hemodialysis Patients Research Articles

Serum Malondialdehyde-Modified Low-Density Lipoprotein Is a Risk Factor for Central Arterial Stiffness in Maintenance Hemodialysis Patients.

Circulating malondialdehyde-modified low-density lipoprotein (MDA-LDL) acts as a marker of oxidative stress and is associated with atherosclerotic cardiovascular disease. The relationship between serum MDA-LDL levels and aortic stiffness (AS) in patients with hemodialysis (HD) was evaluated. There were 155 HD patients enrolled in this study. Carotid-femoral pulse wave velocity (cfPWV) was measured by a validated tonometry system. Patients with cfPWV >10 m/s were used to define the AS group, while those with values of ≤10 m/s were regarded as the control group. Serum MDA-LDL levels were measured using a commercial enzyme-linked immunosorbent assay. Sixty-eight patients (43.9%) who were defined as AS sufferers, and were older, had a higher percentage of diabetes and hypertension and higher systolic blood pressure and serum MDA-LDL level compared to subjects in the control group. After adjusting for factors significantly associated with AS by multivariable logistic regression analysis, it was revealed that serum MDA-LDL levels, diabetes, and hypertension were independent predictors of AS in HD patients. Multivariable forward stepwise linear regression analysis also showed that a logarithmically transformed MDA-LDL level was significantly correlated with cfPWV values in HD patients. In HD patients, a high serum MDA-LDL level was positively associated with cfPWV values and was a significant predictor of the development of high AS.

P1266SERUM MALONDIALDEHYDE-MODIFIED LOW-DENSITY LIPOPROTEIN LEVEL IS A RISK FOR AORTIC STIFFNESS IN MAINTENANCE HEMODIALYSIS PATIENTS

Abstract Background and Aims Circulating oxidized malondialdehyde LDL (MDA-LDL) induced macrophage apoptosis, the release of higher levels of matrix metalloproteinases and TNF-α, therefore, act as a marker of oxidative stress and are associated with atherosclerotic cardiovascular diseases. We evaluated the association between serum MDA-LDL levels and aortic stiffness in patients with hemodialysis (HD). Method A total of 155 patients with HD were enrolled in this study. Carotid-femoral pulse wave velocity (cfPWV) value was measured by a validated tonometry system (SphygmoCor). Patients with cfPWV >10 m/s were used to define the aortic stiffness group, while values ≤ 10 m/s were regarded as the control group, according to the ESH-ESC 2013. Serum MDA-LDL levels were measured using a commercial enzyme-linked immunosorbent assay. Results 68 patients (43.9%) had aortic stiffness and higher percentages of diabetes (p < 0.001), hypertension (p = 0.017), and had older age (p = 0.038), higher systolic blood pressure (P = 0.021), serum MDA-LDL level (p < 0.001) compared to subjects with control group. After adjusting for factors significantly associated with aortic stiffness by multivariable logistic regression analysis revealed that serum MDA-LDL levels (odds ratio (OR): 1.014, 95% confidence interval (CI): 1.007–1.021, p < 0.001), diabetes (OR: 2.893, 95% CI: 1.300–6.437, p = 0.009), and hypertension (OR: 2.408, 95% CI: 1.066–5.436, p = 0.034) were the independent predictors of aortic stiffness in HD patients. Multivariable forward stepwise linear regression analysis also showed that serum logarithmically transformed MDA-LDL level (log-MDA-LDL, β = 0.404, adjusted R2 change = 0.265, p < 0.001), diabetes (β = 0.233, adjusted R2 change = 0.055, p = 0.001), and hypertension (β = 0.132, adjusted R2 change = 0.014, p = 0.048) were the independent predictors of cfPWV values in HD patients. The area under the receiver-operating characteristic (ROC) curve predicting aortic stiffness by serum MDA-LDL level in HD patients was 0.721 (95% CI: 0.643-0.790, p < 0.001). Conclusion In this study, high serum MDA-LDL level was positively associated with cfPWV values and thus was related to aortic stiffness in HD patients.

Relationship between Fragmented QRS Complex and Aortic Stiffness in Chronic Hemodialysis Patients

Objective: This study aimed to evaluate the correlation between fragmented QRS complex (fQRS), aortic stiffness, and diastolic dysfunction in hemodialysis patients. Subjects and Methods: A sample of 56 patients who received hemodialysis treatment was stratified into 2 groups according to their electrocardiography (ECG) patterns with or without fQRS. Baseline characteristics and laboratory parameters of patients were documented. Conventional echocardiographic and Doppler echocardiographic procedures were performed in all patients. The mean early (Em) diastolic and late (Am) diastolic myocardial velocities were calculated. These tests were performed before dialysis. The Student t test, Mann-Whitney U test, χ² test, Spearman correlation, and multivariate linear regression analysis were used to analyze parameters where appropriate. Results: Of the 56 patients under hemodialysis, fQRS in ECG was detected in 26 (46.4%). Echocardiographic evaluation showed that deceleration time (237.57 ± 40.10 ms; p = 0.030), isovolumic relaxation time (126.84 ± 15.62 ms; p < 0.001), early (E)/late (A) ventricular filling velocity (E/A) ratio (1.15 ± 0.40; p ≤ 0.001), and aortic stiffness index value (9.62 ± 4.53; p = 0.016) exhibited a statistical increase in hemodialysis patients with fQRS compared to patients without fQRS. E (58.23 ± 19.96 m/s; p = 0.004), and Em (5.96 ± 2.08 cm/s; p = 0.023) velocity levels were significantly lower in hemodialysis patients with fQRS than patients without fQRS. Aortic stiffness closely correlated with diastolic dysfunction (deceleration time r = 0.273, p = 0.042; isovolumic relaxation time r = 0.497, p < 0.001; E/A ratio r = -0.449, p = 0.001). On multivariate linear regression analysis, fQRS and aortic stiffness were independently associated in hemodialysis patients (β = 0.321, p = 0.049). Conclusions: Increased aortic stiffness and left ventricular systolic dysfunction were observed more frequently in hemodialysis patients with fQRS than in patients without fQRS. fQRS is an important determinant of aortic stiffness in hemodialysis patients.

The impact of warfarin on the rate of progression of aortic stiffness in hemodialysis patients: a longitudinal study.

Accelerated progression of aortic stiffness in patients with advanced chronic kidney disease is not well explained by the traditional cardiovascular risk factors. We hypothesized that vitamin K deficiency may result in an accelerated progression of aortic stiffness in the pro-calcifying uremic milieu. Eighteen hemodialysis (HD) patients on warfarin were matched to 54 HD patients without warfarin (control). Aortic stiffness was determined by carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. In the control group, spontaneous vitamin K deficiency was defined as proteins induced by vitamin K deficiency/absence-II >median. At baseline, clinical characteristics and cf-PWV were similar. Adjusted cf-PWV increased by 0.86 ± 1.87 m/s in control and by 2.24 ± 2.68 m/s in warfarin group (P = 0.024). After adjustments for confounders, warfarin therapy was independently associated with progression of aortic stiffness (P = 0.016). The rate of progression of aortic stiffness showed a linear trend in response to vitamin K status and warfarin therapy, suggesting that at least part of the effects are mediated through reduced availability of vitamin K. The unadjusted and adjusted hazard ratio (HR) of warfarin therapy on mortality were, respectively, 2.40 (P = 0.006) and 2.53 (P = 0.006). In a forward conditional Cox regression analysis, age, albumin, augmentation index (AIx) and a cf-PWV > 13.8 m/s at the time of follow-up (HR: 2.11, P = 0.05) were independent determinants of mortality, whereas warfarin use was not retained as an independent factor. Finally, control patients with poor vitamin K status had an intermediate survival as compared with controls with better vitamin K status and patients with warfarin (P = 0.01). This is the first study to show a temporal association between warfarin, functional vitamin K deficiency and progression of aortic stiffness in HD patients. These findings suggest that the net cardiovascular benefit of long-term warfarin therapy may need to be reevaluated in this population.

Active Vitamin D and Accelerated Progression of Aortic Stiffness in Hemodialysis Patients: A Longitudinal Observational Study

We hypothesized that high-dose active vitamin D therapy in the form of alphacalcidol (α-calcidol), used to treat secondary hyperparathyroidism in chronic kidney disease, could lead to vascular calcification and accelerated progression of aortic stiffness. We conducted an observational study in 85 patients on chronic hemodialysis, among which 70 were taking a weekly dose of α-calcidol of <2 µg and 15 were taking a weekly dose of ≥2 µg (pharmacological dose). Parathyroid hormone, 25-hydroxyvitamin D, fibroblast growth factor 23, and α-klotho were determined. Aortic stiffness was assessed by determination of carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. A multivariable regression model was used to evaluate the impact of pharmacological dose of α-calcidol on the progression of aortic stiffness. At baseline, clinical, biological, and hemodynamic parameters were similar. At follow-up, cf-PWV increased more in patients with pharmacological dose of α-calcidol (0.583±2.291 m/s vs. 1.948±1.475 m/s; P = 0.04). After adjustment for changes in mean blood pressure and duration of follow-up, pharmacological dose of α-calcidol was associated with a higher rate of progression of cf-PWV (0.969 m/s; 95% confidence interval = 0.111-1.827; P = 0.03), and this association persisted after further adjustments for parameters of mineral metabolism. In this study, pharmacological dose of α-calcidol was associated with accelerated progression of aortic stiffness. This study suggest that the vascular safety of active vitamin D posology may need to be specifically addressed in the treatment of chronic kidney disease-related bone mineral disorder.

Determinants of Progression of Aortic Stiffness in Hemodialysis Patients

Aortic stiffness is associated with increased cardiovascular mortality in patients with chronic kidney disease. However, the rate of progression of arterial stiffness and the role of cardiovascular risk factors in the progression of arterial stiffness has never been established in a longitudinal study. In a prospective, longitudinal, observational study, carotid-femoral pulse wave velocity and carotid-radial pulse wave velocity were assessed in 109 hemodialysis patients at baseline and after a mean follow-up of 1.2 years. We examined the impact of age, atherosclerotic cardiovascular disease, diabetes mellitus, dialysis vintage, and pentosidine (a well-characterized, advanced glycation end products) on the rate of progression of aortic stiffness. The annual rate of changes in carotid-femoral pulse wave velocity and carotid-radial pulse wave velocity were 0.84 m/s per year (95% confidence interval, 0.50–1.12 m/s per year) and −0.66 m/s per year (95% confidence interval, −0.85 to −0.47 m/s per year), respectively. Older subjects, and patients with diabetes mellitus or atherosclerotic cardiovascular disease had higher aortic stiffness at baseline, however, the rate of progression of aortic stiffness was only determined by plasma pentosidine levels ( P =0.001). The degree of baseline aortic stiffness was a significant determinant of the regression of brachial stiffness ( P &lt;0.001) suggesting that the regression of brachial stiffness occurs in response to central aortic stiffness. These findings suggest that traditional cardiovascular risk factors may play some role in the progression of aortic stiffness before development of advanced chronic kidney disease, and that the enhanced rate of progression of aortic stiffness in chronic kidney disease patients on dialysis are probably determined by more specific chronic kidney disease–related risk factors such as advanced-glycation end products.

What factors accelerate aortic stiffening in hemodialysis patients? An observational study

Increased aortic stiffness is an independent predictor of death from cardiovascular disease in patients with end-stage renal disease (ESRD). Various factors that contribute to carotid-femoral pulse wave velocity (cfPWV) as a surrogate of aortic stiffness have been identified, but determinants of long-term worsening of aortic stiffness remain to be elucidated. To clarify the factors that accelerate aortic stiffness in hemodialysis patients, 148 patients with ESRD on hemodialysis were evaluated. At baseline, cfPWV and ankle-brachial blood pressure index (ABPI) were measured and clinical status including biochemical parameters, with or without hepatitis c virus (HCV) infection, diabetes mellitus (DM), cardiovascular disease, cerebrovascular disease and peripheral arterial disease at baseline, were evaluated. The cfPWV was measured again after a 3-year follow up and the annual change in cfPWV was calculated. The cfPWV decreased in 54 patients, worsened slowly in 47 (annual change in cfPWV ranged from 0 to 0.33 ms(-1) per year), and worsened rapidly in 47 patients (annual change in cfPWV was more than 0.33 ms(-1) per year). The prevalences of DM, HCV infection and peripheral arterial disease were the highest in the rapid progression group. Univariate analysis showed that age, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, HCV infection, ABPI and number of vasculopathies were significantly associated with annual change in cfPWV. Stepwise regression analysis identified ABPI, LDL-C/HDL-C ratio and HCV infection as independent determinants of worsening of cfPWV. Further studies are needed to investigate the mechanism of HCV-related enhancement of aortic stiffness in ESRD patients.

Association of High-Molecular-Weight to Total Adiponectin Ratio with Pulse Wave Velocity in Hemodialysis Patients

High-molecular-weight adiponectin (HMW ADPN) plays an important role in the regulation of insulin action and atherogenic processes, but the role of HMW ADPN remains to be determined in hemodialysis (HD) patients. In this study, we measured serum total and HMW ADPN in 67 HD patients (age: 67 ± 14 years, time on HD: 75 ± 68 months, male/female = 39/28), and examined an association between HMW ADPN and arteriosclerotic parameters such as aortic pulse wave velocity (PWV), cardio-ankle vascular index (CAVI) and ankle-brachial pressure index (ABI). PWV was significantly correlated positively with log-transformed IL-6 (r = 0.33, p < 0.01). CAVI was significantly related to the percentile of aortic calcification area (%ACA) (r = 0.28, p = 0.03) and log-transformed IL-6 (r = 0.25, p = 0.05). ABI was associated negatively with log-transformed IL-6 (r = –0.35, p < 0.01) and %ACA (r = –0.36, p < 0.01), but positively with albumin (r = 0.33, p < 0.01). The HMW-to-total ADPN ratio, a better predictor for insulin resistance, was significantly and positively correlated with PWV (r = 0.34, p < 0.01) and CAVI (r = 0.24, p = 0.05). A multiple stepwise regression analysis revealed that the HMW-to-total ADPN ratio was an independent determinant for PWV and CAVI but not for ABI. The findings suggest that HMW-to-total ADPN ratio may be positively associated with aortic stiffness in HD patients.

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.

Aortic Stiffness in Patients Undergoing Hemodialysis is Positively Related to Antigen Presenting Cell-Dependent T-Lymphocyte Reactivity

Background. Aortic stiffness is increased in patients undergoing hemodialysis (HD), and it is associated with an increased cardiovascular mortality. Among others, aortic stiffness has been correlated with serum markers of inflammation, indicating a role of the immune system in its pathogenesis. The aim of this study was to evaluate the impact of antigen-presenting cell-dependent T-lymphocyte reactivity on aortic stiffness in HD patients.Patients and methods. Twenty patients were enrolled in the study. Exclusion criteria were medications or conditions, other than HD, that are known to influence the immune response or aortic stiffness. Antigen-presenting cell-dependent T-lymphocyte reactivity was assessed by cell proliferation of peripheral blood mononuclear cells cultured with or without stimulation with Staphylococcal enterotoxin B (SEB). Cell proliferation was estimated by immunoenzymatic measurement of bromodeoxyuridine uptake. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV) measurement.Results. Linear regression analysis revealed a strong positive relation between carotid-femoral PWV and antigen-presenting cell-dependent T-lymphocyte reactivity, when SEB at concentrations of 1 ng/mL or 10 ng/mL was used as stimulant.Conclusion. The present study confirms that aortic stiffness in HD patients is positively related to antigen-presenting cell-dependent T-lymphocyte reactivity. The greater the ability of the immune system to react to a monocyte-dependent stimulant and, consequently, to provoke an inflammatory response, the greater the stiffness of the aorta. This is in agreement with the observation that aortic stiffness in HD patients is positively related to various serum inflammation markers.