Antonios Karpetas

Evaluation of a novel brachial cuff-based oscillometric method for estimating central systolic pressure in hemodialysis patients.

Background/Aims: Elevated wave reflections and arterial stiffness, as well as ambulatory blood pressure (BP) are independent predictors of cardiovascular risk in end-stage-renal-disease. This study is the first to evaluate in hemodialysis patients the validity of a new ambulatory oscillometric device (Mobil-O-Graph, IEM, Germany), which estimates aortic BP, augmentation index (AIx) and pulse wave velocity (PWV). Methods: Aortic SBP (aSBP), heart rate-adjusted AIx (AIx(75)) and PWV measured with Mobil-O-Graph were compared with the values from the most widely used tonometric device (Sphygmocor, ArtCor, Australia) in 73 hemodialysis patients. Measurements were made in a randomized order after 10 min of rest in the supine position at least 30 min before a dialysis session. Brachial BP (mercury sphygmomanometer) was used for the calibration of Sphygmocors waveform. Results: Sphygmocor-derived aSBP and AIx(75) did not differ from the relevant Mobil-O-Graph measurements (aSBP: 136.3 ± 19.6 vs. 133.5 ± 19.3 mm Hg, p = 0.068; AIx(75): 28.4 ± 9.3 vs. 30.0 ± 11.8%, p = 0.229). The small difference in aSBP is perhaps explained by a relevant difference in brachial SBP used for calibration (146.9 ± 20.4 vs. 145.2 ± 19.9 mm Hg, p = 0.341). Sphygmocor PWV was higher than Mobil-O-Graph PWV (10.3 ± 3.4 vs. 9.5 ± 2.1 m/s, p < 0.01). All 3 parameters estimated by Mobil-O-Graph showed highly significant (p < 0.001) correlations with the relevant measurements of Sphygmocor (aSBP, r = 0.770; AIx(75), r = 0.400; PWV, r = 0.739). The Bland-Altman Plots for aSBP and AIx(75) showed acceptable agreement between the two devices and no evidence of systemic bias for PWV. Conclusion: As in other populations, acceptable agreement between Mobil-O-Graph and Sphygmocor was evident for aSBP and AIx(75) in hemodialysis patients; PWV was slightly underestimated by Mobil-O-Graph.

Ambulatory Recording of Wave Reflections and Arterial Stiffness during Intra- and Interdialytic Periods in Patients Treated with Dialysis

BACKGROUND AND OBJECTIVES Wave reflections and arterial stiffness are independent cardiovascular risk factors in ESRD. Previous studies in this population included only static recordings before and after dialysis. This study investigated the variation of these indices during intra- and interdialytic intervals and examined demographic, clinical, and hemodynamic variables related to arterial function in patients undergoing hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Between February 2013 and May 2014, a total of 153 patients receiving maintenance hemodialysis in five dialysis centers of northern Greece underwent ambulatory BP monitoring with the newly introduced Mobil-O-Graph device (IEM, Stolberg, Germany) over a midweek dialysis session and the subsequent interdialytic period. Mobil-O-Graph is an oscillometric device that records brachial BP and pulse waves and estimates, via generalized transfer function, aortic BP, augmentation index (AIx) as a measure of wave reflections, and pulse wave velocity (PWV) as an index of arterial stiffness. RESULTS AIx was lower during dialysis than in the interdialytic period of dialysis-on day (Day 1) (mean±SD, 24.7%±9.7% versus 26.8%±9.4%; P<0.001). In contrast, PWV remained unchanged between these intervals (9.31±2.2 versus 9.29±2.3 m/sec; P=0.60). Both AIx and PWV increased during dialysis-off day (Day 2) versus the out-of-dialysis period of Day 1 (28.8%±9.8% versus 26.8%±9.4% [P<0.001] and 9.39±2.3 versus 9.29±2.3 m/sec [P<0.001]). Older age (odds ratio [OR], 1.09; 95% confidence interval [95% CI], 1.02 to 1.15), female sex (OR, 7.56; 95% CI, 1.64 to 34.81), diabetic status (OR, 8.84; 95% CI, 1.76 to 17.48), and higher mean BP (OR, 1.17; 95% CI, 1.09 to 1.27) were associated with higher odds of high AIx; higher heart rate was associated with lower odds (OR, 0.71; 95% CI, 0.63 to 0.80) of high AIx. Older age (OR, 2.04; 95% CI, 1.61 to 2.58) and higher mean BP (OR, 1.15; 95% CI, 1.05 to 1.27) were independent correlates of high PWV. CONCLUSIONS This study showed a gradual interdialytic increase in AIx, whereas PWV was only slightly elevated during Day 2. Future studies are needed to elucidate the value of these ambulatory measures for cardiovascular risk prediction in ESRD.

Diverse effects of interdialytic intervals on central wave augmentation in haemodialysis patients

BACKGROUND Increased arterial stiffness is a common finding and independent predictor of mortality in end-stage renal disease (ESRD) patients. A long interdialytic interval was associated with increased risk of cardiovascular death in patients receiving conventional haemodialysis (HD). This is the first study to examine the effects of a long (3-day) versus short (2-day) interdialytic period on arterial elasticity in HD patients. METHODS Seventy ESRD patients receiving standard HD three times per week were studied at the start and end of a 3-day and a 2-day interdialytic interval. At each time point, applanation tonometry of peripheral arteries was performed to assess arterial stiffness and wave reflection parameters. Aortic and brachial pulse wave velocities (PWV) were recorded as measures of arterial stiffness and augmentation index (AIx) as a measure of wave reflections. RESULTS AIx, heart-rate-adjusted AIx and augmentation pressure were significantly increased during both interdialytic intervals, whereas aortic and brachial PWVs remained unchanged. The interdialytic increases in all the three AIx parameters were significantly higher during the 3-day interval in comparison to the 2-day interval (P < 0.001 for all comparisons). In contrast, no significant differences in interdialytic changes of aortic (P = 0.355) and brachial (P = 0.319) PWVs were noted between the two intervals. Mixed linear model analysis revealed that central aortic systolic blood pressure (SBP) and body weight, but not aortic or brachial PWV, were independent determinants of the change in heart-rate-adjusted AIx throughout the study. CONCLUSIONS AIx is increased between HD sessions, whereas arterial elasticity is not. This interdialytic increase in central wave augmentation is more pronounced during the 3-day interval, suggesting a mechanism possibly involved in the elevated cardiovascular risk of HD patients at this time point.

Ambulatory aortic blood pressure, wave reflections and pulse wave velocity are elevated during the third in comparison to the second interdialytic day of the long interval in chronic haemodialysis patients

BACKGROUND Increased arterial stiffness and aortic blood pressure (BP) are independent predictors of cardiovascular outcomes in end-stage renal disease. The 3-day interdialytic interval is associated with elevated risk of cardiovascular morbidity and mortality in haemodialysis. This study investigated differences in ambulatory aortic BP and arterial stiffness between the second and third day of the long interdialytic interval. METHODS Ambulatory BP monitoring with Mobil-O-Graph monitor (IEM, Stolberg, Germany) was performed in 55 haemodialysis patients during a 3-day interval. Mobil-O-Graph records oscillometric brachial BP and pulse waves and calculates aortic BP and augmentation index (AIx) as measure of wave reflections, and pulse wave velocity (PWV) as measure of arterial stiffness. RESULTS Ambulatory aortic systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher during the third versus second interdialytic day (123.6 ± 17.0 versus 118.5 ± 17.1 mmHg, P < 0.001; 81.5 ± 11.8 versus 78 ± 11.9 mmHg, P < 0.001, respectively). Similar differences were noted for brachial BP. Ambulatory AIx and PWV were also significantly increased during the third versus second day (30.5 ± 9.9 versus 28.8 ± 9.9%, P < 0.05; 9.6 ± 2.3 versus 9.4 ± 2.3 m/s, P < 0.001, respectively). Differences between Days 2 and 3 remained significant when day-time and night-time periods were compared separately. Aortic SBP and DBP, AIx and PWV showed gradual increases from the end of dialysis session onwards. Interdialytic weight gain was a strong determinant of the increase in the above parameters. CONCLUSIONS This study showed significantly higher ambulatory aortic BP, AIx and PWV levels during the third compared with the second interdialytic day. These findings support a novel pathway for increased cardiovascular risk during the third interdialytic day in haemodialysis.

Ambulatory Pulse Wave Velocity Is a Stronger Predictor of Cardiovascular Events and All-Cause Mortality Than Office and Ambulatory Blood Pressure in Hemodialysis Patients.

Arterial stiffness and augmentation of aortic blood pressure (BP) measured in office are known cardiovascular risk factors in hemodialysis patients. This study examines the prognostic significance of ambulatory brachial BP, central BP, pulse wave velocity (PWV), and heart rate–adjusted augmentation index [AIx(75)] in this population. A total of 170 hemodialysis patients underwent 48-hour ambulatory monitoring with Mobil-O-Graph-NG during a standard interdialytic interval and followed-up for 28.1±11.2 months. The primary end point was a combination of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Secondary end points included: (1) all-cause mortality; (2) cardiovascular mortality; and (3) a combination of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, coronary revascularization, or hospitalization for heart failure. During follow-up, 37(21.8%) patients died and 46(27.1%) had cardiovascular events. Cumulative freedom from primary end point was similar for quartiles of predialysis-systolic BP (SBP), 48-hour peripheral-SBP, and central-SBP, but was progressively longer for increasing quartiles for 48-hour peripheral-diastolic BP and central-diastolic BP and shorter for increasing quartiles of 48-hour central pulse pressure (83.7%, 71.4%, 69.0%, 62.8% [log-rank P=0.024]), PWV (93.0%, 81.0%, 57.1%, 55.8% [log-rank P<0.001]), and AIx(75) (88.4%, 66.7%, 69.0%, 62.8% [log-rank P=0.014]). The hazard ratios for all-cause mortality, cardiovascular mortality, and the combined outcome were similar for quartiles of predialysis-SBP, 48-hour peripheral-SBP, and central-SBP, but were increasing with higher ambulatory PWV and AIx(75). In multivariate analysis, 48-hour PWV was the only vascular parameter independently associated with the primary end point (hazard ratios, 1.579; 95% confidence intervals, 1.187–2.102). Ambulatory PWV, AIx(75), and central pulse pressure are associated with increased risk of cardiovascular events and mortality, whereas office and ambulatory SBP are not. These findings further support that arterial stiffness is the prominent cardiovascular risk factor in hemodialysis.

Hemodiafiltration does not have additional benefits over hemodialysis on arterial stiffness, wave reflections and central aortic pressures.

Background/Aims: The hypothesis that dialytic modality affects arterial stiffness was never investigated. This study includes comparative evaluation of hemodiafiltration versus hemodialysis on arterial function during first and second weekly dialysis sessions. Methods: 24 patients receiving hemodiafiltration and another 24 age- and sex-matched controls receiving hemodialysis were included. Patients were evaluated before and after first and second weekly dialysis sessions. Applanation tonometry of peripheral arteries was applied to determine aortic and brachial pulse wave velocity and heart rate-adjusted augmentation index (AIx(75)). Results: Hemodiafiltration and hemodialysis reduced AIx(75), but not aortic and brachial pulse wave velocity. Intradialytic reductions in AIx(75) did not differ between hemodiafiltration and hemodialysis in first and mid-week dialysis. In multivariate linear regression, predictors of intradialytic reduction in AIx(75) were changes in body weight and central aortic systolic blood pressure, but not dialytic modality. Conclusion: This study showed that hemodiafiltration has similar effects with hemodialysis on wave reflections and stiffness.

Blood pressure variability is increasing from the first to the second day of the interdialytic interval in hemodialysis patients

Objectives: Patients with end-stage renal-disease under hemodialysis have increased cardiovascular risk and experience severe blood pressure (BP) fluctuations during the dialysis session and the subsequent interdialytic period. BP variability (BPV) may be an additional risk factor for cardiovascular events and preliminary data suggest increased BPV with advancing stages of chronic kidney disease. This is the first study to examine BPV during the whole intradialytic and interdialytic period in hemodialysis patients with ambulatory BP monitoring. Methods: A total of 160 patients receiving maintenance hemodialysis had 48-h ambulatory BP monitoring with the Mobil-O-Graph device during a regular dialysis session and the subsequent interdialytic interval. Brachial and aortic BPV were calculated with validated formulas and were compared between Days 1 and 2 of the interdialytic period (44-h), Days 1 and 2 of the total 48-h interval (including the dialysis session), and between the two respective daytime periods and night-time periods. Results: All brachial SBPV indices [SD: 14.75 ± 4.38 vs. 15.91 ± 4.41, P = 0.001; weighted SD: 13.80 ± 4.00 vs. 14.89 ± 3.90, P < 0.001; coefficient of variation (CV): 11.34 ± 2.91 vs. 11.93 ± 2.94, P = 0.011; average real variability (ARV): 11.38 ± 3.44 vs. 12.32 ± 3.65, P < 0.001)] were increasing from Days 1 to 2 of the 44-h interdialytic period. Similarly, all indexes of DBPV were significantly increased in Day 2, except for CV. Aortic SBPV and DBPV indices displayed a similar pattern. Furthermore, all studied brachial SBPV and DBPV indexes were also lower during daytimes 1 than 2 (systolic ARV 11.56 ± 3.98 vs. 12.44 ± 4.03, P = 0.002); systolic ARV was lower in night-time 1 compared with night-time 2 (11.20 ± 5.09 vs. 12.18 ± 4.66, P = 0.045). In multivariate regression analysis prehemodialysis SBP, age and diabetes were independently associated with increased SBP ARV. Conclusion: BPV is increased in interdialytic Day 2 compared with Day 1 in hemodialysis patients; this could be another mechanism involved in the complex cardiovascular pathophysiology and increased cardiovascular mortality of these individuals.

The association of interdialytic blood pressure variability with cardiovascular events and all-cause mortality in haemodialysis patients

BACKGROUND Long-term pre-dialysis blood pressure variability (BPV) in haemodialysis patients is associated with increased cardiovascular risk. The association of the main haemodynamic culprit in dialysis, that is, short-term BPV, with outcomes has not been investigated. We examine the prognostic role of short-term BPV for mortality and cardiovascular events in this population. METHODS A total of 227 haemodialysis patients underwent 44-h ambulatory monitoring during a standard interval and were followed-up for 30.17 ± 17.70 months. We calculated SD, weighted SD (wSD), coefficient of variation (CV) and average real variability (ARV) of BP with validated formulas. The primary endpoint was first occurrence of all-cause death, non-fatal myocardial infarction or non-fatal stroke. Secondary endpoints were: (i) all-cause mortality, (ii) cardiovascular mortality and (iii) a combination of cardiovascular events. RESULTS Cumulative freedom from the primary endpoint was similar for quartiles of pre-dialysis and 44-h systolic BP (SBP), but was progressively longer for increasing quartiles of 44-h SBP-SD (P = 0.014), wSD (P = 0.007), CV (P = 0.031) and ARV (83.9, 71.9, 70.2 and 43.9% for quartiles 1-4; P < 0.001). Higher quartiles of 44-h SBP-ARV were associated with higher risk of all studied outcomes. Among diastolic BPV indices, 44-h diastolic BP (DBP)-CV and 44-h DBP-ARV were associated with increased risk for the composite cardiovascular outcome. In Cox regression analysis, SBP-BPV was related to the primary endpoint, independently of SBP levels and interdialytic weight gain [ARV: hazard ratio (HR) 1.115, 95% confidence interval (95% CI) 1.048-1.185]. This association become insignificant after adjustment for pulse wave velocity (PWV; HR 1.061, 95% CI 0.989-1.137), and further attenuated after additional adjustment for age, dialysis vintage, gender, comorbidities and prevalent cardiovascular disease (HR 1.031, 95% CI 0.946-1.122). CONCLUSIONS Increased BPV during the interdialytic interval is associated with higher risk of death and cardiovascular events, whereas ambulatory BP levels are not. This association was not independent after adjustment for PWV, other risk factors and prevalent cardiovascular disease. Short-term BPV could be a mediator promoting the adverse cardiovascular profile of haemodialysis patients.

Prevalence and control of hypertension by 48-h ambulatory blood pressure monitoring in haemodialysis patients: a study by the European Cardiovascular and Renal Medicine (EURECA-m) working group of the ERA-EDTA

Background Population-specific consensus documents recommend that the diagnosis of hypertension in haemodialysis patients be based on 48-h ambulatory blood pressure (ABP) monitoring. However, until now there is just one study in the USA on the prevalence of hypertension in haemodialysis patients by 44-h recordings. Since there is a knowledge gap on the problem in European countries, we reassessed the problem in the European Cardiovascular and Renal Medicine working group Registry of the European Renal Association-European Dialysis and Transplant Association. Methods A total of 396 haemodialysis patients underwent 48-h ABP monitoring during a regular haemodialysis session and the subsequent interdialytic interval. Hypertension was defined as (i) pre-haemodialysis blood pressure (BP) ≥140/90 mmHg or use of antihypertensive agents and (ii) ABP ≥130/80 mmHg or use of antihypertensive agents. Results The prevalence of hypertension by 48-h ABP monitoring was very high (84.3%) and close to that by pre-haemodialysis BP (89.4%) but the agreement of the two techniques was not of the same magnitude (κ statistics = 0.648; P <0.001). In all, 290 participants were receiving antihypertensive treatment. In all, 9.1% of haemodialysis patients were categorized as normotensives, 12.6% had controlled hypertension confirmed by the two BP techniques, while 46.0% had uncontrolled hypertension with both techniques. The prevalence of white coat hypertension was 18.2% and that of masked hypertension 14.1%. Of note, hypertension was confined only to night-time in 22.2% of patients while just 1% of patients had only daytime hypertension. Pre-dialysis BP ≥140/90 mmHg had 76% sensitivity and 54% specificity for the diagnosis of BP ≥130/80 mmHg by 48-h ABP monitoring. Conclusions The prevalence of hypertension in haemodialysis patients assessed by 48-h ABP monitoring is very high. Pre-haemodialysis BP poorly reflects the 48 h-ABP burden. About a third of the haemodialysis population has white coat or masked hypertension. These findings add weight to consensus documents supporting the use of ABP monitoring for proper hypertension diagnosis and treatment in this population.

PREVALENCE AND CONTROL OF HYPERTENSION WITH THE USE OF AMBULATORY BLOOD PRESSURE RECORDING IN HEMODIALYSIS PATIENTS

Objective: To date, there is no commonly accepted definition for hypertension in patients with chronic kidney disease undergoing hemodialysis. A recent expert consensus suggests hypertension in dialysis to be defined based on ambulatory blood pressure monitoring (ABPM). The aim of this study is to evaluate the prevalence and control of hypertension using ABPM in a large hemodialysis population according to the latest definitions. Design and method: A total of 160 hemodialysis patients underwent 48-hour ABPM, during a regular hemodialysis session and the subsequent interdialytic interval. Hypertension was defined as (i) pre-hemodialysis BP >  = 140/90 mmHg or use of antihypertensive agents (ii) ambulatory BP >  = 130/80 mmHg (over 44-hours or over the second 24hour period) or use of antihypertensive agents. Phenotypes of hypertension control were defined as: 1) concordant control (pre-hemodialysis BP < 140/90 mmHg and ambulatory-BP < 130/80 mmHg), 2) concordant lack of control (pre-hemodialysis BP >  = 140/90 mmHg and ambulatory-BP >  = 130/80 mmHg), 3) “white coat” phenomenon (pre-hemodialysis BP >  = 140/90 mmHg and ambulatory-BP < 130/80 mmHg) and 4) masked hypertension (pre-hemodialysis BP < 140/90 mmHg and ambulatory-BP >  = 130/80 mmHg). Results: Based on pre-hemodialysis BP levels, the prevalence of hypertension was 91.3% Based on the ABPM covering the total 44-hour or the 2nd 24-hour interdialytic period, the prevalence was 88.8%. The proportion of hypertensive patients receiving treatment was 124 (84,9%). With the use of pre-hemodialysis BP and ABPM during 44-hours, 12 (10.1%) of hypertensive patients had concordant BP control, 87 (58.8%) of patients had lack of control, 29 (19.6%) had a white-coat phenomenon, and 17 (11.5) masked hypertension, respectively. In multivariate logistic regression analysis, only use of antihypertensive agents was independently associated with increased odds for lack of control (reverse causation). Conclusions: Hypertension prevalence in hemodialysis patients is overwhelmingly high. The rates of control rates are different when calculated from office and ambulatory BP recordings. In the population studied, almost one out of three patients had white-coat or masked hypertension.