Analysis of the validation of Arteriograph device versus PulsePen device in the determination of arterial stiffness parameters. Results of the Analysis of the validation of Arteriograph device versus PulsePen device in the determination of arterial stiffness parameters.
Mortality in ESRD
Arterial stiffness
Pathophysiology of arterial stiffness
The elastic matrix of the vessel wall is reduced by AGE cross-linking of elastin [43]. A large number of publications and several reviews have reported the various pathophysiological conditions associated with increased arterial stiffness (Table 7).
Measurement of arterial stiffness
The simplest method used for estimating systemic arterial stiffness is to measure brachial PP, which can be accessed by calculating the difference between systolic and diastolic blood pressure. The systemic arterial compliance is then calculated as Ad/[R(Ps-Pd)] (Ad: the area under the diastolic decay curve of the blood pressure from end-systole to end-diastole, R: the total peripheral resistance, Ps: the end-systolic blood pressure , Pd: end-diastolic blood pressure calibrated against brachial arterial pressure).
Parameters of arterial stiffness
The time (Δt) to the inflection point of the first component quantifies the timing of the reflection. According to the 'amplification phenomenon', the amplitude of the pressure wave is greater in peripheral arteries than in central arteries, and brachial PP overestimates central PP in young individuals.
Arterial stiffness and ESRD
Mechanisms of vascular stiffness and calcification in ESRD
Vascular calcification is not only the result of passive Ca-P deposition, but also represents an active process, similar to bone formation - 'ossification' of the vasculature. In summary, both intimal and medial involvement are frequent in dialysis patients and calcification of these layers contributes to stiffening of the great arteries, establishing a pathophysiological link between calcification and increased CV mortality.
Cardiovascular calcification and mortality in ESRD
Hyperphosphatemia and elevated Ca XP promote vascular calcification and are significantly linked to all-cause and CV mortality in ESRD patients [145]. In addition, decreased serum levels of fetuin A have been found to be associated with increased calcification and CV mortality in ESRD patients [135].
Clinical relevance of the parameters of arterial stiffness
Elevated levels of OPG have been associated with the progression of vascular calcification in HD patients, and a recent analysis showed that OPG is also a marker of CV mortality in HD [147]. Increased PWV is also associated with mortality in patients with essential hypertension [159] and type 2 diabetes mellitus [160].
Therapeutic Opportunities of Arterial Stiffness
In summary, clinicians have four parameters of arterial stiffness (PWV, AIx, CPP and AMP) to predict CV mortality in ESRD patients on HD. A number of studies have compared the effects of ACE inhibitors and CCBs on arterial stiffness.
OBJECTIVES
A well-validated device is needed to determine the descriptive parameters of arterial stiffness; parameters that are insufficiently determined lead to the conclusion of false connections between investigated factors and outcomes. Recently, a new oscillometric device (Arteriograph) has been developed and used to measure arterial stiffness, but it has not been previously investigated whether the use of this device is valid in patients with high CV risks such as in ESRD. My third specific objective was therefore to determine the validity of the new Arteriograph device by comparing it with a validated tonometer in the assessment of PWV, AI and the prediction of survival.
PATIENTS AND METHODS
Patients
CV deaths are defined as sudden cardiac death, death related to myocardial infarction, arrhythmia, heart failure, or stroke as assessed by the attending physician at the dialysis center. The outcome measure was death due to a CV event; CV deaths were defined as sudden cardiac death, death related to myocardial infarction, arrhythmia, heart failure, or stroke as assessed by the attending physician at the dialysis center. Baseline demographic and clinical data were collected by chart review, and laboratory parameters were measured at the time of arterial stiffness assessment.
Baseline demographic and clinical data were collected by chart review, and laboratory parameters were measured at the time of the arterial stiffness assessment.
Clinical Measurements
- Recording of the parameters of arterial stiffness
- Laboratory measurements
Augmentation index was measured by automatic identification of the 'first shoulder' (inflection point) on the mean carotid pulse signal by the PulsePen software. CPP was determined by measuring the amplitude of the mean carotid signal after calibration of the carotid curve to the brachial mean and diastolic blood pressure. The principle of the oscillometric method is based on plethysmography and registers pulsating pressure changes in an artery.
Augmentation index corresponds to the pressure difference between the amplitude of the first (forward, P1) and second (reflected, P2) wave relative to the PP.
Statistical analysis
- Analysis of the first study
- Analysis of the second study
- Analysis of the third study
The primary analysis consisted of comparing changes in variables during follow-up between the sevelamer-treated and control groups by Student's t test for independent samples and by the Wilcoxon rank sum test. To assess the validity of the arteriograph device first, Pearson's correlation analysis was performed between the Arteriograph test readings and the "gold standard" PulsePen devices. In this, the difference between each pair of measurements is plotted against the mean of the pair, and the number of paired differences that fall outside the ± 1 SD limit of the mean between-device difference is also calculated.
To assess clinical validity, the prognostic values of PWV and AI readings obtained by each device for cardiovascular mortality were determined by log-rank tests using tertiles of relevant parameters and also by Cox proportional hazard regression using the data as dependent variables and age-adjusted diabetes disease and established cardiovascular diseases.
RESULTS
Results of the first study
After adjustments for age, diabetes, and established cardiovascular disease, pre- and postdialysis PWV and predialysis AMP remained significantly related to cardiovascular mortality (Table 13). Unadjusted and adjusted* hazard ratios for cardiovascular mortality related to the different stiffness parameters measured before and after dialysis. Area under the receiver operating characteristic curves for cardiovascular mortality of the stiffness parameters measured before and after dialysis.
PWV: carotid-femoral pulse wave velocity; AI: carotid augmentation index; CPP: carotid pulse pressure; AMP: carotid-brachial pulse pressure amplification.
Results of the second study
Mean time values were calculated using the results of 3 monthly blood values from baseline to end of follow-up. Bone movement at baseline was higher in patients started on sevelamer, but changes in crosslinking and osteocalcin levels were not significant and did not differ between groups during follow-up. There were no significant differences between groups in fetuin-A, matrix GLA protein, osteoprotegerin, and soluble RANKL levels either at baseline or at the end of follow-up.
In a further forward-selected multivariate model, change in PWV during follow-up was determined by baseline CRP (p=0.034), sevelamer as the dependent variable.
Results of the third study
- Comparison of the two devices
- Survival Analysis
Parameters associated with the change in pulse wave velocity in the final multivariate linear regression model. In separate log-rank tests, only increasing tertiles of PulsePen-measured PWV, but not Arteriograph-measured PWV, PulsePen-measured AI, or Arteriograph-measured AI, were related to CV mortality (log-rank p-values, respectively) (Fig. 15). Kaplan-Meier survival curves for CV mortality according to tertiles of PWV measured with the PulsePen and Arteriograph (a, b) devices.
Kaplan-Meier survival curves for CV mortality according to tertiles of AI as measured by the PulsePen and Arteriograph devices (c, d).
DISCUSSION
Discussing the first study
In my study with ESRD patients, the fact that I failed to find an association between CV mortality and AI is in line with the results of the studies conducted by Covic et al. The popularity of central PP to predict the outcome was further strengthened by the results of the Conduit Artery Function Evaluation Study (CAFE), in which central PP was associated with CV outcomes in hypertensive patients treated with a regimen based on atenolol or amlodipine [168]. Therefore, decreased AMP between these two sites indicates stiffening of the walls of the central aorta [245].
Although both pre- and post-dialysis PWV values were related to outcome in my study, the strength of the relationship was weaker when post-dialysis data were taken into account.
Discussing the second study
However, the change in total cholesterol levels was not related to the observed changes in arterial stiffness. Furthermore, baseline levels and changes in serum concentrations of these inhibitor proteins during follow-up were not associated with the observed change in PWV. Although this may suggest that changes in the mineral metabolism affected PWV, the fact that the change in PWV was not related to changes in P and Ca X P suggests other mechanisms.
In my study, it is tempting to speculate that reduced microinflammation by sevelamer treatment was the primary mechanism responsible for the observed changes in PWV during follow-up.
Discussing the third study
The risk of cardiovascular mortality in ESRD patients on HD is 20- to 30-fold higher than in the general population (see section 1.3.2.). Because of these facts, accurate measurement of arterial stiffness parameters is of clinical importance in end-stage renal disease patients on HD. In another study (Rajzer et al.), the researchers observed differences in the PWV values obtained with the three devices and attributed this to differences in the calculation of the distance traveled [267].
In my validation study, the correlation coefficient between the AI values of the two devices was quite high but statistically significant.
LIMITATIONS OF THE STUDIES
Limitations of the first study
Limitations of the second study
Limitations of the third study
SUMMARY AND FUTURE DIRECTIONS
ABSTRACT
ÖSSZEFOGLALÓ
Brachial-ankle pulse wave velocity as a new measure of arterial stiffness: Present evidence and perspectives. Prognostic value of aortic pulse wave velocity as an index of arterial stiffness in the general population. Elevated aortic pulse wave velocity, a marker of arterial stiffness, predicts cardiovascular events in well-functioning older adults.
Increased pulse wave velocity is not associated with increased growth index in patients with diabetes. Comparison of the effects of felodipine versus hydrochlorothiazide on arterial diameter and pulse wave velocity in essential hypertension. Assessment of arterial stiffness in hypertension: comparison of oscillometric (Arteriograph), tonometric (SphygmoCor) and piezo-electronic (Complior) techniques.
PUBLICATION SUMMARY
Bertalan Cs. Fekete, Gabor Speer, Taha El Hadj Othmane, Adam G. Tabak, Jozsef Egresits, Janos Nemcsik, Andras Szabo, Istvan Kiss, Andras Tisler. Józef Egresits, Taha El Hadj Othmane, Adam Tabak, Bertalan Fekete, János Nemcsik, István Kiss, A Tislér. Bertalan, József Egresits, János Nemcsik, Taha El Hadj Othmane, István Kiss, András Szabó, Tamás Szabó, András Tislér.
Bertalan, Taha El Hadj Othmane, József Egresits, János Nemcsik, István Kiss, András Szabó, András Tislér.
ACKNOWLEDGEMENTS
