Portal de Periódicos da CAPES

Arterial Stiffness Assessed by Digital Volume Pulse Correlates With Comorbidity in Patients With ESRD

2006; Elsevier BV; Volume: 48; Issue: 3 Linguagem: Inglês

10.1053/j.ajkd.2006.05.014

1523-6838

Daniel Sollinger, Markus G. Mohaupt, Albina Wilhelm, Dominik E. Uehlinger, Felix J. Frey, Ute Eisenberger,

Dialysis and Renal Disease Management

Background: Digital volume pulse (DVP), a noninvasive method for indirect assessment of arterial stiffness, was not tested previously in patients with end-stage renal disease (ESRD). Therefore, we compared the DVP-derived stiffness index (SIDVP) with aortic pulse wave velocity (PWV) determined by means of Doppler ultrasonography in 2 groups of patients with ESRD and analyzed the correlation between SIDVP and comorbidity. Methods: Photoplethysmography was performed on the index finger of the dominant hand or the hand from the nonfistula arm in 49 renal transplant (TX) recipients and 48 hemodialysis (HD) patients. Pulse curves were analyzed with computer assistance. Comorbidity was assessed by using an established index. Results: The intrasubject variability of SIDVP was 5.7%. SIDVP and aortic PWV values correlated significantly (r = 0.66; P = 0.001) in patients with ESRD. SIDVP could not be assessed reliably in 25% and 6% of HD patients and TX recipients, respectively. Multivariate regression analyses showed that SIDVP increased with age in both HD patients and TX recipients (r = 0.61; P < 0.001) and with systolic blood pressure (r = 0.53; P < 0.025), mean arterial pressure (r = 0.47; P < 0.05), and pulse pressure (r = 0.52; P = 0.02) in TX recipients. Severity of comorbid status was associated highly with individual residuals of age-adjusted SIDVP in HD patients and TX recipients (P < 0.001). Conclusion: DVP allows the measurement of arterial stiffness in most, but not all, patients with ESRD. SIDVP values correlate with comorbidity in HD patients and TX recipients. Background: Digital volume pulse (DVP), a noninvasive method for indirect assessment of arterial stiffness, was not tested previously in patients with end-stage renal disease (ESRD). Therefore, we compared the DVP-derived stiffness index (SIDVP) with aortic pulse wave velocity (PWV) determined by means of Doppler ultrasonography in 2 groups of patients with ESRD and analyzed the correlation between SIDVP and comorbidity. Methods: Photoplethysmography was performed on the index finger of the dominant hand or the hand from the nonfistula arm in 49 renal transplant (TX) recipients and 48 hemodialysis (HD) patients. Pulse curves were analyzed with computer assistance. Comorbidity was assessed by using an established index. Results: The intrasubject variability of SIDVP was 5.7%. SIDVP and aortic PWV values correlated significantly (r = 0.66; P = 0.001) in patients with ESRD. SIDVP could not be assessed reliably in 25% and 6% of HD patients and TX recipients, respectively. Multivariate regression analyses showed that SIDVP increased with age in both HD patients and TX recipients (r = 0.61; P < 0.001) and with systolic blood pressure (r = 0.53; P < 0.025), mean arterial pressure (r = 0.47; P < 0.05), and pulse pressure (r = 0.52; P = 0.02) in TX recipients. Severity of comorbid status was associated highly with individual residuals of age-adjusted SIDVP in HD patients and TX recipients (P < 0.001). Conclusion: DVP allows the measurement of arterial stiffness in most, but not all, patients with ESRD. SIDVP values correlate with comorbidity in HD patients and TX recipients. ARTERIAL STIFFNESS is a major independent risk factor for cardiovascular morbidity and overall mortality in the general and renal populations.1Covic A. Gusbeth-Tatomir P. Goldsmith D.J. Arterial stiffness in renal patients An update.Am J Kidney Dis. 2005; 45: 965-977Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar, 2Blacher J. Guerin A.P. Pannier B. Marchais S.J. Safar M.E. London G.M. Impact of aortic stiffness on survival in end-stage renal disease.Circulation. 1999; 99: 2434-2439Crossref PubMed Scopus (1862) Google Scholar, 3London G.M. Blacher J. Pannier B. Guerin A.P. Marchais S.J. Safar M.E. Arterial wave reflections and survival in end-stage renal failure.Hypertension. 2001; 38: 434-438Crossref PubMed Scopus (729) Google Scholar, 4Laurent S. Boutouyrie P. Asmar R. et al.Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients.Hypertension. 2001; 37: 1236-1241Crossref PubMed Scopus (3127) Google Scholar Several methods have been considered for the assessment of arterial stiffness in the past. To date, pulse wave velocity (PWV) is the most widely used noninvasive method to determine arterial stiffness.1 PWV, measured between the carotid and femoral artery, reflects the stiffness of the aorta and increases with age and blood pressure (BP).2Blacher J. Guerin A.P. Pannier B. Marchais S.J. Safar M.E. London G.M. Impact of aortic stiffness on survival in end-stage renal disease.Circulation. 1999; 99: 2434-2439Crossref PubMed Scopus (1862) Google Scholar, 5Smulyan H. Siddiqui D.S. Carlson R.J. London G.M. Safar M.E. Clinical utility of aortic pulses and pressures calculated from applanated radial-artery pulses.Hypertension. 2003; 42: 150-155Crossref PubMed Scopus (149) Google Scholar Recently, Millasseau et al6Millasseau S.C. Kelly R.P. Ritter J.M. Chowienczyk P.J. Determination of age-related increases in large artery stiffness by digital pulse contour analysis.Clin Sci (Lond). 2002; 103: 371-377Crossref PubMed Scopus (439) Google Scholar described an index of stiffness based on analysis of digital volume pulse (DVP; SIDVP). The contour of the DVP is characterized by 2 distinct waves, an early systolic peak caused by direct antegrade pressure transmission along the arterial tree followed by a second peak caused by the pressure wave reflected at sites of impedance mismatch, mainly in the lower limb. Increased arterial stiffness of large conduit vessels leads to earlier return of the reflected wave, resulting in elevated SIDVP values. SIDVP is based upon the height of the individual divided by the time between the early systolic peak and inflection point (Fig 1). Because of the simplicity of its determination, assessment of SIDVP might be a valuable noninvasive alternative to detect arterial stiffness in patients with end-stage renal disease (ESRD). So far, the utility of this index was tested only in healthy individuals, patients with hypertension, and diabetes.7Millasseau S.C. Guigui F.G. Kelly R.P. et al.Noninvasive assessment of the digital volume pulse. Comparison with the peripheral pressure pulse.Hypertension. 2000; 36: 952-956Crossref PubMed Scopus (242) Google Scholar, 8Millasseau S.C. Kelly R.P. Ritter J.M. Chowienczyk P.J. The vascular impact of aging and vasoactive drugs Comparison of two digital volume pulse measurements.Am J Hypertens. 2003; 16: 467-472Crossref PubMed Scopus (72) Google Scholar In patients with ESRD, factors causing arterial stiffness are different in part from those in other populations investigated previously because chronic fluid overload, arterial calcifications, microinflammation, and activation of the renin-angiotensin-aldosterone system are more pronounced. As a corollary, observations made in other populations are not directly transferable to patients with ESRD. Therefore, we studied SIDVP in an ESRD population and compared these results with values obtained by measuring PWV, the standard method for assessment of arterial stiffness. To determine the biological significance of arterial stiffness measured by using SIDVP, the values obtained were analyzed with respect to their correlation with comorbidity.9Khan I.H. Campbell M.K. Cantarovich D. et al.Comparing outcomes in renal replacement therapy How should we correct for case mix?.Am J Kidney Dis. 1998; 31: 473-478Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar A cross-sectional study was performed in 140 subjects, consisting of 97 patients with ESRD and 43 healthy volunteers in our institution. All subjects were without signs of acute infection or arrhythmia. The study was approved by the internal review board of the institution, and informed consent was obtained from all participants. Of 97 patients with ESRD, 49 were kidney transplant (TX) recipients with stable graft function and follow-up of at least 3 months, administered either a double (calcineurin inhibitor plus prednisone) or triple (calcineurin inhibitor, prednisone, plus azathioprine or mycophenolic acid) immunosuppressive regimen. In addition, 48 hemodialysis (HD) patients participated in the study. Dialysis was performed on an outpatient basis thrice weekly for more than 3 months. Two patients had previously received a kidney allograft, but were back on dialysis therapy because of TX failure. Comorbidity was scored by using the comorbidity index proposed by Khan et al.9Khan I.H. Campbell M.K. Cantarovich D. et al.Comparing outcomes in renal replacement therapy How should we correct for case mix?.Am J Kidney Dis. 1998; 31: 473-478Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar This index, derived from patient age and a number of comorbidities, appropriately expresses the prognostic impact of comorbidity on mortality in patients with ESRD. For this purpose, the presence of cardiovascular disease (history of myocardial infarction, coronary artery disease, stroke, or peripheral arterial occlusive disease), cardiovascular risk factors, or other comorbidities were reported as indicated in patients' files. Diabetes mellitus was defined as a fasting glucose level of 126 mg/dL or greater (≥7.0 mmol/L) and/or a nonfasting serum glucose level of 200 mg/dL or greater (≥11.1 mmol/L) and/or use of insulin or oral antidiabetic medication. Hypertension was considered to be present if systolic BP (SBP) was 140 mm Hg or greater, diastolic BP (DBP) was 90 mm Hg or greater, and/or at least 1 antihypertensive drug was used. A control group of 43 subjects (27 women; 62.8%) with no history of renal impairment was recruited from the hospital medical staff and local community. Mean age was 46 ± 14 years, 7 subjects (16%) had a history of hypertension; 4 subjects (9%) had a history of diabetes, and 6 subjects (14%) were active smokers. A Pulse Trace PCA (Micro Medical Ltd, Rochester, UK) equipped with an infrared light-emitting diode (940 nm) and a photo diode receiver was used to record DVP photoplethysmographically. A finger clip containing an emitter and receiver was applied to the index finger of the dominant arm or, in the presence of an arteriovenous fistula, the contralateral arm. Determination of SIDVP was described previously in detail.7Millasseau S.C. Guigui F.G. Kelly R.P. et al.Noninvasive assessment of the digital volume pulse. Comparison with the peripheral pressure pulse.Hypertension. 2000; 36: 952-956Crossref PubMed Scopus (242) Google Scholar In brief, the contour of the DVP was recorded and analyzed. The systolic peak and inflection point were obtained by analyzing the first derivative of DVP waveforms. A single waveform was obtained by averaging DVP contours during a period of 10 seconds. The time between the first systolic peak and the inflection point in the waveforms (ΔTDVP) was determined. SIDVP was calculated by using the following equation: body height/ΔTDVP (Fig 1). PWV was recorded using a Pulse Trace PWV (Micro Medical Ltd) with a 4-MHz continuous wave directional Doppler pencil probe. In brief, pulse trace measures PWV by determining the time lag between the R wave of the electrocardiogram and the arrival of the arterial pulse at 2 different sites. After application of electrocardiogram electrodes, the pencil probe was placed over (1) the right carotid artery and (2) the right or left femoral artery. Carotid positioning of the pencil probe was not influenced by the position of an arteriovenous fistula. The femoral position of the probe was chosen randomly, regardless of the position of the allograft, because femoral PWV values obtained by positioning the pencil probe contralateral and ipsilateral to the graft were equal in 5 TX recipients (results not shown). At each site, the position was optimized to achieve a good quality signal and stable pulse waveform. About 10 systolic peaks were recorded at both sites to obtain mean time lag at the carotid artery and time lag at the femoral artery. The distance between the 2 detection sites was recorded. Brachial BP was measured while the subject was recumbent by using a mercury sphygmomanometer, and phases I and V of Korotkoff sounds were considered to represent SBP and DBP, respectively. All subjects were examined at ambient room temperature in a supine position after at least 5 minutes of rest. To ensure a hemodynamically stable condition, BP and heart rate measurements were performed before and after each DVP and PWV determination. All patients examined by both methods were investigated subsequently at the same time. The sequence of methods was randomly assigned. No attention was given to the long (3 days) or short (2 days) dialysis interval in HD patients; all measurements were performed in the middle of the dialysis session while the patients were hemodynamically stable, assessed by using BP measurements. Individual results of 3 to 4 consistent measurements of SIDVP and PWV were averaged. Correlations between PWV, DVP, age, and BP were examined by using univariate and multiple regression analysis. Chi-square or Fisher exact test were applied to analyze categorical variables, whereas 1-way analysis of variance was used for comparison of normally distributed continuous variables. Receiver operating characteristic curves were established to test the association of DVP and PWV measurements with a comorbid risk score (Khan Index) by plotting 1 − specificity versus sensitivity. Unless indicated otherwise, all results are presented as mean ± SD. P of 0.05 or less is considered significant. All statistical analyses were performed using Systat 10.0 software (Systat Software GmbH, Erkrath, Germany). Characteristics of both ESRD study populations at the time of inclusion are listed in Table 1. TX recipients were slightly younger and less frequently had a history of coronary artery disease than patients on dialysis therapy. Analysis of comorbidity score as proposed by Khan et al9Khan I.H. Campbell M.K. Cantarovich D. et al.Comparing outcomes in renal replacement therapy How should we correct for case mix?.Am J Kidney Dis. 1998; 31: 473-478Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar indicated a more severe overall disease state in patients on dialysis therapy compared with TX recipients. Mean PWV was greater in patients on dialysis therapy than in renal TX recipients, whereas the corresponding SIDVP values were not significantly different (Table 1). In 12 of 48 HD patients (25%) and 3 of 49 TX recipients (6.1%), SIDVP could not be assessed reliably because no inflection point was detectable.Table 1Clinical and Demographic Characteristics of TX Recipients and HD PatientsRenal TX RecipientsHD PatientsPNo. of patients (men/women)49 (28/21)48 (33/15)Age (y)50 ± 1460 ± 140.001Body mass index (kg/m2)25 ± 425 ± 50.8Months on dialysis—54 ± 52Months since transplantation59 ± 66—Diabetes (%)33310.9Coronary artery disease (%)18360.03Smoking (%)27190.4Serum creatinine (mg/dL)1.7 ± 0.6—Serum calcium (mg/dL)9.8 ± 0.49.5 ± 0.60.01Serum phosphate (mg/dL)3.2 ± 0.85.6 ± 2.20.001Parathyroid hormone (pg/mL)97 ± 62304 ± 2480.001Khan score Low risk22 (45)9 (19)0.002⁎Cross-tabulation showed a greater presence of high-risk comorbid factors in HD patients (P = 0.002). Medium risk14 (29)10 (21)0.002⁎Cross-tabulation showed a greater presence of high-risk comorbid factors in HD patients (P = 0.002). High risk13 (26)29 (60)0.002⁎Cross-tabulation showed a greater presence of high-risk comorbid factors in HD patients (P = 0.002).SIDVP (m/s)9.0 ± 2.410.3 ± 2.80.1 Men/women (m/s)10.1 ± 2.2/7.6 ± 1.810.7 ± 2.7/9.5 ± 2.6MAP†SIDVP measurements. (mm Hg)100 ± 692 ± 140.02Heart rate†SIDVP measurements. (beats/min)68 ± 1373 ± 150.4PWV (m/s)10.3 ± 2.911.4 ± 4.00.03 Men/women (m/s)10.6 ± 2.5/9.9 ± 3.311.9 ± 4.2/11.1 ± 3.7MAP‡PWV measurements. (mm Hg)99 ± 593 ± 130.03Heart rate‡PWV measurements. (beats/min)69 ± 1467 ± 140.9NOTE: Values expressed as mean ± SD or number (percent) unless noted otherwise. To convert serum creatinine in mg/dL to μmol/L, multiply by 88.4; serum calcium in mg/dL to mmol/L, multiply by 0.2495; serum phosphate in mg/dL to mmol/L, multiply by 0.3229. Cross-tabulation showed a greater presence of high-risk comorbid factors in HD patients (P = 0.002).† SIDVP measurements.‡ PWV measurements. Open table in a new tab NOTE: Values expressed as mean ± SD or number (percent) unless noted otherwise. To convert serum creatinine in mg/dL to μmol/L, multiply by 88.4; serum calcium in mg/dL to mmol/L, multiply by 0.2495; serum phosphate in mg/dL to mmol/L, multiply by 0.3229. To assess the intrasubject variability of SIDVP, 19 patients with ESRD were investigated on 2 occasions. Mean SIDVP values were 8.9 ± 0.3 m/s in kidney graft recipients (n = 8) and 9.4 ± 0.7 m/s in HD patients (n = 11). Within-subject coefficients of variation were 3.7% and 7.2% for patients with ESRD and TX recipients and 5.7% for all 19 patients, respectively. Because PWV, but not SIDVP, values were different between the 2 groups of patients investigated (Table 1), analysis of results of the 49 patients studied with both methods was performed. SIDVP correlated significantly with aortic PWV (r = 0.66; P < 0.001). The Bland-Altman plot (Fig 2) showed acceptable consistency between SIDVP and PWV (mean difference, −1.1 ± 2.59 m/s). The relationship between age and SIDVP is shown in Fig 3. The slope (0.114 versus 0.117 m/s/y) and intercept on the y-axis (3.5 versus 3.4 m/s) of significant linear correlations were virtually identical in TX recipients (r = 0.65; P < 0.0001) and dialysis patients (r = 0.59; P < 0.0001; Fig 3A and B). In all patients with ESRD, SIDVP increased with age (r = 0.61; P < 0.0001). A similar age dependency was observed in 43 controls with no history of renal impairment (slope, 0.099 m/s/y; intercept, 4.9 m/s; r = 0.62; P < 0.0001). Correspondingly, aortic PWV increased with age in renal TX recipients (r = 0.69; P < 0.0001) and dialysis patients (r = 0.61; P < 0.0001). Because arterial stiffness is influenced not only by the age of an individual, but also by other hemodynamic parameters, we tested the relationship between SIDVP and SBP, DBP, mean arterial blood pressure (MAP), or pulse pressure. By means of univariate analysis, SIDVP correlated positively with SBP (r = 0.53; P = 0.03), MAP (r = 0.47; P = 0.05), and pulse pressure (r = 0.52; P = 0.02), but not with DBP in the TX group. Multiple regression analysis confirmed that SIDVP correlated independently with age and MAP in the TX group. Conversely, none of the mentioned hemodynamic parameters correlated with SIDVP in the HD group (data not shown). To analyze whether individual SIDVP value as a marker of arterial stiffness is an age-independent predictor of comorbidity in patients with ESRD, patients were subdivided into groups. For this purpose, the difference between measured SIDVP and a theoretically expected stiffness index derived from the correlation of SIDVP as a function of age (Fig 3A and B) was calculated for every patient. Three subgroups comprising an equal number of subjects were formed according to the residual change in SIDVP, ie, the difference between the expected stiffness index and actual SIDVP (Fig 4). Analysis showed that a cutoff value of ±0.7 m/s (dashed lines in Fig 4) led to the formation of 3 groups of similar size in TX recipients and HD patients. In addition, a fourth group was composed of patients with no detectable SIDVP (12 HD patients, 3 TX recipients). Information about age, sex, cardiovascular risk, and comorbidity of these 4 groups is listed in Table 2.Table 2Distribution of Sex, Cardiovascular Risk Factors, and Comorbidity Status According to Groups of Age-Corrected SIDVP ResidualsGroup 1 SIDVP < ExpectedGroup 2 SIDVP as ExpectedGroup 3 SIDVP > ExpectedGroup 4 SIDVP Not MeasurableTotal patients33 (100)25 (100)24 (100)15 (100)Sex Men15 (45)⁎P = 0.002, group 1 versus group 3.15 (60)19 (79)⁎P = 0.002, group 1 versus group 3.11 (73) Women18 (55)⁎P = 0.002, group 1 versus group 3.10 (40)5 (21)⁎P = 0.002, group 1 versus group 3.4 (27)Cardiovascular risk factors Coronary artery disease5 (15)†P = 0.03, group 1 versus group 3.4 (16)11 (46)†P = 0.03, group 1 versus group 3.7 (47) Diabetes8 (24)8 (32)7 (29)7 (47) Smoking5 (15)8 (32)8 (33)1 (7) Hypertension30 (91)22 (88)23 (96)14 (93)Khan score Low risk18 (55)‡Cross tabulations showed a significant (P = 0.001) deviance from expected values.8 (32)‡Cross tabulations showed a significant (P = 0.001) deviance from expected values.4 (17)‡Cross tabulations showed a significant (P = 0.001) deviance from expected values.1 (7)‡Cross tabulations showed a significant (P = 0.001) deviance from expected values. Medium risk7 (21)‡Cross tabulations showed a significant (P = 0.001) deviance from expected values.10 (40)‡Cross tabulations showed a significant (P = 0.001) deviance from expected values.6 (25)‡Cross tabulations showed a significant (P = 0.001) deviance from expected values.1 (7)‡Cross tabulations showed a significant (P = 0.001) deviance from expected values. High risk8 (24)‡Cross tabulations showed a significant (P = 0.001) deviance from expected values.7 (28)‡Cross tabulations showed a significant (P = 0.001) deviance from expected values.14 (58)‡Cross tabulations showed a significant (P = 0.001) deviance from expected values.13 (86)‡Cross tabulations showed a significant (P = 0.001) deviance from expected values.NOTE. Values expressed as number (percent). P = 0.002, group 1 versus group 3.† P = 0.03, group 1 versus group 3.‡ Cross tabulations showed a significant (P = 0.001) deviance from expected values. Open table in a new tab NOTE. Values expressed as number (percent). A significantly greater percentage of men than women had SIDVP values greater than average (P = 0.015) or a not measurable SIDVP (P = 0.075). Subjects with a greater than expected SIDVP more frequently had (42%) a history of coronary artery disease than patients with an SIDVP value less than average (17%; P = 0.031; Table 2). Severity of comorbid status as defined by the Khan et al9Khan I.H. Campbell M.K. Cantarovich D. et al.Comparing outcomes in renal replacement therapy How should we correct for case mix?.Am J Kidney Dis. 1998; 31: 473-478Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar was associated significantly with SIDVP (Table 2; Fig 5). Fifty-five percent of the group with lower-than-expected SIDVP values had low comorbidity risk, whereas 58% of the group with SIDVP values greater than the age-corrected average had high comorbidity risk (P = 0.002). Patients with no detectable inflection point were older than all other subjects (68 ± 11 versus 54 ± 15 years; P = 0.005; n = 15 versus 81), had significantly greater PWV values than patients with a measurable SIDVP (13.3 ± 3.8 versus 10.4 ± 3.4 m/s; P = 0.05), and predominantly showed a high comorbid risk score (Table 2). Receiver operating characteristic curves were used to compare SIDVP and PWV for their ability to indicate a high- or low-risk group of comorbid score as defined by Khan et al.9Khan I.H. Campbell M.K. Cantarovich D. et al.Comparing outcomes in renal replacement therapy How should we correct for case mix?.Am J Kidney Dis. 1998; 31: 473-478Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar Sensitivity and specificity of SIDVP tended to be greater compared with PWV to identify the group with high comorbid risk (P = 0.08; Fig 6). Sensitivity and specificity for the low-risk group were equally high with both methods (area under the curve for SIDVP and PWV, 0.80 and 0.75, respectively; data not shown). We report for the first time that arterial stiffness, assessed by using contour analysis of DVP, is applicable in patients with ESRD. The study clearly shows that elevated age-adjusted SIDVP values are associated significantly with overall comorbidity in patients with ESRD. Arterial stiffness can be measured by using different methods.1Covic A. Gusbeth-Tatomir P. Goldsmith D.J. Arterial stiffness in renal patients An update.Am J Kidney Dis. 2005; 45: 965-977Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar Aortic PWV is the indirect measurement of large-arterial stiffness most often used, a method applied in many patient populations, including patients with ESRD.1Covic A. Gusbeth-Tatomir P. Goldsmith D.J. Arterial stiffness in renal patients An update.Am J Kidney Dis. 2005; 45: 965-977Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar, 2Blacher J. Guerin A.P. Pannier B. Marchais S.J. Safar M.E. London G.M. Impact of aortic stiffness on survival in end-stage renal disease.Circulation. 1999; 99: 2434-2439Crossref PubMed Scopus (1862) Google Scholar, 3London G.M. Blacher J. Pannier B. Guerin A.P. Marchais S.J. Safar M.E. Arterial wave reflections and survival in end-stage renal failure.Hypertension. 2001; 38: 434-438Crossref PubMed Scopus (729) Google Scholar, 4Laurent S. Boutouyrie P. Asmar R. et al.Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients.Hypertension. 2001; 37: 1236-1241Crossref PubMed Scopus (3127) Google Scholar SIDVP derived by contour analysis of DVP is an alternative simple method to analyze arterial stiffness. SIDVP and aortic PWV do not provide identical information. Aortic PWV, measured over the carotid-femoral region, determines the velocity of pressure transmission between both detection sites and is related inversely to aortal compliance by using the Bramwell-Hill equation,10Bramwell J.C. Hill A.V. Velocity of transmission of the pulse and elasticity of arteries.Lancet. 1922; 199: 891-892Abstract Scopus (261) Google Scholar whereas SIDVP is a composite parameter modulated by elastic properties of the large central arteries and reflective properties of the peripheral arterial bed. In addition to the velocity of pressure wave reflection along large central conduit vessels, the DVP waveform is affected by characteristics of ventricular ejection and the exact distribution of aortic and more peripheral sites of pressure wave reflection. 11van der Heijden-Spek J.J. Staessen J.A. Fagard R.H. Hoeks A.P. Boudier H.A. van Bortel L.M. Effect of age on brachial artery wall properties differs from the aorta and is gender dependent A population study.Hypertension. 2000; 35: 637-642Crossref PubMed Scopus (322) Google Scholar Despite these differences, Millasseau et al6Millasseau S.C. Kelly R.P. Ritter J.M. Chowienczyk P.J. Determination of age-related increases in large artery stiffness by digital pulse contour analysis.Clin Sci (Lond). 2002; 103: 371-377Crossref PubMed Scopus (439) Google Scholar found a significant correlation (r = 0.65; P < 0.001) between SIDVP and PWV in 87 healthy individuals aged 21 to 68 years. In the present investigation of patients with ESRD, the correlation between PWV and SIDVP values was highly significant. However, it was not possible to determine a reliable SIDVP value in 15 of 97 patients. Patients with no detectable SIDVP were significantly older and had significantly greater aortic PWV values than patients for whom SIDVP was detected successfully. Thus, it is possible that PWV and hence arterial stiffness have progressed so far in these patients that the method of contour analysis of the DVP has reached its natural technical limits. Arterial stiffness is increased in patients with ESRD compared with individuals with no history of renal impairment.12Blacher J. Demuth K. Guerin A.P. Safar M.E. Moatti N. London G.M. Influence of biochemical alterations on arterial stiffness in patients with end-stage renal disease.Arterioscler Thromb Vasc Biol. 1998; 18: 535-541Crossref PubMed Scopus (184) Google Scholar, 13Guerin A.P. Blacher J. Pannier B. Marchais S.J. Safar M.E. London G.M. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure.Circulation. 2001; 103: 987-992Crossref PubMed Scopus (906) Google Scholar This finding is not confined to patients with ESRD on HD therapy. PWV also is increased in patients with hypertension with mild to moderate renal dysfunction, defined by decreased creatinine clearance.14Mourad J.J. Pannier B. Blacher J. et al.Creatinine clearance, pulse wave velocity, carotid compliance and essential hypertension.Kidney Int. 2001; 59: 1834-1841Crossref PubMed Scopus (221) Google Scholar This inverse relationship between arterial stiffness and creatinine clearance is stronger in younger patients, presumably because such confounding factors as hypertension and diabetes are less present in this cohort.14Mourad J.J. Pannier B. Blacher J. et al.Creatinine clearance, pulse wave velocity, carotid compliance and essential hypertension.Kidney Int. 2001; 59: 1834-1841Crossref PubMed Scopus (221) Google Scholar, 15Wang M.C. Tsai W.C. Chen J.Y. Huang J.J. Stepwise increase in arterial stiffness corresponding with the stages of chronic kidney disease.Am J Kidney Dis. 2005; 45: 494-501Abstract Full Text Full Text PDF PubMed Scopus (279) Google Scholar The relationship between arterial stiffness and renal function was reported to be bidirectional. Greater PWV values are associated with decreased renal function,2Blacher J. Guerin A.P. Pannier B. Marchais S.J. Safar M.E. London G.M. Impact of aortic stiffness on survival in end-stage renal disease.Circulation. 1999; 99: 2434-2439Crossref PubMed Scopus (1862) Google Scholar whereas impaired renal function is an independent predictor of arterial stiffness acceleration.16Benetos A. Adamopoulos C. Bureau J.M. et al.Determinants of accelerated progression of arterial stiffness in normotensive subjects and in treated hypertensive subjects over a 6-year period.Circulation. 2002; 105: 1202-1207Crossref PubMed Scopus (471) Google Scholar Reported PWV values are in the range of 7.2 to 14.6 m/s, depending on age and severity of renal impairment, in the study population.2Blacher J. Guerin A.P. Pannier B. Marchais S.J. Safar M.E. London G.M. Impact of aortic stiffness on survival in end-stage renal disease.Circulation. 1999; 99: 2434-2439Crossref PubMed Scopus (1862) Google Scholar, 14Mourad J.J. Pannier B. Blacher J. et al.Creatinine clearance, pulse wave velocity, carotid compliance and essential hypertension.Kidney Int. 2001; 59: 1834-1841Crossref PubMed Scopus (221) Google Scholar, 15Wang M.C. Tsai W.C. Chen J.Y. Huang J.J. Stepwise increase in arterial stiffness corresponding with the stages of chronic kidney disease.Am J Kidney Dis. 2005; 45: 494-501Abstract Full Text Full Text PDF PubMed Scopus (279) Google Scholar, 16Benetos A. Adamopoulos C. Bureau J.M. et al.Determinants of accelerated progression of arterial stiffness in normotensive subjects and in treated hypertensive subjects over a 6-year period.Circulation. 2002; 105: 1202-1207Crossref PubMed Scopus (471) Google Scholar Most studies analyzing arterial stiffness in the setting of renal transplantation reported lower PWV values in kidney graft recipients (range, 6.6 to 11.1 m/s) than in patients on maintenance HD treatment (range, 7.2 to 12.8 m/s).17Bahous S.A. Stephan A. Barakat W. Blacher J. Asmar R. Safar M.E. Aortic pulse wave velocity in renal transplant patients.Kidney Int. 2004; 66: 1486-1492Crossref PubMed Scopus (66) Google Scholar, 18Covic A. Goldsmith D.J. Gusbeth-Tatomir P. Buhaescu I. Covic M. Successful renal transplantation decreases aortic stiffness and increases vascular reactivity in dialysis patients.Transplantation. 2003; 76: 1573-1577Crossref PubMed Scopus (97) Google Scholar This most likely is caused in part by differences in age, which is usually younger in graft recipients, and selection bias because younger and healthier patients tend to undergo transplantation more frequently. Interestingly, 2 publications reported a decrease in PWV values after successful renal transplantation.18Covic A. Goldsmith D.J. Gusbeth-Tatomir P. Buhaescu I. Covic M. Successful renal transplantation decreases aortic stiffness and increases vascular reactivity in dialysis patients.Transplantation. 2003; 76: 1573-1577Crossref PubMed Scopus (97) Google Scholar, 19Zoungas S. Kerr P.G. Chadban S. et al.Arterial function after successful renal transplantation.Kidney Int. 2004; 65: 1882-1889Crossref PubMed Scopus (97) Google Scholar In line with previous data, our kidney graft recipients had lower mean PWV and SIDVP values than HD patients, although this comparison is limited by a significant age difference in both groups. Despite these limitations of contour analysis of DVP at high PWV values, SIDVP measurements correlated significantly with age in our patients with ESRD. Thus, age dependency definitely is a hallmark of arterial stiffness in the general20Dillon J.B. Hertzman A.B. The form of the volume pulse in the finger pad in health, atherosclerosis, and hypertension.Am Heart J. 1941; 21: 172-190Abstract Full Text PDF Scopus (43) Google Scholar, 21Avolio A.P. Chen S.G. Wang R.P. Zhang C.L. Li M.F. O'Rourke M.F. Effects of aging on changing arterial compliance and left ventricular load in a northern Chinese urban community.Circulation. 1983; 68: 50-58Crossref PubMed Scopus (816) Google Scholar, 22Avolio A.P. Deng F.Q. Li W.Q. et al.Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension Comparison between urban and rural communities in China.Circulation. 1985; 71: 202-210Crossref PubMed Scopus (676) Google Scholar and renal populations.13Guerin A.P. Blacher J. Pannier B. Marchais S.J. Safar M.E. London G.M. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure.Circulation. 2001; 103: 987-992Crossref PubMed Scopus (906) Google Scholar, 23Blacher J. Safar M.E. Guerin A.P. Pannier B. Marchais S.J. London G.M. Aortic pulse wave velocity index and mortality in end-stage renal disease.Kidney Int. 2003; 63: 1852-1860Crossref PubMed Scopus (454) Google Scholar Arterial stiffness is a prognostic parameter of cardiovascular and overall mortality in patients with renal disease.2Blacher J. Guerin A.P. Pannier B. Marchais S.J. Safar M.E. London G.M. Impact of aortic stiffness on survival in end-stage renal disease.Circulation. 1999; 99: 2434-2439Crossref PubMed Scopus (1862) Google Scholar, 3London G.M. Blacher J. Pannier B. Guerin A.P. Marchais S.J. Safar M.E. Arterial wave reflections and survival in end-stage renal failure.Hypertension. 2001; 38: 434-438Crossref PubMed Scopus (729) Google Scholar, 4Laurent S. Boutouyrie P. Asmar R. et al.Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients.Hypertension. 2001; 37: 1236-1241Crossref PubMed Scopus (3127) Google Scholar, 5Smulyan H. Siddiqui D.S. Carlson R.J. London G.M. Safar M.E. Clinical utility of aortic pulses and pressures calculated from applanated radial-artery pulses.Hypertension. 2003; 42: 150-155Crossref PubMed Scopus (149) Google Scholar, 6Millasseau S.C. Kelly R.P. Ritter J.M. Chowienczyk P.J. Determination of age-related increases in large artery stiffness by digital pulse contour analysis.Clin Sci (Lond). 2002; 103: 371-377Crossref PubMed Scopus (439) Google Scholar, 7Millasseau S.C. Guigui F.G. Kelly R.P. et al.Noninvasive assessment of the digital volume pulse. Comparison with the peripheral pressure pulse.Hypertension. 2000; 36: 952-956Crossref PubMed Scopus (242) Google Scholar, 8Millasseau S.C. Kelly R.P. Ritter J.M. Chowienczyk P.J. The vascular impact of aging and vasoactive drugs Comparison of two digital volume pulse measurements.Am J Hypertens. 2003; 16: 467-472Crossref PubMed Scopus (72) Google Scholar, 9Khan I.H. Campbell M.K. Cantarovich D. et al.Comparing outcomes in renal replacement therapy How should we correct for case mix?.Am J Kidney Dis. 1998; 31: 473-478Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar, 10Bramwell J.C. Hill A.V. Velocity of transmission of the pulse and elasticity of arteries.Lancet. 1922; 199: 891-892Abstract Scopus (261) Google Scholar, 11van der Heijden-Spek J.J. Staessen J.A. Fagard R.H. Hoeks A.P. Boudier H.A. van Bortel L.M. Effect of age on brachial artery wall properties differs from the aorta and is gender dependent A population study.Hypertension. 2000; 35: 637-642Crossref PubMed Scopus (322) Google Scholar, 12Blacher J. Demuth K. Guerin A.P. Safar M.E. Moatti N. London G.M. Influence of biochemical alterations on arterial stiffness in patients with end-stage renal disease.Arterioscler Thromb Vasc Biol. 1998; 18: 535-541Crossref PubMed Scopus (184) Google Scholar, 13Guerin A.P. Blacher J. Pannier B. Marchais S.J. Safar M.E. London G.M. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure.Circulation. 2001; 103: 987-992Crossref PubMed Scopus (906) Google Scholar To evaluate arterial stiffness as an individual risk factor, absolute SIDVP values have to be corrected for age. Blacher et al23Blacher J. Safar M.E. Guerin A.P. Pannier B. Marchais S.J. London G.M. Aortic pulse wave velocity index and mortality in end-stage renal disease.Kidney Int. 2003; 63: 1852-1860Crossref PubMed Scopus (454) Google Scholar showed that transformation of absolute PWV values into an age-dependent PWV index provided information with high predictive power and greater discriminatory prospective significance for mortality than conventional cardiovascular risk factors. Interestingly, our cutoff values for residuals of age-adjusted SIDVP matched the age-dependent PWV increments defined by Blacher et al,23Blacher J. Safar M.E. Guerin A.P. Pannier B. Marchais S.J. London G.M. Aortic pulse wave velocity index and mortality in end-stage renal disease.Kidney Int. 2003; 63: 1852-1860Crossref PubMed Scopus (454) Google Scholar suggesting similar utility of both methods. The comorbidity score proposed by Khan et al9Khan I.H. Campbell M.K. Cantarovich D. et al.Comparing outcomes in renal replacement therapy How should we correct for case mix?.Am J Kidney Dis. 1998; 31: 473-478Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar was shown to be predictive for mortality in a population of 1,407 patients on renal replacement therapy. Our data clearly show that age-adjusted SIDVP is associated with comorbidity in patients with ESRD. This is particularly interesting because the association of such traditional risk factors as serum cholesterol level with incidence or severity of cardiovascular disease is controversial and possibly confounded by nontraditional factors in the ESRD population.24Wanner C. Krane V. Marz W. et al.Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis.N Engl J Med. 2005; 353: 238-248Crossref PubMed Scopus (2212) Google Scholar, 25Kielstein J.T. Zoccali C. Asymmetric dimethylarginine A cardiovascular risk factor and a uremic toxin coming of age?.Am J Kidney Dis. 2005; 46: 186-202Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar In the present investigation, correlation of SIDVP to comorbidity is based on a cross-sectional observation. Therefore, the prognostic value of SIDVP has to be confirmed in a prospective trial in patients with ESRD. In conclusion, results presented here indicate that SIDVP obtained by means of photoplethysmographic analysis of DVP is a reliable marker of vascular aging, and elevated values are associated with a state of increased coronary and overall comorbidity in patients with ESRD. The use of this method is limited in patients on maintenance HD treatment because of an inability to detect correct waveforms in 25% of tested patients.