Journal of Human (2007) 21, 141–148 & 2007 Nature Publishing Group All rights reserved 0950-9240/07 $30.00 www.nature.com/jhh ORIGINAL ARTICLE Relationship between parameters and wave velocity in normotensive and hypertensive subjects: invasive study

EJ Kim1, CG Park1, JS Park1, SY Suh1, CU Choi1, JW Kim1, SH Kim2, HE Lim1, SW Rha1, HS Seo1 and DJ Oh1 1Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Guro-gu, Seoul, Republic of Korea and 2Division of Cardiology, Department of Internal Medicine, Hallym University Medical Center, Youngdeungpo-dong, Seoul, Republic of Korea

Blood pressure (BP) is one of the most important (MAP) showed significant association with PWV. To contributing factors to pulse wave velocity (PWV), a avoid multiple colinearity among SBP, PP and MAP, we classic measure of . Although there performed multiple regression analysis predicting PWV have been many non-invasive studies to show the thrice. Age, DM and each BP were significantly and relation between arterial stiffness and BP, the results consistently correlated to PWV. In the first and third are controversial. The aim of this study is to evaluate modules, compared to age, SBP and MAP were less the role of BP as an influencing factor on PWV using strong predictors, respectively. However, PP was the invasive method. We observed 174 normotensive stronger predictor than age and DM in the second and untreated hypertensive subjects using coronary module. Lastly, we simultaneously forced MAP and PP angiography. Arterial stiffness was assessed through with other variables in the fourth multivariate analysis. aorto-femoral PWV by foot-to-foot velocity method Age, DM and PP remained significantly correlated with using fluid-filled system. And BP was measured by PWV, but the significance of MAP was lost. This is pressure wave at the right common femoral . From the first invasive study to suggest that PP has the univariate analysis, age, diabetes mellitus (DM), hyper- strongest correlation with PWV among a variety of BP tension, waist, waist-to-hip ratio, total cholesterol-to- parameters. high-density lipoprotein cholesterol ratio, systolic BP Journal of Human Hypertension (2007) 21, 141–148. (SBP), pulse pressure (PP) and mean arterial pressure doi:10.1038/sj.jhh.1002120; published online 30 November 2006

Keywords: pulse wave velocity; pulse pressure; large artery stiffness

Introduction quantify stiffness, none of them is a gold standard, 16,17 1 but approximations. It is believed that the most Arterial stiffening increases with age and is asso- reliable (and still probably the best) measure of ciated with generalized atherosclerotic vascular 16 2–4 arterial stiffness is pulse wave velocity (PWV). disease. In population-based studies, aortic stiff- PWV is known to be associated with age, gender, ness is an independent predictor of cardiovascular (BP), heart rate, salt intake, genetic outcomes after adjustment for traditional cardio- factors and others. Although BP is one of the vascular risk factors.4–7 Arterial stiffness has been 8–11 strongest factors influencing PWV, varying correla- shown to predict coronary artery disease and tion coefficients have been reported between the cardiovascular mortality in patients with essential 12 13,14 various PWV (aorta-leg-arm) and BP (systolic, hypertension, end-stage renal disease and diastolic, mean, pulse) using non-invasive meth- impaired glucose tolerance and diabetes mellitus 5,18–24 15 ods. This variation may be attributable, at least (DM). Although there are many measures to in part, to the inherent variability of both PWV and BP within and across individual subjects and also to Correspondence: Professor Dr CG Park, Division of Cardiology, the method of BP25 and PWV measurements. Department of Internal Medicine, Korea University Guro Hospital, The aim of this study is to elucidate the relation- 80 Guro-dong, Guro-gu, Seoul 152-703, Korea. ship between the various BP and aortic PWV E-mail: [email protected] Received 29 May 2006; revised 9 October 2006; accepted 11 through direct measurement of BP wave in the October 2006; published online 30 November 2006 artery using invasive method. Pulse wave velocity and pulse pressure EJ Kim et al 142 Materials and methods Measurement of haemodynamic variables Haemodynamic measurements were obtained from Study subjects patients in supine position. PWV was measured Investigations were carried out in the cardiology along the descending thoraco-abdominal aorta using department at the Korea University Guro Hospital, the foot-to-foot velocity method. Briefly, waveforms Seoul, Korea, between March 2002 and July 2003. To were obtained using a fluid-filled system (5Fr right obtain BP and aortic PWV through a direct pressure Judkin’s catheter) at the descending aorta, just below wave in the artery using invasive method, we the origin of left subclavian artery and the right selected the study population from those who common femoral artery (Figure 1). At each site, the underwent coronary angiography owing to chest pressure waves were simultaneously recorded with symptoms or preoperative evaluation. Of the 435 the electrocardiography using polygraph at the subjects who gave written informed consents for speed of 100 mm/s. We defined T1 as the time PWV measurement, 227 were receiving antihyper- interval from the starting point of QRS complex to tensive drug therapy and 17 were not clear of their the foot of pressure wave in the descending aorta medical history and, therefore, were excluded from and T2 as the time interval from the starting point of the study. Additional 17 patients were excluded QRS complex to the foot of pressure wave in the owing to one or more of the exclusion criteria; acute right common femoral artery. We measured T1 and myocardial infarction, cardiomyopathy, more than T2 from three different QRS complexes and pressure mild valvular disease, post-cardiac surgery, atrial waves, and computed the mean value to minimize fibrillation, aortic dissection and chronic renal the error. The time delay (T) was calculated as failure. Thus, 174 normotensive and untreated T2ÀT1 and the distance (D) was obtained by the hypertensive subjects (101 women; 73 men) were length of the catheter between the two recording observed. Their median age was 59.0712.03 years 7 sites. PWV was calculated by PWV ¼ D (m)/T (s). ( 1s.d.). The study was approved by the local ethics We measured SBP, DBP and pulse pressure (PP) by committee. pressure tracing method in the right common Hypertension was characterized with repeated femoral artery. Mean arterial pressure (MAP) was X measurements of 140 mm Hg systolic BP (SBP) obtained by the formula MAP ¼ DBP þ PP/3. or X90 mm Hg diastolic BP (DBP). DM was defined as a fasting blood glucose concentration X126 mg/dl or antihyperglycaemic drug treatment. Current Statistical analysis smoking was defined as having smoked the last Values were expressed as mean7one standard cigarette less than 1 month before coronary angio- deviation (s.d.). Differences in the mean value of graphy. PWV between the two groups were compared using

Figure 1 The measurement of PWV. Catheter was located on the descending aorta just distal to left subclavian artery (upper left panel), and surface ECG and arterial pressure wave were recorded on a paper with speed 100 mm/s and T1 transit time was measured (upper right panel). Introducing sheath was located on the right common femoral artery (lower left panel) and T2 transit time was measured (lower right panel).

Journal of Human Hypertension Pulse wave velocity and pulse pressure EJ Kim et al 143 a Student’s t-test for a parametric statistical test and three modules also included SBP, PP and MAP, Mann–Whitney’s test for a non-parametric analysis. separately. The results indicated that age and DM A Po0.05 was considered significant. Correlations were significantly and consistently correlated to between each of the measured variables and PWV PWV. And within each analysis, SBP, PP and MAP were assessed by Pearson’s correlation coefficient. also showed significant association with PWV. The The effects of traditional cardiovascular risk factors first and third module showed that age was the and haemodynamic variables on PWV were ana- strongest predictor among 3 significant correlating lysed by multivariate regression analysis. With the factors (age, DM, SBP or MAP). In the second variables selected from univariate analyses, we module, on the other hand, PP was the stronger performed the analysis thrice to avoid multiple predictor than age or DM (for age, b ¼ 0.233, colinearity among SBP, PP and MAP. Variables P ¼ 0.001; for DM, b ¼ 0.201, P ¼ 0.005; for PP, included in the first module were common ones, b ¼ 0.255, Po0.001). When we used age as an index such as age, DM, waist-to-hip ratio, total cholesterol- variable for comparison, this result indirectly de- to-high-density lipoprotein cholesterol (HDL-C) monstrated that PP was the only stronger predictor ratio and SBP. The second and third modules for PWV compared to age among BP parameters. included common variables along with PP and That is, PP showed the most potent correlation with MAP. We also performed the fourth multiple regres- PWV over a variety of BP parameters. sion analysis including the same non-haemo- Lastly, we included both MAP and PP with dynamic variables, PP and MAP with a test of other common independent variables in the fourth variance influence factor. Statistical analyses were multiple regression model (Table 4). Considering performed using the SPSS 10.0 software package continuous characteristic of MAP and pulsatile (SPSS Inc., Chicago, IL, USA). characteristic of PP, we tried to determine whether

Results Table 1 Baseline clinical characteristics of study subjects The baseline clinical characteristics of the study population are presented in Table 1. Table 2 shows Parameters n ¼ 174 the results of the independent-samples t-test for Age (year) 59.0712.03 comparison of the PWV mean value between the Gender (male) 73 (42.0%) two groups according to gender, hypertension, DM Hypertension 82 (47.1%) and smoking status. Compared with subjects who Diabetes 21 (12.1%) did not have hypertension or DM, subjects who had Smoker 38 (21.8%) BMI (kg/m2) 24.473.4 hypertension or DM showed significantly higher 7 7 Height (cm) 161.0 8.2 PWV mean value (for hypertension, 13.2 6.2 vs Waist/hip 0.970.07 10.373.5 m/s, Po0.001; for DM, 15.678.6 vs 11.174.3 m/s, P ¼ 0.003). However, the differences Total cholesterol (mg/dl) 185.9743.8 7 of PWV between men and women, or smoker and HDL-C 46.4 12.0 TG 132.4770.0 non-smoker were not prominent. In bivariate analy- LDL-C 111.4738.5 sis (Table 3), age, waist-to-hip ratio, total cholesterol- Heart rate (b.p.m.) 74.5713.8 to-HDL-C ratio, SBP, PP and MAP were positively correlated with PWV. The relations of PWV to age, Blood pressure (mm Hg) Systolic 146.8725.3 SBP, PP and MAP were displayed in Figures 2–5, Diastolic 78.9713.1 respectively. To avoid multiple colinearity among Pulse 67.9719.0 SBP, PP and MAP, we performed multiple regression Mean 101.5715.8 analysis predicting PWV three times with variables Pulse wave velocity (m/s) 11.675.2 selected from univariate analyses (Table 4). In every multiple regression analysis, age, waist-to-hip ratio, Abbreviations: BMI, body mass index; HDL-C, high-density lipo- protein cholesterol; LDL-C, low-density lipoprotein cholesterol; TG, DM and total cholesterol-to-HDL-C ratio were used triglyceride.Continuous variables are expressed as mean7s.d. except as common independent variables and each of the age, which is expressed as median7s.d.

Table 2 Independent-samples t-test results for pulse wave velocity

Gender Hypertension Diabetes Smoking

Men (n ¼ 73) Women (n ¼ 101) Yes (n ¼ 92) No (n ¼ 82) Yes (n ¼ 21) No (n ¼ 153) Yes (n ¼ 38) No (n ¼ 136)

PWV (m/s) 12.176.0 11.374.5 13.276.2 10.373.5 15.678.6 11.174.3 12.375.2 11.475.2 P 0.321 o0.001 0.003 0.370

Abbreviation: PWV, pulse wave velocity.

Journal of Human Hypertension Pulse wave velocity and pulse pressure EJ Kim et al 144 Table 3 Pearson’s correlation coefficient between pulse wave 30 velocity and clinical parameters

rP

Age 0.357 o0.001 BMI 0.105 0.175 20 Height À0.048 0.536 Waist/hip 0.178 0.021 TC 0.080 0.314 HDL-C À0.129 0.111 TG 0.058 0.473 LDL-C 0.152 0.061 10 TC/HDL-C 0.159 0.048 Heart rate 0.018 0.820 Pulse Wave Velocity (m/s) Systolic BP 0.330 o0.001 Diastolic BP 0.110 0.150 Pulse pressure 0.363 o0.001 Mean BP 0.238 0.002 0 20 40 60 80 100 120 140 Abbreviations: BMI, body mass index; BP, blood pressure; HDL-C, Pulse Pressure (mmHg) high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglyceride. Figure 4 Relation between aortic PWV and PP (r ¼ 0.363, Po0.001).

30 30

20 20

10 10 Pulse Wave Velocity (m/s) Pulse Wave Velocity (m/s)

0 10 20 30 40 50 60 70 80 90 0 Age (years) 40 60 80 100 120 140 160 Figure 2 Relation between aortic PWV and age (r ¼ 0.357, Mean Arterial Pressure (mmHg) Po0.001). Figure 5 Relation between aortic PWV and MAP (r ¼ 0.238, 30 P ¼ 0.002).

PP remained significantly correlated with PWV after other factors including MAP were forced in the 20 model. In the analysis, age (b ¼ 0.356, Po0.001), DM (b ¼ 0.161, P ¼ 0.028) and PP (b ¼ 0.221, P ¼ 0.023) remained significantly correlated with PWV, but MAP lost the significance of correlation with PWV (b ¼ 0.129, P ¼ 0.154). The variance influence factors 10 for all independent variables were less than 2, thereby the multiple colinearity was not prominent. Pulse Wave Velocity (m/s) The analysis was also performed adding SBP as an independent variable (data not shown). However, the result was the same as the fourth module except 0 automatic exclusion of SBP from the analysis 80 100 120 140 160 180 200 220 240 because its multi colinearity was over the limit. In Systolic Blood Pressure (mmHg) our cross-sectional study, it is suggested that the Figure 3 Relation between aortic PWV and SBP (r ¼ 0.330, pulsatile BP had more effect on PWV than the Po0.001). continuous part of BP.

Journal of Human Hypertension Pulse wave velocity and pulse pressure EJ Kim et al 145 Table 4 Multiple linear regression analysis predicting PWV: relationships between PWV and clinical parameters

1st module 2nd module 3rd module 4th module

b P b P b P b P VIF

Age 0.286 o0.001 0.233 0.001 0.333 o0.001 0.356 o0.001 1.30 Waist/hip 0.003 0.961 0.018 0.803 0.006 0.933 À0.014 0.848 1.12 Diabetes 0.219 0.002 0.201 0.005 0.241 0.001 0.161 0.028 1.12 TC/HDL-C 0.114 0.092 0.130 0.059 0.099 0.145 0.138 0.054 1.07 Systolic BP 0.283 o0.001 — — — PP — 0.255 o0.001 — 0.221 0.023 1.98 MAP — — 0.268 o0.001 0.129 0.154 1.73

Abbreviations: BP, blood pressure; HDL-C, high-density lipoprotein cholesterol; MAP, mean arterial pressure; PP, pulse pressure; PWV, pulse wave velocity; TC, total cholesterol; VIF, variance influence factor.

Discussion The causes of controversial results may be different demographic characteristics such as age The key finding of our study was that in normo- range, gender distribution and body size. Whether tensive and untreated hypertensive middle-aged and the subjects were on antihypertensive agents and elderly subjects (median age of 59.0712.03 years) the kinds of drugs, if used, might also affect the PP showed the strongest correlation with aortic results.26 Also, the different methods of BP measure- PWV over other haemodynamic BP parameters. ment (e.g. 24-h ambulatory BP monitoring, casual PWV measured along the aortic and aorto-femoral BP measurement, automatic BP monitoring for pathways has been known to be the most clinically 30 min) could attribute to the results.27 In particular, relevant because the aorta and its first branches are as indirect measurement of DBP by cuff-mercury responsible for most of the pathophysiological sphygmomanometer tends to be overestimated, the effects of arterial stiffness. Although non-invasive true intra-arterial PP might be underestimated, technique showed acceptable reproducibility, the which could also affect the results.28 In terms of length of arterial segment was usually estimated PWV measurement, different methods and locations by direct superficial measurement of the distance were used in the studies, and most non-invasive between two transducers. Therefore aortic PWV by methods basically had a limitation mentioned non-invasive method would be underestimated above, therefore, showed controversial results. because become longer and more tortuous Because this study used invasive method for the with age. In vivo measurement of the travel distance measurement of BP and aortic PWV excluding was calculated by subtracting (i) the known sheath subjects on antihypertensive agents, our findings length and (ii) the external catheter length behind reflect the effect of BP on aortic PWV more clearly. the sheath, from the known length of the total In population-based studies, aortic PWV has been catheter and obtained more accurate PWV. Also, we known to be a superior independent predictor of minimized the error of BP measurement by using cardiovascular outcome even after adjusting the intra-arterial pressure wave. traditional cardiovascular risk factors5,7 and ele- Arterial stiffness has been known to be related to vated PP also has been known to be an independent BP; however, there are controversial results in the risk factor of .29–31 literature regarding the relation between PWV and Haemodynamic patterns of age-related changes in each BP (SBP, DBP, PP and MAP). Ngim et al.19 BP was shown in the Framingham heart study.32 reported that carotid-femoral PWV was correlated After age 50–60 years, DBP declined, PP rose steeply with SBP and also MAP, but not with DBP in and MAP reached a plateau. The changes were untreated hypertensive and normotensive middle- mainly attributed to the age-related large artery aged Malay men. Stompor et al.24 also found out that stiffness. The effect of ageing on the prognostic signi- aortic PWV was correlated significantly with SBP, ficance of BP was reported in hypertensive subjects33 MAP and PP, but not with DBP in peritoneal dialysis and Framingham population.34 By ambulatory intra- patients. Those findings are consistent with our arterial BP monitoring, DBP parameters provided the results. In some studies, PWV was only correlated best prognostic value for cardiovascular outcomes in with SBP,20,21 but in others with both SBP and DBP.22 the middle aged (o60 years), whereas PP parameters Sa Cunha et al.23 suggested gender difference; SBP were the most predictive in the elderly (X60 years) showed correlation with PWV in both genders, individuals.33 With increasing age, the relative prog- whereas DBP was correlated with PWV only nostic value of BP for coronary heart disease was in women. In contrast to the previous studies, gradually shifted from DBP to SBP and then to PP in Nurnberger et al.18 reported that DBP was an only the Framingham heart study.34 In subjects aged o50 important haemodynamic determinant of PWV in years, DBP was the strongest predictor. Age 50–59 young healthy males. years was a transition period when SBP, DBP and PP

Journal of Human Hypertension Pulse wave velocity and pulse pressure EJ Kim et al 146 were similar predictors, whereas from age 60 years correlation with total cholesterol.5,25 The present and over, DBP was negatively related to the risk of findings are in agreement with a recent large coronary events so that PP became a better predictor population-based study by Amar et al.5 These than SBP. We suggest that as the median age of our investigators found no significant relationship subjects is 59 years, these age-related trends of the between PWV and total cholesterol and the various Framingham heart study could be similarly applied components of the metabolic syndrome, including to our research, which demonstrates PP as the body mass index, fasting glucose, insulin, trigly- strongest determinant of aortic PWV. Because our cerides and HDL-C. The lack of correlation of PWV results also showed prognostic significance of SBP with smoking in the present study is also consistent and MAP for aortic PWV and no correlation of DBP with previous reports.5,36–38 with PWV, the findings were in agreement with the The effect of heart rate on arterial stiffness is previous data.32–34 somewhat a controversial issue. In a recent observa- Interestingly, Nurnberger et al.18 reported a con- tional study, Sa Cunha et al.23 showed that high trary result. They showed DBP was the only heart rate was strongly associated with elevated important determinant of PWV among all BP para- PWV even after adjustment for age and BP. The meters. But, the study population included only increase in heart rate by isoproterenol and pacing young (23–35 years old) healthy males, in whom was associated with an increase in PWV.39 Our DBP has been known to be the strongest predictor result, however, demonstrated no significant corre- of coronary heart disease in the Framingham heart lation and is in agreement with other previous study. Although the results of the present study and studies.40–42 There was also a contradictory study Nurnberger’s report are different, together they showing reduced aortic stiffness and increased might reflect the age-related different relation distensibility during incremental pacing.43 There- between BP parameters and PWV. It is suggested fore, in order to clarify the relationship between that aortic PWV and BP are strongly influenced by arterial distensibility and heart rate, and its patho- age, and the role of BP parameters as a predictor physiology, further specific studies are necessary. of PWV could be different according to the age range Several aspects of validity need to be discussed. of the population studied. There was a potential limitation in PWV measure- Elastic properties of the arterial wall are highly ment method, as we could not obtain pressure wave pressure dependent. At low levels of arterial at two recording sites at the same time. However, we pressure, wall stress is supported by compliant think that there were no significant haemodynamic elastin fibres, whereas at higher levels of pressure, variations between the two assessments obtained wall stress is supported by much stiffer collagen from two different sites because it took less than 3 s fibres. An increase in elastic artery stiffness is to disconnect the catheter from the manifolder, related to arterial wall composition and occurs over remove it and connect the side arm of the introducer a long period, for example, with advancing age, sheath to the manifolder. That is, there was a time hypertension and arteriosclerosis. Acute changes interval of less than 3 s between the aortic pressure can occur in elastic arteries with changes in wave and the right common femoral arterial pres- distending MAP, but these are passive. For example, sure wave. Nevertheless, we could not affirm during vasodilation, both pressure and diameter whether there was a variation of BP between the decrease in elastic arteries, causing a passive two assessments, because the patient’s real-time BP decrease in wall stiffness and a decrease in PWV.35 was being monitored and was obtained through the As it was cross-sectional and because there was no catheter at each recording site in the arterial system. BP manipulation, our study reveals chronic changes However, in terms of heart rate, no significant of elastic arteries well. It was further supported by variation between the two assessments was affirmed the fourth module of multiple regression analysis by paired t-test (heart rate in femoral artery, 74.57 (Table 4). MAP, which is more related to acute BP 13.8 b.p.m. vs heart rate in aorta, 74.4713.6 b.p.m., influence on PWV, lost the significance of correla- P ¼ 0.49). In addition, we measured T1 and T2 tion with PWV when it was adjusted for other by electrocardiography gating and averaged the factors. However, age, DM and PP remained sig- values from three measurements at each site nificantly correlated with PWV in the analysis. In (mean T1 ¼ 108.0 ms, mean s.d. ¼ 4.9 ms (0.6– terms of the relationship between PWV and two 13.2 ms); mean T2 ¼ 149.3 ms, mean s.d. ¼ 4.4 ms important BP characteristics, continuous and pulsa- (1.2–13.0 ms)). One other potential problem of our tile, the result also suggested that the pulsatile BP study is the confinement to symptomatic patients had more impact on aortic PWV than the continuous referred for coronary angiography. Thus, our find- part of BP. ings might not be applicable to the general popula- We found no significant relationship of PWV with tion. In terms of the relation between BP parameters total cholesterol, triglycerides, low-density lipo- and aortic PWV, we think, however, the subjects protein cholesterol or HDL-C. Although positive studied matter little to the results. Moreover, it is and negative associations of aortic stiffness with unlikely that confounding explains our results cholesterol have been reported using different because we were able to adjust for many important methods, most studies using PWV have shown no potential confounders.

Journal of Human Hypertension Pulse wave velocity and pulse pressure EJ Kim et al 147 In conclusion, PP showed the strongest correla- 5 Amar J, Ruidavets JB, Chamontin B, Drouet L, Ferrieres tion with aortic PWV among a variety of BP J. Arterial stiffness and cardiovascular risk factors parameters in the normotensive and untreated in a population-based study. J Hypertens 2001; 19: hypertensive middle aged and elderly subjects, 381–387. and it was first confirmed by an invasive method. 6 Meaume S, Rudnichi A, Lynch A, Bussy C, Sebban C, 18,32–34 Benetos A et al. Aortic pulse wave velocity as a marker In combination with the previous studies, the of cardiovascular disease in subjects over 70 years old. present study also suggests that the role of BP J Hypertens 2001; 19: 871–877. parameters as a predictor of PWV could be different 7 Willum-Hansen T, Staessen JA, Torp-Pedersen C, according to the age range of the population studied. Rasmussen S, Thijs L, Ibsen H et al. Prognostic value Further large population-based studies are needed of aortic pulse wave velocity as index of arterial to characterize the age-related changes in the impact stiffness in the general population. Circulation 2006; of BP on large artery stiffness. 113: 664–670. 8 Boutouyrie P, Tropeano AI, Asmar R, Gautier I, Benetos A, Lacolley P et al. Aortic stiffness is an independent What is known about the topic predictor of primary coronary events in hypertensive K BP is one of the most important determinants of PWV, patients: a longitudinal study. Hypertension 2002; 39: a classical measure of arterial stiffness. 10–15. K Although there have been many non-invasive studies to 9 Mattace-Raso FU, van der Cammen TJ, Hofman A, van show the relation between PWV and BP, the results are Popele NM, Bos ML, Schalekamp MA et al. Arterial controversial. stiffness and risk of coronary heart disease and stroke: K Haemodynamic patterns of age-related changes in BP and the Rotterdam Study. Circulation 2006; 113: 657–663. the effect of aging on the prognostic significance of BP were 10 Weber T, Auer J, O’Rourke MF, Kvas E, Lassnig E, shown in the Framingham heart study.32,34 Berent R et al. Arterial stiffness, wave reflections, and What this study adds the risk of coronary artery disease. Circulation 2004; K Because this study used invasive method for the 109: 184–189. measurement of BP and aortic PWV and excluded subjects 11 Lim HE, Park CG, Shin SH, Ahn JC, Seo HS, Oh DJ. on the antihypertensive agents, our findings more clearly Aortic pulse wave velocity as an independent marker reflect the effect of BP on aortic PWV. of coronary artery disease. Blood Press 2004; 13: K In normotensive and untreated hypertensive middle-aged 369–375. and elderly subjects, pulse pressure showed the strongest 12 Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, correlation with aortic PWV over other BP parameters. Guize L et al. Aortic stiffness is an independent K In combination with the previous studies,18,32–34 our findings also suggest that the role of BP parameters as a predictor of all-cause and cardiovascular mortality predictor of PWV could be different according to the age in hypertensive patients. Hypertension 2001; 37: range of the population studied. 1236–1241. 13 Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar Abbreviations: BP, blood pressure; PWV, pulse wave velocity. ME, London GM. Impact of aortic stiffness on survi val in end-stage renal disease. Circulation 1999; 99: 2434–2439. 14 Blacher J, Safar ME, Guerin AP, Pannier B, Marchais Acknowledgements SJ, London GM. Aortic pulse wave velocity index and mortality in end-stage renal disease. Kidney Int 2003; This work was partially supported by a grant from 63: 1852–1860. the Seoul R LBD program, Republic of Korea 15 Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn (10528). G, Gosling RG. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? References Circulation 2002; 106: 2085–2090. 16 O’Rourke MF, Staessen JA, Vlachopoulos C, Duprez D, 1 Ohmori K, Emura S, Takashima T. Risk factors Plante GE. Clinical applications of arterial stiffness; of atherosclerosis and aortic pulse wave velocity. definitions and reference values. Am J Hypertens 2002; Angiology 2000; 51: 53–60. 15: 426–444. 2 Farrar DJ, Bond MG, Riley WA, Sawyer JK. Anatomic 17 Lemogoum D, Van Bortel L, Van den Abeele W, Ciarka correlates of aortic pulse wave velocity and carotid A, Degaute JP, van de Borne P et al. Effect of beta- artery elasticity during atherosclerosis progression adrenergic stimulation on pulse wave velocity in black and regression in monkeys. Circulation 1991; 83: and white subjects. J Hypertens 2004; 22: 2349–2353. 1754–1763. 18 Nurnberger J, Dammer S, Opazo Saez A, Philipp T, 3 O’Neal DN, Dragicevic G, Rowley KG, Ansari MZ, Schafers RF. Diastolic blood pressure is an important Balazs N, Jenkins A et al. A cross-sectional study of the determinant of augmentation index and pulse wave effects of type 2 diabetes and other cardiovascular risk velocity in young, healthy males. J Hum Hypertens factors on structure and function of nonstenotic 2003; 17: 153–158. arteries of the lower limb. Diabetes Care 2003; 26: 19 Ngim CA, Abdul Rahman AR, Ibrahim A. Pulse wave 199–205. velocity as an index of arterial stiffness: a comparison 4 van Popele NM, Grobbee DE, Bots ML, Asmar R, between newly diagnosed (untreated) hypertensive Topouchian J, Reneman RS et al. Association between and normotensive middle-aged Malay men and its arterial stiffness and atherosclerosis: the Rotterdam relationship with fasting insulin. Acta Cardiol 1999; Study. Stroke 2001; 32: 454–460. 54: 277–282.

Journal of Human Hypertension Pulse wave velocity and pulse pressure EJ Kim et al 148 20 Tanaka H, DeSouza CA, Seals DR. Absence of age- predictor of total cardiovascular risk in hypertension. related increase in central arterial stiffness in physi- Hypertension 1998; 32: 983–988. cally active women. Arterioscler Thromb Vasc Biol 32 Franklin SS, Gustin WT, Wong ND, Larson MG, Weber 1998; 18: 127–132. MA, Kannel WB et al. Hemodynamic patterns of age- 21 Blacher J, Asmar R, Djane S, London GM, Safar ME. related changes in blood pressure. The Framingham Aortic pulse wave velocity as a marker of cardiovas- heart study. Circulation 1997; 96: 308–315. cular risk in hypertensive patients. Hypertension 1999; 33 Khattar RS, Swales JD, Dore C, Senior R, Lahiri A. 33: 1111–1117. Effect of aging on the prognostic significance of 22 Yasmin MB. Similarities and differences between ambulatory systolic, diastolic, and pulse pressure augmentation index and pulse wave velocity in in essential hypertension. Circulation 2001; 104: the assessment of arterial stiffness. Q J Med 1999; 92: 783–789. 595–600. 34 Franklin SS, Larson MG, Khan SA, Wong ND, Leip EP, 23 Sa Cunha R, Pannier B, Benetos A, Siche JP, London Kannel WB et al. Does the relation of blood pressure GM, Mallion JM et al. Association between high heart to coronary heart disease risk change with aging? rate and high arterial rigidity in normotensive The Framingham heart study. Circulation 2001; 103: and hypertensive subjects. J Hypertens 1997; 15: 1245–1249. 1423–1430. 35 Nichols WW. Clinical measurement of arterial stiffness 24 Stompor T, Rajzer M, Sulowicz W, Dembinska-Kiec A, obtained from noninvasive pressure waveforms. Am J Janda K, Kawecka-Jaszcz K et al. An association Hypertens 2005; 18: 3S–10S. between aortic pulse wave velocity, blood pressure 36 Mahmud A, Feely J. Effect of smoking on arterial and chronic inflammation in ESRD patients stiffness and pulse pressure amplification. Hyperten- on peritoneal dialysis. Int J Artif Organs 2003; 26: sion 2003; 41: 183–187. 188–195. 37 Rehill N, Beck CR, Yeo KR, Yeo WW. The effect of 25 Asmar R. Arterial Stiffness and Pulse Wave Velocity chronic tobacco smoking on arterial stiffness. Br J Clin Clinical Applications. Elsevier: Paris, 1999, pp 67, Pharmacol 2006; 61: 767–773. 101–102. 38 Kim JW, Park CG, Hong SJ, Park SM, Rha SW, Seo HS 26 Blacher J, Protogerou AD, Safar ME. Large artery et al. Acute and chronic effects of cigarette smoking on stiffness and antihypertensive agents. Curr Pharm arterial stiffness. Blood Press 2005; 14: 80–85. Des 2005; 11: 3317–3326. 39 Millasseau SC, Stewart AD, Patel SJ, Redwood SR, 27 Asmar RG, Brunel PC, Pannier BM, Lacolley PJ, Safar Chowienczyk PJ. Evaluation of carotid-femoral pulse ME. Arterial distensibility and ambulatory blood wave velocity: influence of timing algorithm and heart pressure monitoring in essential hypertension. Am J rate. Hypertension 2005; 45: 222–226. Cardiol 1988; 61: 1066–1070. 40 Wilkinson IB, Mohammad NH, Tyrrell S, Hall IR, Webb 28 Vardan S, Mookherjee S, Warner R, Smulyan H. DJ, Paul VE et al. Heart rate dependency of pulse Systolic hypertension. Direct and indirect BP measure- pressure amplification and arterial stiffness. Am J ments. Arch Intern Med 1983; 143: 935–938. Hypertens 2002; 15: 24–30. 29 de Simone G, Roman MJ, Koren MJ, Mensah GA, 41 Nichols WW, Conti CR, Walker WE, Milnor WR. Input Ganau A, Devereux RB. Stroke volume/pulse pressure impedance of the systemic circulation in man. Circ Res ratio and cardiovascular risk in arterial hypertension. 1977; 40: 451–458. Hypertension 1999; 33: 800–805. 42 Noble MI, Gabe IT, Trenchard D, Guz A. Blood pressure 30 Benetos A, Safar M, Rudnichi A, Smulyan H, Richard and flow in the ascending aorta of conscious dogs. JL, Ducimetieere P et al. Pulse pressure: a predictor of Cardiovasc Res 1967; 1: 9–20. long-term cardiovascular mortality in a French male 43 Stefanadis C, Dernellis J, Vavuranakis M, Tsiamis E, population. Hypertension 1997; 30: 1410–1415. Vlachopoulos C, Toutouzas K et al. Effects of ventri- 31 Verdecchia P, Schillaci G, Borgioni C, Ciucci A, Pede S, cular pacing-induced tachycardia on aortic mechanics Porcellati C. Ambulatory pulse pressure: a potent in man. Cardiovasc Res 1998; 39: 506–514.

Journal of Human Hypertension