Doppler indexes of left ventricular systolic and diastolic function in relation to the arterial stiffness in a general population

(1)

Doppler indexes of left ventricular systolic and diastolic function in relation to the arterial stiffness in a general population

Supplemental Data

Supplemental methods

Study design and participants

From August 1985 until December 2005, we randomly recruited a family-based population sample (FLEMENGHO cohort) stratified by age and sex from a geographically defined area in northern Belgium as described elsewhere (1). Seven Belgian municipalities provided listings of all inhabitants sorted by address. Households, subjects living at the same address, were the sampling unit. They were numbered consecutively and a random number list was generated by a SAS randomisation function (SAS Institute, Car, NC). Households with a list matching number were invited. EPOGH recruited participants from 1999 until 2001. The EPOGH investigators were trained at the Studies Coordinating Centre (KU Leuven, Belgium) and applied the same protocol, questionnaires and follow-up procedures as used in the FLEMENGHO study. The FLEMENGHO and EPOGH studies received ethical approval. The initial response rate at enrolment was 75.0% (2). All subjects provided written informed consent.

The FLEMENGHO and EPOGH participants remained in follow-up. Four centers opted to perform echocardiographic phenotyping and to assess LV function by simultaneous use of TDI indexes and measurements of central hemodynamics. The current study population consisted of 1263 subjects, who were examined from June 2005 until September 2009. We excluded 30 subjects from analysis due to atrial fibrillation (n=6) or insufficient quality of LV Doppler indexes (n= 19) or central hemodynamics (n=5). Thus, the current analysis included

(2)

1233 participants: 745 FLEMENGHO participants (Noorderkempen, Belgium) and 488 EPOGH subjects examined in Gdańsk (n=136) and Kraków (n=235), Poland, and Mirano (n=117), Italy. Due to insufficient quality or absence of color Doppler myocardial images, we additionally discarded 352 subjects from the analysis of LV longitudinal strain and 418 subjects from the analysis of LV radial strain.

Echocardiography

To ensure steady state, echocardiography and measurements of peripheral and central blood pressures were obtained at the same day at the local examination centers after the subjects had rested for at least 15 min in the supine position. All participants refrained from smoking, heavy exercise and drinking alcohol or caffeinated beverages for at least 2h prior to the examination.

Data Acquisition

In each center, one experienced physician did the ultrasound examination using a Vivid7 Pro (GE Vingmed, Horten, Norway) interfaced with a 2.5- to 3.5-MHz phased-array probe, in accordance to a standardized protocol as previously described (3). With the subjects in partial left decubitus and breathing normally, the observer obtained standard 2D images along the parasternal long and short axis and from the apical 4-chamber, 2-chamber and long-axis views, while ECG was recorded simultaneously. M-mode echocardiograms of the LV were recorded from the parasternal long-axis view under control of the two-dimensional image. The ultrasound beam was positioned just below the mitral valve at the level of the posterior chordae tendineae. To record pulsed-wave Doppler LV mitral inflow velocities from the apical window, the observer positioned the Doppler sample volume at the mitral valve tips. Using Tissue Doppler Imaging (TDI), the observer recorded low-velocity, high-intensity myocardial signals at a high frame rate (>190 FPS), while adjusting the imaging angle to

(3)

ensure a parallel alignment of the ultrasound beam with the myocardial segment of interest.

From the apical window, the sonographer placed a 5-mm Doppler sample at the septal, lateral, inferior and posterior sites of the mitral annulus. All recordings lasted at least 5 cardiac cycles and were digitally stored for off-line analysis.

Off-Line Analysis

One experienced physician (T.K.) analyzed the digitally stored images, averaging 3 heart cycles for statistical analysis, using a workstation running the EchoPac version BT11.0.0 (GE Vingmed, Horten, Norway). The LV internal diameter and interventricular septal and

posterior wall thickness were measured at end-diastole from the 2 dimensionally guided M- mode tracing according to guidelines (4). When optimal orientation of M-mode ultrasound beam could not be obtained, the reader performed linear measurements on correctly oriented two-dimensional images. End-diastolic LV dimensions were used to calculate LV mass by an anatomically validated formula (5). LV mass index (LVMI) was LV mass divided by body surface area (BSA), calculated as body weight^0.425 (in kg) x body height^0.725 (in cm) x 0.007184. We measured left atrial (LA) dimensions in 3 orthogonal planes: the parasternal long, lateral, and supero-inferior axes. LA volume was calculated using the prolate-elipsoid method and was indexed to BSA (6). Doppler signal recorded at LV outflow tract (LVOT) from the apical window was used to measure peak LVOT velocity and its velocity time integral (VTI). Stroke volume was calculated from the pulsed wave Doppler velocity profile and the cross-sectional area at the LVOT.

Transmitral blood flow Doppler signals were used to measure peak early (E) and late (A) diastolic velocities and A flow duration. From pulsed-wave TDI recordings, we measured the systolic (s') and early (e') and late (a’) diastolic peak velocities of the mitral annulus displacement at 4 acquisition sites (septal, lateral, inferior and posterior). We calculated the E/e' ratio by dividing transmitral E peak by e' averaged from the 4 acquisition sites.

(4)

LV strain analysis

Based on color Doppler myocardial motion data, the one-dimensional longitudinal and radial regional strain rate and strain curves were calculated by comparing local myocardial velocity profiles using dedicated software as described previously (3). The SPEQLE package version 4.6.2 (KU Leuven, Belgium) allows M-mode tracking of the myocardium to ensure that the sample volume is maintained in the same anatomical position within the myocardial image throughout the cardiac cycle. To compute end-systolic strain, from here on referred to as strain, we averaged 3 consecutive measurements and used their absolute values. We calculated the radial strain of the inferolateral wall and the longitudinal strain of the inferior and inferolateral walls at the level of the posterior chordae tendineae by measuring the spatial velocity gradient over a computation area of 5 mm and 15 mm, respectively. Strain curves were obtained by integrating the mean strain rate profile over time. We used lateral averaging of 5 beams/pixels. The beginning and ending of the ejection phase were

determined from the simultaneously recorded ECG and the continuous-wave Doppler velocity trace at the level of the aortic valve. As reported previously, the interobserver reproducibility valued 15.8% and 18.3% for longitudinal and radial strain, respectively (3).

Reproducibility

To determine intra-observer reproducibility, the experienced physician analyzing the echocardiographic data (T.K.) analyzed the echocardiograms of 17 subjects twice. Intra- observer reproducibility coefficient of a measurement was the 2SD interval about the mean of the relative differences across pairwise readings. The intra-observer reproducibility was 2.2% for LV internal end-diastolic diameter, 4.6% for LV wall thickness and 4.3% for LV mass, whereas the intra-observer reproducibility for the tissue Doppler velocities ranged from 4.5% to 5.3% for e’ velocities and from 4.0% to 4.5% for a’ velocities across the four

(5)

sampling sites. Interobserver reproducibility for longitudinal and radial strain valued 15.8%

and 18.3%, respectively (3).

SphygmoCor Measurements

Brachial (peripheral) BP was the average of three consecutive readings obtained in supine position by a validated OMRON 705CP oscillometric sphygmomanometer (Omron Corp., Tokyo, Japan) at the end of the echocardiographic examination. A standard cuff of 22x12 cm with an inflatable bladder was used for subjects with an arm circumference of less than 32 cm. For greater arm circumferences, a cuff with a 35x15 cm bladder was used.

All arterial measurements were obtained by trained observers according to a standardized protocol (8), after the participant rested in the supine position for at least 15 min. During an 8-second period, they recorded the carotid, femoral and radial arterial

waveforms by applanation tonometry, using a high-fidelity SPC-301 micromanometer (Millar Instruments, Inc., Houston, TX, USA) interfaced with a laptop computer running the

SphygmoCor software version 7.1 (AtCor Medical Pty. Ltd., West Ryde, New South Wales, Australia). Recordings were discarded when the systolic or diastolic variability of consecutive waveforms exceeded 5% or when pulse wave signal was less than 80 mV. The pulse waves were calibrated by the supine brachial BP, which, as described before, was measured immediately before the tonometric recordings. From the radial signal, the SphygmoCor software calculates the aortic pulse wave by means of a validated generalized transfer function. The software returns the central systolic BP and the pressure at the first (P1) and second (P2) peak or shoulder of the central and radial waveforms. Central pulse pressure (cPP) was calculated as the difference between central systolic and diastolic pressure. Mean arterial blood pressure was calculated as diastolic blood pressure plus one third of pulse pressure. Augmentation pressure (AP) was the difference between P2 and P1 of the aortic pulse wave (Supplemental Figure S1). Distances were determined from the carotid sampling site to the suprasternal notch (distance A) and from the suprasternal notch to the femoral

(6)

artery (distance B). PWV distance was calculated as distance B minus distance A. Pulse transit time was defined as the time interval between initial increase in carotid and femoral waveforms and was averaged over 10 consecutive beats. Aortic PWV was calculated as the ratio of the pulse wave distance (in meters) to the transit time (in seconds).

References

(1) Kuznetsova T, Herbots L, López B, et al. Prevalence of left ventricular diastolic dysfunction in a general population. Circ Heart Fail 2009;2:105-112.

(2) Kloch-Badelek M, Kuznetsova T, Sakiewicz W, et al. Prevalence of left ventricular diastolic dysfunction in European populations based on cross-validated diagnostic thresholds.

Cardiovasc Ultrasound 2012;10:10.

(3) Kuznetsova T, Herbots L, Richart T, et al. Left ventricular strain and strain rate in a general population. Eur Heart J 2008;29:2014-2023.

(4) Gottdiener JS, Bednarz J, Devereux R, et al. American Society of Echocardiography recommendations for use of echocardiography in clinical trials. J Am Soc Echocardiogr 2004;17:1086-1119.

(5) Devereux RB, Alonso DR, Lutas EM, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986;57:450-458.

(6) Lang R, Bierig M, Devereux R, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a brang of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440-1463.

(7) Kuznetsova T, Thijs L, Knez J, Herbots L, Zhang Z, Staessen JA. Prognostic value of left ventricular diastolic dysfunction in a general population. J Am Heart Assoc 2014;3(3).

(8) Liu Y, Thijs L, Kuznetsova T, et al. Central systolic augmentation indexes and urinary sodium in a white population. Am J Hypertens 2013;26:95-103.

(7)

Supplemental Table S1. Echocardiographic characteristics of participants by age group

Characteristics

Age Q1 (<35 years)

(n=319)

Age Q2 (35-50 years)

(n=304)

Age Q3 (50-60 years)

(n=329)

Age Q4 (>60 years)

(n=281)

Conventional echocardiography

Left atrium volume index, ml/m² 18.8 ± 4.1 21.2 ± 4.9* 23.7 ± 5.4*† 26.0 ± 7.7*†‡

Relative wall thickness 0.34 ± 0.04 0.36 ± 0.06* 0.39 ± 0.06*† 0.41 ± 0.07*†‡

LV mass index, g/m² 80.0 ± 15.8 87.0 ± 19.5* 94.5 ± 20.3*† 103.1 ± 23.5*†‡

LV stroke volume, ml 78.1 ± 16.4 82.1 ± 16.6* 83.6 ± 17.4* 86.5 ± 17.0*†‡

Ejection fraction, % 62.1 ± 5.6 63.4 ± 5.8 63.7 ± 6.6* 63.6 ± 6.4

Doppler data

E peak, cm/s 83.0 ± 13.6 77.7 ± 15.1* 70.3 ± 67.1*† 67.7 ± 14.3*†‡

A peak, cm/s 48.4 ± 10.4 56.5 ± 12.5* 67.1 ± 13.5*† 77.2 ± 16.1*†‡

E/A ratio 1.79 ± 0.44 1.43 ± 0.39* 1.08 ± 0.26*† 0.91 ± 0.28*†‡

s’ peak#, cm/s 9.77 ± 1.36 9.17 ± 1.20* 8.49 ± 1.33*† 8.03 ± 1.29*†‡

e’ peak#, cm/s 15.2 ± 2.56 12.6 ± 2.5* 9.74 ± 2.22*† 8.02 ± 1.74*†‡

a’ peak#, cm/s 8.03 ± 1.68 9.61 ± 1.80* 10.6 ± 1.73*† 10.9 ± 1.91*†

E/e’ ratio# 5.55 ± 1.08 6.32 ± 1.34* 7.45 ± 1.87*† 8.75 ± 2.32*†‡

TDI Strain

Longitudinal⁺, % 22.4 ± 3.28 22.7 ± 3.16 21.8 ± 3.64*† 21.1 ± 4.15*†

Radial⁺, % 57.3 ± 11.0 59.2 ± 12.1 54.1 ± 12.7*† 50.9 ± 11.9*†‡

Values are mean (±SD). #Averaged of septum, lateral, inferior and posterior mitral annulus sites. ⁺Measurements of longitudinal and radial strain were available for 851 and 815 individuals, respectively. *P≤0.05 vs. age Q1; †P≤0.05 vs. age Q2; ‡P≤0.05 vs. age Q3. LV, left ventricle; TDI, Tissue Doppler Imaging.

(8)

Supplemental Table S2. Multivariable-adjusted association of transmitral Doppler velocities and their ratio with arterial characteristics

E (cm/s) A (cm/s) E/A

Component Additional adjustment

Parameter estimate (95% CI)

P value Parameter estimate (95% CI)

P value

AP (+10 mm Hg) LV mass index 2.10 (0.62, 3.58)

0.0056 2.62 (1.35, 3.88)

<0.0001 ─0.028 (─0.062, 0.0052)

0.10 LA volume index 1.96

(0.33, 3.58)

0.018 2.58 (1.19, 3.98)

0.0003 ─0.032 (─0.067, 0.0043)

0.08

cPP (+14 mm Hg) LV mass index 2.88 (1.78, 3.99)

<0.0001 2.44

(1.49, 3.39) <0.0001 0.024

(─0.002, 0.049) 0.07 LA volume index 2.58

(1.35, 3.81)

<0.0001 2.67 (1.62, 3.76)

<0.0001 0.017 (─0.011, 0.044)

0.23

PWV (+1.8 m/s) LV mass index ─0.32 (─1.44, 0.79)

0.57 0.29 (─0.67, 1.24)

0.56 ─0.004

(─0.028, 0.020)

0.77

LA volume index ─0.41 (─1.61, 0.80)

0.51 0.31 (─0.73, 1.34)

0.56 ─0.0007 (─0.026, 0.024)

0.96

Parameter estimates (95% confidence interval) indicate changes in transmitral Doppler velocities and E/A ratio associated with a 1 standard deviation increase in augmentation pressure (AP), pulse pressure (cPP) and pulse wave velocity (PWV). All parameter estimates were adjusted for family clusters, center, sex, age, BMI, heart rate, antihypertensive drug treatment and mean arterial pressure, while additionally adjusting for LV mass or LA volume index.

(9)

Supplemental Table S3. Multivariable-adjusted association of TDI velocities and E/e’ ratio with arterial characteristics

s’ (cm/s) e’ (cm/s) a’ (cm/s) E/e’

Component Additional adjustment

Parameter estimate (95% CI)

P value Parameter estimate (95% CI)

P value

AP (+10 mmHg) LV mass index ─0.19 (─0.31, ─0.06)

0.0029 ─0.064 (─0.271, 0.143)

0.54 ─0.10 (─0.26, 0.07)

0.25 0.32 (0.15, 0.48)

0.0002

LA volume index ─0.14 (─0.30, ─0.005)

0.042 ─0.014 (─0.241, 0.213)

0.91 ─0.11 (─0.30, 0.08)

0.25 0.24 (0.05, 0.42)

0.013

cPP (+14 mmHg) LV mass index 0.005 (─0.087, 0.098)

0.91 0.25 (0.10, 0.41)

0.0015 ─0.11 (─0.23, 0.02)

0.08 0.33 (0.20, 0.45)

<0.0001

LA volume index 0.015 (─0.088, 0.118)

0.78 0.24 (0.07, 0.41)

0.0064 ─0.13 (─0.27, 0.01)

0.07 0.31 (0.18, 0.46)

<0.0001

PWV (+1.8 m/s) LV mass index ─0.056 (─0.15, 0.037)

0.24 ─0.062 (─0.22, 0.092)

0.43 ─0.17 (─0.29, ─0.047)

0.0066 0.16 (0.033, 0.29)

0.014

LA volume index ─0.024 (─0.13, 0.077)

0.64 ─0.055 (─0.22, 0.11)

0.52 ─0.18 (─0.31, ─0.04)

0.011 0.13 (─0.005, 0.27)

0.058

Parameter estimates (95% confidence interval) indicate changes in TDI velocities and E/e’ ratio associated with a 1 standard deviation increase in augmentation pressure (AP), pulse pressure (cPP) and pulse wave velocity (PWV). All parameter estimates were adjusted for family clusters, center, sex, age, BMI, heart rate, antihypertensive drug treatment and mean arterial pressure, while additionally adjusting for LV mass or LA volume index.

(10)

Supplemental Table S4. Multivariable-adjusted association of transmitral Doppler velocities and their ratio with arterial characteristics by sex

E (cm/s) A (cm/s) E/A

Component Sex Parameter estimate (95% CI)

P value

AP (+10 mm Hg) Male 1.93

(─0.20, 4.07)

0.076 3.38 (1.58, 5.17)

0.0002 ─0.064 (─0.110, ─0.014)

0.013

Female 2.82 (0.84, 4.81)

0.0053 2.26

(0.55, 3.97)

0.0097 0.001 (─0.041, 0.043)

0.95

cPP (+14 mm Hg) Male 3.12

(1.47, 4.77)

0.0002 2.74 (1.35, 4.15)

0.0001 0.009 (─0.031, 0.048)

0.66

Female 2.72 (1.19, 4.25)

0.0005 2.24

(0.91, 3.56)

0.001 0.039 (0.006, 0.071)

0.019

PWV (+1.8 m/s) Male 0.036

(─1.52, 1.53)

0.99 0.057 (─1.21, 1.32)

0.93 ─0.006

(─0.049, 0.028)

0.72

Female ─1.13

(─2.70, 0.45)

0.16 0.22 (─1.16, 1.61)

0.75 ─0.004

(─0.038, 0.029)

0.80

Parameter estimates (95% confidence interval) indicate changes in transmitral Doppler velocities and E/A ratio associated with a 1 standard deviation increase in augmentation pressure (AP), central pulse pressure (cPP) and pulse wave velocity (PWV). All parameter estimates were adjusted for family clusters, center, age, BMI, heart rate, antihypertensive drug treatment and mean arterial pressure.

(11)

Supplemental Table S5. Multivariable-adjusted association of TDI velocities and E/e’ ratio with arterial characteristics by sex

s’ (cm/s) e’ (cm/s) a’ (cm/s) E/e’

Component Sex Parameter estimate (95% CI)

P value Parameter estimate (95% CI)

P value

AP (+10 mmHg) Male ─0.25 (─0.45, ─0.05)

0.015 ─0.06 (─0.37, 0.26)

0.72 ─0.08

(─0.33, 0.17)

0.53 0.23 (─0.01, 0.46)

0.057

Female ─0.11

(─0.26, 0.03)

0.12 ─0.13 (─0.39, 0.14)

0.35 ─0.12 (─0.33, 0.09)

0.26 0.45 (0.21, 0.69)

0.0003

cPP (+14 mmHg) Male 0.03 (─0.13, 0.18)

0.73 0.38 (0.14, 0.62)

0.002 ─0.08 (─0.28, 0.11)

0.43 0.22 (0.04, 0.40)

0.018

Female ─0.03 (─0.14, 0.08)

0.62 0.07 (─0.14, 0.28)

0.50 ─0.20 (─0.37, ─0.04)

0.013 0.46 (0.27, 0.64)

<0.0001

PWV (+1.8 m/s) Male ─0.08 (─0.22, 0.07)

0.31 0.07 (─0.15, 0.30)

0.53 ─0.19 (─0.37, 0.02)

0.033 0.05 (─0.12, 0.21)

0.59

Female ─0.06

(─0.18, 0.05)

0.27 ─0.20 (─0.40, 0.01)

0.064 ─0.15 (─0.32, 0.01)

0.067 0.22 (0.03, 0.41)

0.022

Parameter estimates (95% confidence interval) indicate changes in TDI velocities and E/e’ ratio associated with a 1 standard deviation increase in

augmentation pressure (AP), pulse pressure (cPP) and pulse wave velocity (PWV) by sex. All parameter estimates were adjusted for family clusters, center, age, BMI, heart rate, antihypertensive drug treatment and mean arterial pressure.

(12)

Supplemental Table S6. Relationship between left ventricular longitudinal and radial strain and mean arterial pressure and components of arterial wave reflection and stiffness

Parameter estimates (95% confidence interval) indicate changes in TDI longitudinal and radial strain associated with a 1 standard deviation increase in mean arterial pressure (MAP), augmentation pressure (AP), central pulse pressure (cPP) and pulse wave velocity (PWV). All parameter estimates were adjusted for for family clusters, center, sex, age, body mass index, heart rate and antihypertensive drug treatment. Adjusted Model 2 also included mean arterial pressure. LV indicates left ventricle.

LV longitudinal strain (%) LV radial strain (%) Component Model Parameter estimate

(95% CI)

P value

MAP (+13 mm Hg) Unadjusted -0.75 (-0.99, -0.50) <0.0001 -2.39 (-3.25, -1.51) <0.0001 Adjusted Model 1 -0.33 (-0.62, -0.04) 0.03 0.25 (-0.75, 1.26) 0.62 AP (+10 mm Hg) Unadjusted -0.38 (-0.63, -0.13) 0.003 -1.98 (-2.89, -1.09) <0.0001

Adjusted Model1 -0.25 (-0.63, 0.13) 0.20 0.19 (-1.53, 1.15) 0.78 Model 2 -0.04 (-0.48, 0.39) 0.85 -0.46 (-1.98, 1.06) 0.55 cPP (+14 mm Hg) Unadjusted -0.48 (-0.71, -0.25) <0.0001 -2.11 (-2.97,-1.25) <0.0001

Adjusted Model1 -0.25 (-0.53, 0.03) 0.08 -0.02 (-1.09, 1.00) 0.97 Model 2 -0.12 (-0.44, 0.20) 0.47 -0.18 (-1.33, 0.97) 0.76 PWV (+1.8 cm/s) Unadjusted -0.47 (-0.73, -0.21) 0.0003 -2.95 (-3.91, -1.99) <0.0001

Adjusted Model1 -0.06 (-0.39, 0.27) 0.71 -0.45 (-1.67, 0.78) 0.48 Model 2 -0.001 (-0.34, 0.34) 0.99 -0.55 (-1.80, 0.69) 0.38

(13)

Supplemental Figure S1

Schematic representation of the central (aortic) pressure waveform. From the central pressure waveform, augmentation pressure (AP) is calculated as the difference between the second (P2) and first (P1) peak or shoulder. cDBP indicates central diastolic blood pressure; cSBP, central systolic blood pressure; cPP, central pulse pressure.

(14)

-10 0 10 20 30 40 0

50 100 150

r=0.10 P=0.0003 Augmentation pressure (mmHg)

E peak (cm/s)

0 20 40 60 80 100 0

50 100 150

r=0.15 P<0.0001 cPP (mmHg)

E peak (cm/s)

-10 0 10 20 30 40 0

50 100 150

r=0.12 P<0.0001 Augmentation pressure (mmHg)

A peak (cm/s)

0 20 40 60 80 100 0

50 100 150

r=0.14 P<0.0001 cPP (mmHg)

A peak (cm/s)

-10 0 10 20 30 40 2.5

5.0 7.5 10.0 12.5 15.0

r=-0.084 P=0.0033 Augmentation pressure (mmHg)

s' (cm/s)

0 20 40 60 80 100 0

5 10 15 20 25

r=0.070 P=0.014 cPP (mmHg)

e' (cm/s)

0 20 40 60 80 100 0

5 10 15 20

r=-0.066 P=0.020 cPP (mmHg)

a' (cm/s)

0 5 10 15

0 5 10 15 20

r=-0.083 P=0.009 PWV (m/s)

a' (cm/s)

A. Transmitral Doppler velocities vs arterial properties

B. Tissue Doppler velocities vs arterial properties

Scatter plots of transmitral (A) and tissue (B) Doppler velocities vs. arterial properties in multivariable-adjusted analyses. The full and dotted lines represent the regression line and the 95% confidence interval, respectively. The regression slopes were standardized to the distribution of age, sex and anthropometric characteristics.

(15)

-10 0 10 20 30 40

0 5 10 15 20

r=0.13 P<0.0001

Augmentation pressure (mmHg)

E/e' ratio

0 20 40 60 80 100

0 5 10 15 20

r=0.17 P<0.0001

cPP (mmHg)

E/e' ratio

0.0 2.5 5.0 7.5 10.0 12.5 15.0 0

5 10 15 20

r=0.064 P=0.047

PWV (m/s)

E/e' ratio

Scatter plots of the E/e’ ratio vs. arterial properties in multivariable-adjusted analyses. The full and dotted lines represent the regression line and the 95%

confidence interval, respectively. The regression slopes were standardized to the distribution of age, sex and anthropometric characteristics.

(16)

6.0 8.5 11.0 13.5 16.0

Normal Impaired

relaxation ↑LV filling pressure

†

AP (mmHg)

6.0 8.5 11.0 13.5

16.0

*

Normal Impaired

AP (mmHg)

30 35 40 45 50

55 55

†

Normal Impaired

cPP (mm Hg)

30 35 40 45 50

Normal Impaired

cPP (mm Hg)

*

6.5 7.5 8.5

9.5 † ^9.5

n=474 n=54 n=68

Normal Impaired

PWV (m/s)

6.5 7.5 8.5

n=487 n=47 n=103

Normal Impaired

PWV (m/s)

Men Women

*

Means (95% CI) of AP, cPP and PWV by LV diastolic dysfunction group. Arterial characteristics were adjusted for center, sex, age, BMI, heart rate, MAP and anti-hypertensive treatment. LV diastolic function groups included normal LV diastolic function, impaired LV relaxation and elevated LV filling pressure. †P≤0.0087 vs normal diastolic function group in men; *P≤0.038 vs normal diastolic function in women. LV indicates left ventricular; AP, augmentation pressure; cPP, central pulse pressure; PWV, pulse wave velocity.

(17)

3D surface plots of the radial strain vs. arterial properties and age in multivariable-adjusted analyses. Radial strain and arterial properties (AP, cPP, PWV) were standardized to the distribution of sex, anthropometric characteristics, heart rate and mean arterial pressure. AP indicates augmentation pressure; cPP, central pulse pressure; PWV, pulse wave velocity.