http://www.kidney-international.org
& 2007 International Society of Nephrology
Division of Cardiology and Department of Radiology, Emory University School of Medicine, Atlanta, Georgia, USA; 2Department of
Nephrology, Ospedale San Paolo and University of Milan, Milan, Italy; 3Department of Nephrology, Ospedale Malpighi and University
of Bologna, Bologna, Italy; 4Department of Epidemiology, Tulane University, New Orleans, Louisiana, USA and 5Denver Nephrology
PC, Denver, Colorado, USA
original article
RESULTS
Age (years)
Male (%)
Nonwhite (%)
Dialysis vintage (years)
Current smoker (%)
55.2
50.4
60.3
4.2
18.6
52.9
53.1
57.1
4.3
17.2
61.7
42.4
69.7
3.7
22.6
0.003
0.215
0.195
0.969
0.317
History of
Hypertension (%)
Diabetes mellitus (%)
ASCVD (%)
CHF (%)
Dyslipidemia (%)
96.2
48.1
37.4
21.4
48.9
95.9
38.8
32.7
21.4
48.0
97.0
75.8
51.5
21.2
51.5
0.881
0.004
0.446
0.702
0.821
26.0
146.3
78.5
67.8
9.00
5.12
45.9
404
25.8
144.4
78.6
65.8
8.98
5.28
47.1
410
26.6
151.9
78.0
73.9
9.06
4.66
42.2
384
0.682
0.146
0.561
0.172
0.593
0.046
0.067
0.782
1800
Variable
P -value = 0.002
1852.0
2000
addressed this important question by performing simultaneously four tests in a cross-sectional cohort of hemodialysis
patients: PWV for vascular stiffness, echocardiography to
assess presence of valvular calcification, chest CT to measure
coronary artery and thoracic aorta calcification, and a lateral
lumbar X-ray to assess the presence of abdominal aorta
calcification.
PWV.12 m/s
1600
1400
1200
1000
800
600
P -value = 0.307
470.1
323.3
400
161.5
200
0
Overall
o12 m/s
X12 m/s
P-value
46.2
39.2
10.0
46.4
39.2
9.3
45.5
39.4
12.1
0.692
0.846
0.570
36.2
21.5
30.8
58.5
14.6
34.0
24.7
28.9
57.7
15.5
42.4
12.1
36.4
60.6
12.1
0.729
0.170
0.375
0.668
0.756
803
12.5
P -trend=0.044
11.5
11.1
10.7
10.5
9.5
9.5
8.5
<100
original article
.1000
100999
12.5
P -trend=0.001
10.4
10.5
9.5
8.9
8.5
<135
11.5
10.5
9.5
10.0
9.2
8.5
0
16
12.0
P-trend<0.001
1351924
.1925
11.5
11.5
12.5
P -trend=0.182
11.2
11.5
10.5
10.3
10.1
9.5
8.5
0
?7
Table 3 | Age and multivariate-adjusted difference in pulse wave velocity associated with higher vascular calcification
Level of coronary artery calcium score
o100
Mean age-adjusted PWV
Multivariate-adjusted PWV
100999
0.00 (ref)
0.00 (ref)
X1000
P-value
0.368
0.308
1351924
0.00 (ref)
0.00 (ref)
X1925
1.00 (0.84, 2.84)
1.65 (0.20, 3.51)
0.282
0.083
16
0.00 (ref)
0.00 (ref)
X7
1.75 (0.15,3.35)
2.34 (0.77, 3.90)
0.038
0.004
0.00 (ref)
0.00 (ref)
0.639
0.523
original article
5.0
4.0
1.45
1.58
(0.69, 3.03)
(0.82, 3.03)
3.0
2.0
P -trend=0.25
1.50
1.0
1.00 (ref.)
2.10
(0.81, 5.21)
1.46
(0.57, 3.71)
5.0
4.0
3.0
P -trend=0.11
2.0
1.50
1.0
0.75
1.00 (ref.)
0.75
<100
100999
<135
?1000
1.03
(0.52, 2.04)
5.0
4.0
1.42
(0.67, 3.01)
3.0
2.0
1.65
(0.82, 3.33)
P -trend=0.13
1.50
1.00 (ref.)
1.0
2.0
Prevalence rate ratio
1351924
?1925
0.89
(0.45, 1.76)
1.5
1.00 (ref.)
1.0
P -trend=0.72
0.75
0.50
0.75
0
16
?7
0.25
Figure 3 | Multivariate-adjusted prevalence rate ratio of PWV X12 m/s associated with increased vascular calcification. Prevalence rate
ratios are adjusted for age, race, diabetes mellitus, pulse pressure, systolic blood pressure, and use of calcium acetate.
such as aging (probably linked to atherosclerosis development and change in collagen content in the vessel wall15), and
deposition of advanced glycation end products in diabetes
mellitus. Earlier studies21,22 have indeed demonstrated that
use of breakers of advanced glycation end cross-links reduces
PWV. Additional mechanisms may be responsible for
increased PWV in CKD-5, namely the extensive amount of
calcification found in the vessel wall of these patients. Such
extensive calcification is because of both heavily calcified
atherosclerotic plaques23 and calcification of the muscular
media layer of the vessel wall.24 Calcification of the media
muscularis that occurs mainly in capacitative vessels25 is the
probable explanation for the very good correlation we
observed between aortic PWV and calcification of the aorta.
The association between aortic PWV and coronary artery
calcification, albeit weak, suggests that aortic PWV is a
marker for the development of atherosclerotic coronary
artery disease, as proposed in the general population.26
Congestive heart failure and sudden death are the most
frequent causes of cardiovascular death in hemodialysis,
followed by acute myocardial infarction, stroke, and
peripheral arterial disease (http://www.usrds.org/2006/ref/
H_morte_06.pdf). Increased aortic stiffness induces left
ventricular hypertrophy, which is accompanied by the
formation of islands of myocites among strands of fibrous
tissue, creating an optimal condition for induction of
reentrant arrhythmias.27,28 These two conditions, hypertrophy and fibrosis, may therefore predispose to the development of congestive heart failure and sudden death.
It has been shown that there exists a good correlation
between PWV and bone demineralization in CKD-5
Kidney International (2007) 71, 802807
original article
abdomen was obtained and the aorta was identified as the tubular
structure coursing in front of the anterior surface of the spine. We
utilized a semiquantitative scoring system assigning 13 points to
areas of calcification identified along the anterior or posterior
surface of the aorta extending from the 1st to the 4th lumbar
vertebra.36 The points were assigned as follows: 1 for a small 2 for a
moderate and 3 for a large size calcification according to the length
of each calcified plaque with respect to the craniocaudal length of
the closest vertebra. With this method, the score could vary from a
minimum of 0 to a maximum of 24 points. All X-rays were read by
two investigators (EF and AB) and a consensus was reached on the
interpretation of all films.
Echocardiography
Bi-dimensional echocardiographic studies were performed utilizing
Sequoia 512 (Siemens, Erlangen, Germany) or Vivid 7 (General
Electric, Milwaukee, WI, USA) equipment. Digital loops were
acquired in the long- and short-axis parasternal views, and the
apical four and two-chamber views and stored on magnetic optical
disks for future review. Aortic and mitral valve calcification was
simply assessed as present or absent without applying any
quantification method. All echocardiograms were read by two
experienced investigators (PR and AB) and a consensus was reached
on the interpretation of all tests.
Aorta PWV measurement
PWV was assessed by applanation tonometry with the Sphygmocor
Vx software (AtCor Medical, Sydney, Australia). We measured PWV
within 24 h from the midweek dialysis section after 5 min of bed
resting and this was done systematically in all patients. PWV was
derived using a standard methodology. The first step consisted of
measuring the distance between the sternal notch and the carotid
pulse. We proceeded to measure the distance between the sternal
notch and the femoral artery pulse, and subtracted the first from the
latter measurement. This provided an approximation of the distance
between the heart and the femoral artery. With the tonometer, we
then assessed the timing of the carotid and femoral arterial pulse
upstroke in relation to the R-wave on a simultaneously acquired
electrocardiogram. The time difference between the R-wave and
pressure upstroke at each arterial site was then computed by the
Sphygmocor Vx software and used in the calculation of conduction
velocity (velocity distance between the heart and femoral artery
divided by the time difference between R-wave and pressure
upstroke at each site). As no standard definition for elevated PWV
exists, high PWV was defined as the highest quartile of the
distribution (i.e., PWVX12 m/s). This cut point is consistent with a
finding by Blacher et al.,17 who showed a PWVX12 m/s to have a
significant negative prognostic impact on the survival of CKD-5
patients.
Statistical analyses
The characteristics of the study population are presented as means
for continuous variable and percentages, for the overall population,
and for participants with PWVo12 and X12 m/s, separately. Also,
the distribution of concomitant medication use for these groups was
calculated. Differences across PWV categories were obtained after
adjustment for age by linear regression and binomial regression for
continuous and dichotomous variables, respectively. The median
coronary artery and thoracic aorta calcium scores, separately, were
calculated for persons with PWVo12 and X12 m/s. Coronary
artery calcium scores were divided into three levels (o100, 100999,
Kidney International (2007) 71, 802807
original article
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
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