Normative values and correlates of mean common carotid intima-media thickness in the Korean rural middle-aged population: the Atherosclerosis RIsk of Rural Areas iN Korea General Population (ARIRANG) study


Youn, Y.Jin.; Lee, N.Seok.; Kim, J-Young.; Lee, J-Won.; Sung, J-Kyung.; Ahn, S-Gyun.; You, B-Su.; Lee, S-Hwan.; Yoon, J.; Choe, K-Hoon.; Koh, S.Baek.; Park, J.Ku.

Journal of Korean Medical Science 26(3): 365-371

2011


Carotid intima-media thickness (CIMT) is considered as a surrogate marker for cardiovascular disease (CVD). We determined the normative value of CIMT and correlates of CVD risk factors and Framingham risk score (FRS) in Korean rural middle-aged population. We measured CIMT with a B-mode ultrasonography in 1,759 subjects, aged 40 to 70 yr, in a population-based cohort in Korea. A healthy reference sample (n = 433) without CVD, normal weight and normal metabolic parameters was selected to establish normative CIMT values. Correlates between CIMT and conventional CVD risk factors were assessed in the entire population. Mean values of CIMT (in mm) for healthy reference sample aged 40-49, 50-59, and 60-70 yr were 0.55, 0.59, and 0.66 for men and 0.48, 0.55, and 0.63 for women, respectively. In multivariate regression analysis, CIMT was correlated with older age, higher BMI, male gender, higher LDL-cholesterol level and history of diabetes mellitus. The mean CIMT was also correlated with FRS in both gender (r(2) = 0.043, P < 0.01 for men; r(2) = 0.142, P < 0.01 for women). We identified normative value of CIMT for the healthy Korean rural middle-aged population. The CIMT is associated with age, obesity, gender, LDL-cholesterol, diabetes mellitus and FRS.

ORIGINAL
ARTICLE
Cardiovascular
Disorders
JKMS
DOI:
10.3340ms.2011.26.3.365
J
Korean
Med
Sci
2011;
26:
365-371
Normative
Values
and
Correlates
of
Mean
Common
Carotid
Intima-Media
Thickness
in
the
Korean
Rural
Middle-aged
Population:
The
Atherosclerosis
Risk
of
Rural
Areas
iN
Korea
General
Population
(ARIRANG)
Study
Young
Jin
Yowl',
Nam
Seok
Lee',
Jang-Young
Kim'.',
Jun-Won
Lee',
Joong-Kyung
Sung',
Sung-Gyun
Ahn',
Byung-Su
You',
Seung-Hwan
Lee',
Junghan
Yoon
1
,
Kyung-Hoon
Choe
l
,
Sang
Baek
Kohl-
3
,
and
Jong
Ku
Parka
'Division
of
Cardiology,
Internal
Medicine,
Wonju
College
of
Medicine,
Yonsei
University,
Wonju;
'Institute
of
Genomic
Cohort,
Yonsei
University,
Wonju;
'Department
of
Preventive
Medicine
and
Institute
of
Occupational
Medicine,
Wonju
College
of
Medicine,
Yonsei
University,
Wonju,
Korea
Received:
17
August
2010
Accepted:
6
December
2010
Address
for
Correspondence:
Jang-Young
Kim,
MD
Division
of
Cardiology,
Department
of
Internal
Medicine,
Wonju
College
of
Medicine,
Yonsei
University,
162
Ilsan-dong,
Wonju
220-701,
Korea
Tel:
+82.33-741-0909,
Fax:
+82.33-741-1219
E-mail:
kimjy@yonsei.ac.kr
This
study
was
financially
supported
in
part
by
the
Project
For
Development
of
a
Community
Cohort
for
Health
Management
II
(2005-present)
of
the
Korea
Centers
for
Disease
Control
and
Prevention.
Carotid
intima-media
thickness
(CIMT)
is
considered
as
a
surrogate
marker
for
cardiovascular
disease
(CVD).
We
determined
the
normative
value
of
CIMT
and
correlates
of
CVD
risk
factors
and
Framingham
risk
score
(FRS)
in
Korean
rural
middle-aged
population.
We
measured
CIMT
with
a
B-mode
ultrasonography
in
1,759
subjects,
aged
40
to
70
yr,
in
a
population-based
cohort
in
Korea.
A
healthy
reference
sample
(n
=
433)
without
CVD,
normal
weight
and
normal
metabolic
parameters
was
selected
to
establish
normative
CIMT
values.
Correlates
between
CIMT
and
conventional
CVD
risk
factors
were
assessed
in
the
entire
population.
Mean
values
of
CIMT
(in
mm)
for
healthy
reference
sample
aged
40-49,
50-59,
and
60-70
yr
were
0.55,
0.59,
and
0.66
for
men
and
0.48,
0.55,
and
0.63
for
women,
respectively.
In
multivariate
regression
analysis,
CIMT
was
correlated
with
older
age,
higher
BMI,
male
gender,
higher
LDL-cholesterol
level
and
history
of
diabetes
mellitus.
The
mean
CIMT
was
also
correlated
with
FRS
in
both
gender
(r
2
=
0.043,
P
<
0.01
for
men;
r
2
=
0.142,
P
<
0.01
for
women).
We
identified
normative
value
of
CIMT
for
the
healthy
Korean
rural
middle-aged
population.
The
CIMT
is
associated
with
age,
obesity,
gender,
LDL-cholesterol,
diabetes
mellitus
and
FRS.
Key
Words:
Atherosclerosis;
Intima-Media
Thickness;
Reference
Values
INTRODUCTION
There
is
great
deal
of
interest
in
identifying
high-risk
asymptom-
atic
patients
in
the
general
population
to
prevent
mortality
and
morbidity
due
to
cardiovascular
disease
(CVD)
(1,
2).
Measure-
ment
of
carotid
intima-media
thickness
(CIMT)
with
a
B-mode
ultrasonography
is
a
valid
approach
for
identifying
and
quanti-
fying
the
presence
of
subclinical
atherosclerosis.
It
is
a
noninva-
sive,
sensitive,
and
reproducible
technique
for
identifying
and
quantifying
atherosclerotic
burden
and
CVD
risk
It
is
also
a
well-
validated
research
tool
that
has
been
translated
into
clinical
prac-
tice
(2-4).
The
American
Heart
Association
Writing
Group
3,
National
Cholesterol
Education
Program
Adult
Treatment
Panel
III
(NCEP-ATP
III),
the
American
Society
of
Echocardiography,
Screening
of
Heart
Attack
Prevention
and
Education
(SHAPE)
guideline,
European
Society
of
Hypertension
recommend
mea-
suring
CIMT
for
refining
CVD
risk
assessment
in
patients
with
subclinical
atherosclerosis
(5-8).
Normal
CIMT
values
should
be
defined
on
the
basis
of
age,
gender
and
race/ethnicity
within
a
general
healthy
population
(2).
Various
CVD
risk
stratification
schemes
have
been
devel-
oped
using
prospective
data
derived
predominantly
from
Cau-
casian
populations.
Given
the
ethnic
diversity
in
the
profile
of
CVD,
varied
risk
associations
and
different
levels
of
genetic-en-
vironmental
interactions
in
different
populations,
such
studies
performed
in
Caucasian
populations
cannot
be
directly
applied
to
Korean
populations.
Currently,
there
are
limited
data
for
the
normative
values
of
CIMT
in
the
general
East
Asian
population.
The
aim
of
this
study
was
to
determine
the
normative
values
of
CIMT
for
healthy
Korean
subjects
aged
40
to
70
yr,
based
on
a
cohort
in
Korea
and
assess
the
correlates
of
CVD
risk
factors
and
Framingham
risk
score
(FRS)
in
entire
population.
©
2011
The
Korean
Academy
of
Medical
Sciences.
This
is
an
Open
Access
article
distributed
under
the
terms
ofthe
Creative
Commons
Attribution
Non-Commercial
License
(http://creativecommons.org/licenses/by-nc/3.o)
which
permits
unrestricted
non-commercial
use,
distribution,
and
reproduction
in
any
medium,
provided
the
original
work
is
properly
cited.
pISSN
1011-8934
eISSN
1598-6357
1:11
11111
1
Lt
CCA
IMT
P
Avg
0.53
m
Lt
CCA
IMT
P
Max
0.72
m
Lt
CCA
IMT
P
Min
0.44
m
Lt
CCA
IMT
P
SD
0.07
mm
Lt
CCA
IMT
P
Pts
29
2—
JKMS
MATERIALS
AND
METHODS
Study
population
The
Atherosclerosis
RIsk
of
Rural
Area
iN
Korea
General
popula-
tion
(ARIRANG)
study
is
an
ongoing
cohort
study
of
cardiovas-
cular
and
metabolic
risk
factors
conducted
in
a
rural
area
in
Ko-
rea.
We
analyzed
1,716
subjects
(male:
40.4%)
aged
from
40
to
70
who
underwent
CIMT
measurements.
For
the
assessment
of
normative
CIMT
values,
we
selected
a
healthy
reference
sample
by
excluding
subjects
with
any
of
the
following
conditions:
1)
history
of
stroke
including
cerebral
in-
farction
or
transient
ischemic
attack,
myocardial
infarction,
or
heart
failure;
2)
hypertension
(systolic
blood
pressure
[SBP]
140
mmHg,
diastolic
blood
pressure
[DBP]
90
mmHg,
or
drug
treat-
ment
for
hypertension);
3)
diabetes
mellitus
(fasting
blood
glu-
cose
126
mg/dL
or
drug
treatment
for
diabetes
mellitus);
4)
total
cholesterol
220
mg/dL
or
pharmacologic
therapy
for
dys-
lipidemia;
5)
current
smoking;
and
6)
body
mass
index
(BMI)
30
kg/m
2
.
Laboratory
measurement
All
subjects
underwent
a
complete
cardiovascular
evaluation
after
8
hr
of
fasting,
including:
1) medical
history
for
previous
stroke,
myocardial
infarction,
heart
failure,
hypertension,
dia-
betes
mellitus,
dyslipidemia
or
smoking;
2)
anthropometric
analysis
including
height,
weight,
waist
circumference
and
hip
circumference;
3)
blood
pressure
measurement
(obtained
after
10
min
of
rest
in
the
sitting
position,
expressed
as
the
average
of
three
consecutive
measurements);
4)
serum
glucose
levels;
5)
plasma
lipids
profile
including
total
cholesterol,
triglyceride,
high-density
lipoprotein
cholesterol
(HDL-C),
and
low-density
lipoprotein
cholesterol
(LDL-C)
level;
6)
serum
high
sensitive
C-reactive
protein
(hs-CRP)
level.
Carotid
intima-media
thickness
measurement
The
measurement
was
carried
out
according
to
a
validated
pro-
cedure,
using
a
high-resolution
B-mode
ultrasonography
view
of
the
far
wall
of
the
common
carotid
artery,
with
an
ultrasonog-
raphy
system
(Vivid-7;
General
Electric-Vingmed,
Milwaukee,
WI,
USA)
and
a
phased
array
12-MHz
transducer
(9).
Patients
were
placed
comfortably
in
the
supine
position
with
the
head
directed
away
from
the
side
of
interest
and
the
neck
extended
slightly.
Thereafter,
the
proximal,
mid,
and
distal
com-
mon
carotid
artery
(CCA),
carotid
bifurcation,
and
proximal
por-
tion
of
internal
carotid
artery
were
systematically
interrogated
along
the
long-
and
short-axis
views.
Still
images
of
the
CCA
and
carotid
bifurcation
were
digitally
acquired.
The
CIMT
was
deter-
mined
at
the
far
wall
of
the
CCA
using
the
semi-automated
edge-
detection
software.
Using
this
software,
a
region
of
interest
(about
2
cm
in
length
and
1
cm
away
from
bifurcation)
was
placed
per-
pendicular
to
the
vessel
wall.
The
software
detects
the
lumen-
Youn
YJ,
et
al.
Normative
Values
for
Mean
CIMT
in
Korean
intima
and
the
media-adventitia
interface
at
the
far
wall
of
the
vessel
(Fig.
1).
Because
mean
values
are
more
reproducible,
we
use
the
mean
CIMT
(2).
Framingham
risk
score
Risk
assessment
for
determining
the
10-yr
risk
for
developing
CVD
is
carried
out
using
Framingham
risk
score.
The
risk
fac-
tors
included
in
the
Framingham
calculation
of
10-yr
risk
are:
age,
total
cholesterol,
HDL-C,
SBP,
treatment
for
hypertension,
and
cigarette
smoking.
The
calculation
was
performed
accord-
ing
to
the
ATP
III
guideline
(6).
Statistical
analysis
Data
for
continuous
variables
are
presented
as
the
mean
±
stan-
dard
deviation
and
proportions
are
presented
as
frequencies
and
percentages.
The
CIMT
data
between
the
different
age
groups
were
assessed
by
one-way
ANOVA
and
Post
Hoc
analysis
was
performed
with
Scheffe's
test.
We
evaluated
the
effect
of
tradi-
tional
risk
factors
on
CIMT
(as
a
continuous
variable)
using
lin-
ear
regression
both
with
and
without
adjustment
for
age
and
gender.
Multivariate
regression
analysis
was
performed
using
the
following
variables:
age,
gender,
SBP,
DBP,
triglycerides,
HDL-
C,
LDL-C,
hs-CRP
which
was
log-transformed
because
of
a
pos-
itive
skew
distribution,
BMI,
history
of
diabetes
mellitus
and
smoking
including
current
and
ex-smoking.
The
correlate
of
Framingham
risk
score
and
CIMT
was
assessed
by
simple
lin-
ear
regression
analysis
without
adjustment
of
other
factors.
All
tests
were
two-sided
and
P
<
0.05
was
considered
to
be
statisti-
cally
significant.
SPSS
for
Wmdows-version
15
(SPSS
Inc.,
USA)
was
used
for
analyses.
Ethics
statement
All
subjects
signed
informed
consent
forms
for
participation
in
this
study.
This
study
was
reviewed
and
approved
by
institution-
Fig.
1.
Measuring
Carotid
Intima-Media
Thickness
Measurement
using
a
high-resolu-
tion
B-mode
ultrasonography
view
of
the
far
wall
of
the
common
carotid
artery,
with
an
ultrasonography
system.
The
software
detects
the
lumen-intima
and
the
media-
adventitia
interface
at
the
far
wall
of
the
vessel.
366
http://jkms.org
DOI:
10.3346/jkms.2011.26.3.365
Youn
YJ,
et
al.
Normative
Values
for
Mean
CIMT
in
Korean
JKMS
al
review
board
of
Wonju
Christian
Hospital
(Approval
number:
CR105024).
were
presented
in
Table
1.
RESULTS
Baseline
characteristics
of
study
population
The
study
population
was
consisted
of
1,716
subjects
(693
[40.4%]
men)
aged
40
to
70
yr
(mean
age
55.1),
of
whom
433
(107
[24.7%]
men)
were
found
to
be
healthy
(Fig.
2).
In
entire
population,
men
were
older
and
have
more
frequent
history
of
stroke
and
diabe-
tes
mellitus.
Smoking
was
also
frequent
in
men.
Men
were
taller
and
heavier
than
women,
but
mean
BMI
was
not
different
be-
tween
two
genders.
SBP
and
DBP
were
higher
in
men.
Total
cholesterol
level
was
similar
but
triglyceride
level
was
higher
in
men.
On
contrary,
HDL-C
and
LDL-C
level
was
higher
in
wom-
en.
Higher
hs-CRP
level
was
observed
in
men.
Demographic,
clinical
and
laboratory
characteristics
of
the
study
population
1,716
subjects
(men:
40.4%)
who
underwent
carotid
ultrasound
from
ARIRANG
study
Excluded
(n
=
1,283)
(1)
Past
history
Stroke:
34
(2.0%)
Myocardial
infarction:
44
(2.8%)
Heart
failure:
12
(0.8%)
(2)
Hypertension
SBP
140
mmHg:
672
(39.2%)
DBP
90
mmHg:
503
(29.4%)
Medication:
399
(24.7%)
(3)
Diabetes
mellitus
Fasting
glucose
z
126
mg/dL:
117
(6.8%)
Medication:
149
(9.4%)
(4)
Dyslipidemia
Total
cholesterol
z
220
mg/dL:
483
(28.1%)
Medication:
151
(9.6%)
(5)
Current
smoking:
255
(14.9%)
(6)
Obesity
(BMI
z
30
kg/m
2
):
90
(5.2%)
433
healthy
subjects
(men:
24.7%)
Normative
value
of
CIMT
in
healthy
reference
sample
In
the
healthy
reference
sample,
mean
CIMT
was
higher
in
men
(0.60
±
0.12
mm
vs
0.53
±
0.10
mm,
P
<
0.01).
A
significant
cor-
relation
was
observed
between
age
and
mean
CIMT
for
both
men
(r
2
=
0.144,
P
<
0.01)
and
women
(r
2
=
0.321,
P
<
0.01).
Mean
values
of
CIMT
(in
mm)
in
healthy
subjects
aged
40-49,
50-59,
and
60-70
yr
were:
0.55
±
0.08,
0.59
±
0.13,
and
0.66
±
0.13
mm
for
men
and
0.48
±
0.07,
0.55
±
0.09,
and
0.63
±
0.12
mm
for
wom-
Table
1.
Baseline
characteristics
of
study
population
Men
(n
=
693)
Women
(n
=
1,023)
P
Age
(yr)
Past
history
56
±
8
54
±
8
<0.01
Stroke
26
(3.8)
8
(0.8)
<
0.01
Myocardial
infarction
24
(3.7)
20
(2.2)
0.06
Heart
failure
8
(1.3)
4
(0.4)
0.08
Hypertension
174
(26.7)
225
(23.4)
0.14
Dyslipidemia
57
(8.9)
94
(10.1)
0.49
Diabetes
mellitus
75
(11.6)
74
(7.9)
0.02
Smoking
<
0.01
Never
smoking
244
(35.2)
1,001
(97.8)
Ex-smoking
210
(30.3)
6
(0.6)
Current
smoking
239
(34.5)
16
(1.6)
Obesity*
19
(2.7)
71
(6.9)
<
0.01
Anthropometric
data
Height
(cm)
167
±
5
154
±
5
<
0.01
Weight
(kg)
69
±
9
59
±
9
<
0.01
Waist
circumference
(cm)
88
±
8
81
±9
<
0.01
Hip
circumference
(cm)
97
±
6
95
±
7
<
0.01
BMI
(kg/m
2
)
24.8
±
2.9
24.5
±
3.4
0.16
Blood
pressure
Systolic
(mmHg)
138
±
18
133
±
19
<
0.01
Diastolic
(mmHg)
85
±
11
80
±
11
<
0.01
Laboratory
finding
Fasting
glucose
(mg/dL)
103.0
±
26.9
94.1
±
16.8
<
0.01
Total
cholesterol
(mg/dL)
200.1
±
38.3
203.0
±
38.2
0.14
Triglyceride
(mg/dL)
177.5
±
123.2
133.1
±
85.1
<
0.01
HDL-cholesterol
(mg/dL)
42.4
±
10.1
46.5
±
11.1
<
0.01
LDL-cholesterol
(mg/dL)
113.1
±
31.9
117.3
±
32.2
<
0.01
hs-CRP
(mg/dL)
2.1
±
5.1
1.5
±
2.9
<
0.01
*Defined
BMI
z
30
kg/m
2
.
BMI,
body
mass
index;
HDL,
high-density
lipoprotein;
hs-
Fig.
2.
Flow
chart
describing
disposition
of
healthy
subjects
from
the
ARIRANG
study.
CRP,
high
sensitive
C-reactive
protein;
LDL,
low-density
lipoprotein.
Table
2.
The
mean
value
and
5th,
10th,
25th,
50th,
75th,
90th,
and
95th
percentiles
value
of
carotid
intima-media
thickness
among
men
and
women
according
to
age
group
Age
(yr)
No.
Mean
40-49
31
0.55
50-59
41
0.59
60-70
35
0.66
Total
107
0.60
Age
(yr)
No.
Mean
40-49
165
0.48
50-59
106
0.55
60-70
55
0.63
Total
326
0.53
CIMT,
carotid
intima-media
thickness.
Percentiles
value
of
mean
CIMT
(mm)
in
men
(n
=
107)
5%
10%
25%
50%
75%
90%
95%
0.40
0.43
0.51
0.55
0.62
0.67
0.69
0.44
0.46
0.50
0.57
0.62
0.76
0.94
0.50
0.52
0.58
0.64
0.70
0.85
0.99
0.44
0.48
0.52
0.57
0.65
0.75
0.89
Percentiles
value
of
mean
CIMT
(mm)
in
women
(n
=
326)
5%
10%
25%
50%
75%
90%
95%
0.39
0.41
0.44
0.47
0.52
0.57
0.61
0.43
0.45
0.48
0.54
0.60
0.67
0.75
0.46
0.51
0.55
0.62
0.69
0.80
0.95
0.41
0.43
0.45
0.51 0.57
0.67
0.72
DOI:
10.3346/jkms.2011.26.3.365
http://jkms.org
367
JKMS
Youn
YJ,
et
al.
Normative
Values
for
Mean
CIMT
in
Korean
Table
3.
Association
of
individual
atherosclerotic
risk
factors
with
increasing
CIMT
in
linear
regression
models
with
and
without
adjustment
for
age
and
gender
(n
=
1,716)
Without
adjustment
for
age
and
gender
After
adjustment
for
age
and
gender
ji
95%
CI
P
ji
95%
CI
Age
(per
10
yr)
0.075
0.067-0.083
<
0.01
Female
gender
-0.051
-0.065--0.037
<
0.01
SBP
(per
10
mmHg)
0.013
0.009-0.016
<
0.01
0.004
0.001-0.008
0.02
DBP
(per
10
mmHg)
0.013
0.007-0.019
<
0.01
0.006
0.000-0.011
0.05
Total
chol.
(per
10
mg/dL)
0.004
0.002-0.006
<
0.01
0.003
0.002-0.005
<
0.01
TG
(per
10
mg/dL)
0.001
0.001-0.002
<
0.01
0.001
0.000-0.001
0.01
HDL-C
(per
10
mg/dL)
-0.014
-0.020--0.007
<
0.01
-0.008
-0.014--0.002
<
0.01
LDL-C
(per
10
mg/dL)
0.006
0.004-0.008
<
0.01
0.005
0.003-0.007
<
0.01
hs-CRP
(natural
log)
0.020
0.014-0.026
<
0.01
0.007
0.002-0.013
0.01
BMI
(per
5
units)
0.045
0.034-0.055
<
0.01
0.037
0.027-0.047
<
0.01
History
of
DM
0.065
0.041-0.089
<
0.01
0.033
0.011-0.055
<
0.01
Smoking*
0.021
0.005-0.036
<
0.01
0.021
0.006-0.035
<
0.01
*Defined
as
current
smoking
or
ex-smoking.
BMI,
body
mass
index;
Chol.,
cholesterol;
CI,
confidence
interval;
DBP,
diastolic
blood
pressure;
DM,
diabetes
mellitus;
HDL-C,
high
density
lipoprotein
cholesterol;
hs-CRP;
high
sensitive
C-reactive
protein;
LDL-C,
low
d
ensity
lipoprotein
cholesterol;
SBP,
systolic
blood
pressure;
TG,
triglyceride.
Table
4.
Risk
factors
associated
with
increasing
CIMT
selected
on
stepwise
linear
regression
(n
=
1,716)
ji
95%
CI
r
2
=
0.235
Age
(per
10
yr)
0.63
0.054-0.071
<
0.01
Female
gender
-0.46
-0.064--0.028
<
0.01
SBP
(per
10
mmHg)
0.05
-0.001-0.001
0.08
DBP
(per
10
mmHg)
-0.05
-0.015-0.004
0.28
Triglycerides
(per
10
mg/dL)
0.000
-0.001-0.001
0.76
HDL-cholesterol
(per
10
mg/dL)
-0.004
-0.010--0.003
0.26
LDL-cholesterol
(per
10
mg/dL)
0.004
0.002-0.006
<
0.01
C-reactive
protein
(natural
log)
0.002
-0.004-0.008
0.52
BMI
(per
5
units)
0.026
0.015-0.036
<
0.01
History
of
diabetes
mellitus
0.026
0.004-0.048
0.02
Smoking*
-0.012
-0.032-0.007
0.213
*Defined
as
current
smoking
or
ex-smoking.
BMI,
body
mass
index;
CI,
confidence
interval;
DBP,
diastolic
blood
pressure;
HDL-C,
high
density
lipoprotein
cholesterol;
LDL-C,
low
density
lipoprotein
cholesterol;
SBP,
systolic
blood
pressure.
en,
respectively.
Mean
values
of
CIMT
in
men
were
higher
at
each
age
group
but not
in
subjects
aged
60-70
yr
(0.66
±
0.13
mm
vs
0.63
±
0.12
mm,
P
=
0.38).
Mean
CIMT
values
according
to
age
groups
were
presented
at
Fig.
3.
The
mean
value
and
5th,
10th,
25th,
50th,
75th,
90th,
and
95th
percentiles
value
of
CIMT
among
men
and
women
according
to
age
groups
were
present-
ed
in
Table
2.
Correlates
between
CIMT
and
conventional
CVD
risk
factors
In
the
entire
population,
CIMT
showed
associations
with
age,
gender,
SBP,
DBP,
total
cholesterol,
triglyceride,
HDL-C,
LDL-C,
BMI,
history
of
diabetes
and
smoking
by
simple
linear
regres-
sion.
After
adjustment
for
age
and
gender,
these
associations
were
persistent
(Table
3).
In
multivariate
regression
analysis,
in-
dependent
predictors
of
increasing
CIMT
were
older
age,
high-
er
BMI,
male
gender,
higher
LDL-C
level
and
history
of
diabetes
mellitus
(Table
4).
P=
0.38
P=
0.04
0.80
P<
0.01
Age
group
0.60
E
T
40-49
yr
50-59
yr
E
60-70
yr
0.40
C-3
cri
a)
0.20
Error
Bars:
+/-
2
SE
0.00
Men
Women
Fig.
3.
Estimation
of
mean
carotid
intima-media
thickness
according
to
age
groups
and
genders
in
healthy
reference
(men
=
107;
women
=
326).
CIMT,
carotid
intima-
media
thickness.
Correlates
between
CIMT
and
Framingham
risk
score
Linear
regression
between
increasing
CIMT
and
Framingham
risk
score
was
performed
in
the
entire
population.
A
significant
correlation
was
observed
for
both
men
(r
2
=
0.043,
P
<
0.01)
and
women
(r
2
=
0.152,
P
<
0.01)
but
weak
correlation
in
men
(Fig.
4).
DISCUSSION
We
present
normative
values
of
CIMT
for
healthy
Korean
rural
adults
aged
40-70
yr.
We
also
report
on
the
cross-sectional
asso-
ciations
between
increasing
CIMT
and
conventional
cardiovas-
cular
risk
factors
in
entire
sample.
In
addition,
we
present
the
correlation
CIMT
and
Framingham
risk
score
in
this
population.
The
Oslo
Ischemia
Study
showed
that
a
significant
number
of
participants
remain
asymptomatic
despite
significant
coro-
nary
artery
disease,
but
sudden
cardiac
death
frequently
occurs
at
the
first
presentation
of
coronary
heart
disease
(10).
Thus,
it
368
http://jkms.org
DOI:
10.3346/jkms.2011.26.3.365
0
0
°
8
8
0
0
0
8
0
e
8
0
0
0
6
8
0
®
0
p0000,,og
8
0 0
gieog
6
g
9
9
®
®
8
1
0
0
8
8
0
0
g
g
0
0
0
g-
1.20
0
1.00
2
1—
0.80
0.60
8
°
0.40
0
0 0
0
o
0
o
0
0
Youn
YJ,
et
al.
Normative
Values
for
Mean
CIMT
in
Korean
JKMS
1.40
-g-
1.20
E
1.00
E
.g
0.80
2
5
0.60
g
0.40
0.20
0
R
Sq
Linear
=
0.43
0
0
0
0
0
8
0
8
o
0
8
0
°
8
0
o
1.40
R
Sq
Linear
=
0.152
0
0
0
0
9
o
0
0
6
°
8
20
25
5
10
15
20
0
5
10
15
Framingham
risk
score
Framingham
risk
score
Fig.
4.
Correlation
between
carotid
intima-media
thickness
and
Framingham
risk
score
according
to
gender
(men
=
693;
women
=
1,023).
CIMT,
carotid
intima-media
thickness.
is
very
important
to
identify
subjects
who
are
in
subclinical
ath-
erosclerosis
and
initiate
primary
prevention
for
CVD.
The
extent
of
carotid
atherosclerosis
positively
correlates
with
the
severity
of
coronary
atherosclerosis
and
the
severity
of
CIMT
indepen-
dently
correlates
with
the
risk
of
major
cardiovascular
disease
such
as
transient
cerebral
ischemia,
stroke
and
coronary
events.
Therefore,
measurement
of
CIMT
with
B-mode
ultrasonography
is
a
valid,
noninvasive,
sensitive
and
reproducible
technique
(2).
Although
many
committees
and
studies
have
shown
the
im-
portance
of
CIMT
measurements,
there
is
not
enough
data
re-
garding
normal
CIMT
values,
especially
in
Koreans.
Recent
stud-
ies
including
the
Atherosclerosis
Risk
in
Communities
(ARIC)
and
Multi-Ethnic
Study
of
Atherosclerosis
(MESA)
have
showed
different
CIMT
values
according
to
age,
gender
and
geographi-
cal
origin,
and
therefore
normative
CIMT
values
should
be
de-
fined
based
on
these
factors
(2,
11).
The
American
Society
of
Echocardiography
recommends
population-specific
normative
data
according
to
age,
gender,
and
ethinicity
(2).
Since
data
from
Caucasian
populations
cannot
be
directly
applied
to
Korean
because
of
difference
of
genetic
and
environmental
factors,
the
normative
data
provided
for
CIMT
in
our
study
will
allow
the
application
of
CIMT
measurement
in
individual
subjects
from
this
ethnic
group.
Our
study
is
not
the
first
report
of
normative
CIMT
values
in
Korean.
Bae
et
al.
(12)
and
Cho
et
al.
(13)
already
reported
nor-
mative
CIMT
values
in
Korean.
But,
Cho
et
al.
did
not
use
the
semi-automated
edge-detection
method
for
measuring
CIMT
and
Bae
et
al.
used
subjects
who
had
visited
the
general
hospital
and
BM1
was
not
considered
in
the
criteria
for
healthy
subjects
(12,
13).
The
mean
CIMT
in
our
study
was
thinner
than
those
of
the
two
Korean
studies,
independent
of
age.
Difference
of
mean
CIMT
could
be
explained
that
our
study
was
based
on
a
cohort
and
used
very
strict
criteria
for
healthy
subjects.
The
statistical
difference
of
mean
CIMT
between
men
and
women
was
not
observed
in
subjects
aged
60-70
yr
despite
cor-
relation
of
increasing
CIMT
and
age
in
entire
population.
This
phenomenon
could
be
explained
by
menopause
in
females
and
this
finding
correlates
well
with
a
study
of
the
effect
of
meno-
pause
on
carotid
artery
remodeling
(14).
Since
the
National
Cholesterol
Education
Program
(NCEP)
Expert
Panel
(ATP
III)
recommends
measuring
CIMT
because
the
finding
of
an
elevated
CIMT
(e.g.,
75th
percentile
for
age
and
gender)
could
reclassify
a
person
with
multiple
risk
factors
to
a
higher
risk
category,
we
also
present
the
5th,
10th,
25th,
50th,
75th,
90th,
and
95th
percentiles
value
of
CIMT
among
men
and
women
(5,
6).
Further
evaluation
which
percentiles
of
value
should
be
used
for
cut-off
value
of
abnormal
CIMT
is
needed.
In
our
study,
the
mean
CIMT
was
significantly
correlated
with
age,
gender
and
other
cardiovascular
risk
factors
including
SBP,
DBP,
total
cholesterol,
triglyceride,
HDL-C,
LDL-C,
hs-CRP,
BM1,
history
of
diabetes
mellitus
and
smoking
by
simple
linear
regres-
sion.
But,
in
multivariate
analysis
using
stepwise
linear
regres-
sion,
only
age,
BM1,
gender,
LDL-C
and
history
of
diabetes
mel-
litus
were
correlated
with
increasing
CIMT
in
this
population.
We
could
explain
the
reason
for
this
result
as
following:
First,
there
might
be
the
potential
ethnic
differences
regarding
the
role
of
classic
versus
novel
risk
factor
as
determinants
of
carotid
atherosclerosis
and
cardiovascular
risk
Second,
because
meta-
bolic
components
clustered
closely
with
each
others,
multiple
collinearity
should
be
considered
to
accept
this
result.
To
con-
firm
correlates
with
CIMT,
further
studies
would
be
required.
We
evaluated
the
relationship
between
CIMT
and
Framing-
ham
risk
score
because
the
Framingham
risk
score
accurately
estimates
10-yr
CVD
risk
(2).
In
our
study,
CIMT
was
correlated
well
with
Framingham
risk
score
in
both
genders,
but
the
CIMT
of
men
showed
weak
correlation
with
Framingham
risk
score
compared
with
the
CIMT
of
women.
Because
relatively
small
number
of
men
and
lack
of
diabetes
mellitus
and
obesity
for
calculating
Framingham
risk
score
may
be
the
reasons
that
their
CIMT
values
showed
weak
correlate
with
FRS.
Another
reason
could
be
that
since
Framingham
risk
equations
are
derived
from
a
North
American
population,
consisting
of
mainly
whites,
it
is
DOI:
10.3346/jkms.2011.26.3.365
http://jkms.org
369
Jr
MS
not
dear
if
they
can
directly
be
extrapolated
to
the
Korean
pop-
ulation
and
some
concern
has
been
raised
over
the
fact
that
the
original
Framingham
risk
score
underestimated
risk
(15).
Wheth-
er
the
estimating
the
vascular
age
by
mean
of
measuring
the
CIMT
could
be
a
better
approach
for
calculating
CVD
risk
should
be
evaluated
with
the
long-term
follow-up
data.
Our
study
is
limited
by
its
cross-sectional
nature.
In
addition,
our
examination
for
CIMT
was
limited
to
measurement
of
either
side
of
common
carotid
arteries
and
lack
of
data
for
presence
of
carotid
plaque
which
is
another
important
marker
for
athero-
sclerosis.
Although
we
exclude
the
subjects
with
CVD
by
history
for
previous
stroke,
myocardial
infarction
or
heart
failure,
we
did
not
exclude
the
subjects
of
peripheral
artery
disease
because
of
lack
of
availability
of
the
data.
However,
pending
prospective
data,
our
results
for
normative
CIMT
value
provide
important
insights
into
the
determinants
of
subdinical
vascular
disease
in
this
population.
A
longitudinal
study
is
needed
for
a
better
eval-
uation
of
the
relationships
between
cardiovascular
risk
factors,
subdinical
atherosclerosis
and
the
risk
of
cardiovascular
events
in
this
population.
In
conclusion,
normative
CIMT
values
were
identified
for
the
healthy
Korean
rural
adults
aged
40-70
yr
using
a
B-mode
ultra-
sonography.
The
values
are
closely
associated
with
age,
obesity,
gender,
LDL-C
and
diabetes
mellitus.
Increasing
CIMT
is
cone-
lated
with
Framingham
risk
score
in
both
genders.
REFERENCES
1.
Taylor
AJ,
Merz
CN,
Udelson
JE.
34th
Bethesda
Conference:
executive
summary-can
atherosclerosis
imaging
techniques
improve
the
detection
of
patients
at
risk
for
ischemic
heart
disease?'
Am
Coll
Cardiol
2003;
41:
1860-2.
2.
Stein
JH,
Korcarz
CE,
Hurst
RT,
Lonn
E,
Kendall
CB,
Mohler
ER,
Najjar
SS,
Rembold
CM,
Post
WS;
American
Society
of
Echocardiography
Ca-
rotid
Intima-Media
Thickness
Task
Force.
Use
of
carotid
ultrasonogra-
phy
to
identify
subclinical
vascular
disease
and
evaluate
cardiovascular
disease
risk:
a
consensus
skitementfrom
the
American
Society
of
Echocar-
diography
Carotid
Intima-Media
Thickness
Task
Force.
Endorsed
by
the
Society
for
Vascular
Medicine.
JAm
Soc
Echocardiogr
2008;
21:
93-111.
3.
Stein
JH,
Fraizer
MC,
Aeschlimann
SE,
Nelson-Worel
J,
McBride
PE,
Douglas
PS.
Vascular
age:
integrating
carotid
intima-media
thickness
measurements
with
global
coronary
risk
assessment
Clin
Cardiol
2004;
27:
388-92.
4.
Gepner
AD,
Keevil
JG,
Wyman
RA,
Korcarz
CE,
Aeschlimann
SE,
Busse
KL,
Stein
JH.
Use
of
carotid
intima-media
thickness
and
vascular
age
to
modify
cardiovascular
risk
prediction.
JAm
Soc
Echocardiogr
2006;
19:
1170-4.
5.
Greenland
P,
Abrams
J,
Aurigemma
GP,
Bond
MG,
Clad(
LT,
Criqui
MH,
Crouse
JR
3rd,
Friedman
L,
Fuster
V,
Herrington
DM,
ICuller
LH,
Ridker
PM,
Roberts
WC,
Stanford
W,
Stone
N,
Swan
HJ,
Taubert
ICA,
Wexler
L.
Prevention
conference
V:
beyond
secondary
prevention;
identifying
the
high-risk
patient
for
primary
prevention:
noninvasive
tests
of
atheroscle-
rotic
burden:
Writing
Group
HI.
Circulation
2000;
101:
E16-22.
Youn
YJ,
et
al.
Normative
Values
for
Mean
CIMT
in
Korean
6.
National
Cholesterol
Education
Program
(NCEP)
Expert
Panel
on
De-
tection,
Evaluation,
and
Treatment
of
High
Blood
Cholesterol
in
Adults
(Adult
Treatment
Panel
III).
Third
report
of
the
National
Cholesterol
Ed-
ucation
Program
(NCEP)
Expert
Panel
on
Detection,
Evaluation,
and
Treatment
of
High
Blood
Cholesterol
in
Adults
(Adult
Treatment
Panel
III)
final
report.
Circulation
2002;106:
3143-421.
7.
Naghavi
M,
Falk
E,
Hecht
HS,
Jamieson
MJ,
ICaul
S,
Berman
D,
Fayad
Z,
Budoff
MJ,
Rumberger
J,
Naqvi
TZ,
Shaw
LJ,
Faergeman
0,
Cohn
J,
Bahr
R,
Koenig
W,
Demirovic
J,
luting
D,
Herrera
VL,
Badimon
J,
Goldstein
JA,
RudyY,
Airaksinen
J,
Schwartz
RS,
Riley
WA,
Mendes
RA,
Douglas
P,
Shah
PK;
SHAPE
Task
Force.
From
vulnerable
plaque
to
vulnerable
pa-
tient--Part
Ilk
executive
summary
of
the
Screening
for
Heart
Attack
Pre-
vention
and
Education
(SHAPE)
Task
Force
report
Am
I
Cardiol
2006;
98:
2H-15H.
8.
Mancia
G,
De
Backer
G,
DominiczakA,
Cifkova
R,
Fagard
R,
Germano
G,
Grassi
G,
HeagertyAM,
Kjeldsen
SE,
Laurent
S,
Narldewicz
K,
Ruilope
L,
Rynldewicz
A,
Schmieder
RE,
Struijker
Boudier
HA,
Zanchetd
A,
Va-
hanian
A,
Camm
J,
De
Caterina
R,
Dean
V,
Dickstein
K,
Filippatos
G,
Funck-Brentano
C,
Hellemans
I,
Kristensen
SD,
McGregor
K,
Sechtem
U,
Silber
S,
Tendera
M,
Widimslcy
P,
Zamorano
JL,
Kjeldsen
SE,
Erdine
S,
Narldewicz
K,
IGowsld
W,
Agabiti-Rosei
E,
Ambrosioni
E,
Cifkova
R,
DominiczakA,
Fagard
R,
HeagertyAM,
Laurent
S,
Lindholm
LH,
Man-
cia
G,
Manolis
A,
Nilsson
PM,
Redon
J,
Schmieder
RE,
Struijker-Boudi-
er
HA,
Viigimaa
M,
Filippatos
G,
Adamopoulos
S,
Agabiti-Rosei
E,
Am-
brosioni
E,
Bertomeu
V,
Clement
D,
Erdine
S,
Farsang
C,
Gaita
D,
Kio-
wski
W,
Lip
G,
Manion
JM,
Manolis
AJ,
Nilsson
PM,
O'Brien
E,
Poni-
kowski
P,
Redon
J,
Ruschitzka
F,
Tamargo
J,
van
Zwieten
P,
Viigimaa
M,
Waeber
B,
Williams
B,
Zamorano
JL,
The
task
force
for
the
management
of
arterial
hypertension
of
the
European
Society
of
Hypertension,
The
task
force
for
the
management
of
arterial
hypertension
of
the
European
Society
of
Cardiology.
2007
Guideline
for
the
management
of
arterial
hypertension:
The
Task
Force
for
the
Management
of
Arterial Hyperten-
sion
of
the
European
Society
of
Hypertension
(ESH)
and
of
the
European
Society
of
Cardiology
(ESC).
Eur
Heart
J
2007;
28:1462-536.
9.
O'Leary
DH,
Polak
JF,
ICronmal
RA,
Manolio
TA,
Burke
GL,
Wolfson
SK
Jr.
Carotid-artery
intima
and
media
thickness
as
a
risk
factor
for
myocar-
dial
infarction
and
stroke
in
older
adults
Cardiovascular
Health
Study
Collaborative
Research
Group.
N
Engl
I
Med
1999;
340:14-22.
10.
Thaulow
E,
Erikssen
J,
Sandvik
L,
Erikssen
G,
Jorgensen
L,
Cohn
PE
Ini-
tial
clinical
presentation
of
cardiac
disease
in
asymptomatic
men
with
silent
myocardial
ischemia
and
angiographically
documented
coronary
artery
disease
(the
Oslo
Ischemia
Study).
Am
J
Cardio11993;
72:
629-33.
11.
Chambless
LE,
Heiss
G,
Folsom
AR,
Folsom
AR,
Rosamond
W,
Szklo
M,
Sharrett
AR,
Clegg
DC.
Association
of
coronary
heart
disease
incidence
with
carotid
arterial
wall
thickness
and
major
risk
factors:
the
Atheroscle-
rosis
Risk
in
Communities
(ARIC)
study,
1987-1993.
Am
J
Epidemio11997;
146:
483-94.
12.
Bae
JH,
Seung
KB,
Jung
HO,
Kim
KY,
Yoo
KD,
Kim
CM,
Cho
SW,
Cho
SK,
Kim
YK,
Rhee
MY,
Cho
MC,
Kim
KS,
Jin
SW,
Lee
JM,
Kim
KS,
Hyun
DW,
Cho
YK,
Seong
IW,
Jeong
JO,
Park
SC,
Jeong
JY,
Woo
JT,
Koh
G,
Lim
SW.
Analysis
of
Korean
carotid
intima-media
thickness
in
Korean
healthy
subjects
and
patients
with
risk
factors:
Korea
multi-center
epidemiologi-
cal
study.
Korean
Circ
J
2005;
35:
513-24.
13.
Cho
YL,
Kim
DJ,
Kim
HD,
Choi
SH,
Kim
SK,
Kim
HJ,
Aim
CW,
Cha
BS,
Lim
SK,
Kim
KR,
Lee
HC,
Huh
KB.
Reference
values
of
carotid
intima-me-
370
http://jkms.org
DOI:
10.3346/jkms.2011.26.3.365
Youn
YJ,
et
al.
Normative
Values
for
Mean
CIMT
in
Korean
Jr
MS
dia
thickness
and
association
with
atherosclerotic
risk
factors
in
healthy
subjects
in
Korea.
Korean
I
Med
2003;
64:
275-83.
14.
Muscelli
E,
Kozakova
M,
Flyvbjerg
A,
Kyriakopoulou
K,
Astiarraga
BD,
Glintborg
D,
Konrad
T,
Favuzzi
A,
Petrie
J;
RISC
investigators.
The
effect
of
menopause
on
carotid
artery
remodeling,
insulin
sensitivity,
and
plas-
ma
adiponectin
in
healthy
women.
Am
I
Hypertens
2009;
22:
364-70.
15.
Brindle
PM,
McConnachie
A,
Upton
MN,
Hart
CL,
Davey
Smith
G,
Watt
GC.
The
accuracy
of
the
Framingham
risk-score
in
diffrrent
socioeconom-
ic
groups:
a
prospective
study.
Br
I
Gen
Pract
2005;
55:
838-45.
AUTHOR
SUMMARY
Normative
Values
and
Correlates
of
Mean
Common
Carotid
Intima-Media
Thickness
in
the
Korean
Rural
Middle-aged
Population:
The
Atherosclerosis
RIsk
of
Rural
Areas
iN
Korea
General
Population
(ARIRANG)
Study
Young
J
in
Youn,
Nam
Seok
Lee,
Jang-Young
Kim,
Jun-Won
Lee,
Joong-Kyung
Sung,
Sung-Gyun
Ahn,
Byung-Su
You,
Seung-Hwan
Lee,
Junghan
Yoon,
Kyung-Hoon
Choe,
Sang
Baek
Koh,
and
Jong
Ku
Park
Carotid
intima-media
thickness
(CIMT)
is
considered
as
a
surrogate
marker
for
cardiovascular
disease
(CVD).
We
determined
the
normative
value
of
CIMT
and
correlates
of
CVD
risk
factors
and
Framingham
risk
score
(FRS)
in
a
community
based
cohort
in
Korea.
We
measured
CIMT
with
a
B-mode
ultrasonography
in
a
consecutive
1,759
subjects,
aged
40
to
70
yr.
A
healthy
reference
subject
(n
=
433)
without
CVD,
normal
weight
and
normal
metabolic
parameters
was
selected
to
establish
normative
CIMT
values.
Correlates
between
CIMT
and
conventional
CVD
risk
factors
were
assessed
in
the
entire
population.
Mean
normative
values
of
CIMT
aged
40-49,
50-59
and
60-70
were
0.55,
0.59
and
0.66
mm
for
men
and
0.48,
0.55
and
0.63
mm
for
women,
respectively.
In
multivariate
regression
analysis,
CIMT
was
positively
correlated
with
age,
body
mass
index,
male,
LDL-cholesterol
level
and
history
of
diabetes
mellitus.
The
mean
CIMT
was
also
correlated
with
FRS
in
both
gender
(r
2
=
0.043,
P
<
0.01
for
men;
r
2
=
0.142,
P
<
0.01
for
women).
DOI:
10.3346/jkms.2011.26.3.365
http://jkms.org
371