Shinshu M ed J, 64⑶ :135〜146, 2016The Optimal Cut‑oﬀValue of Ankle Brachial Index for Screening
Cardiovascular Disease Risk in Hemodialysis Patients
Makoto HARADA , Wataru TSUKADA , Osamu TSUKADA
Koji HASHIMOTO and Yuji KAMIJO
1) Department of Nephrology, Shinshu University School of Medicine
2) Department of Nephrology and Urology, Jishyukai Ueda Kidney Clinic

Severe atherosclerosis and vascular calciﬁcation, causing coronary artery stenosis or peripheral arterydiseases (PAD),are frequently detected in hemodialysis (HD)patients.Ankle brachial index (ABI)is a usefulmarker for detecting PAD, as well as being predictive of the development of cardiovascular diseases (CVD).
However,obvious atherosclerotic vascular changes in HD patients might elevate the optimal cut‑oﬀvalue of
ABI for screening CVD over the conventional ABI cut‑oﬀvalue,0.9.Moreover,the ABI cut‑oﬀvalue may bealtered by the presence of diabetes mellitus (DM )in HD patients.This retrospective cohort study involved 110
patients on maintenance HD. The ABI cut‑oﬀ value predicting CVD in HD patients was determined byreceiver operating curve(ROC)analysis.ABI cut‑oﬀvalues were also compared in groups of subjects with andwithout DM.The ABI cut‑oﬀvalue predictive of CVD in all 110 HD patients was 0.960 (area under the curve［AUC］0.761,sensitivity 0.641,speciﬁcity 0.803).The cut‑oﬀvalue of ABI was 1.045 in the DM group (AUC 0.
735,sensitivity 0.813,speciﬁcity 0.606)and 0.960 in the non‑DM group (AUC 0.773,sensitivity 0.714,speciﬁcity
0.868). Kaplan‑Meier analysis showed that patients with ABI below the cut‑oﬀ values in each group weresigniﬁcantly more likely to develop CVD.The optimal ABI cut‑oﬀvalues for screening high‑risk HD patientswith CVD should be set at higher levels than the conventional cut‑oﬀvalue (0.9),and that the optimal cut‑oﬀ
values might diﬀer in HD patients with and without DM ,at 1.045 and 0.960,respectively.Shinshu Med J 64 :135 ―146, 2016
(Received for publication December 3, 2015;accepted in revised form January 15, 2016)
Key words:ankle brachial index (ABI), cardiovascular diseases, hemodialysis
Abbreviations:PAD, peripheral artery diseases;HD, hemodialysis;ABI, ankle brachial index ;CVD, cardiovasculardiseases;DM , diabetes mellitus;ROC, receiver operating curve;AUC, area under the curve

Introduction

major causes of death in HD patients,their detection
is diﬃcult,because theyprogress asymptomatically.

Severe atherosclerosis and vascular calciﬁcation,

Fewer HD patients with acute myocardial infarc-

which can lead to coronary artery stenosis and/ortion (AMI) had chest pain than non‑HD patients .

peripheral artery diseases (PAD), are frequently

Therefore,evaluation of disease severityof atheros-

detected in patients on hemodialysis (HD) .

clerosis could have prognostic implications in HD

Although these cardiovascular diseases (CVD) are

patients and has predictive value for CVDs. In
general, ankle brachial index (ABI) is a useful

Corresponding author:Yuji Kamijo
Department of Nephrology,Shinshu University School of
Medicine, 3‑1‑1 Asahi, M atsumoto, Nagano 390‑8621,

marker for detecting PAD,and for predicting future
CVDs including

myocardial infarction and. Recent reports showed that ABI cut‑oﬀ

JapanstrokeE‑mail:yujibeat＠shinshu‑u.ac.jp

values below 0.9 are useful for predicting future CV

No. 3, 2016135

Harada.Tsukada W .Tsukada O et al.

Fig. 1 Chart of the study ﬂow

events.In HD patients,however,the appropriate

agreed to participate in the study were enrolled.

ABI cut‑oﬀvalue predicting CVD is unknown. We

Patients were excluded if clinical data, including

hypothesized that it would be higher than that ofbackground clinical information,laboratory values,non‑HD patients, since dialysis patients are moremeasurements of ABI,cardio‑ankle vascular index

likely to develop severe arterial calciﬁcation .

(CAVI),and aortic arch calciﬁcation score(AoACS),

Furthermore, previous reports suggested thatwere missing.Patients with severe active infectious

diabetes mellitus (DM )causes more severe arterial

diseases or malignancies at the time of study entry,

calciﬁcation as well as atherosclerotic lesions thanand those who could not be followed up until CVD,

other diseases . The diﬃculties encountered indeath,or December 2013,were excluded.Of the 167

compressing calciﬁed arteries lead to increases inpatients, 57 were excluded.These patients included

blood pressure, suggesting that DM alters the ABI

38 in the geriatric medical care facility for the

cut‑oﬀvalue .

elderly who had dementia, were bedridden, andIn the HD patients including DM patients, sensi-

were in poor physical condition ; 17 who lacked

tivityof the ABI cut‑oﬀvalue below 0.9 for diagnos-

suﬃcient clinical information, such as past compli-

ing PAD was only 29.9 % .Thus,sensitivity of thecations or history of CVD ; and two who refused

ABI cut‑oﬀ value below 0.9 for screening CVD is

informed consent. Thus, 110 outpatients were

expected to be low in HD patients. This study wasenrolled (Fig. 1). The study protocol was approved

therefore designed to determine the optimal ABIby the institutional review board of the ethics com-cut‑oﬀ value for screening high risk HD patients

mittee of Shinshu University (approval number:with CVD,as well as to assess the eﬀects of DM on

1996)and conformed to the Declaration of Helsinki

ABI cut‑oﬀvalues.

as revised in 2008. Written informed consent was

M aterials and M ethods
Study design and subjects

obtained from each patient before study entry.
Baseline examinations
ABI was evaluated in each patient with a VaseraThis retrospective cohort study was designed toVS‑1500A (Fukuda Denshi, Tokyo, Japan) justdetermine the ABI cut‑oﬀvalue predictive of CVD

before the start of an HD session at the beginning ofin HD patients. Beginning in January 2010, 167

a week. Brieﬂy, patients were placed in a supine

patients were undergoing conventional maintenanceposition and their systolic blood pressure was mea-

HD in Jishyukai Ueda KidneyClinic,with almost all

sured in the brachial artery of the arm withoutof them screened by ABI. Stable outpatients who

vascular access and in the posterior tibial arteries

136

Shinshu Med J Vol.64

ABI in HD patientsof both legs. ABI was deﬁned as the ratio of blood

result of the hemorrhage, which was not reversiblepressure in each leg to the blood pressure in thewithin 24 hours.Aortic dissection was deﬁned as theupper arm,with the lower of the two values used for

acute onset of chest or back pain,and a diagnosis ofanalysis. CAVI was evaluated by the same auto-

dissected aorta on computed tomography (CT) fol-matic oscillometric cuﬀ measurement device. The

lowing surgery or medication. An aortic aneurysm

cuﬀs were applied to both upper arms and ankles.

was deﬁned by a dilated aorta diagnosed by CT

Electrodes were ﬁxed to each wrist and a heart

following an operation.The deﬁnitions of AP,AMI,

sound sensor was placed on the second intercostal

CI, and PAD were the same as above.

sternum.The methods of measuring and calculating

Statistical analysis

CAVI have been described . AoACS was calcu-

Continuous variables were compared by M ann‑lated as the number of sectors with aortic arch

Whitney U tests, and categorical variables by Fi-

calciﬁcation in plain chest X‑rays, divided into 16

sherʼ
s exact tests. Factors associated with CVD

circumferences . Blood samples obtained before

were evaluated by Cox proportional hazard regres-the start of an HD session at the beginning of asion analysis.Receiver operating curve (ROC)anal-

week were analyzed by BML, Inc, Japan.

ysis was used to evaluate the ABI cut‑oﬀ value

Endpoint and diagnosis of CVD

predictive of CVD in HD patients. To evaluate

The study endpoint was the incidence of CVD,

whether DM altered the ABI cut‑oﬀvalue,subjects

including ischemic heart diseases (IHDs),PAD,and

were separated into those with and without DM andcerebral infarction (CI). IHDs included angina

their cut‑oﬀvalues compared.Kaplan‑M eier analy-

pectoris (AP) and acute myocardial infarction

sis was used to determine the cumulative incidence(AM I).AP was deﬁned based on coronary angiogra-of CVD. All statistical analyses were performed

phy, followed by percutaneous coronary interven-using SPSS Statistics version 22.0J (IBM Corp.,

tion or coronary artery bypass graft surgery. AM I

Armonk, NY, USA), with statistical signiﬁcancewas deﬁned as symptoms of myocardial ischemia ;deﬁned as a p＜0.05.

new or presumed signiﬁcant ST‑segment to T‑
wave (ST‑T) changes or new left bundle branch
block on electrocardiograms;or an increase in the

Results
Baseline clinical characteristics

cardiac enzyme marker creatinine kinase M B type.

The baseline clinical characteristics of all 110

CI was deﬁned as an acute episode of focal or global

patients enrolled in this study are shown in Table 1.

neurological dysfunction caused by brain, spinal

Of these patients,39 experienced CVD during follow‑

cord, or retinal vascular injury as a result of theup, and 71 did not. Fifteen patients had IHD, 7

infarction,which was not reversible within 24 hours

patients CI,and 17 patients PAD.M edian ABI,rateand was symptomatic. PAD was deﬁned based onof chronic glomerulonephritis (CGN) and hemoglo-

peripheral angiography, followed by percutaneous

bin concentration were signiﬁcantlylower,while theperipheral artery intervention, an open surgicalrates of DM,past history of CVD,and deaths fromprocedure,or medication.The occurrence of a CVD

all causes were signiﬁcantly higher,in the CVD (＋)

for each patient was evaluated by more than two

than in the CVD (−)group. The median follow‑up

researchers.

period was 25 months. None of the other demo-

Past history of CVD was deﬁned as a previous
occurrence of AP, AMI, CI, cerebral hemorrhage,graphic and clinical characteristics diﬀeredsigniﬁcantly in the two groups.

PAD, aortic dissection, or aortic aneurysm. Cere-

Factors associated with the incidence of CVD

bral hemorrhage was deﬁned as an acute episode ofMultivariate Cox proportional hazard regression

focal or global neurological dysfunction caused byanalysis, performed to detect factors independently

brain, spinal cord, or retinal vascular injury as a

associated with the incidence of CVD, showed thatNo. 3, 2016137

Harada.Tsukada W .Tsukada O et al.
Table 1 Background data of all patients with or without CVD
N＝110
Age (years)
Male (n, %)BMI ＞25 kg/m (n, %)Duration of HD (months)
SBP (mmHg)
DBP (mmHg)
HR
ABI
CAVI
AoACS
Past history (n, %)Smoking
Diabetes mellitus
Hypertension
Hyperlipidemia
Past history of CVD
Cause of ESRD (n, %)Diabetes mellitus
Hypertension
CGN
PKD
other
Laboratory data
Hb (g/dl)
Alb (g/dl)
UN (mg/dl)
Cr (mg/dl)
UA (mg/dl)
TC (mg/dl)
HDL‑C (mg/dl)
LDL‑C (mg/dl)
TG (mg/dl)
Adjusted Ca (mg/dl)
iP (mg/dl)
Intact‑PTH (pg/ml)
HbA1c (NGSP %)Medications (n, %)ARB/ACEi
Ca blocker
beta blocker
Diuretics
CPBs
Sevelamer
LanthanVitamin D
Cinacalcet
Statinanti‑platelet agents
Events (n, %)All causes of death
All cases of CVD
IHD
CI
PAD
Asymptomatic CVD
Asymptomatic IHD
Asymptomatic PAD

138

CVD (−)(N＝71)

CVD (＋)(N＝39)

P ‑value

69
77
19
44
146
75
69
1.02
9.1
5

(30‑92)70.0%
17.2%(1‑225)(98‑221)(45‑105)(32‑107)(0.30‑1.29)(5.4‑17.0)(0‑16)

68
47
10
39
146
76
68
1.08
9.2
5

(30‑92)
66.2%
14.1%(1‑225)(105‑221)(48‑105)(47‑107)(0.40‑1.29)(5.4‑12.8)(0‑16)

70
30
9
46
146
72
71
0.84
9
7

(45‑90)76.9 %
23.1%(3‑156)(98‑205)(45‑98)(32‑101)(0.30‑1.21)(6.1‑17.0)(0‑15)

0.28
0.28
0.29
0.47
0.48
0.63
0.39
＜0.001
0.56
0.12

53
65
108
27
29

48.2%
59.1%
98.2%
24.5%
26.3%

34
33
71
18
12

47.9 %
46.5%
100.0%
25.4%
16.9 %

19
32
37
9
17

48.7%
82.1%
94.9 %
23.1%
43.6%

1.00
＜0.001
0.12
1.00
0.003

65
20
16
5
4

59.1%
18.2%
14.5%
4.5%
3.7%

33
14
16
4
4

46.5%
19.8%
22.5%
5.6%
5.6%

32
6
0
1
0

82.1%
15.4%
0.0%
2.5%
0.0%

＜0.001
0.62
0.001
0.65
0.30

10.6
3.7
58
10.1
6.9
146
40
85
95
9
5.2
93
5.7

(5.5‑13.4)(2.3‑4.3)(27‑106)(2.5‑16.4)(4.1‑10.9)(94‑233)(17‑86)(33‑157)(28‑697)(7.8‑10.9)(2.2‑10.6)(8‑497)(4.0‑8.1)

10.8
3.8
56
9.4
7.1
151
39
84
93
8.9
5.1
95
5.8

(5.5‑13.3)(2.3‑4.3)(27‑106)(2.5‑15.8)(4.4‑10.9)(94‑220)(17‑86)(36‑157)(28‑697)(7.8‑10.7)(2.2‑9.1)(19 ‑396)(4.0‑7.6)

10.1
3.7
59
10.4
6.8
133
41
85
102
9
5.2
73
5.7

(6.9 ‑13.4)(2.5‑4.2)(28‑93)(5.2‑16.4)(4.1‑10.4)(95‑233)(17‑84)(33‑137)(39 ‑245)(8.0‑10.9)(3.2‑10.6)(8‑497)(4.2‑8.1)

0.05
0.26
0.89
0.39
0.43
0.14
0.86
0.84
0.25
0.56
0.86
0.25
0.95

85
77
31
62
60
27
18
71
9
19
43

77.3%
70.0%
28.2%
56.4%
54.5%
24.5%
16.4%
64.5%
8.2%
17.3%
39.1%

57
51
18
38
40
13
10
46
5
12
23

80.3%
71.8%
25.4%
53.5%
56.3%
18.3%
14.1%
64.8%
7.0%
16.9 %
32.4%

28
26
13
24
20
14
8
25
4
7
20

71.8%
66.7%
33.3%
61.5%
51.3%
35.9 %
20.5%
64.1%
10.3%
17.9 %
51.3%

0.35
0.67
0.39
0.43
0.69
0.06
0.43
1.00
0.72
1.00
0.07

21
39
15
7
17
16
6
10

19.1%
35.5%
13.6%
6.4%
15.5%
14.5%
5.5%
9.1%

8
0
‑
‑
‑
0
‑
‑

11.3%
0.0%
‑
‑
‑
0.0%
‑
‑

13
39
15
7
17
16
6
10

33.3%
100.0%
38.5%
17.9 %
43.6%
41.0%
15.4%
25.6%

0.010
‑
‑
‑
‑
‑
‑
‑

Shinshu Med J Vol.64

ABI in HD patients
Table 2 Cox proportional hazard regression analysis for the factors associated with CVD
Univariate analysis

M ultivariate analysis

HR

95%CI

P valueHR

95%CI

P value

Age

1.018

0.18

1.026

1.508
0.998
3.058
0.068

0.28
0.53
0.001
＜0.001

1.432
0.994
2.018
0.131

(0.992‑1.061)(0.649 ‑3.157)(0.985‑1.002)(0.950‑4.288)(0.028‑0.619)

0.14

Sex (male)
Duration of HD
Past history of CVD
ABI(0.991‑1.046)(0.716‑3.178)(0.992‑1.004)(1.621‑5.771)(0.021‑0.223)

DM
Hb

3.702
0.855

0.002
0.17

3.024
0.972

Adjusted Ca
iP

1.229
1.068

0.38
0.58

1.591
0.997

(1.632‑8.396)(0.685‑1.068)(0.777‑1.946)(0.849 ‑1.343)(1.190‑7.688)(0.779 ‑1.213)(0.926‑2.735)(0.794‑1.252)

0.37
0.14
0.07
0.010
0.020
0.80
0.09
0.98

Signiﬁcant diﬀerences are indicated with asterisks ( p＜0.001, p＜0.01, p＜0.05).
ABI, ankle brachial index ;Ca, calcium ;CI, conﬁdence interval;CVD, cardiovascular diseases;DM ,diabetes mellitus;Hb, hemoglobin ;HD, hemodialysis;HR, hazard ratio ;iP, inorganic phosphorus.

ABI and the presence of DM were signiﬁcantlyof males;obese individuals (body mass index ＞25

associated with the incidence of CVD (Table 2).

kg/m ); patients with histories of smoking and

ABI cut‑oﬀvalue predictive of CVD between
patients with and without DM

CVD ;IHD ;and treatment with an angiotensin
receptor blocker (ARB) or angiotensin converting

The distribution of ABI is shown in Fig. 2. The

enzyme inhibitor (ACEi), were signiﬁcantly higher

median ABI was 1.02 (range 0.30‑1.29), with noin the DM than in the non‑DM group.ROC analysis

patient having an extremely high ABI (＞1.3). ROC

with Youdenʼs index showed that the ABI cut‑oﬀ

analysis with Youdenʼs index in all patients showedvalues predictive of CVD were 0.960 in the non‑DMan optimal ABI cut‑oﬀvalue predictive of CVD ofgroup (sensitivity 0.714, speciﬁcity 0.868; Fig. 3B)

0.960, with a sensitivity of 0.641 and a speciﬁcity ofand 1.045 in the DM group (sensitivity 0.813,

0.803 (Fig. 3A). We had hypothesized that the ABI

speciﬁcity 0.606; Fig. 3C). Table 4 shows the

cut‑oﬀ value might diﬀer in patients with anddiﬀerences in sensitivity,speciﬁcity,positive predic-

without DM . The baseline characteristics of thetive value (PPV) and negative predictive value

groups of patients with and without DM are shown(NPV)between the conventional ABI cut‑oﬀvaluein Table 3. Duration of HD treatment was(0.9)and the ABI cut‑oﬀvalues for our DM and non‑signiﬁcantly shorter and ABI signiﬁcantly lower in

DM groups in predicting CVD.Sensitivity and NPV

the DM than in the non‑DM group.The percentages

in all patient groups were higher using our proposed

Table 1

Data are presented as follows:continuous variables were expressed as median and range, categoricalvariables were expressed as n number and percentages. Signiﬁcant diﬀerences are indicated with asterisks( p＜0.001, p＜0.01, p＜0.05).
ABI, ankle brachial index ;Alb, albumin ;AoACS, aortic arch calciﬁcation score;ARB/ACEi,angiotensin
type receptor blocker/angiotensin converting enzyme inhibitor;BMI, body mass index ;Ca, calcium ;CAVI, cardio‑ankle vascular index ; CGN, chronic glomerulonephritis; CI, cerebral infarction ; CPBs,
calcium‑containing phosphate binders;Cr,creatinine;CVD,cardiovascular diseases;DBP,diastolic bloodpressure;ESRD, end stage renal disease;Hb, hemoglobin ;HbA1c, hemoglobin A1c;HD, hemodialysis;
HDL‑C, high‑density lipoprotein cholesterol;HR, heart rate;IHD, ischemic heart disease;Intact‑PTH,
intact‑parathyroid hormone; iP, inorganic phosphorus; LDL cholesterol, low‑density lipoprotein cholesterol;PAD, peripheral artery disease;PKD, polycystic kidney disease;SBP, systolic blood pressure;TC,
total cholesterol;TG, triglycerides;UA, uric acid ;UN, urea nitrogen.

No. 3, 2016139

Harada.Tsukada W .Tsukada O et al.

Fig. 2 Distribution of ABI among all patients

Fig. 3

Receiver operating curve analyses showing
ABI cut‑off values predictive of CVD in (A)all
patients, (B) non‑DM patients, and (C) DM
patients

140

Shinshu Med J Vol.64

ABI in HD patients

cut‑oﬀ values. Furthermore, separate analysis

advanced glycation end products triggering arterial

according to the presence of DM improved thecalciﬁcation . Therefore, the combination of DM

sensitivity over the whole patient analysis.Kaplan‑and HD may result in severe vascular calciﬁcation,

Meier analysis showed that patients with ABIs

increasing ABI.

lower than our cut‑oﬀ values in each group weremore likely to develop CVD (Fig. 4A‑C).

Low ABI has been shown to be a risk factor for
IHD,PAD,and CI,making ABI a useful predic-

tor of CVD. ABI is a ratio of blood pressure in the

Discussion

leg to that in the arm,with low ABI values indicat-

To our knowledge,this is the ﬁrst report to show

ing low leg blood pressure,in short,stenosis of a legthat ABI cut‑oﬀ values predictive of CVD in HD

artery. The mechanism by which simple ABI canpatients are altered by DM . The ABI cut‑oﬀvalue

predict CVD is unclear.However,because the diam-

predictive of PAD in HD patients has been reported

eter of the leg artery is larger than that of a coro-

to be 1.05 ,and ABI cut‑oﬀvalues should be set atnary or brain artery, stenosis of these arteries

higher levels in HD than in non‑HD patients.

precedes stenosis of the leg artery,because atheros-Moreover, the presence of DM alters the ABI cut‑

clerotic and vascular calciﬁc lesions, which causeoﬀ value diagnostic of PAD in non‑HD patients,

arterial stenosis,usually occur in systemic arteries.

being 1.04 and 1.00 in patients with and without DM ,Low ABI has been reported to be closely related torespectively . Setting the ABI cut‑oﬀvalue at 0.9

calciﬁcation of main arteries,such as the aorta andtherefore reduced its sensitivity in diagnosing PAD

iliac‑femoral artery, suggesting that systemic arte-in patients with DM

rial calciﬁcation occurs in patients with a low ABI.Most reports indicating that

ABI is predictive of CVD have set ABI cut‑oﬀ
values at ＜0.9

value .

. However, the distribution ofAmong the many non‑invasive methods reported

ABIs moved to higher levels in HD than in non‑HD

to be useful in evaluating the risk of CVD are ABI,

patients , suggesting that an ABI cut‑oﬀvalue ＜CAVI, pulse wave velocity, and AoACS

0.9 may be too low in HD patients. We found that

However,we found that CAVI and AoACS were notsetting the ABI cut‑oﬀ value at ＜0.9 reduced its

predictive of CVD.M oreover,ABI has been report-sensitivity and NPV for CVD in HD patients withed to be a stronger predictor of systemic atheros-

and without DM .In evaluating the risk of CVD,it isclerotic morbidity and mortality than pulse wave

important to use a highly sensitive marker with avelocity in HD patients . Taken together, thesehigh NPV.The ABI cut‑oﬀvalues proposed in HD

ﬁndings suggest that ABI may be useful in evaluat-

patients with and without DM had a higher sensitiv-

ing the risk of CVD in HD patients.

.

ity and NPV than the conventional cut‑oﬀvalue of

The rate of CVD events in this study might be

0.9. Furthermore, using the separate ABI cut‑oﬀ

higher than in previous Japanese reports. Carefulvalues according to the presence of DM improves

checking of all patients in this study to determine

the sensitivity of the predictive value for CVD. To

whether they had a CVD identiﬁed a high percent-screen the high‑risk HD patients with CVD, theseage (40%) with an asymptomatic CVD. CVDs in-

cut‑oﬀ values are more useful than conventional

cluded IHD (AP and AMI), CI, and PAD. Of the 15

ABI cut‑oﬀvalues below 0.9.

patients with an IHD, 14 had AP and one had an

Dialysis patients often experience vascular

AMI.The rate of AP in previous reports cannot be

calciﬁcation in arterial media due to chronicclearly determined, both because of diﬀerences inkidney disease‑mineral and bone disorder . The

the deﬁnition of AP or because the rate ofdiﬃculties encountered in compressing calciﬁed

asymptomatic AP was unclear.Several informativearteries lead to increases in blood pressure .DM isstudies have suggested that 20 to 35.3% ofalso a major cause of vascular calciﬁcation, withasymptomatic HD patients who underwent coro-

No. 3, 2016141

Harada.Tsukada W .Tsukada O et al.
Table 3 Background data of patients with or without diabetes mellitus
DM (−)(N＝45)

142

DM (＋)(N＝65)

P ‑valueAge (years)
Sex (male)
BMI ＞25 kg/m (n, %)Duration of HD (months)
SBP (mmHg)
DBP (mmHg)
HR
ABI
CAVI
AoACS
Past history (n, %)Smoking
Hypertension
Hyperlipidemia
Past history of CVD
Laboratory data
Hb (g/dl)
Alb (g/dl)
UN (mg/dl)
Cr (mg/dl)
UA (mg/dl)
TC (mg/dl)
HDL‑C (mg/dl)
LDL‑C (mg/dl)
TG (mg/dl)
Adjusted Ca (mg/dl)
iP (mg/dl)
Intact‑PTH (pg/ml)
HbA1c (%)
Medications (n, %)ARB/ACEi
Ca blocker
beta blocker
Diuretics
CPBs
Sevelamer
LanthanVitamin D
Cinacalcet
Statinanti‑platelet agents
Events (n, %)All causes of death
All cases of CVD
IHD
CI
PAD

72
25
3
54
140
74
67
1.06
9.1
5

(30‑90)55.6%
6.7%(1‑225)(98‑221)(45‑105)(47‑107)(0.30‑1.29)(5.4‑12.1)(0‑16)

66
52
16
39
149
75
72
0.99
9.1
6

(39 ‑92)
80.0%
24.6%
(1‑198)(109 ‑205)(50‑102)(32‑101)(0.40‑1.28)(5.9 ‑17.0)(0‑15)

0.06
0.010
0.020
0.034
0.10
0.89
0.11
0.047
0.71
0.51

9
44
8
6

20.0%
97.8%
17.8%
13.3%

44
64
19
23

67.8%
98.5%
29.2%
35.3%

＜0.001

10.7
3.8
57.4
10.4
7.1
147
45
88
91
9.1
5.2
95
‑

(6.9 ‑13.3)(2.5‑4.3)(32.4‑97.1)(2.5‑16.4)(4.1‑10.9)(95‑215)(17‑86)(33‑151)(28‑301)(7.9 ‑10.7)(2.2‑8.3)(12‑396)
‑

10.4
3.7
58.2
10.1
6.9
145
39
79
102
8.9
5
84
5.7

(5.5‑13.4)(2.3‑4.3)(26.9 ‑105.8)(3.7‑15.8)(4.4‑10.4)(94‑233)(23‑70)(36‑157)(39 ‑697)(7.8‑10.9)(2.7‑10.6)(8‑497)(4‑8.1)

0.53
0.11
0.59
0.69
0.85
0.96
0.11
0.17
0.07
0.46
0.92
0.26
‑

30
29
9
21
24
11
4
29
5
4
13

66.7%
64.4%
20.0%
46.7%
53.3%
24.4%
8.9 %
64.4%
11.1%
8.9 %
28.9 %

55
48
22
41
36
16
14
42
4
15
30

84.6%
73.8%
33.8%
63.0%
55.4%
24.6%
21.5%
64.6%
6.2%
23.1%
46.2%

0.037
0.30
0.13
0.12
0.85
1.00
0.12
1.00
0.48
0.07
0.08

6
7
2
2
3

13.3%
15.6%
4.4%
4.4%
6.7%

15
32
13
5
14

23.1%
49.2%
20.0%
7.7%
21.5%

0.23
＜0.001
0.023
0.70
0.06

Asymptomatic CVD
Asymptomatic IHD
Asymptomatic PAD

2
0
2

4.4%
0.0%
4.40%

14
6
8

21.5%
9.2%
12.3%

0.06
0.08
0.19

1.00
0.19
0.015

Shinshu Med J Vol.64

ABI in HD patients
Table 4

The relationship between ABI cut‑oﬀvalue and sensitivity, speciﬁcity, positive predictive value, and negative predictive value
Cut oﬀvalue ofABIsensitivity

speciﬁcity

PPV

NPV

0.9
0.960

0.538
0.641

0.887
0.803

0.724
0.641

0.778
0.800

0.9

0.571

0.947

0.571

0.921

0.960

0.714

0.868

0.500

0.943

0.9
1.045

0.531
0.813

0.848
0.606

0.773
0.667

0.651
0.769

All patients

DM (−)DM (＋)

ABI, ankle brachial index ; DM, diabetes mellitus; NPV, negative predictive value; PPV, positive
predictive value.

nary angiography had signiﬁcant coronary arterial

15.5% of our patients experienced PAD. However,stenosis in more than one vessel,with high percent-the deﬁnitions of PAD have been found to diﬀer

ages of patients with stenosis in multiple coronary

widely. Thus, the higher CVD event rate in ourarteries undergoing percutaneous coronary inter-study than in previous Japanese studies was likely

vention or coronary artery bypass graft sur-due to our inclusion of patients with asymptomatic

gery

CVD, amounting to 40% of all CVD patients, and.Based on this description,the incidence of

IHD in our patients would be not so high (13.6%).

the diﬀerences in deﬁnitions of CVD.

The incidence of CI has been reported to be 2.53 perThis study had several limitations, including its

100 person‑years . Estimating the number ofrelatively small sample size,the absence of patientspatients who experienced CI based on this inci-

with extremely high ABI (＞1.3), short follow‑up

dence, the number of patients, 110, and the medianperiod, and being a retrospective study. Patients

follow‑up period, 25 months, we estimated that 5.8

with extremely high ABI have been reported topatients would experience a CI. In actuality, sevenhave a poorer prognosis and a higher incidence ofof our patients experienced a CI, a ﬁnding that did

CVD than patients with high ABI, suggesting the

not diﬀer signiﬁcantly from the estimate. A previ-need to analyze patients with extremely high ABI

ous study assessing PAD found that,of 72 legs with

undergoing HD .Second,ﬁfty‑seven (34%)patientsor without symptoms, 12 (16.7%) had leg artery

were excluded from this single center study, withstenosis ＞75% above the knee . In comparison,

most excluded patients being bedridden and frail.

Table 3

Data are presented as follows:continuous variables were expressed as median and range, categoricalvariables were expressed as n number and percentages. Signiﬁcant diﬀerences are indicated with asterisks( p＜0.001, p＜0.05).
ABI, ankle brachial index ;Alb, albumin ;AoACS, aortic arch calciﬁcation score;ARB/ACEi,angiotensin
type receptor blocker/angiotensin converting enzyme inhibitor;BMI, body mass index ;Ca, calcium ;CAVI, cardio‑ankle vascular index ;CI, cerebral infarction ;CPBs, calcium‑containing phosphate binders;Cr, creatinine; CVD, cardiovascular diseases; DBP, diastolic blood pressure; Hb, hemoglobin ; HbA1c,
hemoglobin A1c;HD, hemodialysis;HDL‑C, high‑density lipoprotein cholesterol;HR, heart rate;IHD,
ischemic heart disease;Intact‑PTH, intact‑parathyroid hormone;iP, inorganic phosphorus;LDL cholesterol,low‑densitylipoprotein cholesterol;PAD,peripheral arterydisease;SBP,systolic blood pressure;TC,
total cholesterol;TG, triglycerides;UA, uric acid ;UN, urea nitrogen.

No. 3, 2016143

Harada.Tsukada W .Tsukada O et al.

Fig. 4 Kaplan‑M eier analysis of cumulative CVD(A)Assessment of all patients,showing that those with ABI ＜0.960 had a higher incidence of CVD
than those with ABI 0.960 (log‑rank test, p＜0.001).
(B) Analysis of non‑DM patients, showing that those with ABI ＜0.960 had a higher incidence of
CVD than those with ABI 0.960 (log‑rank test, p＝0.001).
(C)Analysis of DM patients showing that those with ABI ＜1.045 had a higher incidence of CVD
than those with ABI
144

1.045 (log‑rank test, p＝0.002).
Shinshu Med J Vol.64

ABI in HD patientsThird, the median follow‑up period was short (25patients with and without DM, at 1.045 and 0.960,

months), so we need to analyze a longer duration.

respectively.

Fourth,the current studywas a retrospective cohor-

Acknowledgmentst design. Therefore, large multicenter prospective
cohort studies are needed to properly clarify the
association between ABI and CVD.

We would like to thank Mr. Saika Yanagisawa
and the staﬀ of the Jishyukai Ueda Kidney Clinic

In conclusion,the current study suggests that thefor their support.

optimal ABI cut‑oﬀvalues for screening high‑risk

Disclosure

HD patients with CVD should be set at higher levels
than the conventional cut‑oﬀ value (0.9), and thatthe optimal cut‑oﬀ values might diﬀer in HD

The authors have declared that no conﬂicts ofinterest exist.

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