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Turkish Journal of Medical Sciences Turk J Med Sci

(2016) 46:
http://journals.tubitak.gov.tr/medical/
TBTAK
Research Article doi:10.3906/sag-1410-124

Diagnostic accuracy of ankle-brachial index measurement in peripheral arterial disease


in Turkish adults: a comparison with angiography
1, 1 2 1 3
Tolga DOAN *, lker TAI , Uur BOZLAR , Birol YILDIZ , Cengizhan AIKEL ,
1 4 1 1
Selim SAYIN , Celalettin GNAY , Erol ARSLAN , Kenan SALAM
1
Department of Internal Medicine, Glhane School of Medicine, Ankara, Turkey
2
Department of Radiology, Glhane School of Medicine, Ankara, Turkey
3
Department of Public Health, Glhane School of Medicine, Ankara, Turkey
4
Department of Cardiovascular Surgery, Glhane School of Medicine, Ankara, Turkey

Received: 26.10.2014 Accepted/Published Online: 06.12.2015 Final Version: 00.00.2016

Background/aim: This study aimed to determine the sensitivity and specificity of the ankle-brachial index (ABI) measurement in the
diagnosis of peripheral artery disease (PAD) using angiography as the gold standard in a group of Turkish subjects.
Materials and methods: In this single-center, cross-sectional, and observational study, subjects who had been evaluated using aorta
and lower extremity arterial imaging by angiography subsequently underwent an ABI measurement. Data related to anthropometrics,
cardiovascular risk factors, and blood biochemistry were also recorded. The sensitivity and specificity of a low ABI (0.9) were calculated
in comparison with angiography.
Results: A total of 57 patients (age: 59.1 15.9, male/female: 47/10) were enrolled. Diabetes mellitus, coronary artery disease, and
cerebrovascular disease existed in 40.4%, 42.1%, and 15.8% of the participants, respectively. Three or more cardiovascular risk factors
were present in 54.4%. The angiographic diagnostic method was computerized tomography angiography in 57.9%, digital subtraction
angiography in 38.6%, and magnetic resonance angiography in 3.5% of the subjects. Presence of PAD on angiography was recorded
in 55 of 57 participants. Calculated mean ABI value was 0.6 0.2 in the overall group, and a low ABI (0.9) was found in 82.5% (n =
47). When compared to angiography, the sensitivity of a low ABI test was found to be 83.6% and the specificity was 50%. A positive
predictive value of 97.9% was calculated. When an ABI of 0.95 was used as the diagnostic threshold, the sensitivity of the ABI test
increased to 90.9%.
Conclusion: We found the ABI measurement to be a reliable diagnostic method for lower extremity PAD when compared to the gold
standard of angiographic procedures. Establishing a higher cutoff value (0.95) may improve the diagnostic power of the test in Turkish
patients.

Key words: Ankle-brachial index, peripheral arterial disease, sensitivity, specificity, angiography

1. Introduction has emerged as a powerful, noninvasive diagnostic test


Peripheral artery disease (PAD) is associated with an option in the identification of the disease (4,5).
increased risk of morbidity and death (1). Lower extremity Currently known sensitivity and specificity data regarding
PAD prevalence was reported as 20% in a multicenter ABI measurement mostly originate from the United
survey among Turkish adults aged 50 years or older States, and ethnicity-based variations in ABI are largely
having moderate to high cardiovascular risk (2). However, unknown. Moreover, the worldwide frequency of PAD
a recent study from our clinic showed a frequency of as detected by ABI varies markedly across countries and
PAD around 5% among internal medicine outpatients regions, suggesting that the diagnostic accuracy of ABI
(3). Nonetheless, awareness, detection, treatment, and measurement may also differ. Therefore, the main objective
prevention of a vascular disease with a prevalence of of this research project was to evaluate the sensitivity
5%20% are particularly important. Although a definite and specificity of a low ABI value based on angiography
diagnosis of PAD can only be made using angiographic findings in subjects with suspected lower extremity arterial
procedures, the ankle-brachial index (ABI) measurement stenosis.
* Correspondence: dr_tolgadogan94@yahoo.com
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2. Materials and methods ABI was calculated according to the Trans-Atlantic


2.1. Study population Inter-Society Consensus Document on Management of
This was a single-center, cross-sectional, and observational Peripheral Arterial Disease (TASC II) recommendations
study conducted at the Glhane Military Medical (4). First, ABI was calculated separately for the right and
Academys cardiovascular surgery, geriatrics, and internal left limbs. The highest reading in either the anterior tibial
medicine clinics between March 2012 and May 2013. artery or the posterior tibial artery in each lower extremity
The participants were selected among outpatients and was divided by the highest brachial artery reading (right
inpatients referred to the cardiovascular surgery clinic of or left). The lower one of the right and left ABI values was
the institution. They were ordered routine angiography considered as the final ABI result.
due to a clinical judgement or a suspicious arterial 2.4. Categorical definitions of ABI
stenosis in the ultrasonographic evaluation, regardless Subjects with an ABI value of 0.90 were considered to
of the presence or absence of symptoms. Because of the have PAD (4). In addition, participants were also classified
observational study design the decision of angiography was into four other ABI categories: 0.91 to 1 borderline, 1.0
made before enrollment. The main inclusion criteria were to 1.1 low normal, 1.10 to 1.4 normal, and >1.4 high
having received angiography for aorta and lower extremity (7,8).
arterial system short before enrollment and having no 2.5. Angiographic assessments and radiological
extremity amputation. The presence of cancer or any other classification
terminal illness, and any condition that prevented giving Computerized tomography angiography (CTA), digital
signed, informed consent, were the exclusion criteria. subtraction angiography (DSA), and magnetic resonance
2.2. Data collection arteriography (MRA) were the angiographic procedures
As the main procedure of this study, all included subjects performed to identify PAD. Anatomical classification was
underwent an ABI measurement following angiography. done by an experienced radiologist through reexamination
Demographic and anthropometric data including age,
of imaging records of patients who were diagnosed with
height, body mass index, waist circumference, and hip
PAD by angiography. Locations of stenoses were divided
circumference measurements were recorded on a standard
into 3 main groups: aortoiliac, femoropopliteal, and
chart. Smoking status, presence of hypertension, diabetes
tibioperoneal (9). Aortic stenoses in the aortoiliac group
mellitus, dyslipidemia, coronary artery disease (CAD),
were indicated separately. The degree of any stenosis
cerebrovascular disease or stroke, and current medications
was categorized into two categories: between 0% and
were also recorded. Blood test results obtained in the past
49%, indicating the absence of PAD, and 50% and above,
2 months, including complete blood count, glucose, renal
indicating the presence of PAD.
and liver function tests, and lipid profile, were recorded
from the hospital or the patients self-records. The total 2.6. Statistical analyses
number of major cardiovascular risk factors including Commercially available SPSS software (version 15.0,
diabetes mellitus, dyslipidemia, hypertension, obesity, age, SPSS Inc., Chicago, Illinois) was used for statistical
and cigarette smoking were determined for each patient analyses. Descriptive data were reported as percentages
within four categories as none, one risk factor, two risk for categorical variables and as mean standard deviation
factors, and 3 risk factors. for continuous data. The chi-square test or Fischers exact
2.3. The ankle-brachial index test were used for comparisons of categorical variables.
The ABI measurement was performed using hand- Normality of distribution was tested by the one-sample
held Doppler (Hadeco, Japan) and four standard, fully KolmogorovSmirnov test. Comparisons between
calibrated sphygmomanometers with a Velcro cuff (12 groups were performed using the MannWhitney U test.
cm in size, ERKA, D-83646, Germany). With the patient Correlations were tested using the Pearson or Spearman
in supine position, after a resting period of at least 5 tests where appropriate. P < 0.05 was considered
min, the systolic blood pressure readings were obtained statistically significant. Two different ABI cut-off values
bilaterally from the brachial arteries, anterior tibial were separately tested: 0.90 and 0.95. The ratio of
arteries, and posterior tibial arteries. The first flow sound the detection of PAD as sensitivity and the ratio of the
heard while deflating the cuff was recorded as the target detection of non-PAD as specificity were finally calculated.
reading. Two cycles of measurements were performed
starting from the right arm followed by the right leg, left 3. Results
leg, and left arm. The mean of two readings was used for 3.1. Demographics, clinical characteristics, and
each pulse in the calculation of ABI. Previously developed laboratory findings
improved standardization facilities were used during all A total of 60 patients were initially enrolled, and 57 of them
measurements (6). ABI was measured by an observer (mean age: 59.1 15.9 years, males: 82.5%) were included
blinded to the result of angiography. in the analyses. Three patients were excluded because of

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incomplete angiography images. Basic characteristics of Table 1. Demographic characteristics and laboratory findings.
the study population are presented in Table 1.
Hypertension was present in 27 (47.4%) patients, diabetes Variable Mean SD (minmax)
mellitus in 23 (40.4%), obesity in 6 (10.5%; BMI 30),
dyslipidemia in 33 (57.9%), CAD in 24 (42.1%), and Age (years) 59.1 15.9 (2082)
cerebrovascular disease in 9 (15.8%). Smoking was Sex, male, n (%) 47 82.5
reported in 26 (45%) patients, or in 47 (82.5%) when ex- Anthropometrics Mean SD (minmax)
smokers were included. A total of 45 patients (80.4%) Height (cm) 169.6 9.1 (153185)
were under treatment with cardiovascular medicines, 20 Body weight (kg) 74.0 11.4 (52100)
patients (35.7%) were on antidiabetic drugs, 41 patients
Body mass index (kg/m ) 2
25.9 4.3 (16.737.5)
(73.2%) were taking antithrombotics or warfarin, and 6
patients (10.7%) were on psychiatric medications. Waist circumference (cm) 93.8 12.6 (65137)
3.2. Risk factors for cardiovascular disease Hip circumference (cm) 98.0 10.6 (78147)
The total number of male patients aged >45 years and Waist to hip ratio 1.0 0.8 (0.81.2)
female patients aged >55 years was 43 (75.4%). Nine Blood tests
patients (15.8%) had none or a single risk factor, 17 Hemoglobin (g/dL) 13.9 4.9 (8.017.1)
(29.8%) had 2 risk factors, and 31 (54.4%) had 3 or more
Leukocyte (103/L) 7.5 2.2 (3.212.8)
risk factors.
3.3. ABI vs. angiographic diagnosis of PAD MCV (fL) 84.7 12.1 (56104)
The mean ABI value was 0.6 0.2 in the whole study group, Platelets (103/L) 273.8 96.1 (69523)
with no sex difference (ABI: 0.6 0.2 in males vs. 0.6 0.3 Sedimentation (mm/h) 28.0 29.3 (2131)
in females). According to the predefined ABI classification Glucose (mg/dL) 126.1 67.8 (59340)
(see Section 2), 82.5% of the patients had PAD, 12.3% had Urea (mg/dL) 47.4 32.3 (12172)
a borderline value, 1.8% had a low normal ABI, and 3.5%
Creatinine (mg/dL) 1.3 1.2 (0.68.8)
had a normal ABI (Table 2). The number of subjects who
were classified as having severe PAD with an ABI value of AST (U/L) 20.1 6.2 (1146)
0.4 was 7 (12.3%). There was no correlation between ABI ALT (U/L) 17.4 8.2 (753)
values and laboratory results. GGT (U/L) 37.4 36.5 (7192)
All participants had been evaluated by at least one Total cholesterol (mg/dL) 180.5 48.3 (67277)
angiographic diagnostic method; 33 patients (57.9%) Triglyceride (mg/dL) 149.2 120.5 (40471)
were evaluated by CTA, 22 patients (38.6%) by DSA,
HDL-cholesterol (mg/dL) 47.0 25.3 (2067)
and 2 (3.5%) patients by MRA (Table 2). After a careful
reexamination of the images and their reports, some degree LDL-cholesterol (mg/dL) 113.8 37.6 (36182)
of stenosis was detected in all 57 patients. However, 55 Albumin (g/dL) 4.1 0.4 (2.94.9)
(96.5%) patients were classified as having PAD according Total protein (mg/dL) 7.0 0.4 (6.07.9)
to angiography, while 2 (3.5%) subjects were not found to Sodium (mEq/L) 140.0 2.4 (135146)
have angiographically proven PAD (Table 2). Potassium (mEq/L) 4.3 0.4 (3.25.4)
3.4. Sensitivity and specificity of ABI in the diagnosis of
Calcium (mg/dL) 9.6 0.5 (8.510.4)
PAD with respect to angiography
A low ABI value was found in 46 (83.6%) out of 55 patients LDH (IU/L) 354.1 103.3 (172667)
who had angiographically detected PAD. One of the two
AST: Aspartate aminotransferase; ALT: alanine aminotransferase;
patients with no PAD according to angiography had a low
GGT: gamma glutamyl transferase; HDL: high-density
ABI value (false positive). Finally, the sensitivity of the ABI lipoprotein; LDH: lactate dehydrogenase; LDL: low-density
test to detect angiographically proven PAD was 83.6%, but lipoprotein; MCV: mean corpuscular volume.
the specificity was 50%. A strong positive predictive value
of 97.9% of a low ABI to identify angiographically detected
PAD was calculated. unchanged (50%) due to an insufficient number of
When the same analysis was applied to an ABI 0.95 participants with nondiagnostic angiography for PAD.
threshold for PAD diagnosis, 50 (90.9%) of the 55
angiographically detected PAD patients were categorized 4. Discussion
as having PAD. In this case, both the sensitivity and the This study on a group of Turkish people revealed the ABI
positive predictive value improved (90.9% and 98%, measurement to be a reliable test in the diagnosis of PAD
respectively) (Table 3). However, specificity remained based on angiographically identified disease. To the best

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Table 2. ABI and angiography-based diagnosis of PAD. 84% and 3 risk factors in 54.4% of our participants, with
coexisting hypertension, diabetes mellitus, or CAD in more
ABI Mean SD than 40%, the present study population was quite similar
to those that were previously studied by different authors.
Overall 0.6 0.2 However, the enrollment of a small number of subjects
Female (n = 10) 0.6 0.3 with normal or nondiagnostic angiography for PAD
Male (n = 47) 0.6 0.2 appeared to be a drawback of our study. While ordering
ABI categories n (%) angiography solely for study purposes in asymptomatic
PAD (ABI 0.9) 47 (82.5) subjects with a normal ABI was not possible due to ethical
considerations, it is also not recommended for most cases
Borderline (ABI: 0.911) 7 (12.3)
with a low ABI value (4).
Low-normal (ABI: 1.01.1) 1 (1.8) The ABI has been a sensitive, reliable, and cost-effective
Normal (ABI: 1.111.40) 2 (3.5) method in the diagnosis of PAD (4,10). It has also been
High (ABI >1.4) 0 demonstrated to be useful in the detection of generalized
Angiographic methods n (%) atherosclerosis (11). The presence of a low ABI or
CTA 33 (57.9) subclinical atherosclerosis among older patients without
a history of CAD was shown to be a significant predictor
DSA 22 (38.6)
of all-cause mortality and cardiovascular morbidity (12).
MRA 2 (3.5) Thus, routine, effective use of the ABI measurement can
Angiographic diagnosis of PAD n (%) improve patient management in any population.
PAD (+) 55 (96.5) When compared to DSA, CTA had 96.4% sensitivity and
PAD (-) 2 (3.5) 98.4% specificity for the detection of peripheral arterial
stenoses (13), while the sensitivity and specificity of MRA
ABI: Ankle-brachial index; CTA: computerized tomography were documented to be almost 100% (14). The less invasive
angiography; DSA: digital subtraction angiography; MRA: CTA and MRA have increasingly been preferred to the
magnetic resonance angiography; PAD: peripheral arterial more invasive DSA due to patient comfort and low risk
disease. of complications. Accordingly, despite being considered
a gold-standard imaging method, DSA could only be
performed in less than one-third of our patients.
of our knowledge, this is the first report from Turkey Based on a threshold value of 0.9, the ABI was reported to
presenting evidence for the utility of noninvasive ABI have 79%95% sensitivity and 85%100% specificity with
measurement in the detection of lower extremity PAD. respect to angiographic methods in the diagnosis of PAD
Smoking, older age, diabetes mellitus, hyperlipidemia, and (15). In our study, the sensitivity of the ABI was found to
hypertension were linked to increased PAD incidence, be 83.6% using this threshold, which seems acceptable and
with the presence of at least one cardiovascular disease risk in line with the literature. Although the main objective of
factor in up to 95% of individuals with PAD (1). Given the our study was to determine the sensitivity, the specificity
identification of at least one cardiovascular risk factor in of ABI could be evaluated for only 2 cases that had <50%

Table 3. Sensitivity and specificity of a low ABI in the diagnosis of PAD with respect to
angiography.

Diagnosis according to ABI Diagnosis according to angiography

PAD absent PAD present Total


Absent 1 9 10
Threshold 0.9
Present 1 46 47
Absent 1 5 6
Threshold 0.95
Present 1 50 51
Total 2 55 57

ABI: Ankle-brachial index; PAD: peripheral arterial disease.

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stenosis on angiography. Due to a small sample size, be minimized.


the specificity value of 50% for a low ABI in our study Given the decrease in the sensitivity of ABI measurement
population lacks adequate accuracy. in diabetics and the elderly population who frequently
The sensitivity and specificity of ABI measurement for have calcified vessels, ABI has been considered less
lower extremity PAD diagnosis revealed inconsistent reliable in calcified and incompressible arteries leading to
findings in several studies, depending on various factors falsely higher values (15). As an example, the sensitivity
including observer, equipment, and methods (16). In a of >90% in patients with PAD was reported to decrease
study by Khusrow et al., conducted on 107 patients and to 50% in a group with diabetic neuropathy and to 30%
based on DSA and ABI in the diagnosis of PAD, the in asymptomatic subjects (22,23). Although a high ABI is
sensitivity and specificity of the ABI using higher or lower common among diabetics and/or the elderly population,
ankle pressures were reported as 69%84% and 83%64%, these patients are considered to have the same risk as
respectively (17). The calculation of ABI using lower ankle those having a low ABI value, even when they have no
pressure was associated with improved sensitivity, while symptoms. Although the average age of our participants
it decreased specificity values in other studies (18,19). was 59, diabetes mellitus was recorded in 40% of the whole
However, the American Heart Association and TASC2 study group, but we detected no high ABI values in these
guidelines continue with the recommendation of using participants who had angiographically proven PAD. A
the higher ankle pressure in the calculation of ABI, which
high ABI was also less common in our previous studies
was also the chosen method in the present investigation.
on Turkish subjects compared to other populations (3).
In a recent study by Nam et al., CTA, DSA, and ABI
However, whether ethnic differences in the rate of vessel
were serially performed in 79 patients with intermittent
calcinosis exist has not been clearly reported to date.
claudication. The authors reported relatively lower levels
Although an ABI value below 0.90 is currently accepted
of sensitivity and specificity of ABI of 61% and 87%,
respectively (19). The performance of ABI testing was as a diagnostic for the presence of PAD, a threshold
also evaluated according to the observer, which generally index value of 0.95 was found to improve the diagnostic
revealed a high reproducibility of the method (10,20,21). performance in some studies (24,25). Accordingly, in our
ABI measurement was performed meticulously under study population, the sensitivity of the ABI test increased
improved conditions for each patient in the present study. from 83.6% to 90.9% when the diagnostic cut off was set at
The same trained and experienced observer performed 0.95. Whether some higher ABI threshold values provide
all measurements using the same 8-Hz Doppler and better diagnostic performance in Turkish subjects with
four Velcro-cuff (12 cm width and 2940 cm length) PAD needs to be further tested.
sphygmomanometers wrapped on four extremities at In conclusion, this study on Turkish subjects showed that
the same time. The environment was also arranged the sensitivity of a low ABI value to detect angiographically
specifically with a comfortable stretcher and two metal proven PAD was in the acceptable range, with an impressive
armrests placed at 30 to ensure the comfort of the upper positive predictive value. Moreover, using the value of ABI
extremities. Measurements were performed twice for each 0.95 as the diagnostic threshold markedly improved the
vessel in two rounds and the mean value was used for each sensitivity ratio. Nevertheless, due to the low number of
vessel reading. Therefore, unfavorable factors that could participants without PAD as confirmed by angiography,
affect the result of ABI measurement were considered to clearer specificity values could not be obtained.

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