Short report
Bilateral blood pressure differential as a
►► Additional material is
published online only. To view
please visit the journal online
(http://​dx.​doi.o​ rg/​10.​1136/​
emermed-​2018-​207499).
1
Department of Undergraduate
Medicine, University of Ottawa,
Ottawa, Ontario, Canada
2
Department of Emergency
Medicine, University of Ottawa,
Ottawa, Ontario, Canada
3 Methods  Historical matched case–control study
Emergency Medicine, The
Ottawa Hospital Research
Institute, Ottawa, Ontario,
Canada
Correspondence to
Dr Robert Ohle, The Ottawa
Hospital Research Institute,
Ottawa, ON K1Y 4E9, UK;
​robert.​ohle@​gmail.​com
Received 22 January 2018
Revised 20 June 2018
Accepted 25 June 2018
© Author(s) (or their
employer(s)) 2018. No
commercial re-use. See rights
and permissions. Published
by BMJ.
To cite: Um SW, Ohle R,
Perry JJ. Emerg Med J Epub
ahead of print: [please include
Day Month Year]. doi:10.1136/
emermed-2018-207499
clinical marker for acute aortic dissection in the
emergency department
Sung Wook Um,1 Robert Ohle,2 Jeffrey J Perry2,3
Abstract
Introduction  Interarm systolic BP differential is a
classic sign of acute aortic dissection (AAD). All previous
studies looking at the association of BP differential
with AAD combine systolic BP differential >20 mm
Hg with pulse deficit. Our aim was to assess the
association of systolic BP differential with AAD, and its
role in predicting AAD in the context of other signs and
symptoms.
using patient data collected between 2002 and 2014:
participants were adults >18 years old with a bilateral
BP measurement presenting to two tertiary care EDs or
one regional cardiac referral centre in Canada. Cases
were patients with diagnosed AAD; controls were those
with a triage diagnosis of truncal pain (<14 days) and
an absence of a clear diagnosis on basic investigation.
Cases and controls were matched in a 1:1 ratio by sex
and age. Bilateral BP differential and pulse deficit were
compared between groups.
Results  A total of 222 patients (111 cases and 111
controls) were analysed. On univariate analysis systolic
BP differential >20 mm Hg (OR 2.7, 95% CI 1.39 to
5.25) was significantly associated with AAD. Pulse
deficit (diagnostic OR (DOR) 28.9) in isolation had better
diagnostic accuracy than systolic BP differential >20 mm
Hg in isolation (DOR 2.71) or combined with systolic BP
differential >20 mm Hg (DOR 4.2).
Conclusion  Bilateral systolic BP differentials >20 mm
Hg are associated with non-traumatic AAD. However,
the poor diagnostic accuracy and potential variability in
measurement limits its clinical usefulness.
Introduction
Acute aortic dissection (AAD) results from a tear
in the intimal wall of the aorta. Without treatment,
mortality can reach 40%–50% within the first
48 hours, and 90% at 1 year.1 2 Fortunately with
modern medical and surgical interventions, 30-day
survival is 80%–90%.1 2 However, for patients to
benefit from these advances in treatment, they must
be identified early.
Unfortunately, the miss rate of AAD is as high as
38%.3 The classic teaching is that a bilateral systolic
differential of >20 mm Hg is predictive of AAD.2 4–6
However, all reported studies have grouped systolic
BP differential with pulse deficit in their analysis.
There has been no study assessing the independent
association of systolic BP differential with AAD.
We sought to assess whether a systolic bilateral BP
differential on its own is associated with AAD and
Um SW, et al. Emerg Med J 2018;0:1–3. doi:10.1136/emermed-2018-207499
Emerg Med J: first published as 10.1136/emermed-2018-207499 on 18 July 2018. Downloaded from http://emj.bmj.com/ on 19 July 2018 by guest. Protected by copyright.
Key messages
What is already known on this subject
►► Interarm BP differential is a classic sign of acute
aortic dissection.
►► To our knowledge there has been no previous
study confirming its independent association
with acute aortic dissection.
►► All previous studies combine BP differential
>20 mm Hg with pulse deficit. Our aim was to
assess the association of BP differential with
acute aortic dissection, and its role in predicting
acute aortic dissection in the context of other
signs and symptoms.
What this study adds
►► This study demonstrates an interarm
BP differential >20 mm Hg is associated
with acute aortic dissection but its poor
diagnostic accuracy and potential variability
in measurements limits its usefulness in the
clinical practice.
►► Pulse deficit is more accurate in the diagnosis
of acute aortic dissection.
whether it can be used as an independent predictor
for AAD in the ED.
Methods
We performed a 1:1 age and sex retrospective
case–control study. This was a planned secondary
study from a larger case–control database.7 We
chose 1:1 as we anticipated difficulty in finding
controls with bilateral BP measurements. We
included patients >18 years old who presented to
two tertiary care EDs or a regional cardiac referral
centre from 2002 to 2014 with acute (<14 days)
onset of non-traumatic abdominal/back/chest/flank
pain (truncal pain). AAD cases were identified and
enrolled via ED, in hospital or death certificate
International Classification of Diseases-10 diag-
nosis of aortic dissection, intramural haematoma or
penetrating atherosclerotic ulcer. Patient controls
were enrolled via ED triage diagnosis of chest, back,
abdominal and flank pain and an absence of clear
diagnosis on basic investigation (ie, urinary tract
infection, fracture, bowel obstruction, and so on).
To select controls, we used a database of all patients
presenting with a triage diagnosis of truncal pain
between 2010 and 2011. We assigned each patient
a number, then using random number generator
  1
 Short report
we randomly selected patients for review to see if they met inclu-
Table 1  Characteristics of study participants with bilateral systolic
sion criteria.

Emerg Med J: first published as 10.1136/emermed-2018-207499 on 18 July 2018. Downloaded from http://emj.bmj.com/ on 19 July 2018 by guest. Protected by copyright.
BP measurements recorded
AAD Controls
Clinical variables Characteristics (n=111) (n=111)
Bilateral BPs were recorded if right and left arm systolic BPs were
Gender, n (%)
measured immediately after each other and prior to any surgical
intervention. Two definitions of a systolic BP difference were   Male 75 (68.0) 76 (68.5)
defined a priori for investigation: >10 mm Hg and >20 mm   Female 36 (32.0) 35 (31.5)
Hg. BP was measured using automated device. We used the first Mean bilateral systolic BP difference (±SD), 18.3 (±16.8) 11.3 (±10.2)
available measure of bilateral BP within 12 hours of presentation mm Hg
and before surgical intervention. Measurements are performed Arrival by ambulance*, n (%) 76/111 (69.0) 33/111 (30.0)
by nursing staff and not usually confirmed by a second operator. Type of aortic dissection, n (%)
Pulse deficit/differential was defined as any recorded differ-  Type A 66 (59.4) NA
ence in volume/force or difference in obvious signs of malper-   Type B 45 (40.5) NA
fusion (cold, blue, mottled) between right and left extremities. Course in hospital, n (%)
Index test results were available to those interpreting the refer-   Admission 110 (99.2) 29 (26.1)
ence standard.  Surgical treatment 70 (54.7) 4 (3.6)
  Death 25 (19.5) 0 (0.0)
Data extraction Diagnosis
Data were extracted using a data collection form as per guide-  Unspecified chest pain NA 43 (39.6%)
lines put forward by Jansen et al.8 Data extracted were verified  Acute coronary syndrome (ACS) NA 19 (17.1%)
in multiple sources: ED record of treatment, consultant notes  Unspecified abdominal pain NA 11 (9.9%)
and integrated progress notes. The data form was trialled on 50  Muscular back pain NA 5 (4.5%)
patient charts, refined and trialled on a further 50 charts. Four   Other† NA 32 (28.8%)
reviewers were trained using 50 chart data extractions; data were
*If there was no clear indication in documentation of whether patients arrived by
compared and kappa calculated with clarification and oversight ambulance or not then they were not included for this measure.
provided by a fifth reviewer (RO). To determine interobserver †Other less common diagnoses include: gastro-oesophageal reflux disease,
agreement for the entire study, 40% of total charts were reviewed abdominal aortic aneurysm, valvular pathology, transient ischaemic attack,
by at least two reviewers and the kappa statistic calculated. For acute kidney injury, atrial fibrillation, chest wall pain, congestive heart failure
calculating the kappa, all data from the extraction form were exacerbation, cholelithiasis, choledocholithiasis, diverticulitis, upper gastrointestinal
considered as a single variable; that is, all variables on the form bleeding, back pain not yet diagnosed, among others.
AAD, acute aortic dissection; NA, not applicable.
had to be the same to count as an agreement. Reviewers were
not blind to study objective but had no knowledge regarding the
direction of association of clinical variables. table A-1. In the control group 21 patients underwent CT: 9 CT
thorax, 4 CT abdomen, 8 CT thorax and abdomen; 111 had
Data analysis a CXR, 18 patients had a D-dimer and 12 had transthoracic
We used univariate analysis; diagnostic accuracy was reported echocardiography.
as diagnostic OR (DOR), sensitivity, specificity, and positive A systolic BP differential >10 mm Hg (OR 1.8, 95% CI 1.1 to
and negative likelihood ratios. Using paired indicators can be a 3.1) and systolic BP differential >20 mm Hg (OR 2.7, 95% CI 1.4
disadvantage in comparing the performance of competing tests, to 5.3) were associated with AAD (table 2). Pulse deficit (DOR
especially if one test does not outperform the other on both 28.9) had better diagnostic accuracy than systolic BP differential
indicators. We used the DOR as a measure of test accuracy. The >20 mm Hg (DOR 1.95) (table 3). Combining pulse deficit with
DOR of a test is the ratio of the odds of positivity in disease rela- systolic BP difference >20 mm Hg did not have significant accu-
tive to the odds of positivity in the non-diseased.9 racy (DOR 4.2).
Missing data were addressed through multiple imputations.
Analysis was performed using SAS V.9.4 University Edition. Discussion
A bilateral upper extremity systolic BP differential >20 mm Hg
Sample size is associated with AAD; however, its diagnostic accuracy limits
Sample size was calculated on the basis of an 80% power and CI its usefulness in clinical practice. Pulse deficit in isolation is more
of 95% to detect a DOR of greater than 3. Based on a minimum accurate than systolic BP differential >20 mm Hg and combing
of 20% of controls with any of the independent variables, our the two variables does not increase diagnostic accuracy. The
sample size consisted of 83 cases and 83 controls.
Table 2  Univariate association of systolic BP and/or pulse deficit and
Results acute aortic dissection
Data were collected from 2002 to 2014 yielding 194 cases
AAD Controls P values
of newly diagnosed AAD and 111 with bilateral systolic BP
Variable (n=111) (n=111) (<0.05)
measurements. There were 64 402 control patients presenting
with triage diagnosis of truncal pain in 2010 and 2011. A total Systolic BP differential >10 mm Hg 60 (53.9%) 43 (38.7%) 0.020
of 1301 controls were screened to find 111 eligible controls with Systolic BP differential >20 mm Hg 33 (29.7%) 15 (13.5%) 0.003
bilateral systolic BP (online supplementary figure A-1, table 1). Pulse deficit 27 (21.1%) 1 (0.9%) <0.001
Mean age is 65. The kappa after chart training was 0.85 and for Systolic BP differential >20 mm Hg 49 (44.1%) 16 (14.1%) 0.002
study data extraction 0.91. Univariate analysis of signs and symp- and/or pulse deficit
toms for case and controls is reported in online supplementary AAD, acute aortic dissection.

2 Um SW, et al. Emerg Med J 2018;0:1–3. doi:10.1136/emermed-2018-207499


Table 3  Diagnostic accuracy of systolic BP differential and/or pulse deficit for AAD
AAD Controls Sensitivity
Variable (n=111) (n=111) (95% CI)
Systolic BP differential >10 mm Hg 60 (53.9%) 43 (38.7%) 55.2% (48.8 to 61.3)
Systolic BP differential >20 mm Hg 33 (29.7%) 15 (13.5%) 29.7% (24.4 to 34.0)
Pulse deficit 27 (21.1%) 1 (0.9%) 21.1% (14.4 to 29.2)
Pulse and/or systolic BP differential 49 (44.1%) 16 (14.1%) 76.8% (65.1 to 86.3)
>20 mm Hg
AAD, acute aortic dissection; LR, likelihood ratio.
greater accuracy of pulse deficit is largely driven by its increased
specificity. Therefore, if present the pulse deficit should substan-
tially increase suspicion for AAD, whereas the presence of bilat-
eral systolic BP differential >20 mm Hg only slightly increases
the suspicion for AAD.
Previous studies have all drawn the association of bilateral
systolic BP differential with AAD based on analyses that grouped
systolic BP and pulse deficit together as one variable, or on
observations with no statistical analysis.1 This makes it difficult
to know whether pulse deficit or BP differential is driving the
association and whether they may be better used independently.
We found that pulse deficit alone had better diagnostic accu-
racy than systolic BP differential >20 mm Hg in isolation, and
combining these two variables did not improve the DOR. Only
studies of Armstrong, Eagle and Enia report on an isolated pulse
deficit with a combined sensitivity of 24% (95% CI 13% to 41%)
and specificity of 92% (95% CI 86% to 96%), which is similar to
our results.10 Klompas’ review article in 2002 reported a similar
diagnostic accuracy for the combined variable of systolic BP
differential/pulse deficit with a positive likelihood ratio of 5.7
(1.4–23) and a negative likelihood ratio of 0.7 (0.6–0.9). The
reporting of diagnostic accuracy of pulse deficit and systolic BP
differential is confusing. As seen in the Klompas’ review article,
diagnostic accuracy of the composite variable pulse deficit/bilat-
eral systolic BP differential is often labelled as pulse deficit or
systolic BP differential in isolation.1 2
Although it seems that systolic BP differential has some asso-
ciation with AAD, it does not appear to be a specific sign. Singer
and Hollander observed that up to 53% of ED patients had a
systolic BP differential >10 mm Hg and up to 19% had a differ-
ence >20 mm Hg, none of whom were diagnosed with AAD.11
Many studies have also shown poor reliability of BP measure-
ments in the ED with repeat measurements showing significant
discrepancies, as well as significant interobserver variability.12
Diagnostic utility may be limited; however, it is still important
to check for a systolic BP differential if the diagnosis of AAD is
made, the dissection flap may cause a perfusion deficit to one
limb resulting in a pseudohypotension. BP control should be
aimed at higher of the two measurements.13
Limitations
The data collected were retrospective in nature. This could
potentially lead to misclassification bias with each physician
defining the clinical variables according to their own criteria.
We included only patients who had a bilateral BP measurement
performed. Given the classic association of systolic BP differen-
tial and AAD, it is likely that there is an element of partial veri-
fication bias in that patients with positive index tests are more
likely to receive the gold standard test, and only patients who
get the gold standard are included in the study. The sensitivity
Um SW, et al. Emerg Med J 2018;0:1–3. doi:10.1136/emermed-2018-207499
Short report
Emerg Med J: first published as 10.1136/emermed-2018-207499 on 18 July 2018. Downloaded from http://emj.bmj.com/ on 19 July 2018 by guest. Protected by copyright.
Specificity Positive LR Negative LR Diagnostic
(95% CI) (95% CI) (95% CI) OR
61.3% (54.1 to 68.1) 1.43 (1.06 to 1.93) 0.73 (0.57 to 0.95) 1.95
86.5% (80.4 to 91.5) 2.20 (1.25 to 4.00) 0.81 (0.72 to 0.94) 2.71
99.1% (95.1 to 100.0) 23.41 (3.23 to 169.50) 0.80 (0.70 to 0.92) 28.9
55.9% (48.1 to 63.5) 1.74 (1.41 to 2.15) 0.41 (0.26 to 0.65) 4.2
will be falsely raised and specificity falsely lowered. Controls
are from a population with truncal pain and may not exactly
represent patients from whom clinicians would consider AAD in
their differential. All underwent CXR but only a minority had a
CT scan. Bilateral BP measurements may have been performed
in a different manner between patients; that is, one directly
after the other or one measurement, then a delay followed by a
second measurement.
Conclusion
Bilateral systolic BP differential >20 mm Hg is associated with
non-traumatic AAD. However, the diagnostic accuracy and
potential variability in measurement limits its clinical usefulness.
Contributors  SWU is the first author of this paper, having been primarily
responsible for data collection and writing of the manuscript. This manuscript was
coauthored by RO, his supervisor JJP. JJP provided valuable feedback and statistical
support throughout the process.
Funding  The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not-for-profit sectors.
Competing interests  None declared.
Patient consent  Not required.
Ethics approval  Ottawa Health Science Network Research Ethics Board (OHSN-
REB).
Provenance and peer review  Not commissioned; externally peer reviewed.
References
1 Klompas M. Does this patient have an acute thoracic aortic dissection? JAMA
2002;287:2262–72.
2 von Kodolitsch Y, Schwartz AG, Nienaber CA. Clinical prediction of acute aortic
dissection. Arch Intern Med 2000;160:2977–82.
3 Chua M, Ibrahim I, Neo X, et al. Acute aortic dissection in the ED: risk factors and
predictors for missed diagnosis. Am J Emerg Med 2012;30:1622–6.
4 Nazerian P. Diagnostic performance of the aortic dissection detection risk score in
patients with suspected acute aortic dissection Acute Cardiovascular Care. European
Heart Journal 2014:373–81.
5 Enia F, Ledda G, Lo Mauro R, et al. Utility of echocardiography in the diagnosis of
aortic dissection involving the ascending aorta. Chest 1989;95:124–9.
6 Armstrong WF, Bach DS, Carey LM, et al. Clinical and echocardiographic findings in
patients with suspected acute aortic dissection. Am Heart J 1998;136:1051–60.
7 Ohle R, Um J, Anjum O, et al. High risk clinical features for acute aortic dissection: a
case-control study. Acad Emerg Med 2018;25:378–87.
8 Jansen AC, van Aalst-Cohen ES, Hutten BA, et al. Guidelines were developed for data
collection from medical records for use in retrospective analyses. J Clin Epidemiol
2005;58:269–74.
9 Glas AS, Lijmer JG, Prins MH, et al. The diagnostic odds ratio: a single indicator of test
performance. J Clin Epidemiol 2003;56:1129–35.
10 Ohle R, Kareemi HK, Wells G, et al. Clinical Examination for Acute Aortic Dissection: A
Systematic Review and Meta-analysis. Acad Emerg Med 2018;25:397–412.
11 Singer AJ, Hollander JE. Blood pressure. Assessment of interarm differences. Arch
Intern Med 1996;156:2005–8.
12 Clark CE, Campbell JL, Evans PH, et al. Prevalence and clinical implications of
the inter-arm blood pressure difference: a systematic review. J Hum Hypertens
2006;20:923–31.
13 Strayer RJ, Shearer PL, Hermann LK. Screening, evaluation. Current cardiology reviews
2012;8:152.
3