Lupus (2014) 23, 11421148

http://lup.sagepub.com

PAPER

The correlation between carotid artery atherosclerosis and clinical

ischemic heart disease in lupus patients
L Eder, DD Gladman, D Ibanez and MB Urowitz
University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toto Western Hospital, Toronto, Ontario, Canada

Aim: The extent of subclinical atherosclerosis can be assessed by ultrasound measurement of

carotid intima-media thickness (cIMT) and total plaque area (TPA). We aimed to investigate
the correlation between measures of atherosclerosis as documented on imaging studies of the
carotid vasculature and clinical coronary artery disease (CAD) in systemic lupus erythematosus (SLE). Methods: The study patients were recruited from the University of Toronto prospective cohort of SLE patients. Patients who had a history of CAD were compared to those
without CAD. TPA and cIMT were measured using high-resolution optimized ultrasound
systems. Logistic regression models were used to investigate the strength of association
between ultrasound measures of atherosclerosis and CAD. The strength of association as
expressed by odds ratio (OR) was compared between TPA and cIMT. Results: A total of
103 SLE patients were analyzed (27 patients with a history of CAD). Carotid IMT correlated
only moderately with TPA (r 0.43, p < 0.001). Both measures were significantly associated
with the presence of CAD. However, TPA showed a stronger association than cIMT (OR 9.55
vs. 2.02, respectively). TPA was also more strongly associated with dyslipidemia and hypertension compared to cIMT. Conclusions: In SLE patients, cIMT correlates only moderately
with TPA, suggesting that they measure different phenotypes of atherosclerosis. Carotid TPA
correlated better than cIMT with cardiovascular risk factors and CAD, suggesting that it may
serve as a better tool for the investigation of atherosclerosis in SLE. Lupus (2014) 23, 11421148.
Key words: Atherosclerosis; lupus; ultrasound; surrogate measures

Introduction
Patients with systemic lupus erythematosus (SLE)
have a signicantly increased risk of accelerated
atherosclerosis and clinical coronary artery disease
(CAD). Compared to the general population,
women with SLE have a ve- to six-fold increased
risk of CAD.14 Several clinical risk scores that
were designed to estimate cardiovascular risk in
individuals without known CAD, such as the
Framingham risk score, do not correlate well with
cardiovascular events in patients with SLE.5 These
scores underestimate the actual risk for CAD in
these patients partially because they dont consider
SLE as an independent risk factor.
Correspondence to: Murray B. Urowitz, University of Toronto Lupus
Clinic, Centre for Prognosis Studies in the Rheumatic Diseases
Toronto Western Hospital, 399 Bathurst St., 1E-410B, Toronto,
Ontario, M5T 2S8, Canada.
Email: m.urowitz@utoronto.ca
Received 23 September 2013; accepted 6 May 2014
! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav

Evidence from both observation and intervention studies support the use of ultrasound (US)
imaging for quantifying atherosclerosis of the carotid arteries using the measurements of carotid
intima-media thickness (cIMT) and total plaque
area (TPA) as surrogate measures for clinical cardiovascular events.6,7 Despite their frequent use in
studies, the correlation between these ultrasonographic measures of atherosclerosis and clinical
CAD has not been investigated in SLE patients.
Numerous studies that used various imaging modalities have shown that the prevalence of atherosclerostic plaques is higher in SLE compared to
healthy controls; the extent of plaques, as measured
by TPA, has not been thoroughly investigated in
this population. Furthermore, several recent publications reported similar levels of IMT in SLE and
controls.8,9
Although both cIMT and TPA predict the
occurrence of CAD in the general population, the
pathogenesis of such events in SLE patients may
involve additional mechanisms other than
10.1177/0961203314537696

The correlation between carotid artery atherosclerosis and clinical ischemic heart disease
L Eder et al.

1143

atherogenesis and plaque rupture as occur in the

general population. Since traditional cardiovascular risk factors only poorly predict cardiovascular
events in SLE patients, additional lupus-specic
mechanisms may play a role. Some of the suggested
mechanisms include endothelial dysfunction,
thrombotic tendency due to antiphospholipid antibodies and lupus-related vasculopathy.1012 The
ability of surrogate measures of atherosclerosis to
predict ischemic events in SLE may be low if the
pathogenesis of clinical events is related to these
mechanisms. Therefore, the investigation of the
association between US measures of atherosclerosis
and CAD in SLE patients is an important rst step
to justify their use as surrogates of clinical events.
In this study we aimed to investigate the correlation between measures of atherosclerosis as determined on imaging studies of the carotid vasculature
and clinical CAD in SLE patients. In addition, the
strength of association between each of the measures of atherosclerosis, cIMT and TPA, and CAD
was compared. We hypothesized that the association between TPA and CAD will be stronger
than between cIMT and CAD.

Methods
Study population and data collection
In this cross-sectional study a group of SLE
patients with documented CAD was compared
with a group of patients who did not have a history
of CAD. The study population included adult
(aged > 18 years) SLE patients satisfying the
American College of Rheumatology (ACR) criteria
for classication of SLE.13 They were recruited
from the University of Toronto lupus cohort that
numbers more than 1500 patients. All of the
patients in the lupus clinic participate in a longterm prospective cohort study that assesses prognostic factors in SLE. The patients are followed
in the lupus clinic at the Toronto Western
Hospital every two to six months according to a
standard protocol using validated clinical measurement tools. Information about cardiovascular risk
factors, including hypertension, dyslipidemia, diabetes and smoking, is collected routinely and
entered into a computerized database. Any incident
ischemic cardiovascular events including myocardial infarction (MI) and angina pectoris, as well
as reports of any diagnostic procedure for cardiovascular disease including myocardial perfusion
scan or coronary angiogram, are collected and
entered into the database. In addition, information

about lupus activity and accrual of damage was

recorded using the Systemic Lupus Erythematosus
Disease Activity Index-2000 (SLEDAI-2K) and the
Systemic Lupus International Collaborating Clinics
(SLICC)/ACR Damage Index (SDI).14,15
Patient selection and definition of CAD
The clinic database was searched for patients who
had a history of documented MI or angina pectoris.
Since the underlying mechanism of stroke in SLE
does not necessarily involve atherosclerosis,
patients with a history of stroke or transient ischemic attack (TIA) who did not have CAD were
excluded. The patients charts were reviewed and
only those with documented CAD events that fullled the pre-dened denitions were included. MI
was dened by at least two of the following: symptoms of myocardial ischemia, typical electrocardiographic changes, and elevated myocardial enzymes.
Angina pectoris was dened as chest discomfort
that was aggravated by physical activity and
relieved by rest or the use of nitroglycerine and
conrmed by a cardiologist or abnormal ndings
on myocardial perfusion study or angiography.
Patients with equivocal ndings were excluded.
Eligible patients were then approached and
recruited during their clinic visit.
Consecutive SLE patients who did not have a
history of the following conditions: MI, angina pectoris, abnormal ndings in coronary angiogram or
cardiac perfusion scan, stroke, TIA, ischemic heart
failure, stroke, carotid endarterectomy and peripheral vascular disease, were recruited during their
clinic follow-up visits to serve as the control group.
Cardiovascular risk factor assessment
Blood pressure was measured and subjects were
considered to have hypertension if they were
taking antihypertensive agents or if they had a systolic blood pressure of >140 mmHg and/or a diastolic pressure of >90 mmHg. Lipid prole was
analyzed for total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and
triglycerides (TG) after a 12-hour fast. Total cholesterol levels > 5.2 mmol/l and LDL > 3.4 mmol/l
were considered to be high while HDL levels of
less than 0.77 mmol/l in men and less than
0.9 mmol/l in women were considered low.
Dyslipidemia was dened as having elevated levels
of LDL or low levels of HDL or the use of lipidlowering agents. Smoking status was also recorded.
Diabetes mellitus was dened as the use of antidiabetes medications or fasting glucose levels
>7 mmol/l.
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US assessment
Ultrasonographic measurements of TPA and cIMT
were performed using a high-resolution optimized
US system for carotid imaging (Esaote MyLab 30,
Genoa, Italy) by a single trained physician (LE). A
linear 12-5 probe with a central frequency of
8.5 MHz was used (Esaote).
The scan included detailed B-mode images of
both right and left common carotid arteries as
well as the carotid bulb, internal carotid and external carotid arteries. The mean cIMT was measured
automatically at the far wall of the right and left
common carotid arteries at least 1 cm proximally
from the origin of the bulb using a real time
radio-frequency-based US system for carotid imaging (QIMT tool; Esaote). The composite mean
cIMT was calculated by averaging the common
right and left cIMT values. An atherosclerotic
plaque was dened as a localized thickening of
the intima layer exceeding 1 mm. The burden of
atherosclerotic plaques was measured by the carotid TPA.16 Each plaque was scanned in a longitudinal view until the maximum area of the plaque
was in the plane of view. The image was then frozen
and magnied and the plaque area was measured
by tracing the perimeter with a cursor (Figure 1).
TPA was recorded as the sum of all plaques from
the clavicle to the jaw in the right and left carotid
arteries. TPA was scored 0 in patients without
atherosclerostic plaques. Reading of the US scans
was performed independently from the scanning.
The scans were recorded in digital media and read
at a separate location and later date after blinding
for personal data. Reproducibility and intraobserver variation were checked by rereading 25
images of the study subjects on dierent days.

The intra-observer intra-class correlation coecient for TPA was 0.94.

Statistical analysis
Descriptive statistics (mean and standard deviation
for continuous variables and percentages for categorical variables) were used to compare clinical
and laboratory characteristics in the two groups.
The correlation between cIMT and TPA was
assessed by Pearson correlation coecient. Mean
TPA and cIMT were compared in patients with
and without a history of CAD using the twotailed t test. To facilitate direct comparisons,
cIMT and TPA were transformed into z scores.
Individual logistic regression models were t with
CAD and cardiovascular risk factors as binary outcomes and z score of either TPA or cIMT as an
independent variable. The strength of association
as expressed by odds ratio (OR) was compared
between TPA and cIMT. The eect of covariates
was considered as statistically signicant if the p
value from the two-sided Wald test was <0.05.
The statistical computation was performed using
SAS V.9.2.

Results
A total of 54 patients who have had history of
CAD and were regularly assessed in the lupus
clinic were identied in the database. Of those,
nine patients were excluded for equivocal diagnosis
of CAD. Of the remaining patients, we were able to
recruit 25 patients. Two additional patients who
did not have a history of CAD at the time of enrollment but developed acute MI by the time the study
was completed were included in the CAD group.
The median interval of time between the occurrence
of the CAD event and the US scan was 8.2 years
(range 2.422 years) for the 25 patients who have
had a history of CAD at the time of recruitment.
The control group included 76 patients who did not
have a history of CAD.
The characteristics of the study population are
detailed in Table 1.
Comparison of patients with and without CAD

Figure 1: Measurement of plaque area at the bulb of the

carotid artery (marked in yellow, a total of 0.12 cm2).
Lupus

Patients who had a history of CAD were more

likely to be men (p 0.0003), Caucasians
(p 0.03), were older (p 0.0008) and had a
longer duration of SLE at the time of assessment
(p < 0.0001). With respect to cardiovascular risk
factors, patients with CAD were more likely to be

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L Eder et al.

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Table 1 Characteristics of the study population (N 103)

Age (years)
Sex Female
Race Caucasian
Black
Asian
Other
Age at SLE diagnosis (years)
Disease duration (years)
Blood pressure
Diastolic (mmHg)
Systolic (mmHg)
Use of antihypertensive medications
Hypertensiona
Elevated total cholesterol
Elevated LDL-c
Low HDL-c
Use of lipid-lowering therapy
Statins
Nicotinic acid
Fibrates
Combinations
Dyslipidemiab
Smoker current
Ever
Renal involvement everc
Steroids at the time of assessment
Ever
Cumulative steroids dose (gr)d
SDI
SLEDAI-2K at the time of assessment
Carotid intima media thickness (mm)
Total plaque area (cm2)

55.2  12.0
93 (90.3%)
70 (68.0%)
13 (12.6%)
9 (8.7%)
11 (10.7%)
35.6  13.5
19.1  12.5
74.0  10.3
125.1  15.8
57 (55.9%)
61 (59.2%)
23 (22.3%)
6 (6.0%)
11 (11.0%)
38 (37.6%)
32 (31.1%)
1 (1%)
3 (3%)
1 (1%)
50 (49.0%)
8 (7.8%)
36 (35.3%)
58 (56.3%)
48 (46.6%)
86 (83.5%)
45.3  42.7
2.2  2.3
3.3  3.7
614.1  110.1
0.16  0.31

Diastolic blood pressure > 90 or systolic blood pressure > 140 or the
use of antihypertensive medications.
b
Elevated LDL or low HDL or the use of a lipid-lowering medication.
c
Nephrotic syndrome or dialysis or renal transplant or serum creatinine > 140 or the presence of urinary cellular casts or proteinuria with or
without hematuria and pyuria.
d
Cumulative steroids dose evaluated only in patients who have ever
been on steroids. SLE: systemic lupus erythematosus; LDL-c: lowdensity lipoprotein cholesterol; HDL-c: high-density lipoprotein cholesterol; SDI: Systemic Lupus International Collaborating Clinics/
American College of Rheumatology Damage Index; SLEDAI-2K:
Systemic Lupus Erythematosus Disease Activity Index-2000.

hypertensive (p 0.0006), ever smokers (p 0.02),

and to have dyslipidemia (p 0.0003) and diabetes
mellitus (p 0.004). Patients with CAD also had
higher SDI scores (p < 0.0001) and have used
higher cumulative doses of corticosteroid
(p 0.02) (Table 2).
The correlation between US measures of
atherosclerosis and CAD
The correlation between TPA and cIMT was only
moderate (r 0.43, p < 0.001, Figure 2), suggesting
that they measure partially dierent constructs.
Both TPA and cIMT were signicantly higher in

patients with CAD compared to those without

CAD (0.43  0.49 vs. 0.06  0.12, p < 0.0001 and
688.8  102.4 vs. 587.6  102.4, p 0.0007, respectively). The presence of atherosclerotic plaques
(TPA > 0) was higher in patients with CAD compared with those without CAD (88.8% vs. 37.3%,
p 0.0001, respectively). Furthermore, TPA was
more strongly associated with CAD than was
cIMT (OR 9.55 vs. 2.87, respectively, Table 3).
Only three out of the 27 patients with CAD had
no evidence of plaque (TPA 0), of those one
patient developed MI due to an occlusive blood
clot in the left anterior descending artery secondary
to antiphospholipid syndrome and the remaining
two patients had angina pectoris one of them
with abnormal ndings on angiography.
Furthermore, the two patients who developed clinical CAD following the US assessment had carotid
plaques (TPA of 0.08 and 0.23 cm2). TPA was also
more strongly associated with hypertension, dyslipidemia and ever smoking compared to cIMT
(Table 3). No association was observed with diabetes, total cholesterol, HDL and LDL levels.

Discussion
With the improvement in survival, the accrual of
damage, especially atherosclerosis-related diseases,
has become a major issue in the management of
patients with SLE. Nevertheless, incident cardiovascular events are still relatively infrequent, and
the investigation of cardiovascular diseases in
SLE is limited by the need to follow large groups
of patients for many years. This limitation has
prompted the use of surrogate measures for clinical
events such as the imaging of atherosclerosis. In
this study we have investigated the correlation
between two ultrasonographic measures of atherosclerosis and prevalent CAD. We have found that
both cIMT and TPA correlate with CAD.
However, TPA was more strongly associated with
CAD and with cardiovascular risk factors than
cIMT, suggesting that it may serve as a better surrogate measure for clinical CAD.
Although the measurement of cIMT is a universally accepted US phenotype of atherosclerosis, it
has several limitations. cIMT measures the total
thickness of the intima and the media layers of
the carotid artery wall. cIMT is made up of
approximately 80% media and 20% intima,
whereas atherosclerosis is largely an intimal process. Furthermore, traditional coronary risk factors
account for only 15%17% of the cIMT while the
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1146

Table 2

Comparison of SLE patients with and without CAD

Mean  std or frequency (%)

Sex: Female
Race: Caucasian
Black
Asian
Other
Age at SLE diagnosis (years)
Age at the time of assessment (years)
Age at occurrence of CAD
Disease duration at the time of assessment (years)
Blood pressure
Diastolic (mmHg)
Systolic (mmHg)
Use of antihypertensive medications
Hypertension
Elevated total cholesterol
Elevated LDL
Low HDL
Use of lipid-lowering
agents Dyslipidemia
Smoker current
Ever
Diabetes mellitus
Renal involvement ever
Steroids at the time of assessment
Ever
Cumulative steroids dose (gr)a
SDI
SLEDAI-2K at the time of assessment

Logistic regression

No CAD (n 76)

CAD (n 27)

p value

OR

95% CI

p value

74 (97.4%)
47 (61.8%)
11 (14.5%)
9 (11.8%)
9 (11.8%)
36.0  12.9
52.8  10.7

0.0003
Caucasian
vs. other
0.03

0.16
3.5

0.01,0.32
1.1, 11.3

<0.0001
0.03

0.67
0.0008

0.99
1.07

0.96, 1.03
1.03, 1.12

0.67
0.002

16.4  10.8
73.6  9.9
123.5  15.1
32 (42.7%)
36 (47.4%)

19 (70.4%)
23 (85.2%)
2 (7.4%)
0 (0%)
2 (7.4%)
34.7  15.3
61.7  13.3
53.3  11.7
27.0  13.6
75.1  11.4
129.3  16.9
25 (92.6%)
25 (92.6%)

<0.0001
0.53
0.10
<0.0001
<0.0001

1.08
1.0
1.0
16.8
13.9

1.03, 1.12
1.0, 1.1
1.0, 1.1
3.7, 76.1
3.1, 62.8

0.0004
0.52
0.11
0.0003
0.0006

18 (23.7%)
9 (12.2%)
3 (4.1%)
19 (25.7%)
28 (37.3%)
5 (6.6%)
25 (32.9%)
0 (0%)
39 (51.3%)
33 (43.4%)
61 (80.3%)
38.4  38.2
1.3  1.5
3.0  3.4

5 (18.5%)
2 (7.7%)
3 (11.5%)
19 (70.4%)
22 (81.5%)
3 (11.1%)
15 (59.3%)
4 (14.8%)
19 (70.4%)
15 (55.6%)
25 (92.6%)
62.8  48.9
4.4  2.8
4.1  4.5

0.58
0.72
0.18
<0.0001
<0.0001
0.43
0.02
0.004
0.09
0.28
0.23
0.02
<0.0001
0.20

0.7
0.6
0.3
6.9
7.4
1.8
3.0
NA
2.3
1.6
3.1
1.01
2.1
1.1

0.2, 2.2
0.1, 3.0
0.1, 1.7
2.6, 18.3
2.5, 21.7
0.4, 8.0
1.2, 7.3
NA
0.9, 5.8
0.7, 3.9
0.7, 14.4
1.00, 1.02
1.6, 2.9
1.0, 1.2

0.58
0.53
0.19
0.0001
0.0003
0.45
0.02
NA
0.09
0.28
0.15
0.02
<0.0001
0.20

SLE: systemic lupus erythematosus; CAD: coronary artery disease; HDL: high-density lipoprotein; LDL: low-density lipoprotein; SDI: Systemic
Lupus International Collaborating Clinics/American College of Rheumatology Damage Index; SLEDAI-2K: Systemic Lupus Erythematosus
Disease Activity Index-2000; CI: confidence interval. NA: Not applicable due to lack of events in the No CAD group.
a
Cumulative steroids dose evaluated only in patients who have ever been on steroids.

Figure 2: The correlation between total plaque area (TPA)

and carotid intima-media thickness (cIMT).

most important factors that account for increased

cIMT are age and high blood pressure.6 On the
other hand, each one of the traditional cardiovascular risk factors is independently associated
Lupus

with TPA.17 Furthermore, the presence of plaque

is a stronger predictor of CAD than elevated cIMT
after adjustment for traditional cardiovascular risk
factors.18,19 It was therefore hypothesized that
cIMT and TPA represent dierent phenotypes of
vessel wall insult.20 Most studies that investigated
atherosclerosis in SLE have used cIMT as an outcome measure while only a few have used TPA as a
surrogate measure of atherosclerosis burden in
these patients.
The weaker association of cIMT with CAD is in
agreement with studies in the general population.18,19,21 In fact, when measured in the
common carotid artery, cIMT only weakly correlates with clinical cardiovascular events especially in
women, while its measurement in the bulb or internal carotid artery results in better predictive
ability.21 While the mere presence of plaques is
strongly associated with clinical CAD, the use of
TPA provides a continuous measurement that represents the burden of atherosclerosis as opposed to

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L Eder et al.

1147

Table 3:

The association between the presence of CAD, cardiovascular risk factors and atherosclerosis
TPA-Z score

CAD
Age  50
Sex: Male
Smoking: current
Ever
Hypertension
High total cholesterol
Low HDL
High LDL
The use of lipid-lowering agents
Dyslipidemia
Diabetes mellitus

cIMT-Z Score

OR

95% CI

p value

OR

95% CI

p value

9.55
3.50
2.34
1.36
2.25
11.67
0.68
1.37
0.81
3.77
4.14
1.56

3.46,
1.32,
1.23,
0.68,
1.17,
2.59,
0.32,
0.81,
0.33,
1.69,
1.67,
0.92,

<0.0001
0.01
0.01
0.38
0.02
0.001
0.30
0.24
0.65
0.001
0.002
0.10

2.87
3.80
2.02
1.60
1.53
2.22
1.08
1.50
1.13
1.51
1.53
2.22

1.65, 5.02
1.93, 7.45
1.07, 3.80
0.99, 2.59
1.01, 2.35
1.34, 3.69
0.68, 1.72
0.69, 3.30
0.60, 2.15
0.97, 2.36
0.99, 2.36
0.90,5.48

0.0002
0.0001
0.03
0.06
0.04
0.002
0.74
0.31
0.71
0.07
0.05
0.08

26.39
9.29
4.46
2.71
4.32
52.53
1.43
2.30
2.00
8.41
10.26
2.66

CAD: coronary artery disease; TPA: total plaque area; cIMT: carotid intima-media thickness; HDL: high-density lipoprotein; LDL: low-density
lipoprotein; OR: odds ratio; CI: confidence interval.

a binary outcome (the presence or absence of a

plaque). Despite that advantage of TPA, it has
not been widely used in the research of atherosclerosis in SLE.22 This may be partially related
to the more technically challenging scanning technique that involves the measurement of plaque
area as opposed to the simple method of measuring IMT.
The moderate correlation between TPA and
cIMT probably reects the fact that they measure
two partially dierent phenotypes of vessel wall
insult.23 Two dierent pathological processes
may lead to these two dierent phenotypes. The
rst process involves a hypertrophy of the media
layer as a result of aging and hypertension leading
to IMT of the common carotid artery. The second
process involves plaque formation mostly in the
bulb and the internal carotid artery that represents an advanced stage of atherosclerosis and is
similar to the plaques that are found in the coronary arteries. This hypothesis has been supported by histological ndings of the carotid
artery.20,24
Our study suggests that the high risk of developing CAD in SLE is mediated primarily by atherosclerosis. Although other mechanisms such as
vasoconstriction, increased coagulability due to
antiphospholipid antibodies and vascular insult
due to autoantibodies may contribute to the occurrence of such events, the primary lesion remains the
atherosclerotic plaque. In fact, in our study the
great majority of the patients with CAD had a signicant burden of atherosclerosis. Although this
association is cross sectional, this is the rst study
in SLE patients that shows an association between

direct structural imaging of atherosclerosis and

CAD. Recently, Kao et al. reported that among
392 patients with SLE who were followed prospectively for eight years, both cIMT and the presence of
plaques predicted incident cardiovascular events. It
should be noted, however, that the measurement of
IMT in this study included the internal carotid and
the carotid bulb, therefore likely plaques were part
of the measurement.25
Our study had several limitations, including the
relatively small sample size, the lack of information
about several potential confounders such as sedentary lifestyle, the cross-sectional nature of association between US measures of atherosclerosis and
CAD that precluded rm causal association.
Finally, we did not measure other properties of atherosclerosis, such as plaque vulnerability which
may aect the occurrence of clinical events.
In summary, in this study we have found an
association between two ultrasonographic measures of atherosclerosis, cIMT and TPA, and prevalent CAD in patients with SLE. Furthermore, TPA
was more strongly associated with CAD and traditional cardiovascular risk factors, suggesting that it
may serve as a better surrogate for clinical CAD in
SLE patients. These ndings require conrmation
in prospective observational studies to establish this
association.

Funding
This research received no specic grant from any
funding agency in the public, commercial, or notfor-prot sectors.
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1148

Conflict of interest statement

The authors have no conicts of interest to declare.

Acknowledgments
The Lupus Clinic is supported by University Health
Network, the Arthritis Foundation, and the
Toronto General-Toronto Western Hospital
Foundation.

References
1 Thomas GN, Tam LS, Tomlinson B, Li EK. Accelerated atherosclerosis in patients with systemic lupus erythematosus: A review of
the causes and possible prevention. Hong Kong Med J 2002; 8:
2632.
2 Urowitz MB, Bookman AA, Koehler BE, Gordon DA, Smythe
HA, Ogryzlo MA. The bimodal mortality pattern of systemic
lupus erythematosus. Am J Med 1976; 60: 221225.
3 Nikpour M, Urowitz MB, Gladman DD. Premature atherosclerosis in systemic lupus erythematosus. Rheum Dis Clin North Am
2005; 31: 329354. (vii-viii).
4 Roman MJ, Shanker BA, Davis A, et al. Prevalence and correlates
of accelerated atherosclerosis in systemic lupus erythematosus.
N Engl J Med 2003; 349: 23992406.
5 Goldberg RJ, Urowitz MB, Ibanez D, Nikpour M, Gladman DD.
Risk factors for development of coronary artery disease in women
with systemic lupus erythematosus. J Rheumatol 2009; 36:
24542461.
6 OLeary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL,
Wolfson SK Jr. Carotid-artery intima and media thickness as a risk
factor for myocardial infarction and stroke in older adults.
Cardiovascular Health Study Collaborative Research Group.
N Engl J Med 1999; 340: 1422.
7 Spence JD, Eliasziw M, DiCicco M, Hackam DG, Galil R,
Lohmann T. Carotid plaque area: A tool for targeting and evaluating vascular preventive therapy. Stroke 2002; 33: 29162922.
8 Anania C, Gustafsson T, Hua X, et al. Increased prevalence of
vulnerable atherosclerotic plaques and low levels of natural IgM
antibodies against phosphorylcholine in patients with systemic
lupus erythematosus. Arthritis Res Ther 2010; 12: R214.
9 Oryoji K, Kiyohara C, Horiuchi T, et al. Reduced carotid intimamedia thickness in systemic lupus erythematosus patients treated
with cyclosporine A. Mod Rheumatol 2014; 24: 8692.
10 Mok CC. Accelerated atherosclerosis, arterial thromboembolism,
and preventive strategies in systemic lupus erythematosus. Scand J
Rheumatol 2006; 35: 8595.

Lupus

11 Hansson GK, Robertson AK, Soderberg-Naucler C. Inflammation

and atherosclerosis. Annu Rev Pathol 2006; 1: 297329.
12 Blasi C. The autoimmune origin of atherosclerosis. Atherosclerosis
2008; 201: 1732.
13 Hochberg MC. Updating the American College of Rheumatology
revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725.
14 Gladman DD, Urowitz MB, Goldsmith CH, et al. The reliability
of the Systemic Lupus International Collaborating Clinics/
American College of Rheumatology Damage Index in patients
with systemic lupus erythematosus. Arthritis Rheum 1997; 40:
809813.
15 Touma Z, Urowitz MB, Gladman DD. SLEDAI-2K for a 30-day
window. Lupus 2010; 19: 4951.
16 Spence JD. Technology insight: Ultrasound measurement of carotid plaquepatient management, genetic research, and therapy
evaluation. Nat Clin Pract Neurol 2006; 2: 611619.
17 Spence JD, Barnett PA, Bulman DE, Hegele RA. An approach to
ascertain probands with a non-traditional risk factor for carotid
atherosclerosis. Atherosclerosis 1999; 144: 429434.
18 Polak JF, Pencina MJ, Pencina KM, ODonnell CJ, Wolf PA,
DAgostino RB Sr. Carotid-wall intima-media thickness and cardiovascular events. N Engl J Med 2011; 365: 213221.
19 Inaba Y, Chen JA, Bergmann SR. Carotid plaque, compared with
carotid intima-media thickness, more accurately predicts coronary
artery disease events: A meta-analysis. Atherosclerosis 2012; 220:
128133.
20 Finn AV, Kolodgie FD, Virmani R. Correlation between carotid
intimal/medial thickness and atherosclerosis: A point of view from
pathology. Arterioscler Thromb Vasc Biol 2010; 30: 177181.
21 Johnsen SH, Mathiesen EB, Joakimsen O, et al. Carotid atherosclerosis is a stronger predictor of myocardial infarction in women
than in men: A 6-year follow-up study of 6226 persons: The
Tromso Study. Stroke 2007; 38: 28732880.
22 Ravenell RL, Kamen DL, Spence JD, et al. Premature atherosclerosis is associated with hypovitaminosis D and angiotensinconverting enzyme inhibitor non-use in lupus patients. Am J Med
Sci 2012; 344: 268273.
23 Spence JD. Carotid plaque measurement is superior to IMT
Invited editorial comment on: Carotid plaque, compared with carotid intima-media thickness, more accurately predicts coronary
artery disease events: A meta-analysis-Yoichi Inaba, M.D.,
Jennifer A. Chen M.D., Steven R. Bergmann M.D., Ph.D.
Atherosclerosis 2012; 220: 3435.
24 Rundek T, Arif H, Boden-Albala B, Elkind MS, Paik MC,
Sacco RL. Carotid plaque, a subclinical precursor of vascular
events: The Northern Manhattan Study. Neurology 2008; 70:
12001207.
25 Kao AH, Lertratanakul A, Elliott JR, et al. Relation of carotid
intima-media thickness and plaque with incident cardiovascular
events in women with systemic lupus erythematosus. Am J
Cardiol 2013; 112: 10251032.

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