Lupus (2014) 23, 1142–1148

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 UrowitzUniversity 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 ofcarotid intima-media thickness (cIMT) and total plaque area (TPA). We aimed to investigatethe correlation between measures of atherosclerosis as documented on imaging studies of thecarotid vasculature and clinical coronary artery disease (CAD) in systemic lupus erythemato-sus (SLE). Methods: The study patients were recruited from the University of Toronto pro-spective cohort of SLE patients. Patients who had a history of CAD were compared to thosewithout CAD. TPA and cIMT were measured using high-resolution optimized ultrasoundsystems. Logistic regression models were used to investigate the strength of associationbetween ultrasound measures of atherosclerosis and CAD. The strength of association asexpressed by odds ratio (OR) was compared between TPA and cIMT. Results: A total of103 SLE patients were analyzed (27 patients with a history of CAD). Carotid IMT correlatedonly moderately with TPA (r¼ 0.43, p< 0.001). Both measures were significantly associatedwith the presence of CAD. However, TPA showed a stronger association than cIMT (OR 9.55vs. 2.02, respectively). TPA was also more strongly associated with dyslipidemia and hyper-tension compared to cIMT. Conclusions: In SLE patients, cIMT correlates only moderatelywith TPA, suggesting that they measure different phenotypes of atherosclerosis. Carotid TPAcorrelated better than cIMT with cardiovascular risk factors and CAD, suggesting that it mayserve as a better tool for the investigation of atherosclerosis in SLE. Lupus (2014) 23, 1142–1148.

Key words: Atherosclerosis; lupus; ultrasound; surrogate measures

Introduction

Patients with systemic lupus erythematosus (SLE)have a significantly increased risk of acceleratedatherosclerosis and clinical coronary artery disease(CAD). Compared to the general population,women with SLE have a five- to six-fold increasedrisk of CAD.1–4 Several clinical risk scores thatwere designed to estimate cardiovascular risk inindividuals without known CAD, such as theFramingham risk score, do not correlate well withcardiovascular events in patients with SLE.5 Thesescores underestimate the actual risk for CAD inthese patients partially because they don’t considerSLE as an independent risk factor.

Evidence from both observation and interven-tion studies support the use of ultrasound (US)imaging for quantifying atherosclerosis of the car-otid arteries using the measurements of carotidintima-media thickness (cIMT) and total plaquearea (TPA) as surrogate measures for clinical car-diovascular events.6,7 Despite their frequent use instudies, the correlation between these ultrasono-graphic measures of atherosclerosis and clinicalCAD has not been investigated in SLE patients.Numerous studies that used various imaging mod-alities have shown that the prevalence of athero-sclerostic plaques is higher in SLE compared tohealthy controls; the extent of plaques, as measuredby TPA, has not been thoroughly investigated inthis population. Furthermore, several recent publi-cations reported similar levels of IMT in SLE andcontrols.8,9

Although both cIMT and TPA predict theoccurrence of CAD in the general population, thepathogenesis of such events in SLE patients mayinvolve additional mechanisms other than

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 10.1177/0961203314537696

atherogenesis and plaque rupture as occur in thegeneral population. Since traditional cardiovascu-lar risk factors only poorly predict cardiovascularevents in SLE patients, additional ‘‘lupus-specific’’mechanisms may play a role. Some of the suggestedmechanisms include endothelial dysfunction,thrombotic tendency due to antiphospholipid anti-bodies and lupus-related vasculopathy.10–12 Theability of surrogate measures of atherosclerosis topredict ischemic events in SLE may be low if thepathogenesis of clinical events is related to thesemechanisms. Therefore, the investigation of theassociation between US measures of atherosclerosisand CAD in SLE patients is an important first stepto justify their use as surrogates of clinical events.

In this study we aimed to investigate the correl-ation between measures of atherosclerosis as deter-mined on imaging studies of the carotid vasculatureand clinical CAD in SLE patients. In addition, thestrength of association between each of the meas-ures of atherosclerosis, cIMT and TPA, and CADwas compared. We hypothesized that the associ-ation between TPA and CAD will be strongerthan between cIMT and CAD.

Methods

Study population and data collection

In this cross-sectional study a group of SLEpatients with documented CAD was comparedwith a group of patients who did not have a historyof CAD. The study population included adult(aged > 18 years) SLE patients satisfying theAmerican College of Rheumatology (ACR) criteriafor classification of SLE.13 They were recruitedfrom the University of Toronto lupus cohort thatnumbers more than 1500 patients. All of thepatients in the lupus clinic participate in a long-term prospective cohort study that assesses prog-nostic factors in SLE. The patients are followedin the lupus clinic at the Toronto WesternHospital every two to six months according to astandard protocol using validated clinical measure-ment tools. Information about cardiovascular riskfactors, including hypertension, dyslipidemia, dia-betes and smoking, is collected routinely andentered into a computerized database. Any incidentischemic cardiovascular events including myocar-dial infarction (MI) and angina pectoris, as wellas reports of any diagnostic procedure for cardio-vascular disease including myocardial perfusionscan or coronary angiogram, are collected andentered into the database. In addition, information

about lupus activity and accrual of damage wasrecorded using the Systemic Lupus ErythematosusDisease Activity Index-2000 (SLEDAI-2K) and theSystemic Lupus International Collaborating Clinics(SLICC)/ACR Damage Index (SDI).14,15

Patient selection and definition of CAD

The clinic database was searched for patients whohad a history of documented MI or angina pectoris.Since the underlying mechanism of stroke in SLEdoes not necessarily involve atherosclerosis,patients with a history of stroke or transient ische-mic attack (TIA) who did not have CAD wereexcluded. The patients’ charts were reviewed andonly those with documented CAD events that ful-filled the pre-defined definitions were included. MIwas defined by at least two of the following: symp-toms of myocardial ischemia, typical electrocardio-graphic changes, and elevated myocardial enzymes.Angina pectoris was defined as chest discomfortthat was aggravated by physical activity andrelieved by rest or the use of nitroglycerine andconfirmed by a cardiologist or abnormal findingson myocardial perfusion study or angiography.Patients with equivocal findings were excluded.Eligible patients were then approached andrecruited during their clinic visit.

Consecutive SLE patients who did not have ahistory of the following conditions: MI, angina pec-toris, abnormal findings in coronary angiogram orcardiac perfusion scan, stroke, TIA, ischemic heartfailure, stroke, carotid endarterectomy and periph-eral vascular disease, were recruited during theirclinic follow-up visits to serve as the control group.

Cardiovascular risk factor assessment

Blood pressure was measured and subjects wereconsidered to have hypertension if they weretaking antihypertensive agents or if they had a sys-tolic blood pressure of >140mmHg and/or a dia-stolic pressure of >90mmHg. Lipid profile wasanalyzed for total cholesterol, low-density lipopro-tein (LDL), high-density lipoprotein (HDL) andtriglycerides (TG) after a 12-hour fast. Total chol-esterol levels > 5.2mmol/l and LDL> 3.4mmol/lwere considered to be high while HDL levels ofless than 0.77mmol/l in men and less than0.9mmol/l in women were considered low.Dyslipidemia was defined as having elevated levelsof LDL or low levels of HDL or the use of lipid-lowering agents. Smoking status was also recorded.Diabetes mellitus was defined as the use of antidia-betes medications or fasting glucose levels>7mmol/l.

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US assessment

Ultrasonographic measurements of TPA and cIMTwere performed using a high-resolution optimizedUS system for carotid imaging (Esaote MyLab 30,Genoa, Italy) by a single trained physician (LE). Alinear 12-5 probe with a central frequency of8.5MHz was used (Esaote).

The scan included detailed B-mode images ofboth right and left common carotid arteries aswell as the carotid bulb, internal carotid and exter-nal carotid arteries. The mean cIMT was measuredautomatically at the far wall of the right and leftcommon carotid arteries at least 1 cm proximallyfrom the origin of the bulb using a real timeradio-frequency-based US system for carotid ima-ging (QIMT tool; Esaote). The composite meancIMT was calculated by averaging the commonright and left cIMT values. An atheroscleroticplaque was defined as a localized thickening ofthe intima layer exceeding 1mm. The burden ofatherosclerotic plaques was measured by the caro-tid TPA.16 Each plaque was scanned in a longitu-dinal view until the maximum area of the plaquewas in the plane of view. The image was then frozenand magnified and the plaque area was measuredby tracing the perimeter with a cursor (Figure 1).TPA was recorded as the sum of all plaques fromthe clavicle to the jaw in the right and left carotidarteries. TPA was scored 0 in patients withoutatherosclerostic plaques. Reading of the US scanswas performed independently from the scanning.The scans were recorded in digital media and readat a separate location and later date after blindingfor personal data. Reproducibility and intra-observer variation were checked by rereading 25images of the study subjects on different days.

The intra-observer intra-class correlation coeffi-cient for TPA was 0.94.

Statistical analysis

Descriptive statistics (mean and standard deviationfor continuous variables and percentages for cat-egorical variables) were used to compare clinicaland laboratory characteristics in the two groups.The correlation between cIMT and TPA wasassessed by Pearson correlation coefficient. MeanTPA and cIMT were compared in patients withand without a history of CAD using the two-tailed t test. To facilitate direct comparisons,cIMT and TPA were transformed into z scores.Individual logistic regression models were fit withCAD and cardiovascular risk factors as binary out-comes and z score of either TPA or cIMT as anindependent variable. The strength of associationas expressed by odds ratio (OR) was comparedbetween TPA and cIMT. The effect of covariateswas considered as statistically significant if the pvalue from the two-sided Wald test was <0.05.The statistical computation was performed usingSAS V.9.2.

Results

A total of 54 patients who have had history ofCAD and were regularly assessed in the lupusclinic were identified in the database. Of those,nine patients were excluded for equivocal diagnosisof CAD. Of the remaining patients, we were able torecruit 25 patients. Two additional patients whodid not have a history of CAD at the time of enroll-ment but developed acute MI by the time the studywas completed were included in the CAD group.The median interval of time between the occurrenceof the CAD event and the US scan was 8.2 years(range 2.4–22 years) for the 25 patients who havehad a history of CAD at the time of recruitment.The control group included 76 patients who did nothave a history of CAD.

The characteristics of the study population aredetailed in Table 1.

Comparison of patients with and without CAD

Patients who had a history of CAD were morelikely to be men (p¼ 0.0003), Caucasians(p¼ 0.03), were older (p¼ 0.0008) and had alonger duration of SLE at the time of assessment(p< 0.0001). With respect to cardiovascular riskfactors, patients with CAD were more likely to be

Figure 1: Measurement of plaque area at the bulb of thecarotid artery (marked in yellow, a total of 0.12 cm2).

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hypertensive (p¼ 0.0006), ever smokers (p¼ 0.02),and to have dyslipidemia (p¼ 0.0003) and diabetesmellitus (p¼ 0.004). Patients with CAD also hadhigher SDI scores (p< 0.0001) and have usedhigher cumulative doses of corticosteroid(p¼ 0.02) (Table 2).

The correlation between US measures ofatherosclerosis and CAD

The correlation between TPA and cIMT was onlymoderate (r¼ 0.43, p< 0.001, Figure 2), suggestingthat they measure partially different constructs.Both TPA and cIMT were significantly higher in

patients with CAD compared to those withoutCAD (0.43� 0.49 vs. 0.06� 0.12, p< 0.0001 and688.8� 102.4 vs. 587.6� 102.4, p¼ 0.0007, respect-ively). The presence of atherosclerotic plaques(TPA> 0) was higher in patients with CAD com-pared with those without CAD (88.8% vs. 37.3%,p¼ 0.0001, respectively). Furthermore, TPA wasmore strongly associated with CAD than wascIMT (OR 9.55 vs. 2.87, respectively, Table 3).Only three out of the 27 patients with CAD hadno evidence of plaque (TPA¼ 0), of those onepatient developed MI due to an occlusive bloodclot in the left anterior descending artery secondaryto antiphospholipid syndrome and the remainingtwo patients had angina pectoris one of themwith abnormal findings on angiography.Furthermore, the two patients who developed clin-ical CAD following the US assessment had carotidplaques (TPA of 0.08 and 0.23 cm2). TPA was alsomore strongly associated with hypertension, dysli-pidemia and ever smoking compared to cIMT(Table 3). No association was observed with dia-betes, total cholesterol, HDL and LDL levels.

Discussion

With the improvement in survival, the accrual ofdamage, especially atherosclerosis-related diseases,has become a major issue in the management ofpatients with SLE. Nevertheless, incident cardio-vascular events are still relatively infrequent, andthe investigation of cardiovascular diseases inSLE is limited by the need to follow large groupsof patients for many years. This limitation hasprompted the use of surrogate measures for clinicalevents such as the imaging of atherosclerosis. Inthis study we have investigated the correlationbetween two ultrasonographic measures of athero-sclerosis and prevalent CAD. We have found thatboth cIMT and TPA correlate with CAD.However, TPA was more strongly associated withCAD and with cardiovascular risk factors thancIMT, suggesting that it may serve as a better sur-rogate measure for clinical CAD.

Although the measurement of cIMT is a univer-sally accepted US phenotype of atherosclerosis, ithas several limitations. cIMT measures the totalthickness of the intima and the media layers ofthe carotid artery wall. cIMT is made up ofapproximately 80% media and 20% intima,whereas atherosclerosis is largely an intimal pro-cess. Furthermore, traditional coronary risk factorsaccount for only 15%–17% of the cIMT while the

Table 1 Characteristics of the study population (N¼ 103)

Age (years) 55.2� 12.0

Sex Female 93 (90.3%)

Race Caucasian 70 (68.0%)

Black 13 (12.6%)

Asian 9 (8.7%)

Other 11 (10.7%)

Age at SLE diagnosis (years) 35.6� 13.5

Disease duration (years) 19.1� 12.5

Blood pressure 74.0� 10.3

Diastolic (mmHg) 125.1� 15.8

Systolic (mmHg) 57 (55.9%)

Use of antihypertensive medications 61 (59.2%)

Hypertensiona

Elevated total cholesterol 23 (22.3%)

Elevated LDL-c 6 (6.0%)

Low HDL-c 11 (11.0%)

Use of lipid-lowering therapy 38 (37.6%)

Statins 32 (31.1%)

Nicotinic acid 1 (1%)

Fibrates 3 (3%)

Combinations 1 (1%)

Dyslipidemiab 50 (49.0%)

Smoker current 8 (7.8%)

Ever 36 (35.3%)

Renal involvement everc 58 (56.3%)

Steroids at the time of assessment 48 (46.6%)

Ever 86 (83.5%)

Cumulative steroids dose (gr)d 45.3� 42.7

SDI 2.2� 2.3

SLEDAI-2K at the time of assessment 3.3� 3.7

Carotid intima media thickness (mm) 614.1� 110.1

Total plaque area (cm2) 0.16� 0.31

aDiastolic blood pressure > 90 or systolic blood pressure > 140 or the

use of antihypertensive medications.bElevated LDL or low HDL or the use of a lipid-lowering medication.cNephrotic syndrome or dialysis or renal transplant or serum creatin-

ine > 140 or the presence of urinary cellular casts or proteinuria with or

without hematuria and pyuria.dCumulative steroids dose evaluated only in patients who have ever

been on steroids. SLE: systemic lupus erythematosus; LDL-c: low-

density lipoprotein cholesterol; HDL-c: high-density lipoprotein chol-

esterol; SDI: Systemic Lupus International Collaborating Clinics/

American College of Rheumatology Damage Index; SLEDAI-2K:

Systemic Lupus Erythematosus Disease Activity Index-2000.

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most important factors that account for increasedcIMT are age and high blood pressure.6 On theother hand, each one of the traditional cardiovas-cular risk factors is independently associated

with TPA.17 Furthermore, the presence of plaqueis a stronger predictor of CAD than elevated cIMTafter adjustment for traditional cardiovascular riskfactors.18,19 It was therefore hypothesized thatcIMT and TPA represent different phenotypes ofvessel wall insult.20 Most studies that investigatedatherosclerosis in SLE have used cIMT as an out-come measure while only a few have used TPA as asurrogate measure of atherosclerosis burden inthese patients.

The weaker association of cIMT with CAD is inagreement with studies in the general popula-tion.18,19,21 In fact, when measured in thecommon carotid artery, cIMT only weakly correl-ates with clinical cardiovascular events especially inwomen, while its measurement in the bulb or inter-nal carotid artery results in better predictiveability.21 While the mere presence of plaques isstrongly associated with clinical CAD, the use ofTPA provides a continuous measurement that rep-resents the burden of atherosclerosis as opposed to

Table 2 Comparison of SLE patients with and without CAD

Mean� std or frequency (%) Logistic regression

No CAD (n¼ 76) CAD (n¼ 27) p value OR 95% CI p value

Sex: Female 74 (97.4%) 19 (70.4%) 0.0003 0.16 0.01,0.32 <0.0001

Race: Caucasian 47 (61.8%) 23 (85.2%) Caucasian 3.5 1.1, 11.3 0.03

Black 11 (14.5%) 2 (7.4%) vs. other

Asian 9 (11.8%) 0 (0%) 0.03

Other 9 (11.8%) 2 (7.4%)

Age at SLE diagnosis (years) 36.0� 12.9 34.7� 15.3 0.67 0.99 0.96, 1.03 0.67

Age at the time of assessment (years) 52.8� 10.7 61.7� 13.3 0.0008 1.07 1.03, 1.12 0.002

Age at occurrence of CAD 53.3� 11.7

Disease duration at the time of assessment (years) 16.4� 10.8 27.0� 13.6 <0.0001 1.08 1.03, 1.12 0.0004

Blood pressure 73.6� 9.9 75.1� 11.4 0.53 1.0 1.0, 1.1 0.52

Diastolic (mmHg) 123.5� 15.1 129.3� 16.9 0.10 1.0 1.0, 1.1 0.11

Systolic (mmHg) 32 (42.7%) 25 (92.6%) <0.0001 16.8 3.7, 76.1 0.0003

Use of antihypertensive medications 36 (47.4%) 25 (92.6%) <0.0001 13.9 3.1, 62.8 0.0006

Hypertension

Elevated total cholesterol 18 (23.7%) 5 (18.5%) 0.58 0.7 0.2, 2.2 0.58

Elevated LDL 9 (12.2%) 2 (7.7%) 0.72 0.6 0.1, 3.0 0.53

Low HDL 3 (4.1%) 3 (11.5%) 0.18 0.3 0.1, 1.7 0.19

Use of lipid-lowering 19 (25.7%) 19 (70.4%) <0.0001 6.9 2.6, 18.3 0.0001

agents Dyslipidemia 28 (37.3%) 22 (81.5%) <0.0001 7.4 2.5, 21.7 0.0003

Smoker current 5 (6.6%) 3 (11.1%) 0.43 1.8 0.4, 8.0 0.45

Ever 25 (32.9%) 15 (59.3%) 0.02 3.0 1.2, 7.3 0.02

Diabetes mellitus 0 (0%) 4 (14.8%) 0.004 NA NA NA

Renal involvement ever 39 (51.3%) 19 (70.4%) 0.09 2.3 0.9, 5.8 0.09

Steroids at the time of assessment 33 (43.4%) 15 (55.6%) 0.28 1.6 0.7, 3.9 0.28

Ever 61 (80.3%) 25 (92.6%) 0.23 3.1 0.7, 14.4 0.15

Cumulative steroids dose (gr)a 38.4� 38.2 62.8� 48.9 0.02 1.01 1.00, 1.02 0.02

SDI 1.3� 1.5 4.4� 2.8 <0.0001 2.1 1.6, 2.9 <0.0001

SLEDAI-2K at the time of assessment 3.0� 3.4 4.1� 4.5 0.20 1.1 1.0, 1.2 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.aCumulative 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).

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a binary outcome (the presence or absence of aplaque). Despite that advantage of TPA, it hasnot been widely used in the research of athero-sclerosis in SLE.22 This may be partially relatedto the more technically challenging scanning tech-nique that involves the measurement of plaquearea as opposed to the simple method of measur-ing IMT.

The moderate correlation between TPA andcIMT probably reflects the fact that they measuretwo partially different phenotypes of vessel wallinsult.23 Two different pathological processesmay lead to these two different phenotypes. Thefirst process involves a hypertrophy of the medialayer as a result of aging and hypertension leadingto IMT of the common carotid artery. The secondprocess involves plaque formation mostly in thebulb and the internal carotid artery that repre-sents an advanced stage of atherosclerosis and issimilar to the plaques that are found in the cor-onary arteries. This hypothesis has been sup-ported by histological findings of the carotidartery.20,24

Our study suggests that the high risk of develop-ing CAD in SLE is mediated primarily by athero-sclerosis. Although other mechanisms such asvasoconstriction, increased coagulability due toantiphospholipid antibodies and vascular insultdue to autoantibodies may contribute to the occur-rence of such events, the primary lesion remains theatherosclerotic plaque. In fact, in our study thegreat majority of the patients with CAD had a sig-nificant burden of atherosclerosis. Although thisassociation is cross sectional, this is the first studyin SLE patients that shows an association between

direct structural imaging of atherosclerosis andCAD. Recently, Kao et al. reported that among392 patients with SLE who were followed prospect-ively for eight years, both cIMT and the presence ofplaques predicted incident cardiovascular events. Itshould be noted, however, that the measurement ofIMT in this study included the internal carotid andthe carotid bulb, therefore likely plaques were partof the measurement.25

Our study had several limitations, including therelatively small sample size, the lack of informationabout several potential confounders such as seden-tary lifestyle, the cross-sectional nature of associ-ation between US measures of atherosclerosis andCAD that precluded firm causal association.Finally, we did not measure other properties of ath-erosclerosis, such as plaque vulnerability whichmay affect the occurrence of clinical events.

In summary, in this study we have found anassociation between two ultrasonographic meas-ures of atherosclerosis, cIMT and TPA, and preva-lent CAD in patients with SLE. Furthermore, TPAwas more strongly associated with CAD and trad-itional cardiovascular risk factors, suggesting that itmay serve as a better surrogate for clinical CAD inSLE patients. These findings require confirmationin prospective observational studies to establish thisassociation.

Funding

This research received no specific grant from anyfunding agency in the public, commercial, or not-for-profit sectors.

Table 3: The association between the presence of CAD, cardiovascular risk factors and atherosclerosis

TPA-Z score cIMT-Z Score

OR 95% CI p value OR 95% CI p value

CAD 9.55 3.46, 26.39 <0.0001 2.87 1.65, 5.02 0.0002

Age� 50 3.50 1.32, 9.29 0.01 3.80 1.93, 7.45 0.0001

Sex: Male 2.34 1.23, 4.46 0.01 2.02 1.07, 3.80 0.03

Smoking: current 1.36 0.68, 2.71 0.38 1.60 0.99, 2.59 0.06

Ever 2.25 1.17, 4.32 0.02 1.53 1.01, 2.35 0.04

Hypertension 11.67 2.59, 52.53 0.001 2.22 1.34, 3.69 0.002

High total cholesterol 0.68 0.32, 1.43 0.30 1.08 0.68, 1.72 0.74

Low HDL 1.37 0.81, 2.30 0.24 1.50 0.69, 3.30 0.31

High LDL 0.81 0.33, 2.00 0.65 1.13 0.60, 2.15 0.71

The use of lipid-lowering agents 3.77 1.69, 8.41 0.001 1.51 0.97, 2.36 0.07

Dyslipidemia 4.14 1.67, 10.26 0.002 1.53 0.99, 2.36 0.05

Diabetes mellitus 1.56 0.92, 2.66 0.10 2.22 0.90,5.48 0.08

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.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Acknowledgments

The Lupus Clinic is supported by University HealthNetwork, the Arthritis Foundation, and theToronto General-Toronto Western HospitalFoundation.

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