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Home » Meeting Abstracts » ACR/ARHP Annual Meeting 2013

Abstract Number: 597

Low Complement (C3), Male Gender and Methotrexate Use Are Associated With Noncalcified Plaque In Systemic Lupus Erythematosus

Adnan Kiani1, Armin Zadeh2, Jens Vogel-Claussen1, Joao Lima2, Laurence S. Magder3 and Michelle Petri1, 1Johns Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins University, Baltimore, MD, 3Department of Epidemiology and Public Health, University of Maryland, Baltimore, MD

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Meeting: ACR/ARHP Annual Meeting 2013

Keywords: Systemic lupus erythematosus (SLE)

Session Information

Title: Systemic Lupus Erythematosus - Clinical Aspects I - Renal, Malignancy, Cardiovascular Disease

Session Type: Abstract Submissions (ACR)

Background/Purpose:

New technology (CTA) can measure non-calcified coronary plaque (NCP), which is highly unstable and prone to rupture.  We quantified NCP in SLE and determined the association with SLE manifestations.

Methods:

64 (n=106) or 320 (n=156) slice coronary multidetector computed tomography (MDCT) was performed in 262 SLE patients (90% female, 64% Caucasian, 30% African-American, mean age 50 years). The MDCT scans were evaluated quantitatively by a radiologist, using dedicated software.  NCP score was a sum of plaque severity multiplied by the plaque composition divided by the number of vessels examined.

Results:

Table 1 shows the mean NCP score, by demographics, traditional cardiovascular risk factors, history of lupus serologies and current medications.  In the univariate analysis age, male gender, weight and hypertension were the major variables associated with NCP.  A history of low complement (C3,C4) and anti-dsDNA (but not current) was associated with NCP.  Prednisone and hydroxychloroquine therapy had no effect, but methotrexate use was associated with NCP.  Table 2 shows the multivariate regression model, in which age, male gender, history of low C3 and methotrexate use remained independent predictors. 

Table 1: Mean NCP Score, by Demographics, Traditional CVRF, History of Lupus Serologies and Current Medications

 

Group

Mean NCP Score

p-value

p-value when age is controlled

Age

<45 (n=110)

0.13 (0.20)

<0.0001

—

 

45-55 (n=81)

0.26 (0.29)

 

55+ (n=70)

0.42 (0.32)

Race

White (n=167)

0.26 (0.30)

0.29

0.88

 

Black (n=76)

0.26 (0.26)

Gender

F (n=236)

0.23 (0.26)

0.015

0.031

 

M (n=26)

0.38 (0.44)

History of Smoking

No (n=168)

0.25 (0.29)

0.88

0.20

 

Yes (n=94)

0.24 (0.28)

Menopause

No (n=120)

0.20 (0.25)

0.0060

0.030

 

Yes (n=104)

0.29 (0.28)

Weight

<150 (n=93)

0.18 (0.25)

0.00611

0.0302

 

150-199 (n=113)

0.27 (0.30)

 

200+ (n=49)

0.33 (0.31)

Body Mass Index

<25 (n=97)

0.18 (0.28)

0.00943

0.0724

 

25-29 (n=78)

0.27 (0.31)

 

30+ (n=80)

0.31 (0.27)

Hypertension

No (n=98)

0.17 (0.22)

0.0009

0.0091

 

Yes (n=164)

0.29 (0.30)

Anti-ds DNA

No (n=100)

0.24 (0.26)

0.61

0.049

 

Yes (n=162)

0.26 (0.30)

Anticardiolipin

No (n=91)

0.23 (0.28)

0.38

0.60

 

Yes (n=169)

0.26 (0.29)

Low C3

No (n=116)

0.20 (0.27)

0.15

0.0038

 

Yes (n=146)

0.27 (0.30)

Low C4

No (n=137)

0.24 (0.30)

0.83

0.024

 

Yes (n=125)

0.25 (0.27)

Current Prednisone

No (n=155)

0.26 (0.30)

0.36

0.91

 

Yes (n=79)

0.22 (0.28)

Current Hydroxychloroquine

No (n=42)

0.31 (0.29)

0.13

0.18

 

Yes (n=219)

0.24 (0.29)

Current Azathioprine

No (n=242)

0.25 (0.29)

0.87

0.92

 

Yes (n=20)

0.24 (0.21)

Current Methotrexate

No (n=250)

0.23 (0.27)

0.0002

0.0026

 

Yes (n=12)

0.54 (0.45)

Current MMF

No (n=209)

0.25 (0.29)

0.70

0.13

 

Yes (n=53)

0.23 (0.29)

Current NSAIDS

No (n=185)

0.25 (0.30)

0.97

0.32

 

Yes (n=76)

0.25 (0.26)

1 P<.0001 for trend with weight as a continuous predictor

2 P=.0014 for trend with weight as a continuous predictor, controlling for age

3 P=.0072 for trend with BMI as a continuous predictor

4 P=.036 for trend with BMI as a continuous predictor, controlling for age

Table 2:  Multivariable Regression Model for Mean NCP

Variable

Effect on mean NCP score (95% Confidence Interval)

P-value

Age (per 10 years)

0.094 (0.068, 0.120)

<0.0001

Low BMI (vs. normal)

-0.059 (-0.134, 0.015)

0.12

High BMI (vs. normal)

0.001 (-0.078, 0.081)

0.98

Hypertension

0.062 (-0.005, 0.130)

0.070

History of Low C3

0.091  (0.023, 0.159)

0.0090

History of anti-dsDNA

0.017 (-0.053, 0.086)

0.64

Male sex

0.112 (0.011, 0.214)

0.030

Methotrexate

0.248 (0.100, 0.395)

0.0011

 

Conclusion:

NCP is a measure of immediate risk of a cardiovascular event and contributes to overall atherosclerotic burden.  Male gender, history of low C3 and hypertension associate with semi-quantified noncalcified plaque in SLE.  The association with methotrexate is unexpected, as in rheumatoid arthritis methotrexate reduces cardiovascular risk.  Methotrexate can increase homocysteine, a known risk factor for atherosclerosis, in SLE.  However, methotrexate is also preferentially used to treat lupus arthritis.  Because causality cannot be proven, we cannot recommend stopping the use of methotrexate in SLE at this time.


Disclosure:

A. Kiani,
None;

A. Zadeh,
None;

J. Vogel-Claussen,
None;

J. Lima,
None;

L. S. Magder,
None;

M. Petri,
None.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/low-complement-c3-male-gender-and-methotrexate-use-are-associated-with-noncalcified-plaque-in-systemic-lupus-erythematosus/

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