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.

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