Plasma Myeloperoxidase Levels Are Inversely Associated with Carotid Plaque in SLE

Maureen A. McMahon^1,2, Jennifer M. Grossman^3,4,5, Lori Sahakian^6,7, Elaine Lourenco⁸, John FitzGerald^9,10, Christina Charles-Schoeman³, Alan Gorn^3,10, Michael Weisman¹¹, Daniel J Wallace^12,13, Bevra H. Hahn^3,14 and Brian Skaggs³, ¹Div of Rheumatology, UCLA David Geffen School of Medicine, Division of Rheumatology, Los Angeles, CA, ²Division of Rheumatology, UCLA David Geffen School of Medicine, Los Angeles, CA, ³Medicine, UCLA David Geffen School of Medicine, Division of Rheumatology, Los Angeles, CA, ⁴Div of Rheumatology, UCLA David Geffen School of Medicine, Los Angeles, CA, ⁵Rheumatology, UCLA, Los Angeles, CA, ⁶Division of Rheumatology, Department of Medicine, UCLA David Geffen School of Medicine, Division of Rheumatology, Los Angeles, CA, ⁷Division of Rheumatology, Department of Medicine,, UCLA David Geffen School of Medicine, Los Angeles, CA, ⁸UCLA David Geffen School of Medicine, Division of Rheumatology, Los Angeles, CA, ⁹Rheumatology, UCLA David Geffen School of Medicine, Division of Rheumatology, Los Angeles, CA, ¹⁰Rheumatology, UCLA David Geffen School of Medicine, Los Angeles, CA, ¹¹Rheumatology, Cedars-Sinai Medical Center, West Hollywood, CA, ¹²Division of Rheumatology, Cedars-Sinai Medical Center/David Geffen School of Medicine at UCLA, Los Angeles, CA, ¹³Cedars-Sinai Medical Center, West Hollywood, CA, ¹⁴Rheumatology, Professor Emeritus, Department of Medicine/Rheumatology, David Geffen School of Medicine UCLA, Los Angeles, CA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Atherosclerosis and myeloperoxidase (MPO)

Session Information

Date: Monday, November 9, 2015

Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

: Women with SLE have increased risk of atherosclerosis (ATH) that is not adequately explained by traditional risk factors. We previously discovered that a high risk score on a panel of traditional and novel biomarkers, the PREDICTS score, confers 28-fold increased odds for the presence of any current, progressive, or acquired carotid plaque, both in patients with SLE and in control subjects, and is significantly associated with higher rates of IMT progression. The biomarkers included in the panel are sTWEAK (≥373 pg/mL), pro-inflammatory HDL (piHDL), age≥48, homocysteine ≥ 12 mmol/L, leptin ≥34 ng/dL, and DMII. It is unknown, however, whether other biomarkers of oxidative stress predict future progression of ATH in SLE.

Myeloperoxidase (MPO) is an enzyme and heme protein that catalyzes the formation of several reactive oxygen species, and has been linked to inflammation and ATH in the general population. Furthermore, MPO is present in NETs, and has been implicated in the generation of piHDL. To determine whether plasma MPO levels might predict future development of subclinical ATH and whether piHDL might mediate this effect, we measured baseline plasma MPO levels and the progression piHDL function and of plaque using carotid ultrasound in a cohort of SLE patients.

Methods:

Female SLE subjects not taking statins at baseline were studied. B-mode and Doppler scanning of carotid arteries was performed at baseline and at 24-36 months. Plasma MPO levels were measured in the baseline blood samples using ELISA (R&D Biosystems).

Results:

Repeat carotid ultrasounds and MPO measurements were completed on 202 women with SLE. The mean age of the SLE group was 43.7 ± 12.5 years. Plaque progression (defined as new or increased plaque) was seen in 42 subjects (21%). Mean baseline plasma MPO levels were significantly lower in SLE patients with plaque progression compared to those without: 17.8 ± 15.2 pg/mL in patients with plaque progression vs. 38.2 ± 60.9 pg/mL in SLE without (p<0.001) However, there was no significant difference in baseline MPO levels among subjects with plaque presence at baseline. Baseline MPO levels were inversely correlated with pro-inflammatory HDL function at follow-up (r=-0.33, p<0.001), but no correlation between MPO levels and presence of pro-inflammatory HDL was observed at baseline. Using logistic regression to control for traditional cardiac risk factors and the PREDICTS risk profile, the variables still significantly associated with plaque progression in SLE included high PREDICTS (OR 27.0 p<0.001), MPO levels in the lowest half (OR 4.2, p=0.005), and non-Caucasian ethnicity (OR 4.5, p=0.003).

Conclusion:

Plasma MPO levels are significantly and independently inversely associated with plaque progression on carotid ultrasound in patients with SLE. Lower baseline MPO levels are also significantly associated with future formation of inflammatory piHDL, suggesting that this could be one mechanism to explain the association.

Disclosure: M. A. McMahon, None; J. M. Grossman, NIH, 2; L. Sahakian, None; E. Lourenco, None; J. FitzGerald, None; C. Charles-Schoeman, Pfizer Inc, 2,Pfizer Inc, 5; A. Gorn, None; M. Weisman, None; D. J. Wallace, None; B. H. Hahn, Merck, Exxagen, Biogen Idec, Bristol Myers Squibb, 5; B. Skaggs, None.

To cite this abstract in AMA style:

McMahon MA, Grossman JM, Sahakian L, Lourenco E, FitzGerald J, Charles-Schoeman C, Gorn A, Weisman M, Wallace DJ, Hahn BH, Skaggs B. Plasma Myeloperoxidase Levels Are Inversely Associated with Carotid Plaque in SLE [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/plasma-myeloperoxidase-levels-are-inversely-associated-with-carotid-plaque-in-sle/. Accessed .

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