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Abstract Number: 1509

Serum Nitrite Levels in Rheumatoid Arthritis and Relationship to Cardiovascular Risk Factors and Atherosclerosis Biomarkers

Kimberly P. Liang1, Douglas P. Landsittel2, Bernadette B. Sendon3, Donald M. Jones4, Rachel Gartland3, Suresh R. Mulukutla5, Steven E. Reis6, Flordeliza S. Villanueva5, Ali Hakim Shoushtari7, Cameron Dezfulian8 and Larry W. Moreland4, 1Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, 2Medicine, University of Pittsburgh, Pittsburgh, PA, 3Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, 4Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, 5Division of Cardiology, University of Pittsburgh, Pittsburgh, PA, 6Division of Cardiology and Department of Clinical and Translational Science, University of Pittsburgh, Pittsburgh, PA, 7Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, 8Critical Care Medicine and Clinical and Translational Science, University of Pittsburgh, Pittsburgh, PA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Atherosclerosis, Biomarkers, Cardiovascular disease, rheumatoid arthritis (RA) and risk

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Session Information

Date: Monday, November 9, 2015

Title: Rheumatoid Arthritis - Clinical Aspects Poster II

Session Type: ACR Poster Session B

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

Background/Purpose: Nitric oxide (NO) has been implicated in immune regulation, inflammation, arthritis and atherosclerosis. Raised levels of nitrite (NO2) in serum and synovial fluid have been reported in rheumatoid arthritis (RA). However, impaired NO bioavailability is a hallmark of endothelial dysfunction, an early step in atherosclerosis. Premature atherosclerosis is known to exist in RA. Plasma NO2 has been validated as an excellent measure of NO synthase activity and negatively correlated with CV risk factors in non-RA patients. This study aims to compare the levels of NO2 in RA and controls, and to evaluate the relationship of NO2 to traditional cardiovascular (CV) risk factors, subclinical atherosclerosis, and atherosclerosis biomarkers.

Methods: Traditional CV risk factors of smoking (current/ever vs. never), family history of CV disease, obesity, hypertension (HTN), hyperlipidemia, and diabetes were compared between RA subjects and controls using chi-squared or Fisher’s exact tests. Carotid ultrasounds were performed with measurement of intima-media thickness (cIMT, using maximum of both sides) and plaque presence (of either side), and serum biomarkers (ICAM-1, VCAM-1, E-selectin, MPO, IL-6, CD40L, and MMP-9) were measured by ELISA in all subjects (78 RA cases and 92 controls). NO2 was measured by chemiluminescence (39 RA and 50 controls). NO2 was compared between cases and controls, and between those with and without plaque or individual CV risk factors (both overall and by case status), using t-tests. The relationship between NO2 and each serum biomarker or cIMT was tested by Pearson correlations. The relationship between number of CV risk factors and NO2 or each biomarker was tested by Spearman correlations.

Results: All traditional CV risk factors were similar between RA and controls except for HTN, which was higher in RA (44.9%) than controls (24.4%) (p=0.01). Mean ± SD NO2 levels in RA (0.17 ± 0.08) were similar to levels in controls (0.15 ± 0.09; p=0.35). There were no significant differences in mean NO2 between those with and without plaque either overall (p=0.86) or in the RA group only (p=0.78). NO2 levels were not significantly associated with cIMT or any serum biomarker in RA group, but did have significant negative correlations with CD40L in controls (r -0.28, p=0.048) and with MMP9 in overall group (r -0.22, p=0.03). There were no significant differences in mean NO2 between those with and without each CV risk factor, both overall and in the RA group. In the overall group, number of CV risk factors was slightly positively correlated with NO2 (rs 0.20, p=0.06), and significantly positively correlated with cIMT (rs 0.24, p<0.01) and E-selectin (rs 0.19, p=0.01), but these were not significant within the RA group. Number of CV risk factors was significantly positively correlated with MPO (rs0.26, p=0.02) in the RA group.

Conclusion: NO2 levels in RA are not lower than controls, and were similar in those with or without traditional CV risk factors or plaque. Number of CV risk factors positively correlated with cIMT and E-selectin in the overall group, but not within RA patients. These findings suggest possible different pathways by which NO and CV risk factors mediate subclinical atherosclerosis in RA versus non-RA persons.


Disclosure: K. P. Liang, None; D. P. Landsittel, None; B. B. Sendon, None; D. M. Jones, None; R. Gartland, None; S. R. Mulukutla, None; S. E. Reis, None; F. S. Villanueva, None; A. H. Shoushtari, None; C. Dezfulian, None; L. W. Moreland, None.

To cite this abstract in AMA style:

Liang KP, Landsittel DP, Sendon BB, Jones DM, Gartland R, Mulukutla SR, Reis SE, Villanueva FS, Shoushtari AH, Dezfulian C, Moreland LW. Serum Nitrite Levels in Rheumatoid Arthritis and Relationship to Cardiovascular Risk Factors and Atherosclerosis Biomarkers [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/serum-nitrite-levels-in-rheumatoid-arthritis-and-relationship-to-cardiovascular-risk-factors-and-atherosclerosis-biomarkers/. Accessed .
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