Session Information
Title: Rheumatoid Arthritis - Clinical Aspects II: Clinical Features & Comorbidity/Cardiovascular Disease
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Patients with RA are at increased risk of cardiovascular (CV) comorbidity and premature mortality. While generally attributed to accelerated atherosclerosis, the pathogenesis remains poorly understood.
Methods:
To investigate cardiovascular disease in RA, we measured carotid and aortic wall inflammation by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) uptake and vessel wall morphology by MRI in a cross-sectional study (N=30 pts). We calculated Mean and Maximum Target to Background Ratio (TBR) values as measures of arterial wall inflammation. Left and right carotid TBRs were combined as mean carotid values. Inflammation-related serum analytes were measured by commercial ELISA (sRAGE), and with a custom plasma panel for inflammation-related proteins, including cytokines, matrix metalloproteinases (MMPs), MMP inhibitors and trophic factors (Singulex Inc.). High-sensitivity cardiac troponin I (cTn-I) was also measured (Singulex Inc) as a marker of myocardial injury. IgG antibodies to citrullinated (cit) peptides from fibrinogen (Fib), histone 2A, filaggrin, a-enolase, and vimentin were determined by quantitative ELISA, and CCP3 using a commercial clinical assay (Inova Diagnostics Inc.). Protein peptide-specific ACPA assays were validated with a panel of sera from RA, OA and healthy individuals.
Results:
The mean age was 51.2 years, mean DAS28 score 6.7 (range 2.2-6.7), 80% female and 11(36%) were on biologic DMARDs. Carotid Max TBR was associated with higher levels of cTn-I (r=0.566, p=0.01), indicating an association of carotid wall inflammation with subclinical myocardial injury. Of the 15 inflammatory biomarkers assessed, carotid max TBR values was associated with elevations of sRAGE, VEGF, MMP8, proMMP9 and IL-1b. (Table 1). Similar results were obtained for carotid mean TBR. Strikingly, there was a strong correlation between carotid max TBR and cit-Fib IgG (R=0.72, p=0.0005). Furthermore, patients with a positive Cit-Fib IgG test (n=10) had higher levels of carotid wall inflammation [max TBR (p-0.04), mean TBR (p=0.03)] than Cit-Fib IgG negative pts. No correlation was found between carotid TBR values and levels of IgG CCP3. Neither IgG antibodies nor any of the inflammatory biomarkers correlated with aorta TBR measures. By MRI, we found significant correlations between wall thickness and ACPA IgGs specific for citrullinated fibrinogen, filaggrin, and enolase, as well as plasma hsCRP and pMMP9.levels (p<0.05).
Conclusion:
These FDG-PET studies indicate that a subset of RA patients exhibit inflammatory carotid artery disease. Carotid inflammation was associated with elevations of a distinct profile of innate inflammatory markers and citrullinated self-protein-specific IgG. These data may provide insights into the immunopathogenesis of RA-associated CV disease.
Table: Associations of carotid wall inflammation (max TBR) and biomarkers
|
Biomarker |
Spearman (r) |
P-value |
|
cTn-I |
0.57 |
0.01 |
|
sRAGE |
0.43 |
0.07 |
|
VEGF |
0.59 |
0.008 |
|
MMP8 |
0.62 |
0.004 |
|
pMMP9 |
0.58 |
0.008 |
|
IL1β |
0.48 |
0.03 |
|
IgG anti-Cit-Fib |
0.72 |
0.0005 |
Disclosure:
C. Grönwall,
None;
G. J. Silverman,
None;
Z. Fayad,
None;
V. Mani,
None;
V. Furer,
None;
M. Farkouh,
None;
M. Jain,
None;
C. Oh,
None;
J. Todd,
Singulex,
3;
M. Attur,
None;
S. B. Abramson,
None;
J. D. Greenberg,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/carotid-arterial-wall-inflammation-is-associated-with-a-specific-profile-of-inflammatory-biomarkers-and-anti-citrullinated-protein-antibodies-in-rheumatoid-arthritis-patients/