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Abstract Number: 990

Higher Omega-6 to Omega-3 Fatty Acid Ratio Is Associated with Increased Odds of Inflammatory Arthritis in a Health Fair Population Positive for Anti-Citrullinated Protein Antibodies (ACPA)

Kristen J. Polinski1, Ryan W. Gan2, Elizabeth A. Bemis1, M. Kristen Demoruelle3, Michael J. Clare-Salzler4, V. Michael Holers5, Kevin D. Deane6 and Jill M. Norris7, 1Epidemiology, Colorado School of Public Health, Aurora, CO, 2Colorado School of Public Health, University of Colorado Denver, Aurora, CO, 31775 Aurora Ct, 1775 Aurora Ct, Aurora, CO, 4Experimental Pathology, University of Florida, College of Medicine, Gainesville, FL, 5Rheumatology Division, University of Colorado School of Medicine, Aurora, CO, 6Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, 7Department of Epidemiology, Colorado School of Public Health, Aurora, CO

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ACPA, inflammatory arthritis and lipids

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Session Information

Date: Monday, November 6, 2017

Title: Epidemiology and Public Health Poster II: Rheumatic Diseases Other than Rheumatoid Arthritis

Session Type: ACR Poster Session B

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

Background/Purpose: We previously found that lower levels of omega-3 fatty acids (n-3 FA) were associated with the presence of inflammatory arthritis (IA) as well as risk of developing incident IA in ACPA+ individuals without IA at baseline. Omega-6 fatty acids (n-6 FA) compete with n-3 FA for elongation and desaturation enzymes in the body that help determine the pro- and anti-inflammatory potential of these FA and their derivatives. Western diets tend to have a high n-6 to n-3 ratio that may promote the pathogenesis of inflammatory and autoimmune diseases. We examined the association between n-6 FA levels and the presence of IA/rheumatoid arthritis (RA) in ACPA+ individuals.

Methods: At Colorado-based health fairs from 2008-2014, 47 subjects without a previous diagnosis of RA tested positive for the ACPA, anti-cyclic citrullinated peptide (CCP3, Inova), and were recruited into a follow-up research study. At their immediate post-health fair research visit (baseline), 10 of these ACPA+ subjects were identified as having disease-modifying anti-rheumatic drug (DMARD)-naive IA. Of the 10 ACPA+ subjects with prevalent IA at baseline, 8 were classified as RA by 2010 ACR/EULAR Criteria. Findings in those subjects with IA were compared to those without IA. Specifically, n-3 and n-6 as percent of total lipids in red blood cell membranes (RBC) were measured. Logistic regression assessed the associations between baseline IA and RBC n-6 FA%, as well as the n-6 to n-3 ratio.

Results: Subjects with IA at baseline were more likely to be ever smokers and test positive for rheumatoid factor and C-reactive protein than those without IA (Table 1). In addition, we found that subjects with higher n-6 FA and linoleic acid levels had higher odds of IA (Table 2). Furthermore, analysis of the n-6 to n-3 ratio demonstrated that higher total n-6 FA % relative to total n-3 FA % in RBCs significantly increased the odds of IA by almost 3-fold (Table 2).

Conclusion: We found that a higher n-6 to n-3 ratio was associated with prevalent IA in this ACPA+ population. Building off our previous work, this suggests a potential beneficial role of n-3 FAs in decreasing the risk of transitioning from ACPA positivity to IA. Specifically, our findings herein suggest that decreasing the n-6 to n-3 FA ratio in the body, perhaps either via n-3 FA supplementation or diet may play a role in decreasing the transition from an ACPA+ state to IA, findings that warrant further investigation.

Table 1: Descriptive Characteristics by IA status at Baseline, Colorado Health Fair Population, 2008-2014

Variable

Prevalent IA at Baseline (n=10)

No IA at Baseline (n=37)

p-value

Age, yrs (mean ± SD)

55.9 (10.3)

55.9 (10.4)

0.996

Age ≥ 50 yrs

8 (80.0)

26 (70.3)

0.703

Sex: Female

8 (80.0)

21 (56.8)

0.277

Race/Ethnicity: non-Hispanic White

7 (70.0)

29 (78.4)

0.679

Education: > High school

8 (80.0)

32 (86.5)

0.630

Income: > $40,000

7 (77.8)

25 (71.4)

1

Smoking: Ever

9 (90.0)

16 (43.2)

0.012

Shared Epitope (SE)+

7 (70.0)

16 (43.2)

0.168

Omega 3 supplement use

8 (80.0)

19 (51.3)

0.154

Rheumatoid Factor (RF)+

6 (60.0)

5 (13.5)

0.006

C-Reactive Protein (CRP)+

6 (60.0)

7 (18.9)

0.017

n-6 : n-3 ratio (mean ± SD)

4.00 (1.41)

3.14 (0.81)

0.093

All values reported as n(%) unless otherwise stated. Fisher Exact p-values presented for categorical variables. Satterthwaite p-values reported for continuous variables.

Table 2: Adjusted analyses evaluating the relationship between omega-6 fatty acid % and IA at Baseline (N=47)

FA% in RBC

OR (95% CI)

p-value

n-6 : n-3 FA ratio

2.99 (1.11, 8.05)

0.030

Total n-6 FA

2.96 (1.12, 7.79)

0.028

Linoleic acid

2.63 (1.10, 6.29)

0.030

Gamma linolenic acid

4.91 (0.85, 28.35)

0.075

Arachidonic acid

0.81 (0.21, 3.22)

0.768

The n-6:n-3 FA ratio model adjusted for ever smoking status, SE, RF+, and CRP+; and the OR represents the odds of IA for each unit difference in the n-6:n-3 ratio. The n-6 models adjusted for ever smoking status, n-3 FA supplement use, SE+, RF+, and CRP+; and the ORs represent the odds of IA for a one standard deviation (SD) difference in the n-6 FA% in RBC. The SD for these variables are as follows: Linoleic acid: 1.72, Gamma linolenic acid: 0.06, Arachidonic acid: 1.37, Total n-6: 1.97.


Disclosure: K. J. Polinski, None; R. W. Gan, None; E. A. Bemis, None; M. K. Demoruelle, None; M. J. Clare-Salzler, None; V. M. Holers, None; K. D. Deane, Inova Diagnostics, Inc., 5; J. M. Norris, None.

To cite this abstract in AMA style:

Polinski KJ, Gan RW, Bemis EA, Demoruelle MK, Clare-Salzler MJ, Holers VM, Deane KD, Norris JM. Higher Omega-6 to Omega-3 Fatty Acid Ratio Is Associated with Increased Odds of Inflammatory Arthritis in a Health Fair Population Positive for Anti-Citrullinated Protein Antibodies (ACPA) [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/higher-omega-6-to-omega-3-fatty-acid-ratio-is-associated-with-increased-odds-of-inflammatory-arthritis-in-a-health-fair-population-positive-for-anti-citrullinated-protein-antibodies-acpa/. Accessed .
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