Abstract 11460: Antibodies to Citrullinated Protein Antigens Are Associated with Inflammatory Markers in a Multi-Ethnic Community-Living Population: The Multi-Ethnic Study of Atherosclerosis

Abstract

Introduction: Individuals with antibodies to citrullinated protein antigens (ACPA) have higher risk for cardiovascular disease (CVD). Cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFα), have been identified as pro-atherogenic. While the association between ACPA and cytokines has been studied in rheumatoid diseases, it has not been studied in the general population. We hypothesized that ACPA are positively associated with IL-6, c-reactive protein (CRP), and TNFα; and that gender and race/ethnicity modify this association. Methods: In 1743 Multi-Ethnic Study of Atherosclerosis participants without clinical CVD, we evaluated the association between number of ACPA and IL-6, CRP, and TNFα using multivariable linear regression. We adjusted for demographics, CVD risk factors, and medication use; and tested for interactions by gender and race/ethnicity. ACPA was measured as an array of 38 individual ACPA with the cut-off for positivity for each antibody set at the 95 th percentile. CRP, IL-6, and TNFα were measured in serum of fasting participants; values were log-transformed to reduce skewness. Results: Average age was 64.7±9.7 years; 50% were women, 40% Caucasian, 13% Chinese American, 21% African American, and 26% Hispanic American. Approximately 31% (537) had at least one positive ACPA. In the fully adjusted analysis, each additional ACPA was associated with 0.3±0.1% (p=0.005) higher serum IL-6 and 0.6±0.2% (p=0.007) higher CRP. ACPA was not associated with TNFα. Associations of ACPA with CRP were modified by gender (p interaction = 0.000) and race/ethnicity (p interaction = 0.000). In men, each additional ACPA was associated with 0.4±0.1% (p=0.015) higher IL-6 and 0.7±0.2% (p=0.007) higher CRP. In women, this association was not observed. In Hispanic participants, each additional ACPA was associated with 0.3±0.2% (p=0.049) higher IL-6 and 0.8±0.3% (p=0.010) higher CRP; in Caucasian participants, each additional ACPA was associated with 0.4±0.2% (p=0.014) higher IL-6 and 0.6±0.3% (p=0.026) higher CRP. This association was not observed in Chinese or African American participants. Conclusion: In a multi-ethnic community-dwelling population, higher number of ACPA was associated with higher IL-6 and CRP.