We then tested the association between each group of anti-cit fibrinogen with CAD outcomes using a score test in a logistic regression model, adjusting for traditional CV risk factors

We then tested the association between each group of anti-cit fibrinogen with CAD outcomes using a score test in a logistic regression model, adjusting for traditional CV risk factors. Open in a separate window Figure 1 Principal component analysis of anti-cit-fibrinogen antibodies demonstrating 3 main groupings of anti-cit-fibrinogen antibodies. the anti-cit-fibrinogens clustered into groups. Each group was then also ARRY334543 (Varlitinib) tested for association with CAD. Sensitivity analyses were also performed using a published ICD9 code group for ischemic heart disease (IHD) as the outcome. Results We studied 1,006 RA subjects with mean age 61.0 (SD 13.0) years and 72.2% anti-CCP positive. As a group, anti-cit-fibrinogen was associated with CAD (p=1.110?4). From the PCA analysis, we observed 3 main groups, of which only one group, containing 7 of the 10 anti-cit-fibrinogens, was significantly associated with CAD outcomes (p=0.015). In the sensitivity analysis, all anti-cit-fibrinogens as a group remained significantly associated with IHD (p=2.910?4). Conclusion Anti-cit-fibrinogen antibodies as a group were associated with CAD outcomes in our RA cohort, with the strongest signal for association arising from a subset of the autoantibodies. INTRODUCTION Cardiovascular disease (CVD) is a leading cause of death for patients with rheumatoid arthritis (RA)(1). Several studies have demonstrated that traditional CV risk calculators significantly underestimate CV risk ARRY334543 (Varlitinib) in RA(2). These findings have motivated studies to examine whether biomarkers can assist rheumatologists in identifying RA patients at elevated CV risk. Anti-citrullinated protein antibodies (ACPAs) are used in the diagnosis of RA, and recent studies have identified epitope targets several epitope targets implicated in the disease(3C5). A specific class of ACPAs, autoantibodies targeting citrullinated fibrinogen (anti-cit-fibrinogen) have been studied as potential markers for cardiovascular disease (CVD) in RA(6). In a previously published study, Sokolove an colleagues observed that protein lysates of atherosclerotic plaques from aortic specimens were enriched for citrullinated fibrinogen (cit-fibrinogen)(6). Further, they found that RA patients with higher titers of anti-cit-fibrinogens also had higher atherosclerotic burden as measured by coronary artery calcium (CAC) scores. These data suggested a mechanistic pathway whereby inflammation promoted cit-fibrinogen in atherosclerotic plaques, and thus the development of anti-cit-fibrinogen may be a useful marker of inflammation, atherosclerotic burden and CV risk in RA. Interestingly, a subsequent study from an independent cohort using a different platform to measure anti-cit-fibrinogen found no association between carotid intima press thickness or CAC, and titers of anti-cit-fibrinogen(7). Since earlier studies have only examined surrogate CV results, the objective of this study was to examine the association between anti-cit-fibrinogen and the outcome of CAD. Additionally, fibrinogen is definitely a relatively large molecule(8) with autoantibodies focusing on different portions of the citrullinated fibrinogen. Therefore, a secondary objective of this study was to determine whether there was specificity to the type(s) of anti-cit-fibrinogen associated with CAD. METHODS Study populace We analyzed a validated RA cohort recognized in the electronic medical records (EMR) of two large tertiary care private hospitals in Boston, MA, Brigham and Womens Hospital (BWH) and Massachusetts General Hospital (MGH). Briefly, the RA instances were identified using a validated RA phenotype algorithm utilizing a combination of organized data, e.g. International Classification of Diseases, 9th Revision (ICD9), and ideas extracted from text notes, e.g. smoking status, using natural language processing (NLP). The positive predictive value (PPV) for RA using the algorithm was 94%(9). Discarded blood samples were collected using a biospecimen repository linked to anonymized EMR data and all samples were measured for antibodies ARRY334543 (Varlitinib) to cyclic citrullinated peptide (anti-CCP) ARRY334543 (Varlitinib) using a commercial kit as explained in a earlier publication(10). We analyzed all RA subjects with medical data and available blood samples. CAD Outcome definition Subjects were classified as having CAD if they had analysis of CAD in the medical record with assisting evidence of disease through paperwork of CABG, percutaneous coronary treatment (PCI) with stent or balloon angioplasty, positive stress test, or EKG changes consistent ischemia(11). Subjects with a analysis of CAD without assisting documentation or subjects with no mention of CAD were regarded as not to possess the disease. Covariates Info on covariates and potential confounders were extracted from your organized EMR data including age, gender, self-reported race classified as white or non-white, hypertension (ICD9 401.x, 402.x. 403.x. Vax2 404.x, 405.x), diabetes (249.xx or 250.xx), hyperlipidemia (272.xx), and RA treatments (ever/never use): disease.