medwireNews: Research shows that the risk for venous thromboembolism (VTE) is significantly related to the presence of autoantibodies associated with rheumatoid arthritis (RA).
Immunoglobulin (Ig)G against second-generation cyclic citrullinated peptides (anti-CPP2), the spreading of 20 anti-citrullinated protein antibody (ACPA) fine-specificities, and IgM anti-rheumatoid factor (RF) have previously been linked to the risk for myocardial infarction, stroke, and cardiovascular death, the researchers explain in Rheumatology.
To determine the impact of these autoantibodies on VTE risk in people with RA, Helga Westerlind (Karolinska Institutet, Stockholm, Sweden) and co-workers collated information for 2782 participants of the EIRA study who were registered as having a new diagnosis of RA between 1996 and 2009, and had no history of VTE.
Over a median 15.5 years of follow-up, 213 individuals had a first VTE event, giving a rate of 5.0 events per 1000 person–years.
Overall, 64.6% of the patients were positive for IgG anti-CCP2 and 46.5% positive for IgA anti-CCP2, and these individuals were more likely than their negative counterparts to experience VTE (hazard ratio [HR]=1.33 and 1.35, respectively).
Furthermore, the risk for VTE with IgG anti-CCP2 positivity showed a dose–response relationship, so that compared with negative individuals, those with low (25–<75 AU/mL) and extreme (≥1500 AU/mL) levels were 1.41 and 1.49 times more likely to experience VTE, respectively.
The team identified 18 ACPA fine-specificities that occurred in 10% or more of the cohort, with a median of six per patient.
The risk for VTE increased with the number of ACPA fine-specificities identified, with HRs for one–four, five–10, and 11–17 versus no ACPA fine-specificities of 1.39, 1.68, and 1.56, respectively.
Two fine-specificities were individually associated with an increased risk for VTE, namely hnRNP derived Cit-Peptide-Z1 (HR=1.40) and Cit-Peptide-1 (HR=1.47).
But none of the six autoantibodies against citrullinated fibrinogen were significantly associated with VTE risk, note Westerlind et al.
Three RF isotypes were identified but only IgM RF was significantly linked to VTE risk, with a HR of 1.39, they say.
Information was available on smoking habits and shared epitope for HLA-DRB1 alleles in 2714 patients but adjusting for these confounding factors “had little impact” on the relationship between autoantibody positivity and VTE risk, observe Westerlind and co-authors.
Overall, the researchers say their findings are “in keeping with other studies on [cardiovascular] risks,” but note the “mechanism(s) underlying this association remains unclear.”
And they admit that the lack of longitudinal information on RA disease activity means the study was unable to determine “whether the association between RA-related autoantibodies and VTE risk was mediated by, or independent of, accumulated RA disease activity.”
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