P213 HLA-DRB1 haplotypes predict cardiovascular mortality in inflammatory arthritis

Abstract

Abstract Background/Aims Haplotypes defined by amino acids at HLA-DRB1 positions 11, 71 and 74 associated with susceptibility to rheumatoid arthritis (RA), are associated with radiological outcome, anti-TNF response and all cause-mortality. RA is associated with cardiovascular (CV) morbidity and mortality, but increased prevalence of risk factors of CV disease in RA only partially explains this association. The aim was to investigate whether haplotypes associated with RA disease susceptibility and disease severity are associated with CV mortality. Methods The Norfolk Arthritis register (NOAR) is a primary care-based inception cohort of patients with inflammatory polyarthritis (IP). NOAR patients with at least 2 years of follow-up and available mortality and genetic data were included. Mortality data was provided by the Office for National Statistics. Univariate Cox proportional hazard models were applied using STATA/IC 14.0. Models for CV mortality were adjusted for CV risk factors selected using stepwise regression: namely obesity, gender and hypertension. Hazard models were applied to the entire cohort of patients with inflammatory polyarthritis (IP). When calculating differences between highest and lowest risk genetic factors, bivariate analysis was used. Results HLA-DRB1 amino acids, haplotypes or haplotype groups associated with RA susceptibility are also associated with CV mortality as shown in the table. HLA-DRB1 polymorphisms encoding amino-acid haplotypes associated with an increased or decreased susceptibility to RA consistently show the same magnitude and direction of association for overall and CV mortality in IP. For example, the SEA-haplotype, associated with the lowest susceptibility to RA, and the best radiographic outcome, was found to be associated with decreased CV mortality (HR 0.67, 95% CI 0.47, 0.91, p = 0.023). The relative difference in CV mortality between carriers of the high susceptibility VKA haplotype and carriers of the SEA haplotype was significant (HR 1.67, 95% CI 1.13, 2.48, p = 0.01). Associations were independent of anti-CCP status. Conclusion HLA-DRB1 haplotypes associated with susceptibility to RA also predispose to increased risk of CV mortality in IP, independent of known CV risk factors and anti-CCP status, which suggests that, in the future, genetic factors will add to prediction of risk of cardiovascular mortality beyond serological markers. Disclosure S.D. Sharma: None. D. Plant: None. J. Bowes: Grants/research support; British Heart Foundation. A. Macgregor: None. A. Barton: Grants/research support; BMS. Other; Speaker Fees from Roche Chugai. S. Viatte: None.