OBJECTIVE: Rheumatoid arthritis (RA) has been considered an independent risk factor for cardiovascular disease (CVD), where RA and CVD later manifest following genetic predisposition and an extended preclinical phase.TheHLA-DRB1Shared Epitope (SE)allelespredispose for RA andare associated withhigherrisk of CV mortality in RA patients, but have not been evaluated in a community-living population.Thus, we evaluated whetherHLA-DRB1 (SE) alleleswereassociated with subclinical CVD, CV events, and mortality in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: We performed HLA typing in 955 MESA participants and evaluated associations of SE alleles with coronary artery calcium (CAC) and abdominal aortic calcium (AAC)
risk difference for CAC, AAC severity, and carotid intima media thickness (cIMT)
and associations of SE with all-cause mortality, CVD and non-CVD death, and CV events. RESULTS: Among 955 participants, 30 % were HLA-DRB1 SE positive. SE positivity was not significantly associated with higher risk of CAC, AAC, cIMT, CV events, or mortality. DRB1*10:01 demonstrated 2.63-fold higher risk for CAC (95 % CI 1.17-5.99)
DRB1*14:02 demonstrated 42 % higher risk for AAC (95 % CI 1.17-1.74)
and DRB1*04:05 demonstrated 24 % lower risk for AAC (95 % CI 0.58-0.99). CONCLUSION: In a multi-ethnic community-living population, HLA-DRB1 SE alleles were not associated with subclinical CVD, CV events, or mortality. However, individual allele-associations with subclinical CVD suggested variability in risk.