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Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity.

BackgroundImmune mediated and inflammatory diseases (IMIDs) such a rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis (Ps), and psoriatic arthritis (PsA), are associated with higher rates of cardiovascular (CV) morbidity and mortality, mostly due to accelerated atherosclerosis. Classic CV risk factors do not fully account for the gap observed in the prevalence and incidence of CV disease, when compared to that of the general population.ObjectivesTo analyze the influence of different demographic and clinical variables in the prevalence of CV disease in subjects affected with RA, PsA, Ps, SLE, or inflammatory bowel disease. Additionally, we compared the adjusted prevalence of CV disease among these conditions.MethodsSubjects included in this cross-sectional study were collected as part of the Immune-Mediated Inflammatory Disease Consortium (IMIDC) between 2007 and 2010. Demographic, disease and cardiovascular related clinical data was collected using a standard protocol of questionnaires, after a clinical interview with close questions and review of medical records. Bivariate and multivariate logistic and mixed-effects logistic regression models were performed for each condition, and the overall IMIDC, respectively. Standardize prevalence (SP) for each IMID was calculated using marginal analysis.Results9951 patients were included. When analyzed separately, traditional CV risk factors had a different contribution to CV disease in each IMID. Overall, when analyzed all subjects, older age at study, longer elapsed time from IMID diagnosis to study, presence of traditional CV risk factors (arterial hypertension, type2 diabetes mellitus, dyslipidemia, obesity) and male gender were independently associated with a higher CV disease risk. After adjusting by demographic and traditional CV risk factors, SLE exhibited the highest SP, followed by RA and Ps/Crohn's disease.ConclusionsCardiovascular disease is related to immune-mediated inflammatory diseases. A different impact is shown dependent of particular disease directly affecting the burden of disease.AcknowledgementsWe would like to thank all the patients and physicians for their collaboration.Disclosure of InterestNone declared