Antinuclear antibodies in the general population: positive association with inflammatory and vascular biomarkers but not traditional cardiovascular risk factors

OBJECTIVES: Patients with clinically evident autoimmune disease are at increased risk for premature cardiovascular disease (CVD). Markers of serological autoimmunity such as anti-nuclear antibodies (ANA) are found in approximately 25% of the general population. Yet, the vast majority will not develop clinical autoimmune disease. Serological autoimmunity is a risk factor for CVD death in individuals without autoimmune disease; however, the mechanisms mediating this excess CVD risk have not been elucidated. METHODS: We examined associations of ANA with traditional cardiovascular risk factors, inflammatory mediators, and vascular biomarkers in the Dallas Heart Study - a large, representative multiethnic population-based cohort. Plasma ANA were measured by enzyme linked immunosorbent assay in 3,488 Dallas Heart Study participants aged 30 to 65 years who do not have known rheumatologic disease. Associations of ANA with demographic characteristics, cardiovascular risk factors, and biomarkers were assessed using univariable and multivariable linear regression. RESULTS: Factors independently associated with higher ANA include female sex, African-American race/ethnicity, soluble intracellular adhesion molecule-1, soluble CD40 ligand, chemokine CXCL-2, and Cystatin C (p<0.05 for each). ANA was not associated with traditional cardiovascular risk factors, high sensitivity C-reactive protein, coronary artery calcium scores, or aortic wall thickness. CONCLUSION: ANA are associated with inflammatory mediators and biomarkers of vascular activation, but not with traditional cardiovascular risk factors in a multiethnic population-based cohort. These findings suggest that the cardiovascular risk associated with ANA may involve pathways distinct from traditional risk factors and include dysregulation of endothelial cells and the immune system.