Immune-driven inflammation plays an important part in atherogenesis, and is therefore believed to be paramount for cardiovascular (CV) disease (CVD) development, currently considered as the leading cause of death in the Western world. By fulfilling some of the Koch postulates atherogenesis has even been proposed to be considered as an autoimmune disease, raising the hope that CVD could be prevented by immunomodulation. Nevertheless, the role of the immune system and autoimmune reactions in atherosclerosis appears to be a double edge-sword, some of them being pro-atherogenic, while others anti-atherogenic. For this reason, providing that immunomodulation is to become a therapeutic option for atherosclerosis and CVD, it will be crucial to correctly identify patients that will require a boost of the immune response from those requiring a targeted suppression of deleterious autoimmune responses, which could, among others, be achieved by the detection of specific autoantibodies. In this work, I will present the main clinical studies derived from a translational research project dedicated to autoantibodies directed against apolipoprotein A-1 (anti-apoA-1 IgG), the major proteic fraction of High Density Lipoprotein (HDL). Those studies demonstrate that both in patients with autoimmune disease and in non autoimmune settings, high levels of anti-apoA-1 IgG are associated with a worse CV prognosis. I will also present current data derived from in vitro and in vivo studies supporting a pro-inflammatory, pro-atherogenic, and thus causal role of those autoantibodies in CVD, suggesting that they could also represent an emerging therapeutic target. In this context, autoantibodies to apoA-1 appears as a promising biomarker of cardiovascular autoimmunity allowing the identification of subset of CVD patients that could benefit from immunomodulation in the future, contributing to the development of personalized medicine in the field of CVD.