Atherosclerosis is a chronic inflammatory disease leading to cardiovascular disease (CVD). Since the mid-90s, our group has been interested in how a certain type of fat, phospholipids, once oxidized ("hardened"), can cause the inflammation of atherosclerosis. We have put forward a new hypothesis for atherosclerosis and CVD: low levels of natural antibodies against these fats including phosphorylcholine (anti-PC) cause CVD independently of and in the same order of magnitude as the established risk factors. In experimental studies, we have shown that anti-PC counteracts the very type of inflammation that is central to atherosclerosis. We have also shown that other anti-fat antibodies, such as oxidized cardiolipin and phosphatidylserine (aOxCL and aOxPS), have similar properties. The aim is to develop improved risk assessment and to develop new treatments (vaccines and/or antibodies for atherosclerosis and CVD and potentially for other inflammatory diseases). We combine animal, cell and clinical studies. In the animal trials, we vaccinate with the lipids and give the antibodies themselves. In cell experiments, we test how immune reactions in atherosclerosis are affected, and in clinical studies we investigate the role of the new factors, in several unique cohorts. Atherosclerosis and its consequence cardiovascular disease are dominant health problems. A new type of immunologically relevant risk factors and treatment based on natural immunity where lipids such as PC, OxCL and OxPS are in focus, may be of great importance.