Abstract
Heart disease and stroke represent the major burden of health worldwide and account for a staggering 17 million deaths yearly. This pandemic is, in great part preventable through simple and modifiable preventive measures such as smoking cessation, healthy eating, regular activity and weight loss. In patients with established atherosclerotic vascular disease, lipid lowering agent have had a major impact on reducing risk, along with pharmacological treatment of elevated blood pressure and the use of anti-thrombotic medication. Despite these advances, there remains a significant residual risk and newer approaches are required to decrease atherosclerosis. Innate and acquired immunity play a pivotal role in the initiation, progression and instability of the atherosclerotic plaque. The remarkable complexity of the immune system makes it difficult to target a single pathway for the prevention of cardiovascular disease. Nevertheless, recent data points to possible therapeutic targets that may decrease atherosclerosis, without increasing the risk of infection, decreasing immune surveillance for cancers and without undue toxicity. Here we discuss the clinical trials and registry data associated with the use of inflammation modulation and cardiovascular disease and the ongoing major clinical trial that may change the clinical medicine and preventive cardiology. The selective inhibition of interleukin 1 and the use of low-dose methotrexate are now undergoing large outcome-driven clinical trials to answer these questions.