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Residual Risk That Remains

The prevalence of cardiovascular diseases keeps increasing each year globally. As atherosclerotic cardiovascular diseases (ASCVD) are associated with increased morbidity and mortality, it is important to take ample preventive measures. Despite lifestyle modifications and intensified lipid management, a significant proportion of patients are at "Residual risk". This review describes the various residual risk factors and the results of large-scale clinical trials conducted to address this issue in ASCVD. The major residual risk factors are classified in the inflammatory, thrombotic, and metabolic pathways. Results from the JUPITER and PROVE-IT TIMI 22 show that serum levels of hsCRP play a vital role in defining the residual inflammatory risk in high-risk individuals with hypercholesterolemia. Apart from hsCRP, IL-1, and IL-6 is also crucial in driving the inflammatory risk in patients with atherosclerotic disease. Besides statins, IL-1, IL-6 and chemokine inhibitors, and several other drugs are used to treat patients with residual inflammatory risk. To address the residual thrombotic risk, along with aspirin to reduce the vascular events, ATLAS ACS-2 TIMI 51 and COMPASS clinical trials demonstrated that rivoroxaban was found to be beneficial in improving the clinical outcome. As increased amounts of lipoprotein are linked with a raised risk of myocardial infarction, evolocumab and other novel therapies that target lipoprotein are under development. The role of triglycerides and HDL in atherogenesis is yet to be clearly elucidated. The emergence of SGLT-2 inhibitors and GLP-1 RA in diabetes treatment has also proven beneficial in improving cardiovascular outcomes. It is essential to address the residual risk component for optimum management of patients with ASCVD. Keywords: Atherosclerosis; Residual risk; Inflammation; Thrombosis; Metabolic risk