Mechanistic Insights to Target Atherosclerosis Residual Risk

Current pharmacological and mechanical therapies have reduced future cardiovascular risk. Nonetheless, a significant proportion of patients remained at high risk of recurrent events despite achieving guideline-directed therapeutic targets. This residual risk poses challenges despite tackling ‘traditional’ risk factors. Targeting the residual risk has been the focus of numerous pharmacotherapies which were associated with variable success. Incomplete understanding of the mechanistic nature combined with the lack of tools to precisely quantify the residual risk contributed to the relatively high residual risk after ‘optimal’ medical therapy. The development of atherosclerotic plaque is derived from lipid retention within arterial intima that triggers an inflammatory cascade accelerating atherosclerosis progression and rendering plaque more prone to rupture. The exposed subendothelial space with activated platelets causes arterial occlusion leading to potential fatality. Therefore, a distinctive approach to characterize these features may offer the opportunity to tailor novel antiatherosclerotic to reduce the residual risk. The traditional approach of measuring risk factors is beneficial at population-level but maybe less informative upon quantifying risk at an individual-basis. This review will discuss lipid accumulation, thrombosis, and inflammation as therapeutic targets of atherosclerosis. Additionally, we will summarize previous challenges of antiatherosclerosis therapies and the future role to tackle the residual risk.