Remnant cholesterol, vascular risk, and prevention of atherosclerosis

In patients who have achieved optimal LDL-C control, there remains a residual risk of atherothrombotic cardiovascular disease (ACVD) related to alterations in lipid metabolism, where alterations in triglyceride-rich lipoproteins (TGRLP) and the cholesterol they contain, called remnant cholesterol, play a major role. Remnant cholesterol has an association with residual risk of CVD that is independent of LDL-C and has been demonstrated in epidemiological and Mendelian randomisation studies, and in analyses of clinical trials of lipid-lowering drugs. Remnant TGRLP particles are highly atherogenic, due to their ability to enter and be retained in the arterial wall, their high cholesterol content, their ability to generate “foam cells” and an inflammatory response. Assessment of remnant cholesterol may provide information on residual risk of ACVD beyond the information provided by LDL-C, Non-HDL-C, and apoB, particularly in individuals with hypertriglyceridaemia, type 2 diabetes, or metabolic syndrome. In the Reduce-It study, icosapent ethyl was shown to have a preventive effect against CVD in very high cardiovascular risk patients with hypertriglyceridaemia treated with statins and target LDL-C. New lipid-lowering drugs will help to define efficacy and criteria in the treatment of excess remnant cholesterol and hypertriglyceridaemia in the prevention of ACVD.