Remnant Cholesterol: Quantification, Concentrations by Sex and Age, and Risk of Ischemic Heart Disease

Abstract Background Observational and genetic causal studies have shown an association between high concentrations of remnant cholesterol and increased risk of ischemic heart disease. However, findings from randomized intervention trials that reduced plasma triglycerides, a surrogate marker of remnant cholesterol, have been conflicting. The exact mechanisms by which remnant cholesterol contributes to atherosclerosis and, ultimately, ischemic heart disease remain incompletely understood. Additionally, insight on sex and age differences and the importance of measurement differences of remnant cholesterol in plasma concentrations and risk of ischemic heart disease are sparse. Content This review covers current knowledge regarding remnant cholesterol and its role in ischemic heart disease, with particular attention to measurement and sex- and age-specific differences. Summary Findings from observational, genetic, and mechanistic studies support the notion that higher remnant cholesterol may be an important cause of ischemic heart disease in both women and men. Concentrations of remnant cholesterol vary by age, with a sharp increase at early adulthood for men and around menopause for women. Remnant cholesterol can be calculated from a standard lipid profile and in addition measured directly using manual ultracentrifugation, automated assays, and nuclear magnetic resonance spectroscopy. Irrespective of the method used to assess plasma concentrations, high concentrations of remnant cholesterol are consistently associated with increased risk of myocardial infarction and ischemic heart disease in observational and genetic causal studies; cholesterol rather than triglycerides in remnants drive this risk. Importantly, results from ongoing randomized clinical trials aiming specifically at lowering remnant cholesterol and ischemic heart disease are eagerly awaited.