Widespread lipoprotein alterations in a REDUCE-IT like population: The icosapent ethyl (IPE)-NMR avatar study

Abstract

Background and aim: Triglycerides (TG) are independent cardiovascular risk markers, yet TG-lowering therapies have failed to reduce major adverse cardiovascular events. However, high-dose icosapent ethyl (IPE) significantly reduces cardiovascular events in high-risk patients with controlled low-density lipoprotein cholesterol (LDL-C) and TG > 1.7 mmol/L. Elevated TG levels contribute to widespread lipoprotein metabolism disruptions, which remain undetectable by standard lipid measures but can be characterized using proton nuclear magnetic resonance (¹H NMR) spectroscopy. This study retrospectively analyses lipoprotein alterations in secondary prevention patients with characteristics similar to those in REDUCE-IT, using ¹H NMR spectroscopy (Liposcale® test).

Methods and results: Patients from our institutional databases who had undergone advanced lipoprotein and glycoprotein profiling by ¹H NMR spectroscopy were included. Criteria required a history of major cardiovascular events, lipid-lowering therapy, LDL-C between 1.04 and 2.6 mmol/L, and TG 1.7-5.7 mmol/L. Lipoprotein particle number, size, and composition and glycoproteins A and B were analysed by nuclear magnetic resonance (NMR). A total of 100 patients (25 % female, mean age 63 years, 39 % with diabetes) were selected. The Liposcale test identified significant lipoprotein disturbances, including increased atherogenic small TG-rich remnant lipoproteins and small LDL particles, as well as elevated remnant cholesterol and TG enrichment in high-density lipoprotein. These abnormalities were associated to increasing TG concentrations. The results were visualized through lipid silhouette analysis.

Conclusion: In secondary prevention patients resembling the REDUCE-IT cohort, ¹H NMR profiling revealed extensive proatherogenic lipoprotein alterations associated to increasing TG concentrations. Further research is underway to assess whether IPE mitigates these disturbances beyond its TG-lowering effects.

Keywords: (1)N NMR; Glycoprotein A; Glycoprotein B; Icosapent ethyl; Lipoprotein advance test; Lipoprotein particle number; Lipoprotein particle size; REDUCE-IT.