NMR-based lipoprotein analysis for patients with severe hypercholesterolemia undergoing lipoprotein apheresis or PCSK9-inhibitor therapy (NAPALI-Study).

Taking into account the discordance between low-density lipoprotein cholesterol (LDL-C) and LDL particle (LDL-P) number, cardiovascular risk more closely correlates with LDL-P in patients. The aim of our study was to evaluate the number of lipid particles in patients with severe hypercholesterolemia treated with different lipid-lowering regimens. Four groups of patients differing with respect to lipid-lowering therapy were recruited from hypercholesterolemic outpatients and lipoprotein apheresis (LA) facilities, and were treated with statins alone (group A), with statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (PCSK9i) (group B), with statins and LA (group C), or with statins, PCSK9i, and LA (group D). Cholesterol, triglycerides, LDL-C, high-density lipoprotein cholesterol (HDL-C), LDL-P number and size, HDL-P number and size were determined using nuclear magnetic resonance spectroscopy. The lowest LDL-P number was achieved at the end of LA sessions in combination with statins or in combination with statins and a monoclonal PCSK9i (median; 25th and 75th percentile) (group C: 244 nmoL/L: 237, 244, P < 0.05; group D: 244 nmoL/L: 99, 307, P < 0.05). Comparing LDL-P number at the start of LA (group C: 978 nmoL/L: 728, 1404; group D: 954 nmoL/L: 677, 1521) to the other patient groups (groups A and B), the lowest LDL-P number was measured in patients treated with PCSK9i and a statin (group B): LDL-P (762 nmoL/L: 604, 1043, P < 0.05), large LDL-P (472 nmoL/L: 296, 574, P < 0.05), and small LDL-P (342 nmoL/L: 152, 494, P < 0.05). Very low-density lipoprotein and HDL particle sizes remained approximately the same in all groups. LA in combination with statins or in combination with statins and PCSK9i most reduced LDL-P numbers in hypercholesterolemic patients.