Beyond cholesterol-pleiotropic effects of lipoprotein apheresis.

Cardiovascular disease is a leading cause of mortality worldwide, which is caused mainly by atherosclerosis, a chronic inflammatory disease of blood vessels. Therefore, atherosclerosis represents a complex disorder, which induces damage or imbalance on different levels: for example, genes, cytokines, lipoproteins, cells, vessels, and organs. Lipoprotein apheresis (LA) is a well-established extracorporeal treatment of severe hyperlipoproteinemia. In addition, LA may have simultaneously crucial effects on many other atherogenic factors during the treatments, for example, as vascular inflammation, rheology, mobilization of adult stem cells and gene expressions in blood or endothelial cells, which will be discussed in this short review. In addition, stable microRNAs besides tissues also appear in extracellular compartments, for example, vessels, involved in atherosclerotic processes, were found to be reduced by LA treatments. In summary, LA represents a complex therapeutic procedure, that provides an ideal tool for the treatment of complex disorders such as atherosclerosis.

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.

Significance of Monoclonal PCSK9-Antibodies - New Approaches to the Therapy of Hypercholesterolemia.

Increased concentrations of low-density-lipoprotein (LDL)-cholesterol (LDL-C) and lipoprotein a (Lp(a)) are scientifically accepted, independent risk factors for the development of atherosclerosis. The complications of atherosclerosis occur early and more frequently. They are strongly linked with lifestyle factors and an increase of LDL-C concentrations in industrialized countries. A new therapeutic approach seems to be the modulation of the proprotein convertase subtilisin/kexin type 9 (PCSK9), which reduces the number of LDL-receptors at the cell membrane of the liver cells and thus increases the concentration of LDL-C in the blood. Results of current studies show, that in particular, a combination of PCSK9-AB and statins, independent of the dosage of the statins, is suitable to increase a reduction of LDL-C and Lp(a). This article gives an overview of the pathophysiology, the current study and research situation as well as the possible different approaches to the therapeutic influence of PCSK9 in the future.