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Background: Lipoprotein apheresis (LA) is an extracorporeal treatment that transiently reduces lipoprotein (a) [Lp(a)] by 60% and leads to an 80-92% reduction in major adverse cardiovascular events. LA has a significant impact on lipid profile in serum of patients with atherosclerotic cardiovascular disease., Objective: To investigate the effects of LA on the composition of serum fatty acids (FAs), focusing on those which could have an impact on cardiovascular disease (CVD)., Methods: This is a prospective study in the First Department of Cardiology of the Medical University of Gdansk, Poland. Serum samples were collected from 28 patients before LA, just after the procedure, and 7 days after LA. Additionally, in a smaller group of patients, the samples were collected after a second tour of LA (2 weeks later), as well as after 1 year from the first procedure. The serum FA profile was analyzed using gas chromatography-mass spectrometry., Results: After the LA procedure, a substantial change in serum FA composition along with low-density lipoprotein cholesterol (LDL-C) and Lp(a) decrease were observed 7 days after procedure, but these parameters returned to the values similar to those before procedure after 14 days. Very long-chain FAs (VLCFAs) and very long-chain monounsaturated FAs (VLC-MUFAs) were eluted at 57% and remained low even 7 days after LA (p=0.027 and p < 0.001, respectively). We also observed an increase in the percentage of total branched-chain FAs (BCFAs) (p=0.004) and anteiso BCFAs (p=0.012) after LA. After 1 year of regular LA, a substantial decrease in serum VLC-MUFAs and n3 polyunsaturated LA (PUFAs) were noted., Conclusions: Decreased VLCFAs and VLC-MUFAs involved in CVD development remained low even 7 days after LA. An acute increase in the levels of anti-inflammatory BCFAs was observed. In turn long-term regular administration of LA substantially decreased VLC-MUFA and n3 PUFA., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests related to this manuscript., (Copyright © 2023. Published by Elsevier Inc.)