Background: Familial hypercholesterolemia (FH) is characterized by lifetime exposure to high levels of LDL-c and premature atherosclerotic cardiovascular disease (ASCVD). However, there is heterogeneity in clinical presentation of ASCVD in subjects with FH, in spite of same LDL-c levels. The aim of our study is to evaluate the role of immune-inflammatory system on atherosclerosis development in FH individuals under high-intensity lipid-lowering therapy (HI-LLT). 
Methods: One-hundred patients with definite or probable diagnosis of FH (Simon Broome or Dutch Lipid Clinic Network), of both sexes, under HI-LLT (98%) with statin +/- ezetimibe were submitted to Coronary Computed Tomography Angiography (CCTA) with evaluation of the coronary calcium score and the CAD-RADS score. Samples for lipid profile, apolipoproteins A1, B and Lp(a) (immunonephelometry), genotyping of the LDLR, APOB, PCSK9, LDLRAP-1, LIPA genes (NGS), titers of autoantibodies (IgG and IgM) anti-oxLDL and anti-ApoB-D (ELISA). The phenotype of T and B cells (% and absolute values of T lymphocytes, CD4+ and CD8+, B memory cells, B naive, B1, B2), as well as the levels of monocyte, endothelial and platelet microparticles (MP) were determined by flow citometry. The spontaneous production of IgM by B1 cells, purified after "sorting" was quantified by ELISPOT, serum IgM determined by ELISA. The detection of cytokines (TNF-α, IFN-gamma, IL-10, IL-6, IL-4, and IL-2) in the supernatant of cultured B and T cells was determined by flow citometer BD FACSCantoIITM. 
Results: There were no differences on lipid parameters among subjects with CCS=0 vs. CCS>0. Mean treated LDL-c level was 154±52 mg/dL. Mean and maximal CCS were 173 and 2139 UA, respectively, with median and P75th of 75 and 512 UA. No differences in the distribution of immune cells, Ab to oxLDL, Apo B-D, or MPs among CCS (0 vs. >0; 0, 1-99, 100-399, 400-999, and > 1000; P≥75th vs. P<75th) or CAD-RADS (0-5) categories. 
Conclusions: The immune-inflammatory system does not influence CCS in subjects with FH under HI-LLT. Atherosclerosis in FH subjects may result from the balance between exposure to LDL levels and to lipid-lowering therapy.

01 - ROLE OF INNATE AND ADAPTIVE IMMUNITY ON ATHEROSCLEROSIS IN SUBJECTS WITH FAMILIAL HYPERCHOLESTEROLEMIA