家族性高胆固醇血症患者的动脉粥样硬化严重程度：T 淋巴细胞和 B 淋巴细胞的作用。

Atherosclerosis severity in patients with familial hypercholesterolemia: The role of T and B lymphocytes.

作者信息

Fonzar Waleria T, Fonseca Francisco A, Fonseca Henrique A, Silva Tuany P, Rodrigues Alfredo A, Teixeira Daniela, Ishimura Mayari E, Coste Maria E, França Carolina N, Bianco Henrique T, Gidlund Magnus, Morais Rafael L, Bittencourt Clarissa A, Fonzar Carlos A, Sant'Anna Viviane A, Maugeri Ieda L, Pesquero Joao B, Izar Maria C

机构信息

Department of Medicine, Universidade Federal de São Paulo, São Paulo, SP, Brazil.

Academic Research Organization - Hospital Albert Einstein, São Paulo, SP, Brazil.

出版信息

Atheroscler Plus. 2022 Mar 18;48:27-36. doi: 10.1016/j.athplu.2022.03.002. eCollection 2022 Apr.

DOI:10.1016/j.athplu.2022.03.002

PMID:36644561

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9833267/

Abstract

BACKGROUND AND AIMS

Familial hypercholesterolemia (FH) is characterized by lifelong exposure to high LDL-c concentrations and premature atherosclerotic cardiovascular disease; nevertheless, disease severity can be heterogeneous.We aimed at evaluating if the immune-inflammatory system could modulate atherosclerosis burden in FH.

METHODS

From a cohort of subjects with confirmed FH (Dutch Lipid Clinic Network and genotype), 92 patients receiving high-intensity lipid-lowering therapy (statin ± ezetimibe) were included. The extension and severity of coronary atherosclerosis was assessed by standardized reporting systems (CAD-RADS) for coronary computed tomography angiography (CCTA) and coronary artery calcium (CAC) scores. Lipids, apolipoproteins, -oxLDL and anti-apolipoprotein B-D peptide (-ApoB-D) autoantibodies (IgM and IgG), lymphocytes subtypes, platelet, monocyte and endothelial microparticles (MP), IgM levels (circulating or produced by B1 cells) and cytokines in the supernatant of cultured cells were determined. Multiple linear regression models evaluated associations of these biomarkers with CAC and CAD-RADS scores.

RESULTS

In univariate analysis CAC correlated with age, systolic blood pressure, TCD4+ cells, and titers of IgM -ApoB-D. In multiple linear regression [ANOVA F = 2.976; = 0.024; R = 0.082), CD4+T lymphocytes (B = 35.289; beta = 0.277; = 0.010; 95%CI for B 8.727 to 61.851), was independently associated with CAC. CAD-RADS correlated with age, systolic blood pressure, titers of IgM -ApoB-D, and endothelial MP in univariate analysis. In multiple linear regression, [ANOVA F = 2.790; = 0.032; R = 0.119), only age (B = 0.027; beta = 0.234; = 0.049; 95% CI for B 0.000 to 0.053) was independent predictor.

CONCLUSIONS

In subjects with FH, under high-intensity lipid-lowering therapy, age and CD4+T cells were associated to atherosclerosis burden.

摘要

背景与目的

家族性高胆固醇血症（FH）的特征是终生暴露于高LDL-c浓度和早发性动脉粥样硬化性心血管疾病；然而，疾病严重程度可能存在异质性。我们旨在评估免疫炎症系统是否能调节FH患者的动脉粥样硬化负担。

方法

从确诊为FH的受试者队列（荷兰脂质诊所网络和基因型）中，纳入92例接受高强度降脂治疗（他汀类药物±依泽替米贝）的患者。通过用于冠状动脉计算机断层扫描血管造影（CCTA）的标准化报告系统（CAD-RADS）和冠状动脉钙化（CAC）评分来评估冠状动脉粥样硬化的范围和严重程度。测定血脂、载脂蛋白、氧化型低密度脂蛋白（oxLDL）和抗载脂蛋白B-D肽（-ApoB-D）自身抗体（IgM和IgG）、淋巴细胞亚群、血小板、单核细胞和内皮微粒（MP）、IgM水平（循环或由B1细胞产生）以及培养细胞上清液中的细胞因子。多元线性回归模型评估这些生物标志物与CAC和CAD-RADS评分之间的关联。

结果

在单因素分析中，CAC与年龄、收缩压、TCD4 +细胞以及IgM -ApoB-D滴度相关。在多元线性回归中[方差分析F = 2.976；P = 0.024；R = 0.082]，CD4 + T淋巴细胞（B = 35.289；β = 0.277；P = 0.010；B的95%置信区间为8.727至61.851）与CAC独立相关。在单因素分析中，CAD-RADS与年龄、收缩压、IgM -ApoB-D滴度和内皮MP相关。在多元线性回归中[方差分析F = 2.790；P = 0.032；R = 0.119]，只有年龄（B = 0.027；β = 0.234；P = 0.049；B的95%置信区间为0.000至0.053）是独立预测因子。