Review High-density lipoprotein cholesterol efflux capacity and cardiovascular risk in autoimmune and non-autoimmune diseases Anouar Hafiane a, ⁎, Elda Favari b, ⁎, Stella S. Daskalopoulou c , Nicolas Vuilleumier d,e , Miguel A. Frias d,e a Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, McGill University, 1001 Decarie Blvd, Bloc E01. 3370H, Montréal, Qc H4A 3J1, Canada b Department of Food and Drug, University of Parma, Parco Area delle Scienze, 27/A, 43124 Parma, Italy c Department of Medicine, Division of Internal Medicine, McGill University, Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, EM1.2230, Montreal, Quebec H4A 3J1, Canada d Division of Laboratory Medicine, Diagnostic Department, Geneva University Hospitals, 1211 Geneva, Switzerland e Division of Laboratory Medicine, Department of Medical Specialties, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland abstract article info Article history: Received 30 October 2019 Accepted 5 January 2020 Keywords: High-density lipoprotein (HDL) HDL-cholesterol HDL function Cardiovascular risk Cholesterol efflux capacity Autoimmune disease Cardiovascular disease (CVD). Functional assessment of cholesterol efflux capacity (CEC) to high-density lipoprotein (HDL) is an emerging tool for evaluating morbidity and mortality associated with cardiovascular disease (CVD). By promoting macrophage reverse cholesterol transport (RCT), HDL-mediated CEC is believed to play an important role in atherosclerotic lesion progression in the vessel wall. Furthermore, recent evidence indicates that the typical inverse associations between various forms of CEC and CV events may be strongly modulated by environmental systemic factors and traditional CV risk factors, in addition to autoimmune diseases. These factors influence the complex and dynamic composition of HDL particles, which in turn positively or negatively affect HDL-CEC. Herein, we review recent findings connecting HDL-CEC to traditional CV risk factors and cardiometabolic conditions (non-autoimmune diseases) as well as autoimmune diseases, with a specific focus on how these factors may influence the associa- tions between HDL-CEC and CVD risk. © 2020 Elsevier Inc. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2. HDL function in CVD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2.1. Moving from HDL-C hypothesis to HDL functionality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2.2. HDL role in cholesterol efflux . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 3. HDL composition and cholesterol efflux capacity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 3.1. HDL composition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 3.2. Triglycerides and CEC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 3.3. Serum amyloid A and CEC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 3.4. A novel role of sphingosine-1-phosphate in CEC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 4. HDL function in non-autoimmune diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 4.1. HDL ABCA1-CEC and cardiovascular risk prediction in human studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 4.2. HDL-CEC in primary prevention and association with traditional CV risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 4.2.1. Smoking and HDL-CEC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 4.2.2. Age and HDL-CEC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 4.2.3. Gender and HDL-CEC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Metabolism Clinical and Experimental 104 (2020) 154141 ⁎ Corresponding authors. E-mail addresses: anouar.hafiane@mail.mcgill.ca (A. Hafiane), elda.favari@unipr.it (E. Favari), stella.daskalopoulou@mcgill.ca (S.S. Daskalopoulou), nicolas.vuilleumier@hcuge.ch (N. Vuilleumier), miguel.frias@hcuge.ch (M.A. Frias). https://doi.org/10.1016/j.metabol.2020.154141 0026-0495/© 2020 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Metabolism Clinical and Experimental journal homepage: www.metabolismjournal.com