Cross-Sectional Associations between HDL Structure or Function, Cell Membrane Fatty Acid Composition, and Inflammation in Elderly Adults

Abstract

ABSTRACT Background Cell membrane fatty acid composition has been related to inflammation and cardiovascular disease (CVD) risk. Dysregulation of HDL function is also considered a CVD risk factor. Objectives We aimed to investigate whether the content of cell membrane fatty acids and HDL functionality are linked to each other as well as to inflammation. Methods This cross-sectional analysis involved 259 participants (mean age: 67.9 y) with overweight/obesity (mean BMI: 29.5 kg/m2) from a coronary artery disease case-control study nested within the PREDIMED (PREvención con DIeta MEDiterránea) trial for which HDL functional parameters [apoA-I, apoA-IV, and apoC-III; cholesterol efflux capacity (CEC); HDL oxidative inflammatory index (HOII); sphingosine-1-phosphate (S1P); serum amyloid A (SAA); and complement-3 (C3) protein] were quantified. We also assessed 22 fatty acids in blood cell membranes using GC and inflammatory markers (IFN-γ and IL-1b, IL-6, IL-8, and IL-10) in serum. Associations of HDL-related variables with cell membrane fatty acids and with inflammatory markers were assessed using multivariable linear regression analyses with elastic net penalty. Results ApoA-I, apoC-III, CEC, HOII, S1P, and SAA, but not apoA-IV and C3 protein, were associated with membrane fatty acids. S1P and SAA were directly associated with IL-6, whereas apoA-I and C3 protein showed inverse associations with IL-6. Specific fatty acids including myristic acid (14:0) and long-chain n–6 fatty acids being negatively and positively associated with IL-8, respectively, were also found to be positively associated with SAA. Conclusions This study suggests interrelations between indicators of inflammation and both blood cell membrane fatty acid composition and HDL structure/functional parameters in a Mediterranean population at high CVD risk. This trial was registered at www.isrctn.com as ISRCTN35739639.