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

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.

High density lipoprotein functionality and cardiovascular events and mortality: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The aim of this systematic review and meta-analysis is to synthesize studies assessing the associations between high-density lipoprotein functionality and risk of cardiovascular disease and mortality. METHODS: We searched Medline and Embase for the identification of observational studies meeting the inclusion criteria. This meta-analysis was conducted following the PRISMA statement and was registered in PROSPERO (CRD42017065857). We pooled risk estimates with a random-effect model separately for cardiovascular disease (fatal and non-fatal) and all-cause mortality. RESULTS: Out of 29 manuscripts, 20 articles investigated cholesterol efflux capacity (13 prospective and 7 cross-sectional), 10 antioxidant capacity (7 prospective and 3 cross-sectional) and two anti-inflammatory capacity of high-density lipoprotein (1 prospective and 1 cross-sectional). A greater cholesterol efflux capacity was associated with lower risk of cardiovascular disease in 8 studies (RR for 1SD increase: 0.86; 95% CI: 0.76-0.98) and of mortality in 5 studies (RR for 1SD increase: 0,77; 0.60-1.00). Better antioxidant capacity was non-significantly associated with lower cardiovascular disease risk in 2 studies (RR for 1SD increase 0.70; 0.32-1.53) and significantly with mortality in 3 studies (RR for 1SD increase 0.48; 0.28-0.81). High-density lipoprotein anti-inflammatory ability was associated with a lower cardiovascular disease risk in the only prospective study. CONCLUSIONS: Greater high-density lipoprotein cholesterol efflux capacity and antioxidant/anti-inflammatory capacities were associated with lower risk of cardiovascular disease. However, the heterogeneity between studies and evidence of publication bias warrants caution and highlights the need for larger prospective studies with standardized assays and specific outcomes.