Heightened monocyte-derived foam cell formation in older men is not explained by inflammatory or oxidized lipid biomarkers

Background Atherosclerosis is a leading cause of cardiovascular disease (CVD), particularly in older individuals. We previously demonstrated that monocytes from older men with no self-reported history of CVD had a higher propensity to form foam cells ex vivo . Ageing is associated with chronic low-grade inflammation (inflamm-ageing) which may impact monocyte biology, but whether inflammatory or oxidative pathways predict this heightened foam cell capacity of monocytes in older men is unclear. Methods Monocyte-derived foam cell formation and soluble and cellular measures of inflammation, lipids and monocyte activation were quantified from younger (n=34, median [IQR] age: 31 [27 – 33]) and older (n=40; 73 [68 – 79]) men. Correlative and linear regression analyses were performed to identify the relationships between inflammatory biomarkers, modified lipids, age and monocyte-derived foam cell formation ex vivo . Results Monocytes from older men exhibited higher levels of ex vivo foam cells compared to younger men (P=0.0021). Levels of inflammatory analytes (Serum amyloid A, d-dimer, soluble [s]TNF-RII, IL-6), measures of myeloid activation/microbial translocation (lipopolysaccharide-binding protein, sCD14, CXCL10), and oxidized LDL were higher in older men as compared to younger men (P<0.05 for all). Linear regression analyses demonstrated that neither inflammation or oxidized lipid was positively associated with foam cell formation, however age remained independently associated with foam cell formation in all multivariate models. Discussion Whilst measures of inflammation, monocyte activation and oxidized lipids remain elevated in older men, age itself was the strongest independent predictor of foam cells supporting mechanisms beyond those captured by conventional inflammatory or cholesterol biomarkers.