As NHHR levels increase, chronic inflammation induces glycation of apolipoprotein A1 (apoA1) in HDL-C, replacing functional components with pro-inflammatory mediators (e.g., SAA1, apo CIII), transforming HDL-C into a pro-atherogenic particle (59).Cumulative LDL-C exposure (quantified as LDL-C burden, LCB) correlates positively with CVD risk (60), activating the TLR4/NF-κB axis and recruiting neutrophils via CXCL1/CXCR2 signaling, further destabilizing plaques (6, 57, 61, 62).An increase in NHHR may contribute to metabolic disorders. Here, SAA1 is linked to metabolic disease.