The association between non-Lp(a)-ApoB / Lp(a) ratio and plaque vulnerability according to lipid oxidation status

Background Lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease and plaque vulnerability. Lp(a) carries oxidized phospholipids and is more atherogenic per particle than other lipoproteins containing apolipoprotein B-100 (apoB). The non-Lp(a)-apoB / Lp(a) ratio represents the relative dominance of metabolically regulated non-Lp(a)-apoB particles versus genetically determined Lp(a) particles. However, its association with plaque vulnerability across different levels of lipid oxidation has not been fully characterized. Purpose The present study aimed to investigate the association between the non-Lp(a)-apoB / Lp(a) ratio and plaque morphology according to lipid oxidation status. Methods Lp(a), apoB, and malondialdehyde-modified low-density lipoprotein (MDA-LDL) were measured in 280 patients undergoing optical coherence tomography (OCT). non-Lp(a)-apoB was obtained by subtracting the molar concentration of Lp(a) (nmol/l) from that of apoB (nmol/l). Patients were divided into tertiles of non-Lp(a)-apoB/Lp(a) ratio. High lipid oxidation status was defined as an MDA-LDL-C / low-density lipoprotein cholesterol ratio ≥ 1.1. Plaque morphology was assessed at the target lesion by OCT. Results Among the 280 patients, 69 had high lipid oxidation levels. These patients more frequently had diabetes mellitus and exhibited lower Lp(a) and apoB concentrations compared with those in the low-oxidation group. There were no differences in the non-Lp(a)-apoB / Lp(a) ratio between the two groups. In patients with high lipid oxidation, thin-cap fibroatheroma (TCFA) became numerically more prevalent (high vs moderate vs low: 20.7% vs 33.3% vs 45.5%; p for trend = 0.059) (Figure 1) and lipid accumulation assessed by lipid index and macrophage infiltration assessed by macrophage grade were greater as non-Lp(a)-apoB / Lp(a) ratio decreased (high vs moderate vs low: 1244 vs 2075 vs 3049; p for trend = 0.007; 6 vs 6 vs 10; p for trend = 0.001; respectively) (Figure 2). No such associations were observed in patients with low lipid oxidation. In multivariable analyses, the non-Lp(a)-apoB / Lp(a) ratio negatively correlated with TCFA prevalence, lipid index, and macrophage grade only in patients with high lipid oxidation after adjustment for confounders, but not in those with low lipid oxidation. Conclusion The non-Lp(a)-ApoB / Lp(a) ratio was associated with OCT features of plaque vulnerability in patients with high lipid oxidation, but not in those with low oxidation. These findings suggest that lipid oxidation levels may modify the relationship between Lp(a)-related lipid composition and plaque inflammation.