Association of the non–lipoprotein(a) apolipoprotein b–to–lipoprotein(a) ratio with renal dysfunction in cardiovascular disease patients: implications for atherosclerotic burden and prognosis

Background Lipoprotein(a) [Lp(a)] is an apolipoprotein B (apoB)–containing atherogenic lipoprotein particle whose circulating concentration and clinical relevance may vary across chronic kidney disease (CKD) stages. The non–Lp(a) apoB/Lp(a) ratio is a recently proposed index that reflects the relative atherogenic contributions of non–Lp(a) apoB and Lp(a). Purpose To examine whether renal dysfunction is associated with a lower non–Lp(a) apoB/Lp(a) ratio and whether a low ratio is linked to atherosclerotic burden and 1-year prognosis. Methods We analyzed 549 cardiovascular disease (CVD) patients stratified by renal function (G1–G2, n=244; G3–G4, n=249; G5, n=56). CKD was defined as stage ≥G3. In fasting blood samples, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), apoB, and Lp(a) were measured; apoB and Lp(a) were expressed in nmol/L. Non–Lp(a) apoB was calculated as total apoB minus Lp(a)-related apoB, and the non–Lp(a) apoB/Lp(a) ratio was derived. Atherosclerotic burden was assessed using a polyvascular disease score. The endpoint was 1-year major adverse cardiovascular events (MACE). Multivariable Cox proportional hazards analyses were performed in CKD (n=305; 44 events). Results Statin use did not differ across renal function categories. LDL-C and HDL-C declined across stages (G1–G2 96.5 and 49.4; G3–G4 90.0 and 46.3; G5 80.0 and 42.3 mg/dL; both p<0.001), whereas TG did not differ significantly (p=0.0669). With worsening renal function, Lp(a) increased (36.3, 42.9, 68.5 nmol/L; p=0.0031) while total apoB (1560, 1423.5, 1335.8 nmol/L; p<0.001) and non–Lp(a) apoB (1481.1, 1342.2, 1255.5 nmol/L; p<0.001) decreased, resulting in a marked reduction in the non–Lp(a) apoB/Lp(a) ratio (140.6, 114.4, 65.8; p<0.001). In CKD, a low non–Lp(a) apoB/Lp(a) ratio (below the median value) was associated with greater atherosclerotic burden (p=0.013) and higher 1-year MACE risk (log-rank p=0.005), whereas no association was observed in non-CKD (p=0.186; p=0.920). In CKD, a low ratio independently predicted MACE after adjustment for age, sex, C-reactive protein, and hemoglobin (hazard ratio 2.25, 95% confidence interval 1.13–4.50; p=0.0217). Conclusions Renal dysfunction was accompanied by higher Lp(a), lower apoB, and a lower non–Lp(a) apoB/Lp(a) ratio. In CKD, a low ratio identified greater atherosclerotic burden and poorer 1-year prognosis, supporting renal function–tailored risk stratification beyond conventional lipid measures.