Lp(a) independently predicts premature coronary disease 5-fold regardless of PCSK9, Malaysian cohort of 204 (Sci Rep 2026)

Coronary artery disease (CAD) has been associated with elevated Lp(a) levels, yet the mechanism driving the pro-atherogenic and inflammatory effects remains unclear. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of lipid metabolism with emerging roles in vascular inflammation. This study explored the relationship between Lp (a) and PCSK9 in an Asian cohort with angiogram-proven premature CAD (AP-pCAD), with and without familial hypercholesterolemia (FH). Patients were recruited from Cardiology and Specialist Lipid Clinics; grouped into pCAD with FH (n = 70), pCAD without FH (n = 65), and normal controls (G3; n = 69). FH was clinically diagnosed using the Dutch Lipid Clinic Network. Lp(a) and PCSK9 levels were measured using an automated chemistry analyser and ELISA. Lp(a) and PCSK9 levels were significantly higher in pCAD groups compared to controls. No significant correlation between Lp(a) and PCSK9 was observed in individual pCAD subgroups (G1 or G2); a weak positive correlation was found in the normal control group (G3; r = 0.366, p = 0.019). In multivariate analysis, Lp(a) emerged as a significant independent predictor of pCAD (adjusted OR: 5.036, p = 0.015). In conclusion, Lp(a) independently predicts pCAD, while its association with PCSK9 appears modest and context-dependent, suggesting a more complex interplay possibly influenced by lipid-lowering therapy such as statin use.