Lp a and CAC score 0: the hidden risk phenotype

Background Lipoprotein(a) [Lp(a)] is a genetically determined, established independent cardiovascular risk factor associated with atherosclerotic cardiovascular disease. Beyond its role in plaque initiation, Lp(a) has been implicated in the progression and calcification of atherosclerotic lesions through different mechanisms. In the setting of acute coronary syndromes (ACS), Lp(a) may play a dual pathophysiologic role, contributing not only to atherosclerotic plaque burden but also to plaque instability and thrombosis. However, its clinical significance in patients with a coronary artery calcium (CAC) score of 0 Agatston Units (AU) remains insufficiently characterized. Purpose We analyzed the association between elevated Lp(a) levels and the presence of coronary artery disease (CAD) in patients with CAC = 0 undergoing Coronary computed tomography angiography (CCTA) for low- to intermediate-risk acute coronary syndromes (ACS). Methods We conducted an observational analytical study including 119 patients with CAC = 0 AU who underwent CCTA for low- to intermediate-risk ACS. Patients were stratified into elevated Lp(a) (n = 15) and normal Lp(a) groups (n = 104). The primary endpoint was the presence of CAD of any degree. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess the association between elevated Lp(a) and CAD prevalence. Data collection was carried out between May 11, 2022 and February 20, 2026. Results CAD was identified in 10 of 15 patients (66.7%) in the elevated Lp(a) group compared with 35 of 104 patients (33.7%) in the normal Lp(a) group. Elevated Lp(a) was significantly associated with a higher prevalence of CAD (RR 1.98; 95% CI 1.26–3.10; p = 0.002). Elevated Lp(a) was associated with a higher prevalence of CAD (RR 1.98; 95% CI 1.26–3.10; p=0.002) and remained a strong predictor in multivariable analysis (OR 3.94; 95% CI 1.29–12.05; p=0.002). Conclusion In patients with an ACS and a CAC score = 0 AU, elevated Lp(a) levels were associated with nearly a fourfold higher odd of coronary artery disease (OR 3.94; 95% CI 1.29–12.05; p = 0.002). Our data appear to identify a hidden risk phenotype—patients with elevated Lp(a) who harbor coronary artery disease despite a CAC score =0. These findings highlight Lp(a) as a marker of residual atherosclerotic risk even in the absence of coronary calcification, with potential implications for enhanced risk stratification and preventive strategies in this subgroup of patients.