Elevated Lipoprotein(a) and Adverse Outcomes in Advanced Coronary Artery Calcification: An Intravascular Ultrasound Study

Coronary artery calcification (CAC) signifies advanced atherosclerosis and portends increased cardiovascular risk. Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerosis; however, its association with in vivo lesion morphology and clinical outcomes in patients with symptomatic, advanced CAC remains incompletely characterized. This study aimed to investigate the association between elevated Lp(a) levels and both in vivo lesion morphology and clinical outcomes in this high-risk population. In this retrospective cohort, 292 patients with intravascular ultrasound(IVUS)-confirmed CAC were stratified into elevated (≥50mg/dL,n=77) or low (<50mg/dL,n=215) Lp(a) groups. The primary endpoint was major adverse cardiovascular events (MACEs). Associations were assessed via multivariable Cox models adjusted for clinical covariates. Patients in the elevated Lp(a) group presented a greater incidence of aortic valve calcification (p<0.001). IVUS revealed constrictive remodeling with a smaller lumen and vessel dimensions. During a median follow-up of 17.2 months, the elevated Lp(a) cohort had a significantly higher MACE rate (37.7% vs. 15.8%; adjusted hazard ratio [aHR] 2.60, 95% CI 1.55–4.35, p<0.001). Elevated Lp(a) independently predicted increased risks of ischemic stroke (aHR 7.14) and in-stent restenosis (aHR 2.78). In symptomatic patients with IVUS-confirmed CAC, elevated Lp(a) identifies a high-risk phenotype characterized by constrictive vascular remodeling and a markedly increased risk of MACEs, driven particularly by ischemic stroke and in-stent restenosis. These findings support the integration of routine Lp(a) testing into the risk stratification of patients with severe CAC, thereby identifying a precise high-risk phenotype that warrants intensified monitoring and represents an ideal target for emerging Lp(a)-lowering therapies. • Elevated Lp(a) (≥50 mg/dL) identifies high-risk patients with symptomatic, IVUS-confirmed coronary artery calcification. • High Lp(a) is associated with a distinct constrictive vascular remodeling phenotype on IVUS. • Elevated Lp(a) confers a >7-fold higher risk of ischemic stroke in this advanced CAC cohort. • In-stent restenosis risk is nearly tripled in patients with elevated Lp(a) and severe calcification. • Aortic valve calcification is over 4 times more prevalent in patients with elevated Lp(a).