Dear Editor
We read with great interest the intravascular ultrasound based investigation by Xiao and colleagues examining lipoprotein(a) in advanced coronary artery calcification [1]. The lesion level intravascular ultrasound phenotyping with longitudinal follow up provides useful mechanistic context, and the endpoint specific analysis of stroke and in stent restenosis adds clinically relevant detail.
Translation of the reported risk gradients into clinical decision making requires caution. The adjusted hazard ratio of 2.60 for major adverse cardiovascular events corresponds to an absolute difference of approximately 22 percentage points over 17.2 months. In a cohort with substantial baseline risk, this pattern suggests lipoprotein(a) may function primarily as a risk amplifier rather than an independent procedural determinant [2]. Evidence remains limited that routine measurement meaningfully alters revascularization strategy or secondary prevention intensity.
Interpretive complexity also arises from the discordance between similar calcium burden and smaller vessel dimensions. Despite comparable calcification metrics, elevated lipoprotein(a) was associated with reduced lumen and external elastic membrane measurements, raising the possibility of an underlying diffuse small vessel phenotype. The greater prominence of this pattern in men suggests potential sex related vascular remodeling heterogeneity that may influence procedural planning. Event specific estimates also warrant caution. The large stroke hazard ratio is derived from few absolute events with limited secondary endpoint power, which may affect estimate stability and clinical prioritization [3].
The authors advance lesion specific understanding of lipoprotein(a) in severe coronary artery calcification. Larger multicenter studies with longer follow up may clarify how lipoprotein(a) testing should inform individualized risk stratification after percutaneous coronary intervention.
CRediT authorship contribution statement
Neeraj Singh: Conceptualization, Methodology, Project administration, Supervision, Validation, Writing – original draft, Writing – review & editing. Monika Srivastav: Writing – original draft, Writing – review & editing.
Contributor Information
Neeraj Singh, Email: neeraj.singh.work@proton.me.
Monika Srivastav, Email: monika.srivastav@proton.me.
References
- 1.Xiao S, Zeng M, He J, Xiao D, Chen Y. Elevated Lipoprotein(a) and adverse outcomes in advanced coronary artery calcification: an intravascular ultrasound study. Internat. J. Cardiology. Cardiovascu. Risk. Prevent. Published online February 2026:200606. 10.1016/j.ijcrp.2026.200606. [DOI] [PMC free article] [PubMed]
- 2.Williams M.C., Dweck M.R. Unraveling the association between lipoprotein(a) and cardiovascular events with coronary computed tomography angiography. Circ. Cardiovasc. Imaging. 2022;15(12) doi: 10.1161/circimaging.122.015035. [DOI] [PubMed] [Google Scholar]
- 3.Forman R., Viscoli C.M., Bath P.M., et al. Central vs site outcome adjudication in the IRIS trial. J. Stroke Cerebrovasc. Dis. 2022;31(9) doi: 10.1016/j.jstrokecerebrovasdis.2022.106667. [DOI] [PubMed] [Google Scholar]