Subclinical Carotid Atherosclerosis Endotypes

Summary

Subclinical carotid atherosclerosis endotypes combine clinical and molecular data to separate individuals with different cardiovascular risk and biological drivers. Multi-omics and causal analyses implicate IL6R signaling, with possible involvement of the IL6R/OSMR pathway, in specific higher-risk endotypes.

Evidence

The IMPROVE cohort defined four endotypes spanning low to very high cardiovascular risk. Follow-up proteomic, genetic and Mendelian-randomization analyses investigated why these groups differ and supported endotype-specific inflammatory mechanisms rather than a single pathway shared by all subclinical disease.[1]

The accompanying editorial emphasized that endotypes may help align mechanism-directed interventions with the patients most likely to benefit, while noting that prospective validation is required before clinical use.[2]

Citations

[1] Chen et al. (2025), "A multi-omics approach uncovers causality of IL6R on endotypes of subclinical carotid atherosclerosis and the possible role of the IL6R/OSMR pathway" [2] Tarkin and Butterworth (2025), "Towards defining endotype-specific mechanisms of sub-clinical atherosclerosis to advance precision medicine for cardiovascular disease"