PREreview of Ferritin and transferrin predict common carotid intima-media thickness in females: a machine-learning informed individual participant data meta-analysis

Carotid intima-media thickness (CC-IMT) lacks universally accepted measurement protocols and normal reference values, undermining its use as a reliable, comparable surrogate across diverse cohorts. This variability is linked to inconsistencies in anatomical site, measurement methodology, and population differences.

CC-IMT increases may reflect medial hypertrophy rather than atherosclerotic intimal thickening, especially in cases of hypertension, confounding interpretation regarding vascular pathology. The broader clinical community has raised concerns about CC-IMT’s predictive value. In many settings, including routine practice, its utility is debated or considered marginal. So, if the CC-IMT metric is noisy, nonspecific, or only loosely tied to clinical outcomes, any purported relationship with iron biomarkers (like ferritin or transferrin) could be spurious or clinically irrelevant.

The study focused on CC-IMT but excluded plaque presence (>1.5 mm). However, IMT and plaque represent different pathological processes. Failure to distinguish between adaptive vascular remodeling and early atherosclerotic changes further weakens the interpretive clarity.

The meta-analysis aggregated CC-IMT data from 21 studies, but ultrasound protocols, operator expertise, and imaging equipment likely varied substantially. This introduces measurement heterogeneity and betrays the assumption of comparability across datasets.

Finally, without incontrovertible validation of CC-IMT’s relevance and consistency, the reported associations are at high risk of being artefactual. The complex modeling applied, machine learning, and spline regression cannot salvage findings built on an unreliable foundation.

Competing interests

The author declares that they have no competing interests.