Integrating Fetuin-A and Lipid-Based Phenotyping as Markers of Cardiometabolic Risk in Subclinical Hypothyroidism

The aims of the study were to evaluate fetuin-A (FA) as an integrative biomarker for cardiometabolic risk in subclinical hypothyroidism (SCH) and to investigate lipid-based metabolic heterogeneity.

In this cross-sectional study, 192 participants (105 SCH, 87 controls) were evaluated for thyroid function, metabolic parameters, lipid profiles, FA, and high-sensitivity C-reactive protein (hs-CRP). Lipid phenotyping was performed using principal component analysis (PCA) and latent profile analysis (LPA). A composite cardiovascular disease risk index (CVDRI) incorporating FA and the atherogenic index of plasma (AIP) was calculated. Correlation, regression, and receiver operating characteristic (ROC) analysis were conducted.

SCH patients exhibited significantly elevated thyroid-stimulating hormone (TSH), insulin resistance, dyslipidemia, hs-CRP, and FA compared to controls (p < 0.0001). FA showed strong correlations with TSH, lipid parameters, insulin resistance, and CVDRI (ρ = 0.60-0.77, p < 0.001). PCA and LPA identified three distinct SCH phenotypes, each showing progressively adverse metabolic and inflammatory profiles. ROC analysis showed excellent discriminatory performance for FA and CVDRI (AUCs >95%), whereas lipid-derived indices distinguished high-risk phenotypes.

FA is a promising integrative biomarker linking thyroid dysfunction with cardiometabolic risk in SCH. Lipid-based phenotyping highlights disease heterogeneity and supports the use of composite biomarker strategies for early risk stratification and personalized management.