Background and aims: Inflammation is a pathophysiological mechanism of atherosclerosis, and several mediators have been proposed as biomarkers. Acute-phase serum glycoproteins are upregulated in the liver during systemic inflammation. Because of their unique biochemical characteristics, they can be measured by 1H-NMR, and their role as subclinical inflammation markers is under clinical evaluation. We aimed to assess the clinical value of plasma glycoproteins in familial hypercholesterolemia (FH) patients.

Methods: We recruited 295 FH patients (75.6% with FH-associated genetic variants). At baseline, a full glycoprotein profile, glycoprotein A and B (GlycA and B) concentrations and their height and width ratios (H/W) were analysed by 1H-NMR. A carotid artery ultrasound study was performed at baseline and prospectively at the 5-year follow-up in 144 FH patients.

Results: At baseline, the GlycA and GlycB concentrations and their H/W ratios were correlated with lipid profile and adiposity parameters, with the correlation between the GlycA and triglyceride concentrations (r = 0.780; p < 0001) being the strongest. Glycoprotein concentrations were also correlated with inflammation markers, mainly hsCRP. Higher glycoprotein concentrations were observed in patients with higher intima media thickness, arterial rigidity and presence of arteriosclerotic plaques. In the multivariate and random forest analyses, the baseline GlycB concentration showed a significant contribution to the detection of FH individuals prone to develop carotid plaques.

Conclusions: The concentrations of serum glycoproteins as assessed by 1H-NMR are robust markers of subclinical inflammation. In FH patients, they are increased in the presence of subclinical vascular damage and could be considered atherosclerosis risk markers in the long term.