Circulating N-Linked Glycoprotein Acetyls and Longitudinal Mortality Risk

Area of Science:

• Biochemistry
• Epidemiology
• Biomarkers

Background:

• Circulating glycoprotein N-acetyl glucosamine residues are linked to cardiovascular disease and diabetes.
• These findings highlight potential novel biomarkers for disease risk.

Purpose of the Study:

• To investigate the longitudinal association between plasma glycan biosignature (GlycA) and mortality in initially healthy individuals.
• To validate findings in an independent cohort.

Main Methods:

• Quantified GlycA using 1H nuclear magnetic resonance spectroscopy in 27,524 participants (Women's Health Study).
• Assessed all-cause mortality as the primary outcome, with secondary examination of cardiovascular and cancer mortality.
• Replicated findings in an independent cohort of 12,527 participants (JUPITER trial).

Main Results:

• In the Women's Health Study (median 20.5 years follow-up), elevated GlycA was associated with increased all-cause mortality risk (HR per SD increment: 1.14; 95% CI: 1.09-1.16).
• Similar associations were observed in the JUPITER cohort (HR: 1.33; 95% CI: 1.21-1.45).
• Elevated GlycA also predicted increased cardiovascular disease and cancer mortality risk.

Conclusions:

• Elevated baseline GlycA in initially healthy individuals is a significant predictor of long-term all-cause, cardiovascular, and cancer mortality.
• GlycA may reflect cumulative risk from multiple systemic inflammation pathways.