Glycoprotein Acetyls: A Novel Inflammatory Biomarker of Early Cardiovascular Risk in the Young

Abstract

Background Low-grade inflammation in the young may contribute to the early development of cardiovascular disease. We assessed whether circulating levels of glycoprotein acetyls (GlycA) were better able to predict the development of adverse cardiovascular disease risk profiles compared with the more commonly used biomarker high-sensitivity CRP (C-reactive protein). Methods and Results A total of 3306 adolescents and young adults from the Avon Longitudinal Study of Parents and Children (mean age, 15.4±0.3; n=1750) and Cardiovascular Risk in Young Finns Study (mean age, 32.1±5.0; n=1556) were included. Baseline associations between inflammatory biomarkers, body composition, cardiovascular risk factors, and subclinical measures of vascular dysfunction were assessed cross-sectionally in both cohorts. Prospective risk of developing hypertension and metabolic syndrome during 9-to-10-year follow-up were also assessed as surrogate markers for future cardiovascular risk. GlycA showed greater within-subject correlation over 9-to-10-year follow-up in both cohorts compared with CRP, particularly in the younger adolescent group (r=0.36 versus 0.07). In multivariable analyses, GlycA was found to associate with multiple lifestyle-related cardiovascular disease risk factors, cardiometabolic risk factor burden, and vascular dysfunction (eg, mean difference in flow-mediated dilation=-1.2 [-1.8, -0.7]% per z-score increase). In contrast, CRP levels appeared predominantly driven by body mass index and showed little relationship to any measured cardiovascular risk factors or phenotypes. In both cohorts, only GlycA predicted future risk of both hypertension (risk ratio [RR], ≈1.1 per z-score increase for both cohorts) and metabolic syndrome (RR, ≈1.2-1.3 per z-score increase for both cohorts) in 9-to-10-year follow-up. Conclusions Low-grade inflammation captured by the novel biomarker GlycA is associated with adverse cardiovascular risk profiles from as early as adolescence and predicts future risk of hypertension and metabolic syndrome in up to 10-year follow-up. GlycA is a stable inflammatory biomarker which may capture distinct sources of inflammation in the young and may provide a more sensitive measure than CRP for detecting early cardiovascular risk.

Keywords: ALSPAC; CRP; GlycA; Young Finns Study; cardiovascular disease.

Figure 1. Associations between GlycA, high‐sensitivity CRP, and early markers of cardiovascular risk.

(A) Bivariate correlations between inflammatory biomarkers and cardiovascular risk factors in both ALSPAC and YFS cohorts. (B) Independent associations between BMI, waist circumference, and inflammatory biomarkers during the transition from early to mid‐life. Models adjusted for age, sex, BMI, waist circumference, triglycerides, HDL cholesterol, glucose, other inflammatory biomarker, physical activity levels and socioeconomic status. (C) Mean difference in inflammatory biomarker levels per number of adverse cardiovascular risk factors, with results presented unadjusted (blue), and adjusted for age, sex, and body mass index (red). Data in B and C presented as means and 95% CI. ALSPAC indicates Avon Longitudinal Study of Parents and Children; BMI indicates body mass index; CRP, high‐sensitivity C‐reactive protein; DBP, diastolic blood pressure; Gluc indicates glucose; GlycA, glycoprotein acetyls; HDL, high‐density lipoprotein; HOMA, homeostasis model assessment; Ins, insulin; LDL, low‐density lipoprotein; MetS, Metabolic Syndrome; SBP, systolic blood pressure; Trig, triglycerides; WC, waist circumference; and YFS, Young Finns Study.

Figure 2. Associations between GlycA, high‐sensitivity CRP, and endothelial dysfunction in the young.

Relationship between inflammatory biomarkers and endothelial function assessed via flow‐mediated dilation. Data presented as means and 95% CI adjusted for age, sex, body mass index, triglycerides, high‐density lipoprotein cholesterol, glucose, diastolic blood pressure, and baseline vessel diameter. ALSPAC indicates Avon Longitudinal Study of Parents and Children; CRP indicates C‐reactive protein; FMD, flow‐mediated dilation; GlycA, glycoprotein acetyls; and YFS, Young Finns Study.