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Elevated glycoprotein acetyl levels in adolescence and early adulthood predict adverse cardiometabolic profiles and risk of metabolic syndrome in up to 10 year follow-up

By Scott T Chiesa, Marietta Charakida, Georgios Georgiopoulos, Justin D Roberts, Simon J Stafford, Chloe Park, Juha Mykkänen, Mika Kähönen, Terho Lehtimäki, Mika Ala-Korpela, Olli Raitakari, Alun D Hughes, Naveed Sattar, NJ Timpson, John E Deanfield

Posted 30 Sep 2020
medRxiv DOI: 10.1101/2020.09.30.20204479

Objective: Low-grade inflammation in the young may contribute to the early development of adverse cardiometabolic risk profiles. We assessed whether measures of glycoprotein acetylation (GlycA) were better able to detect the development of these changes compared to the more commonly used biomarker high-sensitivity C-reactive protein (CRP), and investigated whether these relationships differed in an adolescent compared to young adult cohort. Research Design and Methods: A total of 3306 adolescents (Avon Longitudinal Study of Parents and Children - ALSPAC; mean age 15.4 {+/-} 0.3; n=1750) and young adults (Cardiovascular Risk in Young Finns Study - YFS; mean age 32.1 {+/-} 5.0; n=1556) were included. Inflammatory biomarkers (GlycA/CRP), body composition (BMI / waist circumference) and cardiometabolic risk factors (blood pressure, triglycerides, HDL-c, glucose, insulin, and homeostasis model of insulin resistance [HOMA_IR]), were measured at baseline and again in 9-10 year follow-up. Metabolic Syndrome (MetS) was defined using adolescent-specific National Cholesterol Education Programme (NCEP) guidelines in ALSPAC and standard NCEP guidelines in YFS. Results: GlycA levels showed greater within-subject correlation over the 9-10 year duration of follow-up in both cohorts when compared to CRP, particularly in the younger adolescent group. In adjusted models, only GlycA was found to increase in line with cardiometabolic risk factor burden at baseline, and to predict adverse changes in several cardiometabolic risk factors in follow-up. In both cohorts, GlycA predicted future risk of MetS (OR [95%CI] for Q4 vs. Q1 = 1.95 [1.08,3.53] and 2.74 [1.30,5.73] for ALSPAC and YFS, respectively), whereas CRP showed a neutral or even negative relationship in fully-adjusted models (OR [95%CI] = 0.50 [0.29,0.86] and 0.93 [0.53,1.64]). Conclusions: Chronic inflammation is associated with adverse cardiometabolic risk profiles from as early as adolescence and predicts risk of future cardiometabolic risk and MetS in up to 10 year follow-up. GlycA may be a more sensitive inflammatory biomarker to CRP for detecting early cardiometabolic and cardiovascular risk in the young.

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