Inflammatory marker glycoprotein acetyls detects early and worsening cardiac damage better than high-sensitivity C-reactive protein in youth: a 7-year longitudinal study

Background Glycoprotein acetyls (GlycA) is a novel inflammatory marker that reflects a chronic inflammatory state, while high-sensitivity C-reactive protein (hsCRP) is widely used in detecting low-grade inflammation. Among healthy youth with extremely low hsCRP, the predictive ability of hsCRP to detect early cardiovascular risk is reduced. The scarcity of repeated echocardiography and GlycA measures has left the comparison of this inflammatory marker in detecting cardiac alterations unresearched. This evidence could be useful in early screening and detection of cardiovascular risks in a non-clinical young population. Purpose To examine whether GlycA and hsCRP similarly predict the risk of structural and functional cardiac damage or if differences exist. Methods From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents were included. At ages 17 and 24 years follow-up, GlycA were measured by nuclear magnetic resonance metabolomics while hs-CRP was measured by automated particle-enhanced immunoturbidimetric assay. Repeated echocardiography measured left ventricular mass indexed for height2.7 (LVMI2.7), relative wall thickness (RWT), LV diastolic function from mitral E/A ratio (LVDF), and LV filling pressure from E/e´ ratio (LVFP) were available at ages 17 years and age 24 years follow-up. LVMI2.7 ≥51g/m2.7, RWT ≥0.44, LVDF<1.5, and LVFP ≥8 were categorised as LV hypertrophy, high RWT, LVD dysfunction, and high LVFP, respectively. Generalized linear mixed-effect models with logit-link analyses adjusted for sex, socioeconomic status, family history of cardiometabolic diseases and time-varying covariates measured at both baseline and follow-up such as age, heart rate, systolic blood pressure, fat mass, lean mass, smoking status, sedentary time, light physical activity, moderate-to-vigorous physical activity, and fasting low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol glucose, and insulin was conducted. Results Among 1595 adolescents (mean [SD] age at baseline, 17.74 [0.38] years), the mean (SD) GlycA at ages 17 and 24 years were 1.22 (1.14) and 1.23 (1.17), respectively, while the median (IQR) of hsCRP were 0.50 (0.91) and 0.78 (1.64). The prevalence of LV hypertrophy increased from 2.6% to 7.9%, over 7 years. In a fully adjusted model, increased GlycA was significantly associated with higher odds of progressively worsening LV hypertrophy (odds ratio 2.78 [95% CI, 1.003 – 7.58], p=0.049), high RWT (2.46 [1.08 – 5.56], p=0.032), and LVD dysfunction (4.33 [1.85 – 10.10], p<0.001), but not high LVFP. HsCRP was unrelated to cardiac damage. Conclusion GlycA is potentially a clinically useful and stable inflammatory marker for detecting early cardiovascular risk in an apparently healthy young population, significantly better than hsCRP.