Temporal causal longitudinal associations of high-sensitivity C-reactive protein with carotid intima-media thickness progression in adolescents: the ALSPAC birth cohort study
Authors: Agbaje A O , Barmi S , Sansum K M , Baynard T , Barker A R , Tuomainen T P 
Published: October 2022

Abstract

Background
The causal role of high-sensitivity C-reactive protein (hsCRP) in the evolution of preclinical cardiovascular disease remains unclear. A previous longitudinal study concluded that hsCRP measured in childhood was not associated with a single measure of carotid intima-media thickness (cIMT) assessed at mid-adulthood. The use of hsCRP samples stored for 25 years prior to analysis might have confounded this previous findings. In the young population of adolescents and young adults no study has investigated whether elevated hsCRP temporally precedes higher cIMT or if bi-directional associations exist, due to the lack of repeated measures of cIMT.

Purpose
To examine the temporal causal longitudinal associations between repeated measures of cIMT and hsCRP in a young population.

Methods
We studied 3862 adolescents, aged 17.7 years, followed-up for 7 years, from Avon Longitudinal Study of Parents and Children, birth cohort, UK. Fasting plasma hsCRP was assessed at age 17.7 and 24.5-year clinic visits. cIMT from the right and left common carotid arteries at 17 years was assessed by ultrasound using a linear 12-MHz transducer (Vivid7, GE Medical, Chicago, Illinois) and cIMT from the right and left common carotid arteries at 24 years was measured using an ultrasound machine (CardioHealth Panasonic and a 13.5 MHz linear array broadband transducer (probe; centre frequency 9.0 MHz). We conducted autoregressive cross-lagged structural equation model path analyses to untangle temporal and bi-directional associations. We adjusted for sex, time in years between ages 17.7 and 24.5 years, age, low-density lipoprotein cholesterol, insulin, triglyceride, high-density lipoprotein cholesterol, fasting plasma glucose, systolic blood pressure, heart rate, dual-energy Xray absorptiometry measured total fat mass and lean mass, ActiGraph measured moderate to vigorous physical activity at 15.5 years, smoking status, and family history of cardiovascular and metabolic diseases.

Results
Among 3862 adolescents (55.5% female), median (IQR) hsCRP values at 17.7 and 24.5 years were 0.56 (0.98) mg/L and 0.84 (1.62) mg/L, respectively. The median (IQR) cIMT values at 17.7 and 24.5 years were 0.48 (0.05) mm and 0.54 (0.09) mm, respectively. Higher hsCRP at age 17.7 years was associated with cIMT [Standardized β = 0.062, standard error = 0.004, p=0.035] at age 24.5 years. However, higher cIMT at age 17.7 years was not associated with higher hsCRP [β = −0.014, standard error = 0.284, p=0.523] at 24.5 years.

Conclusion
These findings in the largest adolescent population to date suggest that higher inflammation in adolescence temporally precede higher carotid thickness 7 years later and there was no bi-directional relationship. Clinical and public health interventions targeted at reducing low-grade inflammation to potentially attenuate the development of atherosclerotic cardiovascular disease in the young population are warranted.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Finnish Cultural Foundation