Sex-specific trajectories of molecular cardiometabolic trait concentrations through childhood, adolescence and young adulthood: a cohort study
Authors: O’Keeffe Linda M. , Tilling Kate , Bell Joshua A. , Lee Matthew A. , Lawlor Deborah A. , Smith George Davey , Kearney Patricia M. 
Published: July 2021

AbstractBackgroundCausal risk factors and predictive biomarkers for cardiometabolic diseases are increasingly being identified from comprehensive metabolomic profiling in epidemiological studies. The changes which typically occur in molecular cardiometabolic traits across early life are not well characterised.MethodsWe quantified sex-specific trajectories of 148 metabolic trait concentrations including various lipoprotein subclasses from age 7y to 25y. Data were from offspring of the Avon Longitudinal Study of Parents and Children birth cohort study. Outcomes included concentrations of 148 traits quantified using nuclear magnetic resonance spectroscopy measured at 7y, 15y, 18y and 25y. Sex-specific trajectories of each trait concentration were modelled using linear spline multilevel models with robust standard errors.Findings7,065-7,626 participants (11,702-14,797 repeated measures) were included in analyses. Females had higher very-low-density lipoprotein (VLDL) particle concentrations at 7y. VLDL particle concentrations decreased from 7y to 25y with larger decreases in females, leading to lower VLDL particle concentrations at 25y in females. For example, females had 0.25 SD (95% Confidence Interval (CI), 0.20, 0.31) higher very small VLDL particle concentration at 7y; mean levels decreased by 0.06 SDs (95% CI, −0.01, 0.13) in males and 0.85 SDs (95% CI, 0.79, 0.90) in females from 7y to 25y leading to 0.42 SD (95% CI, 0.35, 0.48) lower very small VLDL particle concentrations in females at 25y. Females also had higher low-density lipoprotein (LDL) particle concentrations at 7y; these increased from 7y to 25y in both sexes and increases were larger among males. By age 25y, LDL particle concentrations remained higher in females but the sex difference was smaller than in early childhood. Females had lower high-density lipoprotein (HDL) particle concentrations at 7y. HDL particle concentrations increased from 7y to 25y with larger increases among females leading to higher HDL particle concentrations in females at 25y.InterpretationChildhood and adolescence are important periods for the emergence of sex differences in atherogenic lipids and predictive biomarkers for cardiometabolic disease, mostly to the detriment of males.FundingWellcome Trust, Medical Research Council UK, Health Research Board, IrelandResearch in contextEvidence before this studyCausal risk factors and novel predictive biomarkers for cardiometabolic diseases are increasingly being identified from the recent application of comprehensive metabolomic profiling in epidemiological studies but the change which typically occur in these traits across childhood, adolescence and early adulthood is not well u understood.Added value of this studyIn this prospective cohort study with repeat assessments of 148 molecular cardiometabolic traits from comprehensive metabolomic profiling at age 7y, 15y, 18y and 25y, we demonstrate that marked change in levels of causal risk factors and novel predictive biomarkers for cardiometabolic diseases occur from childhood to early adulthood. In addition, our findings suggest that childhood and adolescence are an important life stage for the development of sex differences in atherogenic lipids and predictive biomarkers for cardiometabolic disease, mostly to the detriment of males.Implications of all the available evidenceFindings suggest that cardiometabolic disease prevention targeting childhood and adolescence should be prioritised for both lifelong cardiometabolic disease prevention and sex differences in cardiometabolic risk to the disadvantage of males across the life course.