Sex differences in the prevalence of cardiometabolic risk factors as well as the prevalence and presentation of disease outcomes have been well documented,1 2 prompting questions about the biological mechanisms through which these sex differences may arise. Metabolomics has the ability to improve our understanding of cardiometabolic diseases, by quantifying small-molecule metabolites in biological specimen that are downstream to genetic sequence but proximal to the disease phenotype. Unlike DNA sequence, which is largely static since birth within each individual, metabolites are relatively dynamic, reflecting the interplay between intrinsic and extrinsic factors. Furthermore, technological advances increasingly allow for the quantification of molecules that have not been previously well measured. For example, many lipoprotein subclasses have historically only been indirectly estimated,3 and other metabolites with potential implications for cardiometabolic disease have been less well studied. Thus, studying lipoproteins and other related metabolites through a targeted metabolomics approach may offer insights into sex differences in cardiometabolic diseases.

It is well established that apolipoprotein B-containing lipoproteins that transport cholesterol and other lipids throughout the body play a key role in the development of atherosclerosis.4 Indeed, previous research indicates that circulating lipids and lipoprotein concentrations in childhood are strong predictors of subsequent levels in adulthood.4 5 However, less is known about how these traits change and differ by sex from childhood and adolescence into early adulthood, a critical period of time during which atherosclerosis begins. Therefore, identifying potential sex differences in circulating concentrations of lipoproteins and other cardiometabolic molecular risk factors over the course of childhood and early adulthood is …