Glycerophosphocholine Metabolites and Cardiovascular Disease Risk Factors in Adolescents: A Cohort Study
Background—Glycerophosphocholine (GPC) metabolites modulate atherosclerosis and thus risk for cardiovascular disease (CVD). Pre-clinical CVD may start during adolescence. Here, we used targeted serum lipidomics to identify a new panel of GPCs, and tested whether any of these GPCs are associated - in adolescence - with classical risk factors of CVD, namely excess visceral fat (VF), elevated BP, insulin resistance and atherogenic dyslipidemia.
Methods—We studied a population-based sample of 990 adolescents (12-18 years, 48% male), as part of the Saguenay Youth Study. Using liquid chromatography-electrospray ionization-mass spectrometry, we identified 69 serum GPCs within the 450-680 m/z range. We measured VF with magnetic resonance imaging.
Results—We identified several novel GPCs that were associated with multiple CVD-risk factors. Most significantly, PC16:0/2:0 was negatively associated with VF (P=1.4x10-19), blood pressure (P=7.7x10-5), and fasting triacylglycerols (P=9.0x10-5), and PC14:1/0:0 was positively associated with VF (P=3.0x10-7), fasting insulin (P=5.4x10-32) and triacylglycerols (P=1.4x10-29). Sobel's test of mediation revealed that both GPCs mediated their respective relationships between VF (as a potential primary exposure) and CVD-risk factors (as outcomes, P-values< 1.3x10-3). Further, a GPC shown recently to predict incident coronary heart disease in older adults, PC18:2/0:0, was associated with several CVD-risk factors in adolescents; these associations were less strong than those with the newly identified GPCs.
Conclusions—We identified novel GPCs strongly associated with multiple CVD-risk factors in adolescents. These GPCs may be sensitive indicators of obesity-related risk for CVD outcomes in adults, and may improve biological understanding of CVD risk.
- Received April 21, 2016.
- Revision received August 10, 2016.
- Accepted September 6, 2016.