Abstract P181: Circulating Second-messenger Glycerophosphocholines and Cardiovascular Risk Factors in a Population-based Sample of Adolescents

Circulating second-messenger glycerophosphocholines (smGPCs), including lysophosphatidylcholines and platelet-activating factors, are low-abundance plasma phospholipids that modulate atherosclerosis and inflammation and, in turn, the risk for cardiovascular disease (CVD). Although CVD is a slow-progressing disease culminating in middle-to-late adulthood, its initial stages may be seen already in adolescence. Here, we investigated whether circulating smGPCs are associated with classical CVD risk factors - excess body fat, elevated BP, insulin resistance and low-grade inflammation - during adolescence. We studied a population-based sample of 1029 adolescents (52% females, 12-18 years), as part of the Saguenay Youth Study. We used targeted serum lipidomics (LC-ESI-MS) to identify and quantify circulating smGPCs within the 440-640 Da range. In all participants, we also measured: (i) visceral fat with MRI and total body fat with bioimpedance; (ii) blood pressure (BP) beat-by-beat for five minutes under standard clinical conditions; and (iii and iv) fasting serum insulin (as an index of insulin resistance) and CRP (as an index of low-grade inflammation). We identified a total of 81 smGPCs that varied by the length and saturation of their fatty acyl residues and the type of linkage these residues are attached to the glycerol backbone. Over 30 of them were associated with multiple CVD risk factors (pu003c6x10-4). Most of these associations were inverse and involved ‘medium’ mass smGPCs. Positive associations were also seen and these involved ‘low’ or ‘high’ mass smGPCs. Most strongly inversely associated smGPCs were: (i) PC(20:6/0:0) and PC(O-18:6/2:0), which were associated with total body fat (pu003c3x10-14) and CRP (pu003c8x10-36); and (ii) PC(16:0/2:0), which was associated with visceral fat (p=2x10-18) and BP (pu003c1x10-5). The most strongly positively associated smGPC was PC(14:1/0:0), which was associated with visceral fat (p=8x10-8) and fasting insulin (p=2x10-24). Thus, specific circulating smGPCs are strongly associated with multiple CVD risk factors in adolescence; some of these associations may be ‘protective’ whereas others ‘adverse’. Circulating smGPCs may serve as novel biomarkers of early risk for CVD.