Abstract 679: HDL Apolipoproteomic Score, Cardiometabolic Risk, And Exercise Training

Background: Previous studies have derived and validated an HDL apolipoproteomic score (pCAD) that predicts coronary artery disease risk. However, the relationship between pCAD and the cardiometabolic profile in healthy adults, as well as the effects of regular exercise on pCAD are unknown. Methods: A total of 642 inactive but healthy adults (56% female, 36% Black, 35±13 yrs) completed 20 weeks of endurance exercise training. HDL-bound proteins were measured in APOA1-tagged serum using targeted LC-MS/MS (Quest Diagnostics). The pCAD index was calculated as a weighted sum of five HDL-associated apolipoproteins (APO A1, C1, C2, C3, C4) with scores from 0 to 100 (higher score=higher risk). Age-, sex-, and race-specific baseline pCAD quartiles were created. Results: The mean (SD) pCAD score at baseline was 29 (32). At baseline, increasing pCAD quartile was associated with a poorer cardiometabolic profile, including higher total and visceral fat, blood pressure, inflammation, and fasting glucose and lower insulin sensitivity and lipoprotein lipase activity ( Table ). In the total sample, pCAD significantly decreased with exercise training by 4.7 (25) pts or ~16%. Across pCAD quartiles, mean decreases in pCAD were 4.6 in quartile 3 and 21.3 in quartile 4, compared to mean increases of 3.6 in quartile 1 and 3.5 in quartile 2 (p<0.05 for all within group changes). The exercise-induced decrease in pCAD was largely driven by increases in HDL-associated APOA1 and APOC1 levels and inversely correlated with changes in HDL-C (r= -0.17, p<0.0001) and HDL size (r= -0.14, p=0.0006). Otherwise, changes in pCAD were not correlated with changes in other cardiometabolic traits. Conclusions: A higher pCAD index was associated with a poor cardiometabolic profile at baseline and improved with regular exercise in healthy adults with the worst profiles. These findings highlight the potential role of HDL apolipoproteins as a theranostic target for lifestyle interventions in these individuals.