ANGPTL3, CAROTID IMT AND ADVANCED LIPID PROFILING IN DYSLIPIDEMIAS: DATA FROM THE ADSL PROJECT

Objectives: ADSL (Advanced Diagnostics in Lipidology) is a collaborative Study in patients with genetic or acquired dyslipidemias and control subjects. It aims to evaluate non-conventional lipid parameters and to relate them to common carotid intima-medial thickness (ccIMT) and to other risk determinants, among which Angiopoietin-like Protein 3 (ANGPTL3), a liver-secreted protein known to affect lipoprotein metabolism by inhibiting lipoprotein and endothelial lipases. Methods: In a subset of investigated subjects (50 controls, 50 diabetics and 50 individuals with stage 2-3 chronic kidney failure -CKD-) we assessed the plasmatic levels of ANGPTL3 by ELISA evaluation (AdipoGen AG, Liestal, Switzerland). They were compared and correlated with common lipid variables, LDL and HDL dimensional distribution pattern (®Lipoprint), LDL oxidative susceptibility (lag-phase) and oxidized LDLs, ABCA1-mediated cellular cholesterol efflux capacity (CEC) and ccIMT. Results: ANGPTL3 was almost twice as much in normal (402±18 ng/ml) and CKD subjects (385±23 ng/ml) compared to patients with diabetes (207±13 ng/ml, p<0.001). We did not find any significant correlation with tryglicerides, LDL-chol and HDL-chol both overall and within subgroups. Similarly ANGPTL3 did not seem to relate to LDL oxidative parameters, lipoprotein diameter and functionality (CEC), while it was related to carotid atherosclerosis both in controls (ccIMT-mean R=0.453, p<0.01; ccIMT-max R=0.390, p<0.05) and diabetics (ccIMT-max R=0.402, p<0.01) while in CKD patients the association was not significant. Conclusion: We did not observe decreased ANGPTL3 levels in subjects with slight CKD, contrary to what has been found in dialysis and predialysis patients. To our surprise we could not detect any significant correlation between plasma ANGPTL3, triglycerides and HDL-chol in our investigational setting: other observed only a direct relationship with HDL-chol. Eventually the association between increasing ANGPTL3 values and indexes of subclinical atherosclerosis is a relatively new finding in the diabetic population, widening an isolated previous observation in normal subjects that we also confirmed.