Circulating Angiopoietin-like Protein 3 level and plaque calcification: insights from optical coherence tomography imaging analysis

Abstract Background Angiopoietin-like Protein 3 (ANGPTL3) regultates metabolism of triglyceride-rich lipoproteins. Pathophysiologically, ANGPTL3 has a property to inhibit lipoprotein lipase activity and endothelial lipase activity which diminishes the clearance of triglyceride-rich lipoproteins.Furthermore, inhibition of endothelial lipase with ANGPTL3 has been shown to increase LDL-C levels in circulation. These observations emerge the hypothesis that ANGPTL3 may be a potential driver associated with atherosclerosis. Purpose To elucidate whether ANGTL3 associates with plaque features by employing Optical coherence tomography imaging. Methods We analyzed 58 CAD patients (89 non-culprit lesions) receiving OCT-guided PCI. ANGPTL3 was measured using an enzymatic method (Immuno-Biological Laboratories Co.Ltd., Fujioka, Japan). Clinical demographics and OCT-derived plaque features were compared in subjects stratified according to tertile of ANGPTL3 levels. Results ANGPTL3 level was 356.2±158.9 ng/mL (statin=98.2%, LDL-C=74.5±21.7mg/dL). Patients with tertile 3 of ANGPTL3 level were older with lower eGFR levels (Table). The proportions of stable CAD and ACS were 60.3 and 39.6%, respectively. There were no significant differences in lipid-lowering therapies, and the averaged LDL-C level was 74.5 ± 21.7 mg/dL. On OCT imaging analysis, lipid arc, fibrous cap thickness and other plaque microstructures did not differ in three groups, whereas increased ANGPTL3 levels were associated with larger calcification arc and longer calcification length (Table). Multivariate analysis demonstrated ANGPTL3 (β-coefficient=0.143, 95%CI=0.07-0.21, p0.001) and eGFR (β-coefficient=-1.380, 95%CI=-2.53--0.22, p=0.019) as independent factors affecting maximum calcification arc. ANGPTL3 (β-coefficient=0.013, 95%CI=0.010-0.016, p0.001) levels remained to independently associate with calcification length. ROC analyses revealed ANGPTL3≥410.9 ng/mL (AUC=0.815, 95%CI=0.718-0.913, p0.001) and eGFR≤65.2 mL/min/1.73m2 (AUC=0.759, 95%CI=0.645-0.873, p0.001) as the best cut-off values of predicting OCT-derived greater calcification (calcification arc87.7°+calcification length5.6mm). Of note, the proportion of greater calcification increased in association with the number of these measures (Table). The association of ANGPTL3 level with maximum calcification arc and calcifcation length were similary observed in both ACS and stable CAD subjects (maximum calcification arc: ACS, r=0.415, p=0.018, stable CAD, r=0.650, p0.001, calcifcation length: ACS, r=0.390, p=0.027, stable CAD, r=0.670, p0.001). Conclusions The current findings suggest ANGPTL3 as a potential factor associated with plaque calcification in patients with CAD. Measurement of ANGPTL3 may guide physicians to estimate severity of plaque calcification and then strategize anti-atherosclerotic managements.