Circulating Angiopoietin-Like Protein 3 Level and Plaque Calcification: An Optical Coherence Tomography Imaging Analysis

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Background Angiopoietin-like protein 3 (ANGPTL3) regulates lipoprotein metabolism, and its genetic deficiency reduces the risk of ASCVD. However, the association between ANGPTL3 expression and atherosclerotic plaque formation remains unclear. Methods We analyzed 58 patients with CAD (89 non-culprit lesions) who underwent optical coherence tomography (OCT)-guided PCI. ANGPTL3 levels were measured by an enzymatic method (Immuno-Biological Laboratories, Gunma, Japan). Clinical demographics and OCT-derived plaque features were compared among patients stratified according to tertiles of ANGPTL3 levels. Results The ANGPTL3 level was 356.2±158.9 ng/mL (statin=98.2%; LDL-C=74.5±21.7 mg/dL). Patients in tertile 3 of ANGPTL3 were older (p=0.025) and had a lower eGFR (p=0.010). On OCT imaging, the lipid arc (p=0.139), fibrous cap thickness (p=0.826), and other plaque microstructures did not significantly differ among the three groups, whereas increased ANGPTL3 levels were associated with a larger calcification arc (p<0.001) and longer calcification length (p<0.001). Multivariate analysis demonstrated ANGPTL3 (β-coefficient=0.143, 95%CI=0.07–0.21, p<0.001) and eGFR (β-coefficient=−1.380, 95%CI=−2.53-0.22, p=0.019) as independent factors affecting the maximum calcification arc. ANGPTL3 (β-coefficient=0.013, 95%CI=0.010-0.016, p<0.001) levels remained independently associated with calcification length. Receiver operating characteristic curve analyses revealed ANGPTL3≥410.9 ng/mL (AUC=0.815, 95%CI=0.718–0.913, p<0.001) and eGFR≤65.2 mL/min/1.73 m 2 (AUC=0.759, 95%CI=0.645–0.873, p<0.001) as the best cutoff values of predicting OCT-derived greater calcification (calcification arc>87.7°+calcification length>5.6 mm). The proportion of patients with greater calcification increased with the number of these features (p<0.001). Conclusions ANGPTL3 expression was associated with plaque calcification in patients with CAD. Further studies are required to confirm ANGPTL3 as a therapeutic target for modulating calcification.

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