Abstract
BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) regulates lipoprotein metabolism, and its genetic deficiency reduces the risk of atherosclerotic cardiovascular disease. However, the association between ANGPTL3 expression and atherosclerotic plaque formation remains unclear. METHODS: We analyzed 58 patients with coronary artery disease (89 non-culprit lesions) who underwent optical coherence tomography (OCT)-guided percutaneous coronary intervention. 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%; low-density lipoprotein cholesterol = 74.5 ± 21.7 mg/dL). Patients in tertile 3 of ANGPTL3 level were older (P = 0.025) and had a lower estimated glomerular filtration rate (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 3 groups, whereas increased ANGPTL3 levels were associated with a larger calcification arc (P < 0.001) and a longer calcification length (P < 0.001). Multivariate analysis demonstrated that ANGPTL3 (β-coefficient = 0.143, 95% confidence interval [CI] = 0.07-0.21, P < 0.001) and eGFR (β-coefficient = -1.380, 95% CI = -2.53-0.22, P = 0.019) are 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 that ANGPTL3 ≥ 410.9 ng/mL (area under the curve = 0.815, 95% CI = 0.718-0.913, P < 0.001) and eGFR ≤ 65.2 mL/min per 1.73 m(2) (area under the curve = 0.759, 95% CI = 0.645-0.873, P < 0.001) are the best cutoff values for 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 coronary artery disease. Further studies are required to confirm ANGPTL3 as a therapeutic target for modulating calcification.