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

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.

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.

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 m² (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).

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.