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

IF 2.5 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

CJC Open Pub Date : 2025-09-01 DOI:10.1016/j.cjco.2025.06.006

Yu Kataoka MD, PhD , Kota Murai MD , Stephen J. Nicholls MBBS, PhD , Yoshiyuki Tomishima MD , Takamasa Iwai MD , Kenichiro Sawada MD , Hideo Matama MD , Satoshi Honda MD, PhD , Kensuke Takagi MD, PhD , Masashi Fujino MD, PhD , Shuichi Yoneda MD, PhD , Kazuhiro Nakao MD, PhD , Fumiyuki Otsuka MD, PhD , Yasuhide Asaumi MD, PhD , Teruo Noguchi MD, PhD

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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 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).

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.

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循环血管生成素样蛋白3水平和斑块钙化：光学相干断层成像分析

生成素样蛋白3 （ANGPTL3）调节脂蛋白代谢，其基因缺乏可降低动脉粥样硬化性心血管疾病的风险。然而，ANGPTL3表达与动脉粥样硬化斑块形成之间的关系尚不清楚。方法对58例冠状动脉疾病患者（其中非罪魁祸首病变89例）行光学相干断层扫描（OCT）引导下经皮冠状动脉介入治疗进行分析。用酶法测定ANGPTL3水平（日本群马免疫生物实验室）。根据ANGPTL3水平的分位数进行分层，比较患者的临床人口学特征和oct衍生斑块特征。结果ANGPTL3水平为356.2±158.9 ng/mL（他汀类药物= 98.2%，低密度脂蛋白胆固醇= 74.5±21.7 mg/dL）。ANGPTL3水平的第3组患者年龄较大（P = 0.025），估计肾小球滤过率（eGFR; P = 0.010）较低。在OCT成像上，三组患者的脂质弧（P = 0.139）、纤维帽厚度（P = 0.826）和其他斑块微结构无显著差异，而ANGPTL3水平升高与更大的钙化弧（P < 0.001）和更长的钙化长度（P < 0.001）相关。多因素分析表明，ANGPTL3 （β-系数= 0.143,95%可信区间[CI] = 0.07-0.21, P < 0.001）和eGFR （β-系数= - 1.380,95% CI = - 2.53-0.22, P = 0.019）是影响最大钙化弧的独立因素。ANGPTL3 （β-系数= 0.013,95% CI = 0.010-0.016, P < 0.001）水平与钙化长度独立相关。受试者工作特征曲线分析显示，ANGPTL3≥410.9 ng/mL（曲线下面积= 0.815,95% CI = 0.718-0.913, P < 0.001）和eGFR≤65.2 mL/min / 1.73 m2（曲线下面积= 0.759,95% CI = 0.645-0.873, P < 0.001）是预测oct衍生的更严重钙化（钙化弧度>； 87.7°+钙化长度>； 5.6 mm）的最佳截止值。钙化程度较高的患者比例随着这些特征的增多而增加（P < 0.001）。结论sangptl3表达与冠心病患者斑块钙化有关。需要进一步的研究来证实ANGPTL3作为调节钙化的治疗靶点。

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