Department of Cardiology, University Hospital of the RWTH Aachen, Aachen, Germany.
Department of Pediatrics, University Hospital of Cologne, Cologne, Germany.
PLoS One. 2018 Oct 24;13(10):e0205984. doi: 10.1371/journal.pone.0205984. eCollection 2018.
The presence of plaque macrophages and microcalcifications are acknowledged features of plaque vulnerability. Experimental data suggest that microcalcifications promote inflammation and macrophages foster microcalcifications. However, co-localization of plaque macrophages and calcification (ColocCaMa) in coronary segments and its impact on plaque phenotype and lesion vulnerability is unexplored.
Plaque morphology including ColocCaMa of calcified coronary target segments in patients with stable coronary artery disease (n = 116) was analyzed using optical coherence tomography (OCT) prior to coronary intervention. Therefore we considered macrophages co-localized with calcification if their distance in an OCT frame was <100μm and OCT-defined microcalcifications with a calcium arc <22.5°.
ColocCaMa was present in 29/116(25.0%) coronary segments. Calcium burden was greater (calcium volume index:1731±1421°*mm vs. 963±984°*mm, p = 0.002) and calcifications were more superficial (minimal thickness of the fibrous cap overlying the calcification 35±37μm vs. 64±72μm, p = 0.005) in the presence of ColocCaMa. Segments with ColocCaMa demonstrated a higher incidence of newly suggested features of plaque vulnerability, with a 3.5-fold higher number of OCT-defined microcalcifications (0.7±1.0 vs. 0.2±0.6, p = 0.022) and a 6.7-fold higher incidence of plaque inflammation (macrophage volume index:148.7±248.3°*mm vs. 22.2±57.4°*mm, p<0.001). Clinically, intima-media thickness (IMT) in carotid arteries was increased in patients with ColocCaMa (1.02±0.30mm vs. 0.85±0.18, p = 0.021). In a multivariate model, IMT (OR1.76 for 100μm, 95%CI 1.16-2.65, p = 0.007), HDL-cholesterol (OR0.36 for 10mg/dl, 95%CI 0.16-0.84, p = 0.017), calcium volume index (OR1.07 for 100°*mm, 95%CI 1.00-1.14, p = 0.049), macrophage volume index (OR5.77 for 100°*mm, 95%CI 2.04-16.3, p = 0.001) and minimal luminal area (OR3.41, 95%CI 1.49-7.78, p = 0.004) were independent predictors of ColocCaMa.
Plaque macrophages co-localize with calcifications in coronary target segments and this is associated with high-risk morphological features including microcalcifications and macrophage infiltration as well as with greater calcification burden. Our data may add to the understanding of the relationship between plaque macrophages, vascular calcification and their clinical impact.
斑块巨噬细胞和微钙化被认为是斑块易损性的特征。实验数据表明，微钙化促进炎症，而巨噬细胞则促进微钙化。然而，冠状动脉节段中斑块巨噬细胞和钙化的共定位（ColocCaMa）及其对斑块表型和病变易损性的影响尚未得到探索。
在接受冠状动脉介入治疗之前，使用光学相干断层扫描（OCT）分析稳定型冠状动脉疾病患者（n=116）的斑块形态，包括钙化的冠状动脉靶段的 ColocCaMa。因此，如果 OCT 帧中的距离<100μm，并且 OCT 定义的微钙化的钙弧<22.5°，则认为巨噬细胞与钙化共定位。
在 116 个冠状动脉段中，有 29 个（25.0%）存在 ColocCaMa。钙负荷更大（钙体积指数：1731±1421°*mm 与 963±984°*mm，p=0.002），钙化更浅表（钙化上方纤维帽的最小厚度 35±37μm 与 64±72μm，p=0.005）在 ColocCaMa 存在的情况下。具有 ColocCaMa 的节段表现出更高比例的新提出的斑块易损性特征，OCT 定义的微钙化数量增加了 3.5 倍（0.7±1.0 与 0.2±0.6，p=0.022），斑块炎症的发生率增加了 6.7 倍（巨噬细胞体积指数：148.7±248.3°*mm 与 22.2±57.4°*mm，p<0.001）。临床方面，颈动脉内-中膜厚度（IMT）在存在 ColocCaMa 的患者中增加（1.02±0.30mm 与 0.85±0.18，p=0.021）。在多变量模型中，IMT（每增加 100μm 的 OR1.76，95%CI 1.16-2.65，p=0.007）、HDL-胆固醇（每增加 10mg/dl 的 OR0.36，95%CI 0.16-0.84，p=0.017）、钙体积指数（每增加 100°*mm 的 OR1.07，95%CI 1.00-1.14，p=0.049）、巨噬细胞体积指数（每增加 100°*mm 的 OR5.77，95%CI 2.04-16.3，p=0.001）和最小管腔面积（OR3.41，95%CI 1.49-7.78，p=0.004）是 ColocCaMa 的独立预测因子。
斑块巨噬细胞与冠状动脉靶段中的钙化共定位，这与高风险的形态特征有关，包括微钙化和巨噬细胞浸润，以及更大的钙化负荷。我们的数据可能有助于理解斑块巨噬细胞、血管钙化及其临床影响之间的关系。
