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“看似”健康，为何发生心血管事件或突然猝死？或与这个因素有关

学郑刚医生约 9 分钟
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动脉粥样硬化是影响全球范围内人群的重要健康问题，其发病率、住院率和死亡率均很高。近年来，冠状动脉疾病（CAD）治疗取得了重大进展，但仍有部分“看似”健康的人群，发生心血管（CV）事件或无征兆猝死，可能原因是受到动脉易损斑块的影响。
壁剪切应力（WSS）是粘性血液在内皮上产生的切向力，在动脉粥样硬化过程中起着重要作用。研究表明，WSS对斑块负荷和成分有不同的影响，高WSS与斑块易损性增加有关，但目前临床实践对此尚未达成共识。若能有更多关于WSS在预测斑块稳定性作用方面的证据，将有助于促进临床更深层次地了解动脉粥样硬化过程。
一项荟萃分析评估了WSS对冠状动脉斑块特征和易损性的影响。该荟萃分析旨在评估血管内超声测量的WSS与冠状动脉斑块特征的关系，共纳入7项研究，涉及615例患者、28276个动脉段（中位随访：7.71个月），研究结果显示，高WSS与斑块纤维面积的回归有关，加权平均差（WMD）为0.11（P=0.02），纤维脂肪区WMD为0.09（P=0.02），斑块总面积减少，WMD为0.09；与低WSS相比，WMD为0.04（P=0.03）。高和低WSS的致密钙沉积保持不变（0.01 vs. 0.02 mm2；P>0.05）。高WSS导致实质性重塑（40% vs. 18%，P<0.05），并且比低WSS导致更具重塑（78% vs. 40%，P<0.01）。
早期的研究表明，高WSS可能对局部功能产生影响，并将其描述为“正常壁剪应力”。与此相反，最近发现高WSS与局部脆弱性之间存在密切关系。这种有争议的观点需要评估WSS与部位特征之间关系的现有证据。
上述研究表明，在高WSS后至少6个月，冠状动脉斑块特征和动脉腔无显著变化，斑块面积减小，动脉腔方向相反。血管内超声技术可以识别导致这些跨动脉发现的局部特征的更详细变化。高WSS与斑块纤维化面积、纤维脂肪面积和坏死核心面积增加有关。这些变化描述了具有高WSS的远期动脉重塑。相反，尽管低WSS与一些收缩性重塑有关，但这些变化并未发生。值得注意的是，钙密度不会因WSS的严重程度、高或低而直接变化。
实验研究表明，对低WSS有不同的重塑反应。之前荟萃分析显示，与低WSS相比，基线高WSS与易损斑块的明显特征相关，如更大的坏死核心面积和更高的斑块密度，与收缩性动脉重塑相关。基于这些发现，研究者进一步了解不同WSS和斑块特征随时间变化之间的潜在关联，试图建立直接关系。在6个月的随访结束时，分析表明，只有高WSS患者的斑块脆弱性特征有显著差异，而低或中度WSS患者则没有。这清楚地显示了坏死核心面积的增加，以及纤维细胞和脂肪细胞的退化。这些发现表明，高WSS是冠状动脉和颈动脉斑块破裂的一个因素。
一项为期3年的随机临床试验表明，在稳定的冠状动脉疾病中，高WSS可以预测心肌梗死。高WSS对斑块表型变化的影响是基于刺激内皮细胞产生转化生长因子b，引起平滑肌细胞凋亡，从而导致薄帽和斑块脆弱性。另一个影响是基于一氧化氮产生增加，导致平滑肌电池受到抑制。此外，剪切应力对内皮细胞具有机械传递作用，涉及几个连续步骤：第一，细胞表面的物理变形；第二，应激的细胞内传递；第三，将机械力转化为化学活性（“真正的”机械反导）；第四，具有反馈的下游生化信号。分析的研究没有足够的细节，无法确定导致高WSS斑块易损性增加的最可能机制。此外，高WSS会导致更广泛的重塑。与低WSS相比，冠状动脉循环中的高WSS与斑块易损性的恶化特征和更深刻的动脉壁重塑的发展有关。
本文作者：泰达国际心血管病医院 郑刚
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参考资料（可上下滑动查看）

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免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。
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