Division of Cardiovascular Medicine, Stanford Cardiovascular Institute (V.S.P., T.N., Y.K., T.K., D.P.L., W.F.F., A.C.Y., J.A.T.), Stanford School of Medicine, CA.
Quantitative Sciences Unit, Department of Medicine (J.H.L., E.K.H.C., R.L.B.), Stanford School of Medicine, CA.
Circ Cardiovasc Interv. 2020 Apr;13(4):e008587. doi: 10.1161/CIRCINTERVENTIONS.119.008587. Epub 2020 Apr 13.
Intracoronary acetylcholine (Ach) provocation testing is the gold standard for assessing coronary endothelial function. However, dosing regimens of Ach are quite varied in the literature, and there are limited data evaluating the optimal dose. We evaluated the dose-response relationship between Ach and minimal lumen diameter (MLD) by sex and studied whether incremental intracoronary Ach doses given during endothelial function testing improve its diagnostic utility.
We evaluated 65 men and 212 women with angina and no obstructive coronary artery disease who underwent endothelial function testing using the highest tolerable dose of intracoronary Ach, up to 200 μg. Epicardial endothelial dysfunction was defined as a decrease in MLD >20% after intracoronary Ach by quantitative coronary angiography. We used a linear mixed effects model to evaluate the dose-response relationship. Deming regression analysis was done to compare the %MLD constriction after incremental doses of intracoronary Ach.
The mean age was 53.5 years. Endothelial dysfunction was present in 186 (68.1%). Among men with endothelial dysfunction, there was a significant decrease in MLD/10 µg of Ach at doses above 50 μg and 100 µg, while this decrease in MLD was not observed in women (<0.001). The %MLD constriction at 20 μg versus 50 μg and 50 μg versus 100 μg were not equivalent while the %MLD constriction at 100 μg versus 200 μg were equivalent.
Women and men appear to have different responses to Ach during endothelial function testing. In addition to having a greater response to intracoronary Ach at all doses, men also demonstrate an Ach-MLD dose-response relationship with doses up to 200 μg, while women have minimal change in MLD with doses above 50 µg. An incremental dosing regimen during endothelial function testing appears to improve the diagnostic utility of the test and should be adjusted based on the sex of the patient.
冠状动脉内乙酰胆碱（Ach）激发试验是评估冠状动脉内皮功能的金标准。然而，文献中 Ach 的剂量方案差异很大，并且评估最佳剂量的相关数据有限。我们通过性别评估了 Ach 与最小管腔直径（MLD）之间的剂量反应关系，并研究了在进行内皮功能测试时给予递增的冠状动脉内 Ach 剂量是否能提高其诊断效用。
我们评估了 65 名男性和 212 名患有心绞痛且无阻塞性冠状动脉疾病的女性，他们接受了最高耐受剂量的冠状动脉内 Ach 激发试验，最高可达 200μg。通过定量冠状动脉造影术，将心外膜内皮功能障碍定义为冠状动脉内 Ach 后 MLD 减少>20%。我们使用线性混合效应模型来评估剂量反应关系。使用 Deming 回归分析比较递增剂量的冠状动脉内 Ach 后 %MLD 收缩情况。
平均年龄为 53.5 岁。186 例（68.1%）存在内皮功能障碍。在存在内皮功能障碍的男性中，在 50μg 和 100μg 以上剂量时，Ach 每增加 10μg，MLD 均显著减少，而在女性中则未观察到这种 MLD 减少（<0.001）。20μg 与 50μg 及 50μg 与 100μg 之间的 %MLD 收缩率并不相等，而 100μg 与 200μg 之间的 %MLD 收缩率则相等。
女性和男性在进行内皮功能测试时似乎对 Ach 有不同的反应。除了在所有剂量下对冠状动脉内 Ach 的反应更大之外，男性在高达 200μg 的剂量范围内也显示出 Ach-MLD 剂量反应关系，而女性在 50μg 以上剂量时 MLD 变化很小。在进行内皮功能测试时，递增剂量方案似乎可以提高该测试的诊断效用，并且应该根据患者的性别进行调整。
