Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-Ku, Sapporo, 060-8638, Japan.
Department of Radiology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
Heart Vessels. 2021 Jul;36(7):917-923. doi: 10.1007/s00380-020-01767-x. Epub 2021 Jan 23.
Endothelin-1 contributes to the constrictor response of the coronary arteries in patients with ischemia with normal coronary arteries. There is thus increasing evidence that endothelin-1 plays a role in coronary microvascular dysfunction (CMD). We investigated whether elevated endothelin-1 is associated with CMD in patients with coronary artery disease (CAD). We prospectively studied 49 consecutive CAD patients with 1- or 2-vessel disease (age 71 ± 10 years, 43 males). Myocardial blood flow (MBF) was measured by O-water PET/CT at rest and during stress, and the coronary flow reserve (CFR) was calculated by dividing the stress MBF by the rest MBF. A CFR of less than 2.0 in non-obstructive regions was defined as a marker of CMD. Eighteen out of 49 (37%) CAD patients had CMD. Endothelin-1 in patients with CMD was significantly higher than in those without CMD (2.27 ± 0.81 vs. 1.64 ± 0.48 pg/mL, P = 0.001). Accordingly, univariate ROC analysis showed that the continuous endothelin-1 levels significantly discriminated between the presence and absence of CMD (area under the curve = 0.746 [95%CI 0.592-0.899]). The dichotomous treatment of elevated endothelin-1 as 1.961 pg/mL or more yielded the optimal discriminatory capacity, with a sensitivity of 72.2% and a specificity of 71.0%. High endothelin-1 was still a significant predictor of CMD after adjusting for diabetes mellitus (odds ratio = 6.64 [1.75-25.22], P = 0.005). Endothelin-1 is associated with CMD in non-obstructive territories in patients with CAD, suggesting that endothelin-1 is a potential target for treating CMD in CAD patients.
内皮素-1 参与了正常冠状动脉缺血患者的冠状动脉收缩反应。因此，越来越多的证据表明内皮素-1 在冠状动脉微血管功能障碍（CMD）中发挥作用。我们研究了内皮素-1 升高是否与冠心病患者的 CMD 有关。我们前瞻性研究了 49 例连续的冠心病患者，这些患者患有 1 或 2 支血管疾病（年龄 71±10 岁，43 名男性）。通过 O-水 PET/CT 在休息和应激时测量心肌血流（MBF），并通过将应激 MBF 除以静息 MBF 计算冠状动脉血流储备（CFR）。非阻塞区域的 CFR 小于 2.0 定义为 CMD 的标志物。49 例冠心病患者中有 18 例（37%）患有 CMD。CMD 患者的内皮素-1 明显高于无 CMD 患者（2.27±0.81 对 1.64±0.48 pg/mL，P=0.001）。因此，单变量 ROC 分析显示，连续内皮素-1 水平能显著区分 CMD 的有无（曲线下面积=0.746 [95%CI 0.592-0.899]）。将升高的内皮素-1 定义为 1.961 pg/mL 或更高的二分类治疗方法具有最佳的区分能力，其敏感性为 72.2%，特异性为 71.0%。调整糖尿病后，高内皮素-1 仍然是 CMD 的显著预测因子（比值比=6.64 [1.75-25.22]，P=0.005）。内皮素-1与 CAD 患者非阻塞性区域的 CMD 相关，提示内皮素-1可能是 CAD 患者 CMD 的潜在治疗靶点。
