Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.
Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China.
Cardiovasc Toxicol. 2020 Apr;20(2):101-110. doi: 10.1007/s12012-019-09525-w.
Normotensive patients with acute pulmonary embolism (APE) are accompanied by heterogeneously adverse events. Responding to tissue injury, lipocalin-2 (LCN-2) is elevated in experimental APE model and associated with short-term prognosis. However, the prognostic value of LCN-2 in normotensive patients with APE for long-term major adverse events (MAEs) remains unknown. We evaluated the association of plasma LCN-2 levels with the median 467-day outcome in 170 normotensive patients with APE. We also assessed whether LCN-2 could improve risk stratification. MAEs consisted of mortality or recurrence of venous thromboembolism. During follow-up, 17 (10%) patients suffered from MAEs. These patients had higher LCN-2 levels compared with patients without MAEs (median: 13.97 vs. 8.55 ng/ml, P = 0.01). The proportion of MAEs in the intermediate-low-risk group (14.0%) was higher than that in the intermediate-high-risk group (5.3%). LCN-2 levels independently had prognostic value for MAEs in overall (HR = 3.40, 95% CI 1.46-7.90) and intermediate-risk group (HR = 3.88, 95% CI 1.63-9.23). LCN-2 also showed incremental value in overall (ΔC-index: 0.13, 95% CI 0.02-0.24; category-based NRI = 0.25, 95% CI 0.07-0.42) and intermediate-risk patients (ΔC-index: 0.13, 95% CI 0.05-0.31; category-based NRI = 0.44, 95% CI 0.24-0.65). Adding LCN-2 (cut-off value = 11 ng/ml) to the current risk algorithm improved MAEs of intermediate-risk reclassification (intermediate-high vs. intermediate-low = 25.6% vs. 6.0%, P = 0.002). Elevated plasma LCN-2 levels predict long-term MAEs among normotensive patients with APE. LCN-2 might be a useful biomarker for risk stratification in the intermediate-risk group.
血压正常的急性肺栓塞（APE）患者伴有异质性不良事件。在实验性 APE 模型中，反应组织损伤时，载脂蛋白 2（LCN-2）升高，并与短期预后相关。然而，LCN-2 在血压正常的 APE 患者中对长期主要不良事件（MAEs）的预后价值尚不清楚。我们评估了血浆 LCN-2 水平与 170 例血压正常的 APE 患者中位 467 天结局之间的关系。我们还评估了 LCN-2 是否可以改善风险分层。MAEs 包括死亡或静脉血栓栓塞复发。在随访期间，17（10%）名患者发生 MAEs。这些患者的 LCN-2 水平高于无 MAEs 的患者（中位数：13.97 与 8.55ng/ml，P=0.01）。中低危组（14.0%）的 MAEs 比例高于中高危组（5.3%）。LCN-2 水平对总体（HR=3.40，95%CI 1.46-7.90）和中危组（HR=3.88，95%CI 1.63-9.23）的 MAEs 具有独立的预后价值。LCN-2 对总体（ΔC 指数：0.13，95%CI 0.02-0.24；基于类别 NRI=0.25，95%CI 0.07-0.42）和中危患者（ΔC 指数：0.13，95%CI 0.05-0.31；基于类别 NRI=0.44，95%CI 0.24-0.65）也具有增量价值。将 LCN-2（截断值=11ng/ml）添加到当前风险算法中可改善中危患者的 MAEs 重新分类（中高危与中低危相比=25.6%与 6.0%，P=0.002）。升高的血浆 LCN-2 水平可预测血压正常的 APE 患者的长期 MAEs。LCN-2 可能是中危患者风险分层的有用生物标志物。
