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Lipocalin-2 Predicts Long-Term Outcome of Normotensive Patients with Acute Pulmonary Embolism

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Abstract

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.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant No. 81790622), Beijing Municipal Science & Technology Commission (Grant No. Z171100000417002), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (Grant No. 2017-I2 M-3-003), and Capital Clinical Characteristic Application Program (Grant No. 2018-BKJ01). We thank Ellen Knapp, PhD, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.

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Authors and Affiliations

  1. Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China

    Haixu Yu, Zhuohui Liu, Jie Lu, Xinying Yang, Yuhong Mi, Yulin Li & Jie Du

  2. Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China

    Haixu Yu, Zhuohui Liu, Jie Lu, Xinying Yang, Yulin Li & Jie Du

  3. Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing, China

    Haixu Yu, Zhuohui Liu, Jie Lu, Xinying Yang, Yulin Li & Jie Du

  4. Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, China

    Zhuohui Liu

  5. State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy Medical Sciences, No. 167, Beilishi Road, Beijing, 100037, China

    Xin-Xin Yan, Lu Hua & Zhi-Cheng Jing

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Yu, H., Liu, Z., Lu, J. et al. Lipocalin-2 Predicts Long-Term Outcome of Normotensive Patients with Acute Pulmonary Embolism. Cardiovasc Toxicol 20, 101–110 (2020). https://doi.org/10.1007/s12012-019-09525-w

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