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

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.