Simplified Pulmonary Embolism Severity Index is Associated with Recurrent Venous Thromboembolism in Patients with Pulmonary Embolism
Pulmonary embolism (PE) is a critical condition with a substantial risk of recurrent venous thromboembolism (VTE), which carries heightened mortality risks. While prolonged anticoagulation therapy reduces recurrence, it concurrently increases bleeding complications. Thus, precise risk stratification is essential to balance the benefits and risks of long-term anticoagulation. Current evidence on risk factors for VTE recurrence, such as male gender, advanced age, thrombophilia, obesity, persistent D-dimer elevation, and residual thrombosis, primarily derives from non-Asian populations. However, data specific to Chinese and Asian cohorts remain limited. This prospective cohort study aimed to evaluate the incidence and predictors of VTE recurrence in Chinese patients with acute PE, with a specific focus on the prognostic value of the simplified Pulmonary Embolism Severity Index (sPESI).
Study Design and Patient Population
Between January 2014 and December 2017, 836 patients with acute symptomatic PE were screened at West China Hospital of Sichuan University. After exclusions for prior VTE history or incomplete data, 710 patients were enrolled. The sPESI score was calculated at diagnosis, with one point assigned for each of six criteria: age >80 years, cancer history, chronic heart failure, chronic pulmonary disease, heart rate >110 beats/min, or systolic blood pressure <100 mmHg. Patients scoring ≥1 were classified as high-risk, and those with 0 as low-risk. Follow-up occurred at 3, 6, 9, 12, 18, and 24 months post-diagnosis, evaluating VTE recurrence through clinical assessments and imaging.
Key Findings
Over 24 months, 53 patients (7.5%) experienced VTE recurrence. Cumulative recurrence rates were 3.5% at 3 months (95% CI: 2.2%–4.9%), 4.5% at 6 months (3.0%–6.1%), 6.4% at 12 months (4.6%–8.2%), and 7.5% at 24 months (5.6%–9.5%). Patients with recurrence had significantly higher median sPESI scores (1 [interquartile range (IQR): 1–2] vs. 1 [IQR: 0–1], P = 0.001).
Univariable analysis identified nephrotic syndrome (23.8% vs. 7.0% recurrence rate, P = 0.002), cancer, chronic heart failure, chronic pulmonary disease, high-risk sPESI, and suboptimal anticoagulation as factors linked to recurrence. In multivariable Cox regression, nephrotic syndrome (hazard ratio [HR]: 4.32; 95% CI: 1.71–10.91; P = 0.002) and sPESI high-risk classification (HR: 2.41; 95% CI: 1.31–4.46; P = 0.005) independently predicted recurrence.
sPESI as a Predictor of VTE Recurrence
The sPESI, originally designed for mortality risk stratification in acute PE, demonstrated prognostic utility for long-term VTE recurrence. High-risk sPESI patients had a 9.9% 2-year recurrence rate compared to 4.4% in low-risk patients (P = 0.006) (Figure 1A). This association may stem from sPESI components reflecting underlying conditions—such as cancer, chronic cardiopulmonary diseases, and advanced age—that perpetuate hypercoagulable states or impede thrombus resolution. Additionally, higher sPESI scores may correlate with greater clot burden or residual thrombosis, predisposing to recurrence. These findings align with prior studies showing that disease severity indices like the 2008 European Society of Cardiology (ESC) model predict recurrence, likely through overlapping mechanisms.
Nephrotic Syndrome and Early Recurrence Risk
Nephrotic syndrome emerged as a potent independent predictor of recurrence (23.8% vs. 7.0% at 24 months; P = 0.002), with most events occurring within the first 3 months (Figure 1B). The hypercoagulable state in nephrotic syndrome arises from urinary loss of anticoagulant proteins (antithrombin III, protein C/S) and increased hepatic synthesis of procoagulants like fibrinogen. Concomitant glucocorticoid therapy during early disease phases may further elevate thrombotic risk. Despite standard anticoagulation, these patients exhibited high early recurrence rates, suggesting a need for intensified monitoring and potentially extended or more aggressive antithrombotic regimens.
Clinical Implications and Future Directions
This study highlights sPESI’s dual role in guiding acute management and long-term recurrence risk assessment. High-risk sPESI patients may benefit from extended anticoagulation, while low-risk patients could avoid unnecessary bleeding risks. Nephrotic syndrome warrants heightened vigilance, particularly during the initial months post-PE.
Limitations include the single-center design and absence of residual thrombosis or D-dimer dynamics data, which might refine recurrence predictions. Future multicenter studies should validate these findings and explore mechanisms linking sPESI components to recurrence.
Conclusion
In Chinese patients with acute PE, sPESI high-risk status and nephrotic syndrome independently predict VTE recurrence. Integrating sPESI into post-PE care could optimize anticoagulation duration, while nephrotic syndrome necessitates early aggressive management. These insights underscore the need for tailored strategies balancing thrombotic and bleeding risks in diverse populations.
doi.org/10.1097/CM9.0000000000001162
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