|Year : 2022 | Volume
| Issue : 3 | Page : 183-186
Neutrophil-to-Lymphocyte Ratio and Outpatient Management of Low-Risk Acute Pulmonary Embolism
Abdolmohammad Ranjbar1, Bahram Sohrabi2, Reza Hajizadeh3, Mahdi Karimi Shoar2, Hadiseh Kavandi2, Sahar Ghodratizadeh4, Hanieh Sakha2, Kamran Mohammadi2
1 Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
2 Cardiovascular Research Center, Tabriz University of Medical Science, Tabriz, Iran
3 Department of Cardiology, Urmia University of Medical Sciences, Urmia, Iran
4 Anesthesiology, Urmia University of Medical Sciences, Urmia, Iran, Iran
|Date of Submission||13-Mar-2021|
|Date of Acceptance||02-Sep-2022|
|Date of Web Publication||30-Sep-2022|
Dr. Reza Hajizadeh
Department of Cardiology, Urmia University of Medical Sciences, Taleghani Hospital, Urmia
Source of Support: None, Conflict of Interest: None
Purpose: Low-risk pulmonary thromboembolism (PTE) outpatient management has been described recently. The blood neutrophil/lymphocyte ratio (NLR) has been shown to be a useful marker of cardiovascular disease and an independent predictor of cardiac mortality. The predictive value of NLR in predicting mortality of low-risk PTE was evaluated in this study. Materials and Methods: The total of 168 patients with definite pulmonary embolism diagnosed by computed tomography angiography whose on-admission simplified Pulmonary Embolism Severity Index (PESI) score was zero enrolled in this study. The survival rate of patients according to their NLR was evaluated. Results: During 12 months' follow-up period, eight patients (4.7%) died. None of the patients with an NLR of <3.2 died during the follow-up. The median values of NLR in the nonsurvivor and survivor groups were 9.2 ± 3.03 (2–29.5) and 4.69 ± 0.43 (0.8–24.5), respectively. NLR values were significantly higher in nonsurvivors compared to survivors (P = 0.043). Conclusion: This study suggests that patients with zero PESI score and NLR <3.2 could be managed patiently with good results.
Keywords: Low risk, neutrophil/lymphocyte ratio, outcome, pulmonary embolism, simplified pulmonary embolism severity index
|How to cite this article:|
Ranjbar A, Sohrabi B, Hajizadeh R, Shoar MK, Kavandi H, Ghodratizadeh S, Sakha H, Mohammadi K. Neutrophil-to-Lymphocyte Ratio and Outpatient Management of Low-Risk Acute Pulmonary Embolism. Heart Mind 2022;6:183-6
|How to cite this URL:|
Ranjbar A, Sohrabi B, Hajizadeh R, Shoar MK, Kavandi H, Ghodratizadeh S, Sakha H, Mohammadi K. Neutrophil-to-Lymphocyte Ratio and Outpatient Management of Low-Risk Acute Pulmonary Embolism. Heart Mind [serial online] 2022 [cited 2023 Mar 29];6:183-6. Available from: http://www.heartmindjournal.org/text.asp?2022/6/3/183/357544
| Introduction|| |
Pulmonary thromboembolism (PTE) is a life-threatening disease. After acute coronary artery disease and stroke, it is the third cause of cardiovascular death worldwide. Autopsy studies have shown that mortality due to PTE in the general population is higher than previous reports. Sudden pulmonary artery lumen obstruction in massive PTE, can result in acute right ventricular failure, hemodynamic instability, and even shock state, and sudden cardiac death which mostly occurs in the early hours.
Despite these findings, mortality of low-risk PTE is not high and recent researchers support outpatient management of low-risk PTE according to a simplified pulmonary embolism severity index (S-PESI) score. It seems that because clinicians are afraid of adverse events, they prefer inpatient treatment of low-risk PTE which is not cost-benefit in many cases., Recently, some papers reported systemic inflammation as an important factor in PTE.
Leukocytosis is a known marker of inflammation. An increase in neutrophils and a decrease in the number of lymphocytes is a novel marker of inflammation.
The blood neutrophil/lymphocyte ratio (NLR) is a useful marker of cardiovascular disease and an independent predictor of cardiac mortality.,
Since NLR is a part of routine blood analysis, can be obtained easily by the whole blood count, and is quite easy to calculate, we investigated the prognostic value of NLR in patients with low-risk PTE in an outpatient survey.
| Materials and Methods|| |
A total of 168 patients with definite pulmonary embolism were diagnosed by computed tomography angiography whose on-admission S-PESI score was zero enrolled in this study. On admission, a 1 cc blood sample was taken for complete blood count analysis.
Exclusion criteria were active infection, recent surgery during the past 3 months, using a corticosteroid, active inflammation, and, any recent tissue injury such as burning and cancer. Patients' demographic data and laboratory data were gathered from patients' files. All patients were admitted at least for 3 days, followed up for 12 months after admission for mortality was done by telephone call and routine visits monthly. The association between on-admission NLR and midterm mortality was analyzed to reach a cutoff point in which patients could be managed safely in outpatient type management. S-PESI score uses six variables for risk stratification of patients with pulmonary embolism. These variables include chronic cardiopulmonary disease, heart rate >110 beats per minute, systolic blood pressure <100 mm Hg, arterial oxygen saturation <90%, previous cancer, and the age of the patient more than 80 years. Each variable gets 1 point and if the sum is zero patient is defined as low risk. Any patient with a score 0–1 is defined as high risk. A zero S-PESI score shows that a patient with pulmonary embolism has a good prognosis and low probability for death.
Continuous data were expressed as mean ± standard deviation for normal variables; categorical data were expressed as percentage. The predictive value of NLR was assessed by receiver operating characteristic (ROC) analysis, estimating the area under the curve (AUC). SPSS software, version 23.0 (SPSS Inc, Chicago, Illinois, USA) was used for data analysis. Independent t-test, Fisher's exact test, and one Mann–Whitney U-test were used for data analysis.
This research was approved by ethics committee of Tabriz University of Medical Sciences with approval code of 93/1-5/13.
| Results|| |
Two cardiologists evaluated 210 patients with a definitive diagnosis of PTE based on the S-PESI. Finally, 184 patients had zero scores according to the S-PESI score and were defined as low-risk patients. Sixteen patients with low-risk PTE, including eight patients who had undergone a recent surgical procedure or missing follow-up due to death related to a car accident, four patients with cancer, two with chronic inflammatory disease and, two with a history of corticosteroid consumption were excluded from the study. Finally, 168 patients enrolled in the study. The characteristics of patients are described in [Table 1]. The mean age of patients was 59.17 ± 1.87, according to the gender of patients, 69 patients (41.0%) were female and 99 patients (58.9%) were male, 25 patients (14.9%) have a history of smoking, 57 patients (33.9%) have hypertension, 16 patients (9.5%) had hyperlipidemia, 20 patients (11.9%) had a history of heart failure, 20 patients (11.9%) had chronic obstructive pulmonary disease (COPD), 25 patients (14.9) had a history of immobilization, and 3 patients (1.8%) had recent long travel. Treatment started in the emergency room, 16 patients (9.5%) took fibrinolytic therapy following unfractionated heparin (UFH) therapy, and other patients (90.5%) took only UFH following warfarin therapy with a goal of international normalizing ratio (INR) = 2–3. INR during the hospital course, two patients developed hypotension and took vasopressor therapy, one patient went under mechanical ventilation.
|Table 1: Association of age and complete blood count parameters on low-risk pulmonary thromboembolism mortality|
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During 12 months' follow-up, eight patients (4.7%) died. Four patients developed low blood pressure or decreasing O2 saturation during their hospital course, two patients developed severe pulmonary hypertension, one patient developed sudden death and one patient developed paradoxical embolization. The mean value of NLR in the nonsurvivor and survivor groups was 9.2 ± 3.03 (2–29.5) and 4.69 ± 0.43 (0.8–24.5), respectively. NLR values were significantly higher in nonsurvivors compared to survivors (P = 0.043).
Although NLR values were significantly higher in nonsurvivors, an optimal cutoff value was achieved by ROC curve analysis [Figure 1]. According to the ROC curve, an NLR >3.2 with a sensitivity of 89.5% and specificity of 100% could predict 12 months' mortality in low-risk patients. There was no significant difference in neutrophil counts between nonsurvivors and survivors (AUC = 0.941, P < 0.001).
|Figure 1: ROC curve shows a cutoff point for NLR value according to 30 days' mortality. NLR = Neutrophil/lymphocyte ratio, ROC = Receiver operating characteristics, AUC = Area under the curve|
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| Discussion|| |
We evaluated the association between NLR and the prognosis of PTE based on the S-PESI score. The S-PESI score is a useful method for predicting the short-term mortality of patients with pulmonary embolism. Our findings suggest that NLR may be an independent predictor of mortality in low-risk PTE.
Elevated NLR implies a greater increase in neutrophils compared to lymphocytes count. Neutrophil plays a major role against infection and also regulates and links innate and adaptive immunity.
An increase in apoptosis or higher corticosteroid level may lead to lymphocytopenia in stressful conditions such as PTE and inflammatory disorders. Recently, it has been demonstrated that mortality increased with an increase in NLR in patients with acute coronary syndrome. One study showed that elevated NLR was significantly associated with heart failure and cancer. Neutrophils are important in different lung diseases especially COPD. COPD exacerbation can be predicted in the early stages by increased NLR. Dying neutrophils should be cleared from lung tissue, otherwise, they can aggravate lung disease by enhancing autoimmune damage by releasing various phlogistic cargoes.
By increasing chemokines secretion from epithelial cells, neutrophil elastase plays a major role in enhancing inflammation in COPD exacerbations. Cardiovascular events can be increased in lymphocytopenia.
Karataş et al. showed that PESI scores (P = 0.01) and elevated NLR (P = 0.01) were independently associated with mortality in PTE. A report by Cavuş et al. showed that NLR values >5.465 could predict higher mortality in PTE (P < 0.001). In this study, according to the ROC curve, an NLR >3.2 could predict 6 months' mortality in low-risk patients. Lower cutoff point in our study could be due to lower disease severity in our study and only low-risk patient enrollment.
C-reactive protein as an inflammatory marker is increased (P = 0.002) and albumin as an anti-inflammatory marker, is decreased in patients with higher NLR values (P = 0.001). In Soylu et al.'s study, 142 patients with PTE were included. They found that NLR may be used as an independent predictor of in-hospital mortality., Hence, NLR can be an indicator of the adverse function of different systems and an effective tool in evaluating patients affected by PTE. Although previous studies have shown the prognostic value of NLR in PTE patients, our study showed that even in low-risk subgroup of patients NLR can be a reliable tool for differentiating patients at risk of mortality. To the best of our knowledge, this is the first study that shows that NLR can be helpful in predicting mortality in low-risk PTE.
Recently, some reports have suggested outpatient treatment for low-risk PTE. The outpatient management of PTE ranges from 4% to 50% in different studies which shows we do not have a definite strategy in this era of medicine. Outpatient management has some advantages for patients and the health-care system such as better quality of life and lower costs. Nowadays, we do not have strong evidence supporting outpatient management of low-risk PTE. Roy et al. showed that the overall risk of mortality in those with low-risk PTE according to PESI or S-PESI was <3% and they suggested that outpatient management in these patients is safe. Among patients with low-risk PTE, NLR may be helpful to differentiate those who can be treated at home and those who need hospital admission. There are few studies investigating the outcome of patients with pulmonary embolism taking an outpatient treatment. Although some authors believe that a zero S-PESI score alone could be used for selecting those patients who could receive outpatient treatment, more investigations could give more evidence for such treatment.
Our study has several limitations. First, our study was a single-center study. Second, because we did not have a large sample size, subgroup analysis especially according to the age of patients was not done.
| Conclusion|| |
Increased NLR is a simple, nonspecific marker of inflammation that is associated with increased mortality in patients with low-risk PTE. We suggest outpatient management of low-risk patients with PTE with NLR <3.2.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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