Combined Use of the National Early Warning Scores (News), TnI and NT-proBNP increased predictive performance of NEWS in patients with Cardiovascular Disease
Xinchao Zhang1*, Lu Yang2, Kai Wang3, Shuangyu Yang1, Hu Zhen1 and Chunyi Fu1
1Department of Emergency, Beijing Hospital, Beijing 100730, China
2Department of Emergency, QingDao Municipal Hospital (Group), Qing Dao, 266000, China
3Department of Pharmacy, The Affiliated Hospital of QingDao University, QingDao 266000, China
Submission: January 06, 2020; Published: January 31, 2020
*Corresponding author: Xinchao Zhang, Department of Emergency, Beijing Hospital, Dong Dan DaHua Road, Dong Cheng District, Beijing, China
How to cite this article:GXinchao Z, L Yang, Kai W, Shuangyu Y, H Zhen, et al. Combined Use of the National Early Warning Scores (News), TnI and NT-proBNP
increased predictive performance of NEWS in patients with Cardiovascular Disease. J Cardiol & Cardiovasc Ther. 2020; 15(5): 555922.
Introduction: National Early Warning Score (NEWS) is able to evaluate the integral stress level and function status of the body through vital signs, TnI and NTproBNP can reflect the degree of myocardial injury and cardiac function to a certain extent. Whereas, there is no study working on the estimate value of the combined index of NEWS and TnI or NTproBNP in patients with cardiovascular disease so far. We assumed that the combined index was more strongly associated with prognosis compared to NEWS alone.
Method: This was a prospective observational cohort study of adult admissions to emergency department with the diagnosis of cardiovascular disease. NEWS was calculated respectively and combined with TnI and NTproBNP in multivariable logistic regression models. The primary outcome was 30-day mortality after ED arrival, capturing all patients with cardiac arrest at our institution.
Result: All of 221 cases were followed up in 30 days, the mortality in 30-day was 19.5% (43/221). 56 patients (25.3%) died or were admitted to ICU within 48h of ED admission. The area under receiver operator characteristic curve (AUROC) of combined index as NT, NP, NTP for 30d mortality were higher than NEWS alone (0.75, 0.77, 0.79 vs 0.67, p<0.05 respectively). The predictive value of NT, NTP were superior to the NEWS alone (AUROC: 0.76, 0.78 vs 0.67; p<0.05).
Conclusion: Combined indexes showed better able to predict values for 30-day mortality than the NEWS alone in cardiovascular disease. The combinations of NT, NTP also had better evaluating ability for ICU admission and mortality in 48 hours than NEWS
Keywords: National Early Warning Score (NEWS); Cardiovascular disease (CVDs); Cardiac troponin I (cTnI); N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP)
Cardiovascular disease (CVDs) remains the number one cause of death globally: more people die annually from CVDs than from any other cause [1-2]. According to a World Health Organization report in 2016 , An estimated 17.5 million people died from CVDs in 2012, representing 31% of all global deaths. However, many patients with CVDs do not have significant symptoms such as chest pain and dyspnea, and this makes diagnosis challenging. Early diagnosis and prognosis evaluation of CVDs patients presenting to the emergency room is critical to save lives.
Early Warning Scores (EWS) are often used to identify patients at risk of deterioration . There are many types of EWS
used in clinic, to standardise EWS, the Royal College of Physicians introduced the ‘National Early Warning Score (NEWS)’ in 2012 (Table 1) , which has been widely adopted [5-6]. NEWS is associated with admission to a critical care unit and death in studies of patients with medical diagnosis [7-8]. However, there is poor evidence of the application of NEWS in CVDs.
Point of care testing (POCT), like cardiac troponin (cTn) and
the N-terminal fragment of pro-B-type natriuretic peptide (NTproBNP)
are popularly used to detect CVDs. cTnI has been well
described as the preferred biomarker for diagnosis and prognosis
evaluate of myocardial infarction [9-10]. NT-proBNP serve as
serum biomarkers for the diagnosis of heart failure . TnI and
NTproBNP can reflect the degree of myocardial injury and cardiac
function to a certain extent, and NEWS is able to incarnate the
integral stress level and function status of the body through vital
signs. Whereas, it is unknown whether cTn, NT-proBNP could
improve the utility of NEWS in predicting clinical outcome.
The aim of this study was to investigate whether the
combinations of NEWS, cTnI and NT-proBNP on admission to
emergency department (ED) are associated with mortality in
30 days and intensive care unit (ICU) admission or death within
the first 48h of hospital admission. We hypothesize that NEWS
combined with cTnI and NT-proBNP is more strongly associated
with outcome compared to NEWS alone.
This was a prospective observational cohort study performed
at the ED of the BeiJing Hospital. The nurse firstly triages patients
on their admission to ED by their symptoms and vital signs such
as blood pressure, heart rate. Secondly, doctor on call inquires
symptoms in detail, checks the patients systemically and issues
necessary examinations, in order to evaluate patient’s condition
and decide whether the patient need to be treated in hospital or
be admitted to an intensive care unit.
The study included patients who were admitted to the rescue
room on admission to ED with the diagnosis of cardiovascular
disease such as acute coronary syndrome (ACS) and heart failure
(HF) from 23 January to 30 September 2015. The diagnosis criteria
of ACS and HF refer to guidelines [12-13]. The following were
excluded: patients aged less than 18 years of age, any admissions
with missing or invalid data, patients who stayed in the rescue
room less than 24 hours, patients with advanced cancer, anyone
who turned down or failure to observe the medical treatment.
Vital signs and baseline data such as sex, age was collected
on admission. Vital signs measurements contained: heart rate,
respiration rate, systolic blood pressure, temperature, SpO2,
the inspired gas at the time of SpO2 measurement, and the
patient’s conscious level (AVPU). Recruiting researchers use this
information to calculate an early warning score. Besides, blood
tests results including blood routine, blood biochemistry were
extracted from the hospital databases.
cTnI, NT-proBNP levels for patients were measured on
admission by recruiting researchers using PATHFAST immunity
analyzer. The detection with immunofluorescence technique
needs 250ul K3EDTA plasma to obtain results in 15 minutes. The
diagnosis concentration for cTnI, NT-proBNP are 0.02ng/ml and
450pg/ml respectively. All the data were summarized together
The primary outcome was 30-day mortality after ED arrival,
capturing all patients with cardiac arrest at our institution. The
secondary outcome was intensive care unit (ICU) admission or
death within the first 48h of hospital admission.
We use SPSS version 19 to analyze the data (Lenovo, Windows
10). NEWS, cTnI and NT-proBNP are considered as continuous
variables. Non-normally distributed data are expressed as the
median and IQR. Categorical variables are reported as count and
percentages. Comparison of non-normally distributed data was
performed using the Mann-Whitney U test. For categorical data,
the X2 test of Fisher exact test was used. Results were considered
significant at a threshold of P<0.05(2 tailed).
To integrate the NEWS with TnI and NT-proBNP, we performed
logistic regression analysis to calculate regression coefficients of predictors as previous research did . The predictive
values were tested using the areas under the receiver operating
characteristic (ROC) curves analysis. The SEM and p values for the
ROC were calculated following the method of Hanley and McNeil
, as well as the comparisons between them was. Statistical
significance was set at p<0.05 for all analyses. All results were
reported along with their associated 95% CIs and p values.
Data from 269 patients were eligible in the study. 23 patients
with missing predictors were excluded from the primary analysis,
25 patients were excluded from the analysis because the followup
result was not available, leaving 221 patients in the primary
analysis (supplemental Figure 1).
All of 221 cases were followed up in 30 days. 56 patients
(25.3%) died or were admitted to ICU within 48h of ED admission.
The mortality in 30-day was 19.5% (43/221). 125 (56.5%)
patients were men and the median age of all the cases was 77 (IQR
14). There were significant differences between survivors and
non-survivors in 30 days in NEWS, TnI and NT-proBNP (0.41 vs
0.11umol/l, 7.98 vs 2.92nmol/l, p<0.05). Lactate, SpO2, diastolic
blood pressure and CRP were also significantly lower in nonsurvivors
On a logistic regression analysis with 30-day mortality as the
dependent variable and NEWS and TnI levels as the covariate
variables, the coefficient of NEWS was 0.60 and that of TnI was
0.67. We rounded these coefficients up and composed formula as following: NT (NEWS-TnI) = NEWS + TnI (umol/l). In the same
way, we designed another two formulas: NP (NEWS-NTproBNP)
= NEWS + NTproBNP (nmol/l); NTP (NEWS-TnI-NTproBNP) =
(NEWS*2) + (TnI*2) (umol/l) + NTproBNP (nmol/l). Figure 1
showed the number of patients and mortality rates of each class.
NEWS was classified by risk level, the other three combined
variables were divided into quartiles (NT: first quartile [Q1] <
3.07, 3.07 ≤ second quartile [Q2] < 5.76, 5.76 ≤ third quartile [Q3]
< 9.43, and 9.43 ≤ fourth quartile [Q4]; NP: Q1< 9.78, 9.78 ≤Q2 <
19.07, 19.07 ≤Q3 < 33.40, and 33.40 ≤ Q4; NTP: Q1 < 9.18, 9.18 ≤
Q2 < 17.57, 17.57 ≤ Q3 < 33.14, and 33.14 ≤ Q4). The mortality
of group with NEWS score below four was 13.6% (16/118),
significantly lower than that of the group with NEWS score above
12 (46.7%, 7/15). In NTP parameter group, 30d mortality was
3.6% in Q1, 9.1% in Q2, 19.6% in Q3, and 45.4% in Q4. The same
trend can be seen in NP parameter group. The distribution of
patients and relevant ICU admission and mortality in 48h after
ED arrival were shown in supplemental Figure 2, and the data
tendency were similar to that on above.
We figured up the area under receiver operator characteristic
curve (AUROC) to test the predictive ability of NEWS and TnI, NT
proBNP for the primary outcome. The AUROC of NEWS, TnI and
NTproBNP were all 0.67, 0.67, 0.74. The AUROC of the NT, NP and
NTP scores were higher than that of NEWS alone (AUROC = 0.75,
0.77, 0.79, p<0.05). However, there was no significant difference
between the AUROC of the NTP and NT or NP (p>0.05), although
the AUROC of the NTP was larger than that of NT or NP (Table 3
& Figure 2).
The predictive values of the NEWS and joint parameters for
ICU admission and mortality in 48h were compared also (Table
4, Supplemental Figure 2). The predictive value of NT and NTP
were superior to the NEWS (0.76 vs 0.67, 0.78 vs 0.67; p<0.05).
Nevertheless, the difference between the AUROC of the NTP and
NT was not significant (p>0.05), although the AUROC of the NTP
was larger than that of NT (Table 3 & Figure 2).
Diagnostic performance including sensitivity, specificity, PPV,
NPV, LR+, and LR- were assessed (Table 2, 3). The cutoff value was
calculated by the Youden index. Table 2 showed that at a cutoff
point of 22.81 of the NTP, sensitivity, specificity, and NPV value
were 76.7%, 73.6%, and 92.9%, respectively; better than those of
the NEWS, NT and NP index. The efficiency index of the ROC for
secondary outcome was showed in Table 3.
The principal finding of this study was that the combined
index of NEWS and TnI or NTproBNP exhibited a reformative
ability to predict 30-day mortality in CVDs in ED compared with
the NEWS alone. The NTP index showed the greatest ability to
predict 30-day mortality, with higher sensitivity, specificity and
NPV than NEWS, NT, and NP. We also found that NTP and NT
showed better predictive values to ICU admission and mortality
in 48h after ED arrival.
Recent studies have shown that NEWS had a poor to moderate
value in evaluating the risk of patients and prognosis [7,16]. All of
physiological variables included in NEWS can be acquired within
a few minutes, making a rapid evaluation of patients possible.
However, there is no effective system for rapid assessment of
CVDs so far, only preliminary diagnosis by blood index such as TnI
and NTproBNP [10-11]. TnI and NTproBNP can also be assessed
within a few minutes. Therefore, we would like to investigate
whether the combination of news and TnI or NTproBNP can
be used to improve the early risk assessment and prognosis
evaluation of cardiovascular disease.
The AUROC of TnI for 30d mortality and ICU admission and
mortality in 48h in our study were 0.67 and 0.68 respectively,
indicating a poor value to prognosis evaluation and risk
assessment. In the previous study , the AUROC of TnI for
30d mortality and ICU admission were all 0.74. In our study, the
AUROC of NTproBNP for primary and secondary outcome was
0.74 and 0.67, higher than the AUROC of other study (0.61) .
Differences between them were likely due to demographical
Scoring systems based on combined physiological and
laboratory data have been introduced for years . A recent
study  showed that the NEWS-L score combining NEWS and
lactate exhibited an improved ability to predict mortality in CAP
patients compared with the NEWS alone (AUROC: 0.73 VS 0.70,
P<0.05). In our study, the AUROC of NEWS alone was 0.67, which
was lower than that of previous study, and this difference may be
related to the different types of diseases in the study. Besides, our
study also revealed that with the increase of NEWS scores, the 30d
mortality showed an upward trend. The AUROC of combined index
as NT, NP and NTP for 30d mortality were higher than NEWS alone
(0.75, 0.77, 0.79 vs 0.67, p<0.05 respectively), showed a moderate
prognostic evaluation value.
Cardiovascular markers such as TnI and NTproBNP can reflect
the degree of myocardial injury and cardiac function to a certain
extent, and NEWS is able to incarnate the integral stress level
and function status of the body through vital signs. They assess
the severity of the cardiovascular disease from different angles.
We have reasons to belive that the combination of NEWS and
cardiovascular markers can evaluate the severity and prognosis
of cardiovascular disease from two aspects of organ functional
status and overall stress level, making a more accurate and
comprehensive assessment of the severity and prognosis of
cardiovascular disease, and improve the efficiency of each index.
This study has several limitations. First, the number of
patients enrolled in the study was small, and the data of the study
was collected in a single-center ED, which made that the statistical
result might differ by sample size and region. Additionally, patients
with CVDs in our study had a higher mortality, even in the low-risk
group, which might due to that most of the patients in our hospital
were elderly with poor compensative ability and stress capacity.
Combined indexes with NEWS and TnI, NEWS and NTproBNP,
NEWS and TnI and NTproBNP showed better able to predict
values for 30-day mortality than the NEWS alone in cardiovascular
disease. The combinations of NEWS and TnI, NEWS and TnI and
NTproBNP also had better evaluating ability for ICU admission
and mortality in 48 hours than NEWS