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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 1  |  Page : 18-23

Correlation between Troponin I, N-terminal pro–B-type natriuretic peptide, and left ventricular ejection fraction in acute coronary syndrome patients with mortality


1 Department of Medicine, Poona Hospital and Research Centre, Poona Hospital and Research Centre, Pune, Maharashtra, India
2 Department of Research, Poona Hospital and Research Centre, Poona Hospital and Research Centre, Pune, Maharashtra, India

Date of Submission22-Nov-2020
Date of Decision04-Jan-2021
Date of Acceptance05-Jan-2021
Date of Web Publication30-Mar-2021

Correspondence Address:
Dr. Darshit Pansuriya
Department of Medicine, Poona Hospital and Research Centre, Sadashiv Peth, Pune - 411 030, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/heartindia.heartindia_50_20

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  Abstract 


Background: Troponin I (Trop 1) and N-terminal pro–B-type natriuretic peptide (NT-ProBNP) can be a discerning marker for the patients presenting with symptoms of acute cardiac ischemia and risk of death. The present study was to find a correlation between NT-ProBNP, troponin 1, and left ventricular ejection fraction (LVEF) in acute coronary syndrome (ACS) patients with mortality.
Methods: Ninety ACS patients >18 years of age were included for this prospective observational study. Each patient was subjected to detailed clinical history, clinical examination, Trop I, NT-ProBNP, and LVEF at the time of admission. The primary outcome measures were to study the correlation of NT-ProBNP and Trop I and LVEF at the time of admission with mortality, whereas the secondary outcome measure was to study LVEF after ACS up to 1 month. Medians of continuous variables of two groups and three groups were tested.
Results: The median Trop 1 levels were 12.0, 378.0, and 2454.0 in patients of unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI), respectively (P = 0.001). The median NT-ProBNP levels were 1027.0, 1494.0, and 3728.5 in patients of UA, NSTEMI and STEMI, respectively (P = 0.002). The median Trop 1 levels were 5433.0, 627.5, and 92.0 in patients whose LVEF was <40%, 40%–50%, and >50%, respectively (P = 0.001). The median NT-ProBNP levels were 14,554.0, 2009.0, and 306.0 in patients whose LVEF was <40%, 40%–50%, and >50%, respectively (P = 0.001). The median Trop 1 levels were 11439.0 and 570.0 in patients who expired and survived, respectively (P = 0.001). The median NT-ProBNP levels were 21047.0 and 1869.5 in patients who expired and survived, respectively (P = 0.001). The median LVEF were 30.0 and 45.0 in patients who expired and survived, respectively (P = 0.001). Trop I showed a significant positive correlation (r = 0.636) with NT-ProBNP levels (P < 0.001).
Conclusion: Trop I, NT-ProBNP, and LVEF at the time of admission are strong predictors of 1-month mortality in ACS.

Keywords: Acute coronary syndrome, correlation, left ventricular ejection fraction, mortality, N-terminal pro–B-type natriuretic peptide, Troponin I


How to cite this article:
Pansuriya D, Khadke V, Bahulikar A, Phalgune D. Correlation between Troponin I, N-terminal pro–B-type natriuretic peptide, and left ventricular ejection fraction in acute coronary syndrome patients with mortality. Heart India 2021;9:18-23

How to cite this URL:
Pansuriya D, Khadke V, Bahulikar A, Phalgune D. Correlation between Troponin I, N-terminal pro–B-type natriuretic peptide, and left ventricular ejection fraction in acute coronary syndrome patients with mortality. Heart India [serial online] 2021 [cited 2021 Jun 20];9:18-23. Available from: https://www.heartindia.net/text.asp?2021/9/1/18/312490




  Introduction Top


Acute coronary syndrome (ACS) includes a range of clinical conditions such as unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). When there is severe myocardial damage due to ischemia, a diagnosis of NSTEMI can be made. The biomarkers of myocardial necrosis such as cardiac-specific Troponin T or Troponin I (Trop 1) or creatine kinase (MB) are released into the circulation because of myocardial necrosis. In patients with UA, these biomarkers are not detected in the bloodstream after the onset of ischemic chest pain. Troponin is a potent tool for risk stratification across the spectrum of patients presenting with symptoms of acute cardiac ischemia. Even a minor elevation of Troponin signifies an adverse prognosis and helps in identifying high-risk patients who will benefit from specific therapies, such as glycoprotein IIb/IIIa inhibitors.[1] There is a quantitative relationship between the scale of increase of Troponin levels and the risk of death.[2]

Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) was not incorporated in the early risk stratification algorithms, but it is a strong predictor of mortality in patients with STEMI and NSTEMI coronary diseases.[2],[3],[4],[5],[6] Factors which affect outcomes among ACS patients presenting with varying degrees of left ventricular (LV) dysfunctions are not thoroughly studied. There is a close correlation between N-terminal pro–B-type natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) levels in patients with LV dysfunction. It was stated that an absolute increment of NT-proBNP exceeded that of BNP and NT-proBNP can be a more sensitive marker for the detection and evaluation of cardiac dysfunction than BNP.[7]

Articles comparing Trop-I and its relation to morbidity and mortality are published covering western and European countries. There are no similar data about the Indian population and articles which correlate all the three parameters Trop-I, NT-ProBNP, and LVEF. The aim of the present study was to find a correlation between Trop I and NT ProBNP and correlation of Trop I, NT-ProBNP, and LVEF in ACS patients with 1-month mortality.


  Methods Top


This prospective observational study was conducted between June 2018 and August 2019. After approval from the institutional ethics committee, written informed consent was obtained from the patients prior to enrolment explaining the risks and benefits of the procedure. ACS patients aged >18 years of both genders admitted to the intensive care unit and wards were included in the study. Patients having chronic kidney disease and other associated conditions such as sepsis, myocarditis, malignancy, pulmonary embolism, and stroke which affect biomarker levels were excluded from the study.

NSTEMI/STEMI was defined as follows: A rise/fall of cardiac troponin (at least one value above the 99th percentile of the upper reference limit) and one of the followings:

(1) symptoms of ischemia (chest pain, sweating, nausea, vomiting, anxiety, and a sense of impending doom), (2) electrocardiogram (ECG) changes of new ischemia (ST depressions or ST elevations), (3) new pathological Q waves, (4) imaging evidence of new loss of viable myocardium, or (5) identification of a coronary thrombus by angiography including intracoronary imaging.[8]

UA was defined as follows: ACS with the absence of biochemical evidence of myocardial damage, characterized by specific clinical findings of >20 min angina at rest, new onset of severe angina, angina that is increasing in frequency, longer in duration, or lower in the threshold, or angina that occurs after a recent episode of myocardial infarction.[9]

Patient's detailed clinical history was taken followed by thorough physical examination and laboratory workup. Data were collected on risk factors, ECG changes, Trop-I (by chemiluminescent microparticle immunoassay method on ARCHITEC), NT-ProBNP (by enzyme-linked fluorescent assay on VIDAS), and LVEF by two-dimensional ECHO at the time of admission and after 1 month. Cutoff values for Trop 1 were 34.2 ng/L and 15.2 ng/L for males and females, respectively. Cutoff values of NT-ProBNP were 450 pg/mL, 900 pg/mL, and 1800 pg/mL for patients <50 years, 50–75 years, and >75 years, respectively. The patients were divided into three groups, LVEF <40%, 40%–50%, and >50%. Mortality within 1 month from the date of admission was noted.

The primary outcome measures were to study the correlation of NT-ProBNP and Trop I and correlation of Trop 1, NT-ProBNP, and LVEF at time of admission with mortality, whereas the secondary outcome measure was to study LVEF after ACS up to 1 month. Castro et al. reported a highly significant correlation between NT-proBNP and Trop 1 levels (r = 0.425, P < 0.001).[10] The sample size was calculated by formula n = ([Zα+Zβ]/C)2 + 3 where C = 0.5 × ln([1 + r]/[1 − r]).[11] We have taken Zα a standard normal variate at 1% type 1 error (2.58) and Zβ the standard normal deviation for β power 90% at type II error (1.28). A total sample size of 75 was calculated by the above method. To validate the results, 90 patients were included in the study.

Data collected were entered into Excel 2007 and analysis of data was done using the Statistical Package for the Social Sciences for Windows, version 20.0, from IBM Corporation, Armonk, NY, USA. The data on categorical and continuous variables are shown as n (% of cases) and mean and standard deviation (SD), respectively. For nonparametric data, median and interquartile range was used. The intragroup comparison of means of LVEF and percentage of LVEF at the time of admission and 1-month follow-up was done using paired 't' test and Wilcoxon's signed-rank sum test, respectively. The intergroup comparison of medians of continuous variables of two groups and three groups was done using Mann–Whitney U-test and Kruskal–Wallis H-test, respectively. Correlation analysis was performed using Spearman's method. The confidence limit for significance was fixed at a 95% level with P < 0.05.


  Results Top


Ninety patients of ACS were included in the present study. Trop I, NT-ProBNP, and LVEF were noted at the time of admission. LVEF was again measured in 66 patients who had come for follow-up (12 expired patients and 12 patients who did not come for follow-up were excluded). The correlation between Trop I, NT-ProBNP, and LVEF with mortality at the end of 1 month was studied.

Of 90 patients, 17 (18.9%), 43 (47.8%), and 30 (33.3%) were <50, 50–60, and >60 years, respectively. The mean ± SD of age of patients was 57.4 ± 7.1 years. Of 90 patients studied, 58 (64.4%) were male and 32 (35.6%) were female. Of 90 cases studied, 15 (16.7%), 29 (32.2%), and 46 (51.1%) had UA, NSTEMI, and STEMI, respectively.

Median Trop I levels and median NT-ProBNP levels were significantly higher in STEMI, followed by NSTEMI, whereas in UA, they were lowest [Table 1]. Median Trop 1 and median NT-ProBNP levels were significantly higher in patients who had LVEF <40.0% [Table 2]. Of 90 cases studied, 12 (13.3%) expired and 78 (86.7%) survived. Median Trop I and median NT-ProBNP levels were significantly higher in the group of expired patients compared to the group of survived patients. Median LVEF was significantly lower in the group of expired patients compared to the group of survived patients [Table 3]. Trop I showed a statistically significant positive correlation (r = 0.636) with NT-ProBNP levels in the entire study group (P < 0.001) [Figure 1]. Of 66 patients who were followed after 1 month, the mean LVEF after 1 month (50.0 ± 9.9) was significantly higher compared to mean LVEF at the time of admission (46.1 ± 9.6) (P < 0.001). In <40% ejection fraction (EF) group, two-third patients showed no improvement in EF, while one-third patients showed improvement in EF. In 40%–50% EF group, half of the patients showed improvement in EF at 1 month. In >50% EF group, 95% of patients showed improvement in EF at 1 month. Hence, it was found that low LVEF at the time of admission had poor recovery after 1 month [Table 4].
Figure 1: Scatter diagram showing correlation analysis between Trop I levels, and NT-Pro-BNP levels. Trop I: Treponin 1, NT-ProBNP: N-terminal pro–B-type natriuretic peptide

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Table 1: Median Treponin 1 and median N.terminal pro-B.type natriuretic peptide according to diagnosis

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Table 2: Median Treponin 1, and median N-terminal pro-B-type natriuretic peptide levels according to left ventricular ejection fraction

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Table 3: Median Troponin 1 and median N-terminal pro-B-type natriuretic peptide levels and median left ventricular ejection fraction according to mortality

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Table 4: Comparison of ejection fraction at admission and at 1-month follow-up

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The incidence of mortality was 0/15 (0.0%), 2/29 (6.9), and 10/46 (21.7%) in UA, NSTEMI, and STEMI group, respectively, which was not statistically significant (P = 0.113).


  Discussion Top


Ninety patients of ACS were included in this study, of which 15 (16.7%), 29 (32.2%), and 46 (51.1%) patients had UA, NSTEMI, and STEMI, respectively. Trop I levels were significantly higher in STEMI which shows more myocardial insult and necrosis in STEMI. NT-ProBNP levels were higher in STEMI probably because of low LVEF and more hemodynamic compromise. Median Trop 1 and median NT-ProBNP levels were significantly higher in patients who had EF <40.0%. Trop I and NT-ProBNP levels showed a significant positive correlation. Median Trop I and NT-ProBNP levels were significantly higher and median LVEF was significantly lower in expired patients than survivors.

In a study conducted by Antman et al.,[2] Kiris et al.,[12] and Ye et al.,[13] the mean age of the study population was 58.9, 62.2, and 60.2 years, respectively, which is comparable to the present study. Antman et al.,[2] Kiris et al.,[12] and Ye et al.[13] reported that 67%, 74%, and 68.0% were male patients, respectively, which is comparable to the present study. In a study conducted by Khaled and Matahen, 57/299 (19.1%), 113/299 (37.8%), and 129/299 (43.1%) of patients had UA, NSTEMI, and STEMI, respectively.[14] In a study conducted by Kiris et al., 8.3%, 28.9%, and 62.8% of patients had UA, NSTEMI, and STEMI, respectively.[12] Syyli et al. reported that 12.8%, 51.1%, and 36.1% of patients had UA, NSTEMI, and STEMI, respectively.[15] In the present study, 16.7%, 32.2%, and 51.1% had UA, NSTEMI, and STEMI, respectively, which is comparable with the above studies.

Habib et al. reported that Trop I levels in NSTEMI and STEMI group of patients were 0.95 ng/mL and 2.61 ng/mL, respectively, which was not statistically significant.[16] In a study conducted by Radwan et al., Trop I levels in STEMI, NSTEMI, and UA patients were 31.8 ng/mL, 1.1 ng/mL, and 0.11 ng/mL, respectively, which was statistically significant.[17] Inanc et al. reported that median Trop I levels in NSTEMI and STEMI patients were significantly higher than UA patients (11.31 ng/mL vs. 0.005 ng/mL).[18] In a study conducted by Salama et al., Trop T levels were significantly higher in STEMI patients as compared to NSTEMI patients (P < 0.0001).[19] Munir et al. reported that the mean Trop I levels were 0.06 mg/dL, 5.1 mg/dL, and 9.9 mg/dL in UA, NSTEMI, and STEMI patients, respectively, which was statistically significant.[20] Our study substantiated these findings.

Zdravkovic et al. reported that NT-ProBNP levels were higher in NSTEMI patients (1358 pg/mL) as compared to STEMI patients (566 pg/mL).[21] These results were in contrast with the present study, but patients having Killip class ≥2 were excluded from the study conducted by Zdravkovic et al. In a study conducted by Castro et al., median NT-ProBNP levels were 262.4 pg/mL in UA patients and 796 pg/mL in NSTEMI patients, which was statistically significant (P < 0.001).[10] Radwan et al. reported that the mean NT-ProBNP levels in UA, NSTEMI, and STEMI patients were 1317.7 pg/mL, 1686.7 pg/mL, and 2295 pg/mL, respectively, which was statistically significant.[17] These results corroborated with the present study. Radwan et al. reported that NT-ProBNP levels were significantly higher in patients with EF <40% (2569.5) than other subgroups with EF from 40% to 50% (1342.5) and more than 50% (328.4).[17] Our study substantiated these findings.

Zdravkovic et al.,[21] Santos et al.,[22] Aguado-Romeo et al.,[23] and Hamm et al.[24] reported that 34.3%, 4.4%, 9.6%, and 1.1% of patients died, respectively, within 30 days, whereas in the present study, the mortality rate was 13.3%. In a study conducted by Zdravkovic et al., Trop I serum levels were 3.8 μg/L and 3.12 μg/L in died and survived patients, respectively (P = 0.027).[21] In a study conducted by Syyli et al., Trop T levels were significantly higher in the expired population (97.2%) as compared to the survived population (83.8%) (P < 0.001).[15] Kaura et al. reported that raised Trop I level was associated with increased mortality, regardless of age.[25] The present study substantiated these findings. In a study conducted by Zdravkovic et al., the median NT-pro-BNP serum levels were 2130 pg/mL and 680 pg/mL in patients who died and who survived, respectively, 1 month after ACS (P < 0.0005).[21] This result was corroborated with the present study.

Perelshtein Brezinov et al. reported that mortality rates were 36%, 10%, and 4% for patients with severe LV dysfunction, mild–moderate LV dysfunction, and preserved LV function, respectively, at 1 year (P < 0.001). They further stated that mortality was higher in EF <30% group.[26] Ye et al. reported that inhospital mortality of patients with EF ≥50% and patients with EF <50% was 0.12% and 3.68%, respectively (P < 0.001).[13] In a study conducted by Mamas et al., 30-day mortality was 0.5%, 2.0%, and 10.0% in patients who had good LV function, moderately impaired LV function, and poor LV function, respectively.[27] Syyli et al. reported that the mortality rate at 6-month follow-up was 20.0%, 8.7%, and 3% in patients whose LVEF was <40%, 40%–49%, and ≥50%, respectively.[15] These studies reported a higher mortality rate in lower EF patients which was consistent with the present study.

Zdravkovic et al. reported that there was a positive correlation between serum levels of NT-proBNP and Trop I in NSTEMI (r = 0.338, P = 0.008) and STEMI (r = 0.441, P < 0.0005).[21] In a study conducted by Castro et al., NT-ProBNP levels in NSTEMI patients were significantly correlated with Trop I levels (r = 0.425, P < 0.001). They further reported that median levels of NT-proBNP were significantly higher in NSTEMI patients (796.7 pg/mL) than in patients with UA (262.4 pg/mL) (p-value < 0.001).[10] The present study substantiated these findings In the present study, Trop I and NT-ProBNP levels showed a significant negative correlation with EF levels in UA, NSTEMI, and STEMI patients.

In a study conducted by Sjöblom et al.,[28] changes in EF at 1 month were monitored in 100 ACS patients who had EF <40% at the time of admission. The mean EF was 31 ± 5.8% and 38 ± 11% at the time of admission and after 1 month, respectively (P < 0.001). Our findings were similar to this study.

Jang et al.[29] reported that reassessment of LVEF at 1 month after ACS can help to stratify the risks of all-cause death and adverse cardiovascular events in ACS patients. It was further stated that the higher mortality was observed in patients who had decreased EF. The present study also showed that decreased LVEF on admission was associated with poor recovery from LV dysfunction at 1-month follow-up.

Potential limitations of the study merit consideration. Patients were enrolled from a single medical center; thus, it is difficult to generalize the results. The sample size and study duration were small. Multicentric studies with a larger sample size are needed to validate our results.


  Conclusions Top


Median Trop I levels and NT-ProBNP levels were significantly higher in STEMI. Median Trop I levels and NT-ProBNP levels were significantly higher in patients who had EF <40.0% at the time of admission. Median Trop I and NT-ProBNP levels at the time of admission were significantly higher in expired patients. Median EF was significantly lower in expired patients. There was a positive significant correlation between Trop I and NT-ProBNP levels at the time of admission. Mean EF after 1 month was significantly higher in survived patients compared to mean EF at the time of admission. Two-third of the patients in <40% LVEF group showed no improvement in LVEF after 1 month as compared to half of the patients in 40%–50% group. Low LVEF at the time of admission can be a marker of poor recovery after 1 month.

Ethical approval

Institutional ethics committee approved the study (Letter No. RECH/EC/2018-19/185).

Authors' contributions

Author 1: Research design, acquisition of data, analysis of data, interpretation of data, revising critically, approving the submitted version.

Author 2: Research design, interpretation of data, revising critically, approving the submitted version.

Author 3: Research design, interpretation of data, revising critically, approving the submitted version.

Author 4: Research design, analysis of data, interpretation of data, drafting the paper, revising critically, approving the submitted version.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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