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| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 13
| Issue : 1 | Page : 41-44 |
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Troponin levels in COVID-19 patients and its correlation with the severity of disease and clinical outcomes
Vaibhav Shukla, Advait Munagekar
Department of Medicine, Eras Lucknow Medical College, Lucknow, Uttar Pradesh, India
| Date of Submission | 07-Oct-2021 |
| Date of Decision | 08-Dec-2021 |
| Date of Acceptance | 08-Dec-2021 |
| Date of Web Publication | 24-Jan-2022 |
Correspondence Address:
Dr. Vaibhav Shukla
Department of Medicine, Eras Lucknow Medical College, Lucknow, Uttar Pradesh
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/injms.injms_115_21
Introduction: The epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) has become a major health problem globally. The most common cardiac manifestation of COVID-19 infection is acute cardiac injury observed in patients even without any prior cardiac comorbidities. It is seen that several patients positive for COVID-19 showed increased concentrations of cardiac troponin, which lead to confusion in clinical interpretation. Our study was performed to observe the correlation between elevated troponin levels with clinical outcomes and the severity of COVID-19 disease. Aim: To observe the correlation between elevated troponin levels with clinical outcomes and severity of COVID-19 disease. Materials and Methods: This was a cross-sectional study among 100 reverse transcription–polymerase chain reaction positive COVID-19 patients with measurement of troponin-I on the 1st and 5th days of admission. Results: The greatest number of deaths were reported in patients with troponin-I ≥ 0.39 ng/ml. Higher Troponin levels were seen in the elderly population. Higher Troponin Levels were also seen in severe diseases. Conclusion: The present study showed that higher troponin levels were associated with increased mortality in COVID-19 patients and higher values were observed with severe disease.
Keywords: Cardiac, COVID-19, hypertension, Severe acute respiratory syndrome coronavirus 2, troponin-I
How to cite this article:
Shukla V, Munagekar A. Troponin levels in COVID-19 patients and its correlation with the severity of disease and clinical outcomes. Indian J Med Spec 2022;13:41-4 |
How to cite this URL:
Shukla V, Munagekar A. Troponin levels in COVID-19 patients and its correlation with the severity of disease and clinical outcomes. Indian J Med Spec [serial online] 2022 [cited 2023 Mar 31];13:41-4. Available from: http://www.ijms.in/text.asp?2022/13/1/41/336426 |
| Introduction | |  |
The epidemic of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) has become a major health problem globally. It was declared as an outbreak by the World Health Organization as a Public Health Emergency of International Concern on January 30, 2020, and as a global pandemic on March 11, 2020 when more than 150 countries reported the spread.[1]
The most common cardiac manifestation of COVID-19 infection is acute cardiac injury observed in patients even without any prior cardiac comorbidities. Cardiovascular risk factors such as diabetes mellitus, hypertension, and coronary artery disease (CAD) also predispose to cardiac injury affecting the severity of illness and mortality. Nonischemic myocardial injury secondary to cytokine storm is thought to be the predominant mechanism of acute cardiac injury associated with COVID-19, leading to poor outcomes in patients with cardiac injury.[2]
It is seen that several patients positive for COVID-19 showed increased concentrations of cardiac troponin (cTn), which lead to confusion in clinical interpretation. When myocardial infarction (MI) is associated with acute infectious respiratory disease, the majority of COVID-19 patients demonstrate stable cTn rather than the dynamically changing values indicative of an acute coronary syndrome.[3]
This study was performed to observe the correlation between elevated troponin levels with clinical outcomes and severity of COVID-19 disease.
| Materials and Methods | | |
This was a cross-sectional study, which was conducted in a tertiary care institution, designated as L-3 COVID-19 hospital. For this study, 100 patients who were reverse transcription–polymerase chain reaction (RT-PCR) positive for COVID-19 infection and were admitted to the facility, were enrolled. Patients were differentiated into mild/moderate/severe cases according to MOH/GOI guidelines. Baseline laboratory values were analyzed on blood samples collected at the time of hospitalization which included cTn I quantitatively measured in human serum and plasma in Plain vial using VITROS ECI/ECIQ Immunodiagnostic Techniques on day 1 and day 5 of admission, and the higher value of the two readings was considered in our study. Normal troponin values upper reference limit diagnostic cut-off in our laboratory was <0.034 ng/ml. Any values >0.034 ng/ml were considered to be deranged. Necessary ethical clearance and patient consent were taken before the enrollment of the study participants.
Data were collected and analyzed using descriptive statistics and making comparisons among various groups. Categorical data were summarized as proportions and percentages (%) while discrete (quantitative) as mean/standard deviation. Pearson's correlation was used to measure the strength of correlation of troponin level with biochemical parameters. Receiver operating characteristic (ROC) analysis was performed to find the optimum cut-off for troponin level to detect the mortality, while binary logistic regression analysis was performed to predict mortality by troponin level and other significant predictors. Statistical analyses were performed using SPSS version 23.0 (SPSS Inc., Chicago, IL, USA). P < 0.05 was considered statistically significant.
| Results | | |
The study was conducted on 100 RT-PCR positive COVID-19 patients. There were 71 Males and 29 females. The mean age of patients that were included in the study was 59.29 years and the mean Troponin levels measured on day 1 was 0.038 ng/ml and on day 5 was 0.040 ng/ml and mean Troponin levels measured on day 1 and day 5 together was 0.039 ng/ml.
A higher troponin level was found in raised proportion among the elderly age group, however no gender effect was observed. Further, no significant association of troponin level was found with age (P = 0.268) and gender (P = 0.984).
When we consider the troponin levels distribution in the study population, 65 patients had a level <0.04 ng/ml, 31 had a level between 0.04 and 0.39 ng/ml and 4 had troponin levels > 0.39 ng/ml.
The maximum deaths were observed for the troponin level more than 0.39 ng/ml (100%) followed by the level 0.04–0.39 ng/ml (54.8%). Hence, a highly significant association was found between the troponin level and outcome (P < 0.001) [Table 1].
The mean troponin level of death cases was always more than the recovered cases either day 1, day 5, or their average. However, significant difference was found only at day 5 (P = 0.045) and mean of day 1 and 5 (P = 0.041). The mean troponin levels (on the day 1 and 5) were 0.039 + 0.059 ng/ml in recovered cases while they were 0.280 ± 0.625 ng/ml in patients who expired.
Further troponin level was significantly raised among hypertensive cases (P = 0.027), but no significant association was found with Type 2 diabetes mellitus (T2DM) (P = 0.381), CAD (P = 0.570) and chronic kidney disease (CKD) (P = 0.050) [Table 2].
Troponin level showed significant positive correlation with SGPT (r = 0.204, P = 0.043), SGOT (r = 0.408, P < 0.001), S. Bilirubin (r = 0.545, P < 0.001), fasting plasma sugar (r = 0.224, P = 0.026), and serum triglycerides (r = 0.294, P = 0.003).
The study participants were divided into mild, moderate, and severe illness category and Troponin levels were studied in these patients, here the Chi-square value was about 32.6 and P < 0.001 which was statistically significant, which showed that troponin levels were increased as the severity of illness increased. Hence, this had a positive correlation with elevated troponin levels and severity of COVID-19 [Table 3]. | Table 3: Distribution of troponin levels according to the severity of COVID-19
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The ROC analysis showed optimum cut-off of troponin level for predicting mortality is TL ≥0.039 ng/ml for day 1 and day 5 mean and TL ≥0.036 ng/ml for day 5 only. Day 5 troponin level predicted more accurately than mean of day 1 and day 5 as its area under the ROC value was larger. Further, the sensitivity and specificity for mean TL was 71% and 79.4%, respectively, and for day 5 it was 77.4% and 80.9%, respectively [Table 4] and [Figure 1]. | Table 4: ROC analysis to find optimal cut-off for troponin level to predict mortality
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 | Figure 1: Receiver operating characteristic analysis to find the optimal cut-off for troponin level to predict mortality
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When we did a binary logistic regression analysis taking the predictors troponin level with age, Sex, T2DM, HTN, CAD, CKD, SGPT, SGOT, serum bilirubin, fasting plasma glucose and serum triglycerides, the conditional backward step logistic regression leave age, hypertension, and troponin level as the only significant predictors of mortality [Table 5]. | Table 5: Binary logistic regression analysis to predict mortality by troponin level and other significant predictors
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| Discussion | | |
The present study shows that among COVID-19 patients, a raised troponin level is associated with higher mortality irrespective of the underlying cardiac status. The mean troponin levels were higher in patients who died in comparison to patients who recovered. Moreover, this difference was statistically significant. Among the patients who had elevated Troponin levels, there was mortality in 60% of patients while only 40% recovered.
There are various possible mechanisms for the increase in troponin levels in COVID-19 patients. One of the mechanisms is cytokine storm. Severe lung inflammation and impaired pulmonary gas exchange in COVID-19 have been suggested to be due to the upregulation of proinflammatory cytokines. In healthy controls, Ang-1–7 limits the synthesis of proinflammatory and profibrotic cytokines. Thus, downregulation of angiotensin-converting enzyme 2 (ACE2) by SARS-CoV-2, with a consequent decrease in Ang-1–7 levels, may magnify the cytokine storm, resulting in an overwhelming inflammatory response. Cytokines have been extensively studied in patients with heart failure owing to their role in inflammatory modulation, myocyte stress or stretch, myocyte injury and apoptosis, fibroblast activation, and extracellular matrix remodeling, release favored by ACE2 suppression, causing both direct and indirect myocardial injury.
Another possible mechanism is microangiopathy. SARS-CoV-2 uses ACE2 as its entry receptor and subsequently downregulates ACE2 expression. In addition to the heart and lung, ACE2 is localized in the intestinal epithelium, vascular endothelium, and kidneys. In the renin-angiotensin–aldosterone system, ACE2 catalyzes the conversion of Ang-II to Ang-1-7, which opposes the vasoconstrictor, pro-inflammatory, pro-oxidant, proliferative, and profibrotic actions exerted by Ang-II via AT1 receptors. As a result, suppression of ACE2 expression and subsequent increase in Ang-II levels may represent another threat to the heart and vessels in patients with COVID-19.
MI also could be one of the causes for raised troponin levels in COVID-19 Patients. Patients with pre-existing CAD and those with risk factors for atherosclerotic cardiovascular disease (CVD) are at an increased risk of developing an acute coronary syndrome during acute infections, as demonstrated previously in epidemiologic and clinical studies of influenza and other acute inflammatory conditions. This outcome could result from imbalance between oxygen supply and demand in the acute setting, and hence that the troponin elevation may be interpreted as a type 2 MI. Reduced oxygen supply in patients with COVID-19 is typically caused by hypoxic respiratory failure, a feature that is more common in deceased patients than in patients who recover and is a marker of disease severity.
In this study, the greatest number of deaths were observed for the troponin level more than 0.39 ng/ml (100%) followed by the level 0.04–0.39 ng/ml (54.8%). A highly significant association was found between the troponin level and outcome (P < 0.001). Similar to our study it was seen by Manocha et al.[3] that troponin-I ≥0.34 ng/mL was the only independent predictor of 30-day mortality (adjusted odds ratio, 4.38; P < 0.001). Lombardi et al.[4] also observed that there was a significant increase in mortality among patients with elevated troponin I level with a more than two-fold increase in major complications, including such as sepsis, acute kidney failure, multiorgan failure, pulmonary embolism, and major bleeding. Furthermore, observed was an increase in the incidence of heart failure and non–ST-elevation acute MI in the patients with increased troponin levels compared with others.
It was also seen in our study that the mean troponin level of death cases was always more than the recovered cases either on day 1, day 5, or their average. However, a significant difference was found only on days 5 (P = 0.045) and the mean of days 1 and 5 (P = 0.041). Salvatici et al.[5] observed in their study that when Troponin-I was compared between deceased and nondeceased patients, the levels were significantly higher among deceased patients, especially on the 2nd day and was statistically significant. Our result was thus in accordance with the study. However, Wang et al.[6] observed no statistical difference in levels of troponin-I in patients at the time of admission, but during the duration of hospital stay high troponin levels were responsible for poor prognosis and death.
As observed in our study the higher troponin level was found in raised proportion among elder age groups, however, no gender effect was observed. Further, no significant association of troponin level was found with age (P = 0.268) and gender (P = 0.984). Similar results were also seen in the studies of Manocha K et al. Salvatici M et al. and Lombardi C et al. It thus shows that a higher age group led to poor prognosis in COVID-19 infection and mortality.
The present study also revealed that troponin level was significantly raised among hypertensive cases (P = 0.027), but no significant association was found with T2DM (P = 0.381), CAD (P = 0.570) and CKD (P = 0.050). Our observation was contrary to the study of Wibowo et al.[7] where no correlation between Troponin-I and other comorbidities was observed. However, Du et al.[8] observed correlation between high troponin-I and cerebrovascular and CVD with poor prognosis in patients having comorbidity.
Taking the predictors troponin level with age, sex, T2DM, hypertension, CAD, CKD, SGPT, SGOT, serum bilirubin, fasting plasma glucose, and triglycerides, the conditional backward step logistic regression leave age, hypertension, and troponin level only as significant predictors of mortality. Further, it showed that chances of mortality increased with elderly age, hypertension, and high troponin level because either they were associated with positive regression coefficient or their conjugate were associated with negative regression coefficient.
In this study, participants were divided into mild, moderate, and severe illness category and Troponin levels were studied in these patients, which showed that troponin concentration increased as the severity of illness increased. Hence, it was observed that there was a positive correlation with elevated troponin levels and the severity of COVID-19 disease.
One limitation of the study was, that a two-dimensional echocardiography (ECHO) could not be done in patients as they were in COVID wards and could not be shifted out. Portable ECHO machine was available, but the findings could not be relied upon.
| Conclusion | | |
The results of the present study show that troponin concentration was significantly higher in patients in COVID-19 infection who died than in patients who survived. Further binary logistic regression analysis showed that troponin levels were independently linked to mortality. The study also showed that higher troponin levels were observed in severe diseases.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Mishra AK, Sahu KK, George AA, Lal A. A review of cardiac manifestations and predictors of outcome in patients with COVID-19. Heart Lung 2020;49:848-52.  |
| 2. | Gaze DC. Clinical utility of cardiac troponin measurement in COVID-19 infection. Ann Clin Biochem 2020;57:202-5. |
| 3. | Manocha KK, Kirzner J, Ying X, Yeo I, Peltzer B, Ang B, et al. Troponin and other biomarker levels and outcomes among patients hospitalized with COVID-19: Derivation and validation of the HA 2T 2 COVID-19 mortality risk score. J Am Heart Assoc 2021;10:e018477. |
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| 5. | Salvatici M, Barbieri B, Cioffi SM, Morenghi E, Leone FP, Maura F, et al. Association between cardiac troponin I and mortality in patients with COVID-19. Biomarkers 2020;25:634-40. |
| 6. | Wang Y, Shu H, Liu H, Li X, Zhou X, Zou X, et al. The peak levels of highly sensitive troponin I predicts in-hospital mortality in COVID-19 patients with cardiac injury: A retrospective study. Eur Heart J Acute Cardiovasc Care 2021;10:6-15. |
| 7. | Wibowo A, Pranata R, Akbar MR, Purnomowati A, Martha JW. Prognostic performance of troponin in COVID-19: A diagnostic meta-analysis and meta-regression. Int J Infect Dis 2021;105:312-8. |
| 8. | Du RH, Liang LR, Yang CQ, Wang W, Cao TZ, Li M, et al. Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: A prospective cohort study. Eur Respir J 2020;55:2000524. |
[Figure 1]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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