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ELEVATED TROPONIN OF NON-CORONARY ETIOLOGY A REVIEW

Marcelo Flavio Gomes Jardim Filho1

Abstract: Elevated troponin levels are traditionally associated with acute myocardial infarction (AMI)

and are widely used as a specic marker for the diagnosis of ischemic myocardial injury. However,

recent studies have shown that elevated troponin levels can occur in several non-coronary conditions,

requiring a more careful diagnostic approach to avoid misinterpretations and inadequate management.

This study aimed to perform a systematic review of the literature on the non-coronary causes of

important marker of severity and poor prognosis in several systemic conditions. Troponin levels should

be interpreted carefully, taking into account the clinical context and underlying conditions of each

patient.

Keywords: Troponin, Non-coronary etiology, Sepsis, Chronic renal failure, COPD, Prognosis.

1 Cardiologist, Specialist in Cardiology from SBC, Specialist Certicate in Hypertension from

the Brazilian Society of Hypertension, Major Doctor of the Military Police of RJ, On-Call Doctor at

the Coronary Unit of the Salgado Municipal Hospital, Municipal Public Servant

INTRODUCTION

Troponins are essential proteins that participate in the mechanism of regulating muscle

contraction in striated and cardiac muscles. These proteins include three subtypes: Troponin T (cTnT),

has two main domains, called N and C terminals, which are connected by a central ligand and have

an inhibitory component of the troponin complex, suppressing muscle contraction when calcium levels

are low in plasma. Martins (2009) explains that Troponin I has, like Troponin C, an N terminal (which

plays an inhibitory role) and a C terminal (responsible for binding to actin). The interaction between

actin and the inhibitory domain of troponin I results in the inhibition of myosin ATP-ase activation,

of high specicity and importance in the evaluation of myocardial damage.

The most important isoforms of troponins for the diagnosis of acute myocardial infarction

universal gold standard for the diagnosis of infarction. Although CK-MB and troponins have similar

diagnostic performance in the rst 12 to 24 hours of infarct progression, the accuracy of troponins

makes them more useful for more sensitive and ongoing evaluation.

In recent years, De Lemos (2013) has highlighted that assays for the detection of troponins

have evolved signicantly, becoming ultra-sensitive and capable of detecting very low concentrations

of these proteins in the blood, which provides an early and high-precision diagnosis.

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the release of degradation products, or increased cell membrane permeability (Sheyin, 2015). These

factors highlight the importance of interpreting troponin elevation with caution, taking into account the

patient’s clinical context.

According to Harada and Potter (2023), the Troponin C subunit binds to calcium, triggering

structural changes that allow the interaction between actin and myosin, which results in muscle

contraction. Troponin C is present in both skeletal muscle bers and cardiac bers, which makes it less

specic for the diagnosis of myocardial injury. In contrast, the Troponin I and Troponin T subunits are

highly specic for the heart, and are therefore used as markers of myocardial injury.

Troponin I acts as a contraction inhibitor by binding to actin and preventing the interaction

between actin and myosin in the absence of calcium, as reported by Wagner et al. (2024). This action

detect small amounts of troponin in the blood is essential, as it allows for the early identication of

myocardial lesions that would not be detectable with other biomarkers, such as CK-MB, which is less

specic for cardiac tissue.

diagnosis of acute myocardial infarction, due to its specicity and its ability to remain elevated for long

periods after myocardial injury. The accuracy of ultrasensitive assays reinforces troponin as a reliable

(WHF), the universal denition of acute myocardial infarction (AMI) highlights the rise and/or fall of

troponin levels as essential criteria for diagnosis, as long as they are associated with the patient’s clinical

context (Thygesen et al., 2019). This denition reinforces the importance of troponins as highly specic

and sensitive biomarkers for the detection of myocardial injury.

After an AMI, several proteins, including myoglobin, troponin I, troponin T, and creatine

below 0.01 ng/mL, while levels above 0.3 ng/mL after a few hours of an acute event are indicative of

infarction (Thygesen; Jaffe, 2020).

Also, according to Jatene et al. (2022), in patients with compensated heart failure, high-

the limitation of these methods in the context of medical emergency, since they are not portable and

require specic laboratory infrastructure. In this scenario, immunosensors based on nanomaterials and

biomolecules have emerged as a promising alternative, especially due to the speed of results and the

possibility of portability (Chen et al., 2019).

On the other hand, it is important to emphasize that elevated troponin levels, detected by

means of ultrasensitive assays, are not always indicative of acute myocardial infarction. According to

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Finally, regarding the reference values of troponin levels, according to Thygesen; Jaffe (2020),

the following parameters are used as a reference: for cardiac Troponin T (cTnT), normal values are below

0.014 ng/mL, while for cardiac Troponin I (cTnI), normal values are below 19.8 pg/mL for men and 11.6

pg/mL for women. Troponin elevation begins between 3 and 6 hours after the onset of myocardial

injury, reaches a peak in 24 hours, and may take 7 to 14 days to normalize (Thygesen; Jaffe, 2022).

METHODOLOGY

This study used a systematic review of the literature with the objective of identifying the main

non-coronary causes of elevated troponin levels. To this end, searches were carried out in the PubMed,

Scopus, and Web of Science databases between January 2014 and December 2024. The keywords used

inadequate methodological analyses, were excluded.

The PRISMA method was used to conduct the systematic analysis of the studies, ensuring

transparency and reproducibility in the selection of articles. Initially, 312 articles were identied, of

which 198 were excluded after the initial screening, focusing only on abstracts. Of the remaining 114

articles, 79 were removed after full reading because they did not meet the established criteria, resulting

analysis of the factors that contribute to troponin elevation in contexts unrelated to myocardial infarction,

providing a solid basis for the discussion of clinical outcomes and implications for the management of

Initially, two studies on elevated troponin in hospitalized patients with COVID-19 were selected,

which the studies pointed out to be associated with greater disease severity and increased mortality,

even in the absence of type 1 myocardial infarction. The study by Bardají et al. (2021) analyzed 1,032

patients, of which 273 had troponin elevation. Patients with elevated troponin had higher complication

rates, such as the need for mechanical ventilation (45.7% versus 22.3% in patients with normal troponin),

such as interleukin-6 (IL-6) and C-reactive protein (CRP), suggesting that systemic inammation and

2020; BARDAJÍ et al., 2021). Inammation and prolonged hypoxemia resulting from respiratory failure

caused by COVID-19 were highlighted as the main factors responsible for troponin elevation, without

the presence of signicant coronary ischemia.

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Other studies show that the relationship between troponin elevation and pulmonary embolism

traditionally associated with ischemic myocardial injury, is also observed in non-coronary conditions,

such as PE. The article by López-Morales et al., (2021) investigated the correlation between troponin-I

elevation and echocardiographic ndings in patients with hemodynamically stable pulmonary

embolism. Patients with troponin-I elevation had signicant right ventricular dysfunction, as evidenced

by both echocardiography and computed tomography angiography (PCI). Right ventricular overload

was considered the main mechanism of myocardial injury in these patients.

Elevated troponin-I was observed in 44% of patients with hemodynamically stable PE and

was associated with a higher prevalence of right ventricular dysfunction and, consequently, a higher

of hemodynamic stability where troponin elevation was observed in 54% of patients, with higher levels

correlated with higher mortality. Right ventricular dysfunction, as measured by echocardiography, was

signicantly more common in these patients, suggesting that pressure overload in the right ventricle

resulting from pulmonary arterial obstruction is one of the main factors responsible for troponin

elevation.

In this study, patients with elevated troponin had a mortality rate of 28%, compared with 8% in

marker of PE severity (Rodrigues et al., 2023).

It should be noted here that both studies emphasize the usefulness of troponin as a prognostic

marker in patients with PE, regardless of typical ischemic symptoms. Right ventricular dysfunction,

caused by pressure overload, has been identied as the main mechanism underlying troponin elevation.

In both studies, elevated troponin was consistently associated with a worse prognosis, including a higher

risk of death, need for ICU admission, and more aggressive therapeutic interventions.

The study by Bolaños et al. (2023) provided clear evidence on the relationship between troponin

elevation and adverse hospital outcomes in patients with septic shock. The research demonstrated that

elevated troponin, identied within the rst 24 hours of hospitalization, was a predictive marker of high

sensitivity for mortality and signicant clinical worsening in patients with septic shock. Among the

2023). These ndings are in line with data in the literature, which point to an increase in troponin in

prognosis, both in terms of mortality and in the need for intensive therapeutic interventions (JAVED et

ROC (Receiver Operating Characteristic) curve, which is a graphical representation of the performance

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Figure 1: Results of ROC troponin I curve.

clinical management of septic patients.

The next study, Toledo (2022) evaluated serum troponin I levels in patients with chronic kidney

disease (CKD) without clinical evidence of myocardial injury, with the aim of analyzing the occurrence

of “false positive” results. The samples tested included 60 patients with CKD on hemodialysis and

10 healthy individuals (control group). The results showed that 17.1% of the patients with CKD had

elevations in troponin I levels, while 8.6% had elevations in CK-MB levels and 1.4% showed simultaneous