We found that in critically ill medical patients, elevated cTnI is associated with increased mortality and longer duration of mechanical ventilation. cTnI does not, however, independently contribute to the prediction of 28-day mortality beyond that provided by APACHE II.
Cardiac troponin I and T are the most specific and sensitive laboratory markers of myocardial cell injury and may be elevated in patients presenting with many conditions other than acute coronary syndrome [9
]. Elevated cTnI levels also correlate with decreased left ventricular function in both coronary and non-coronary patients [13
]. Cardiac dysfunction during sepsis is fairly well documented and has been associated with poor prognosis [5
]. Moreover, a small recent study evaluated the value of brain natriuretic peptide (BNP) plasma levels as a marker of systolic myocardial dysfunction during severe sepsis [19
]. This study suggested that systolic dysfunction is present in 44% of patients with severe sepsis, BNP is useful in its detection and high plasma levels of BNP are associated with poor outcome [19
]. It remains unclear though whether, in this context, elevated cTnI reflects reversible or irreversible myocardial damage [7
]. Our data indicate that in patients over 65 there is a stronger correlation between elevated cTnI and mortality, which can probably be attributed to the extent, and possibly irreversibility, of myocardial damage in this age group. An interesting finding of this study was that most deaths among younger patients occurred within the first five days, whereas in the elderly group the majority of deaths (60%) occurred after this time frame. This data may suggest that younger patients who survive the initial insult do relatively well. Our study, however, was not designed nor powered to address the effect of age on outcome.
Several studies have addressed the prognostic value of elevated cTnI in non-coronary patients. In selected groups such as COPD and hemodyalisis patients, elevated cTnI correlated with poor outcome [20
]. A study in emergency department patients has shown that there is a significant correlation between cTnI elevation and outcome. APACHE II is not provided, however, nor were the patients stratified by cause of admission. Therefore, no comparison between this study and ours could be performed [17
]. Relos et al
], evaluating surgical ICU patients, suggested that moderate elevation of serum troponin I, which are below the threshold required to diagnose overt myocardial infarction, may reflect ongoing myocardial injury in the critically ill and are associated with a higher mortality rate and longer hospital and ICU length of stay. To the best of our knowledge, only one study suggested an independent predictive value of elevated cTnI after controlling for severity of illness assessed by APACHE II [23
]. A strong correlation between mortality and elevated cTnI in critically ill medical patients without coronary disease was shown in this study. The sample size was rather small (58 patients), however, and the majority of patients had sepsis (88%), which limits the interpretation of these results. In contrast to these studies, Kollef et al
] suggested that serial measurements of cTnI do not independently contribute to the prediction of hospital mortality beyond that provided by clinically recognized cardiac dysfunction. Differences in design and patient mix preclude meaningful comparisons between this study and ours. Our observation that cTnI elevation is not an independent predictor of mortality is not surprising because troponin reflects a single system malfunction while the multivariable APACHE II reflects several highly relevant systems in the context of critically ill patients. It is, therefore, unlikely that a single assay will provide an independent additional value beyond that provided by APACHE II. Nonetheless, our finding that cTnI elevation is an important marker of severity of illness and is associated with high mortality rate is still clinically relevant, particularly in view of the fact that the Kaplan-Meier analysis indicates that the discriminative effect of cTnI elevation is evident from the first day.
The present study included a relatively small number of patients, limiting the significance of post-hoc subgroup analysis and our ability to identify other independent determinants of early mortality. The fact that the frequency of ischemic heart disease (IHD) was similar among cTnI positive patients and cTnI negative patients supports the assumption that the elevated cTnI in our study should not be attributed to ACS. As we did not systematically perform echocardiography or evaluation of coronary flow in these patients, more objective assessment of coronary anatomy and myocardial function is not available. Therefore, any correlation between cTnI levels, in these patients, and irreversible myocardial dysfunction or ACS remains deductive. As indicated earlier, however, elevated cTnI has been previously shown to correlate with left ventricular function. In our study, cTnI was sampled only once upon admission. Even though the time course and kinetics of cTnI and its relation to outcome may be of interest, the main purpose of our study was to determine whether early cTnI elevation is of clinically relevant importance.