Troponin or not troponin, what is the (clinical) question?

Troponin testing was first approved and employed as a test for myocardial infarction (MI) in 1995 and, with its improved specificity, quickly made other cardiac biomarkers essentially obsolete,1 so much so that troponins, and no other biomarkers, are now part of the diagnostic criteria for both MI and "myocardial injury."1 In cases of Type 1 MI, or acute coronary syndrome (ACS), troponin elevations are due to coronary artery thrombus or atherosclerotic plaque disruption causing myocyte death, while Type 2 MIs result when any of a myriad of underlying conditions cause oxygen supply/demand imbalance causing myocardial injury not secondary to atherosclerotic coronary artery disease.1, 2 Elderly patients may be more likely to suffer Type 1 MI without typical features such as chest pain or dyspnea.3-5 Knowing this, clinicians frequently engage in workups including troponin testing in elderly patients with nonspecific complaints such as weakness, falls, or malaise to avoid missing a "silent" Type 1 MI as the cause of their symptoms.6 This issue of Academic Emergency Medicine includes an important addition to existing literature questioning whether routine troponin testing is beneficial in elderly patients with complaints seemingly not suggestive of ACS. The authors report a very small rate of acute MI but a high rate of elevated highly sensitive troponin levels among elderly patients being evaluated in the emergency department (ED) for a ground-level fall. Unsurprisingly, troponin elevation was associated with increased risk of 30-day mortality. The results of the current study are consistent with previous work showing a similar trend of frequent troponin elevation but low proportion of patients experiencing ACS in an elderly population without symptoms suggestive of MI.6 With nearly universal incorporation of highly sensitive troponin assays, even more patients than in the past will be identified as having "abnormal" troponin levels, typically defined as those above the 99th percentile in a healthy population, which we should note is generally not determined using elderly patients. Unsurprisingly then, the specificity of standard troponin cutoff values, highly sensitive or not, is known to diminish with advanced age.7 As a test for ACS, troponins, and especially highly sensitive troponins, appear to have low specificity and very low positive predictive value in elderly patients without suggestive symptoms. This leaves the clinician with a conundrum. Should we be routinely testing these patients for ACS to identify a small proportion of patients with MI or at elevated risk for poor outcomes, knowing the test has poor specificity and may lead to further testing, interventions, or hospitalizations that have the potential for harm? While some will argue that more prognostic information or more information in general can't hurt, there is some potential for harm with a test that has a high "false positive" (if considering it a test for ACS) rate. Patients with elevated troponin are likely to be admitted even in the absence of suspicion of ACS,6 and elderly patients are at relatively high risk for adverse events when hospitalized, including delirium and nosocomial infections.8-10 Troponin elevation may lead to more invasive testing such as cardiac catheterization, which is a higher risk procedure in elderly patients.11 Perhaps one of the worst applications of troponin tests in these patients is to try to blindly identify a patient as "higher risk" with the goal of easily admitting them for no other definable reason. This may be seen as safe for the emergency physician who will likely never be criticized for overtesting, but could actually increase the risk for harming the patient unintentionally. Proponents of liberal troponin testing will emphasize its prognostic properties for mortality prediction. The current study is also consistent with many others in demonstrating a strong association between troponin elevation, regardless of cause, and increased risk of short-term death,12-14 although the same could be said for a slew of other laboratory markers that we do not feel compelled to order on every patient with a simple fall. What we do not know is whether these patients had other markers that already identify them as higher risk. For example, the history, physical examination, vital signs, or other laboratory markers such as creatinine, electrolytes, lactate, etc., may have already identified such patients as high risk, meaning the troponin elevation may have produced little value added and potentially confused the picture by suggesting ACS as a cause or contributor of illness. Alternatively, we also do not know whether an isolated troponin elevation outside of other clinical variables suggesting elevated risk carries the same prognostic implications. Regression models may indicate an "independent association" but essentially never account for the clinician's judgment. A study to determine the true incremental prognostic ability of troponin is unlikely, as it would have to prospectively incorporate the other variables we use to determine risk, most importantly clinical impression and gestalt. Our belief, albeit one without solid evidence to prove or refute it, is that troponin testing as an isolated prognostic tool likely adds very little to the other variables we use to determine a patient's risk. Additionally, as pointed out by the authors, identifying risk only holds real value if there is some way to mitigate it. An essential aspect of caring for elderly and especially frail patients is the importance of delineating each individual patient's goals of care. Two of the three patients in this study (one was 102 years old, and the other 94 years old) who were adjudicated as having an MI ultimately refused further invasive examinations or aggressive treatment. This begs the question: should we be routinely ordering tests or chasing diagnoses for which the patient would not want further evaluation or treatment? Testing in EDs continues to steadily increase.15, 16 There are surely many causes for this, including increased patient volume and documentation requirements resulting in decreased ability to spend time at the bedside, a heightened medical–legal environment that physicians practice in, and just wider availability of diagnostic tests. However, more tests, especially without a plan of how to act on the results, may not always be in our patients' best interest. When possible, we should talk about goals of care for our elderly patients to understand their health care preferences before initiating a slew of testing that can quickly cascade. Of course, we agree that some elderly patients with falls or nonspecific complaints will be appropriate for troponin and ACS testing. Clinical suspicion for ACS is an obvious indication for troponin testing in most patients. In selected cases with a defined underlying condition (e.g., pulmonary embolism), further risk stratification with troponins may hold some incremental value or identify those more likely to benefit from aggressive therapies, although how much or little value is added is not clear. When troponin testing is undertaken in patients like these, where ACS is rare but troponin elevation is common, clinicians should have a plan for how to interpret and act on the results. Different cutoffs for elderly patients may be more appropriate than using 99th percentile in a healthy younger population. While mortality risk increases with increasing troponin levels, it remains unclear what constitutes a "dangerous" elevation outside the setting of ACS, and this will depend on the underlying condition, if any, as well as risk tolerance, which may vary widely, especially in an elderly population. We agree with the authors that this study does not support routine troponin testing in this specific patient population, despite the well-established relationship between troponin elevation and risk for morbidity and mortality. Especially in elderly patients, we should seek to understand our patients' goals of care and individualize their medical testing, treatment, and risk evaluation according to their wishes and preferences. Alfred Z. Wang and Benton R. Hunter contributed to concept and design, interpretation of data, drafting of the manuscript, and critical revision of the manuscript. The authors declare no conflicts of interest.