Ability of myoglobin to predict mortality in patients admitted for exclusion of myocardial infarction

doi:10.1016/j.ajem.2007.01.002

The American Journal of Emergency Medicine

Volume 25, Issue 8, October 2007, Pages 873-879

https://doi.org/10.1016/j.ajem.2007.01.002 Get rights and content

Abstract

Background

Myoglobin can be used as an early marker to diagnose myocardial infarction (MI); and although nonspecific for myocardial necrosis, it seems to be a strong mortality predictor. Because myoglobin elevations are often present in patients with renal insufficiency, it is possible that the predictive value of myoglobin is secondary to identifying patients with renal insufficiency.

Methods

Consecutive patients admitted for MI exclusion without ST elevation on the initial electrocardiogram underwent serial assessment of cardiac markers (creatine kinase [CK], CK–myocardial band [MB], and troponin I [TnI]). Myoglobin was assessed at the time of admission and/or 3 hours later. Renal insufficiency was defined as a creatinine clearance <60 mL/min. Multivariate analysis was performed to identify predictors of 30-day and 1-year all-cause mortality.

Results

A total of 3461 patients were included in the analysis. Overall 30-day and 1-year mortality was 2.4% and 9.7%. Myoglobin was elevated in 675 (20%), CK-MB in 421 (12%), and TnI in 517 (15%). Among the 993 patients with renal insufficiency, myoglobin was elevated in 43%, CK-MB in 17%, and TnI in 21%. Independent predictors of 30-day and 1-year mortality were similar and included age ≥65 years, prior MI, and an ischemic electrocardiogram, whereas myoglobin was the strongest multivariate predictor (odds ratio [OR] 2.8, 95% confidence interval [CI] 2.1-3.7), including those with renal insufficiency (OR 2.3, 95% CI 1.6-3.4). Troponin I had borderline predictive value (P = .08, OR 1.4, 95% CI 0.96-2.0), whereas CK-MB was not predictive in either group.

Conclusions

Despite the absence of cardiac specificity, an elevated myoglobin strongly predicts mortality, even in patients with renal insufficiency.

Introduction

Over the past 50 years, a variety of markers have been used for the diagnosis of acute myocardial infarction (MI). In the past 10 years, the ones that have been used most commonly include myoglobin, creatine kinase–myocardial band (CK-MB), and cardiac troponin T or troponin I (TnI). Each of these markers has its intrinsic advantages and limitations for identifying patients who have necrosis. Based on its superior diagnostic sensitivity and specificity, troponin is now recognized as the criterion standard for the detection of myocardial necrosis [1]. Its major limitation is its suboptimal early sensitivity because of its delayed appearance in the blood after the onset of necrosis [2]. In contrast, myoglobin is a small cytosolic protein released early after onset of necrosis and is thus usually detected before elevations in other markers. Because myoglobin lacks cardiac specificity, elevations cannot necessarily be attributable to cardiac damage. Although CK-MB has higher specificity for myocardial necrosis than myoglobin, it becomes elevated later, although earlier than troponin [3]. However, elevations across serial samples over short periods have a sensitivity for the early detection of myocardial necrosis comparable with serial sampling with myoglobin, with a significantly higher specificity [4].

Recent data indicate that a multimarker strategy that takes advantage of each marker's sensitivity release kinetics is a superior means for early diagnosis of MI [5], [6]. Importantly, the multimarker strategy seems to better identify patients at risk for short-term death [5], [6]. Despite an absence of cardiac specificity, combining myoglobin with troponin significantly improved the ability to identify those at risk for increased mortality over that of either marker individually [5], [6].

In contrast to other cardiac markers, myoglobin is cleared by renal filtration [7], [8] so that elevations are common in asymptomatic patients with renal insufficiency. Importantly, renal insufficiency itself is now recognized as an adverse prognostic factor in patients with acute coronary syndromes (ACSs) [9], [10], [11]. Therefore, increases in myoglobin may be identifying patients at higher risk as a result of underlying renal failure rather than detecting myocardial necrosis.

The purpose of this analysis was to assess the comparative ability of multiple cardiac markers and clinical variables for predicting short- and long-term mortality in a large cohort of patients without ST elevation on the initial electrocardiogram (ECG) who were admitted for exclusion of myocardial ischemia. In addition, we analyzed the predictive ability of cardiac markers in patients who had underlying renal insufficiency.

Section snippets

Methods

This study was performed at a 600-bed inner city hospital with approximately 85 000 Emergency Department (ED) visits and 1500 Coronary Care Unit (CCU) admissions a year. The chest pain protocol used at our institution has been described in detail previously [12]. In brief, after the initial evaluation, patients thought to be at high risk (eg, ischemic ECG changes or known coronary disease experiencing typical symptoms) were admitted directly to the CCU. Patients considered low to moderate risk

Results

Baseline characteristics of the patients are shown in Table 1. Myoglobin was elevated in 675 (20%), CK-MB in 421 (12%), and TnI in 517 (15%). When compared with patients who had only elevated myoglobin, those who had increased TnI had more risk factors and characteristics associated with increased cardiovascular risk, although they were less likely to have renal insufficiency. Variables associated with increased cardiovascular risk were intermediate in patients who had increased CK-MB compared

Discussion

We found that the combination of myoglobin, CK-MB, and TnI added incremental prognostic value for identifying patients at risk for dying, both at 30 days as well as 1 year. In a multivariate analysis, myoglobin was the cardiac marker most predictive of mortality and was a stronger predictor than TnI. Despite the potential for nonspecific elevations unrelated to myocardial necrosis in patients with renal insufficiency, myoglobin remained the best independent predictor of mortality.

We found that

Limitations

Not all patients had myoglobin measured and so were excluded, presenting a potential bias. However, there was no difference in risk or mortality between the patients who did or did not have myoglobin sampled. We did not measure myoglobin at all time points, but only in the first 3 hours after presentation. It is unclear if this would have increased or decreased its predictive value. In most cases, we did not have reliable information on symptom duration. However, higher-risk patients tend to

Conclusions

Troponin I, myoglobin, and CK-MB predict cardiac mortality, with myoglobin being the strongest independent predictor. This was consistent when all patients were assessed, as well as when patients with renal insufficiency were analyzed separately. Patients who have elevations in more than one marker are at increased risk for short- and long-term mortality.

References (22)

M.C. Kontos et al.
Early diagnosis of acute myocardial infarction in patients without ST-segment elevation
Am J Cardiol
(1999)
J. McCord et al.
The prognostic significance of serial myoglobin, troponin I, and creatine kinase–MB measurements in patients evaluated in the emergency department for acute coronary syndrome
Ann Emerg Med
(2003)
G.X. Brogan et al.
Improved specificity of myoglobin plus carbonic anhydrase assay versus that of creatine kinase–MB for early diagnosis of acute myocardial infarction
Ann Emerg Med
(1996)
P.A. McCullough et al.
Risks associated with renal dysfunction in patients in the coronary care unit
J Am Coll Cardiol
(2000)
S. Yusuf et al.
Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial
Lancet
(2003)
S. Matetzky et al.
Acute myocardial infarction with isolated ST-segment elevation in posterior chest leads V7-9
J Am Coll Cardiol
(1999)
J. Sanchis et al.
Usefulness of concomitant myoglobin and troponin elevation as a biochemical marker of mortality in non–ST-segment elevation acute coronary syndromes
Am J Cardiol
(2003)
J.A. de Lemos et al.
The prognostic value of serum myoglobin in patients with non–ST-segment elevation acute coronary syndromes. Results from the TIMI 11B and TACTICS-TIMI 18 studies
J Am Coll Cardiol
(2002)
J.S. Alpert et al.
Myocardial infarction redefined—a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction
J Am Coll Cardiol
(2000)
A.H.B. Wu et al.
National Academy of Clinical Biochemistry Standards of Laboratory Practice: recommendations for use of cardiac markers in coronary artery disease
Clin Chem
(1999)

J. Zimmerman et al.

Diagnostic marker cooperative study for the diagnosis of myocardial infarction

Circulation

(1999)

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Each year, a large number of patients are seen in the Emergency Department with presentations necessitating investigation for possible acute myocardial infarction. Patients can be stratified by symptoms, risk factors and electrocardiogram results but cardiac biomarkers also have a prime role both diagnostically and prognostically. This review summarizes both the history of cardiac biomarkers as well as currently available (established and novel) assays. Cardiac troponin, our current “gold standard” biomarker criterion for the diagnosis of myocardial infarction has high sensitivity and specificity for this diagnosis and therapies instituted in patients with elevated troponin have been shown to influence outcomes. Other markers of myocardial necrosis, inflammation and neurohormonal activity have also been shown to have either diagnostic or prognostic utility, but none have been shown to be superior to troponin. The measurement of multiple biomarkers and the use of point of care markers may accelerate current diagnostic protocols for the assessment of such patients.
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Two large studies have shown that myoglobin elevation was independently predictive of worse outcomes.12, 13 A recent study by Kontos et al18 demonstrated the prognostic significance of myoglobin in 3,461 patients with chest pain. This finding was independent of cTnI elevation and renal insufficiency.
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Original ContributionAbility of myoglobin to predict mortality in patients admitted for exclusion of myocardial infarction

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Limitations

Conclusions

Am J Cardiol

Ann Emerg Med

Ann Emerg Med

J Am Coll Cardiol

Lancet

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

Myocardial infarction redefined—a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction

J Am Coll Cardiol

National Academy of Clinical Biochemistry Standards of Laboratory Practice: recommendations for use of cardiac markers in coronary artery disease

Clin Chem

Diagnostic marker cooperative study for the diagnosis of myocardial infarction

Circulation

Original Contribution
Ability of myoglobin to predict mortality in patients admitted for exclusion of myocardial infarction