International Journal of Cardiology 104 (2005) 238 – 240

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Letter to the Editor

Role of biochemical markers in diagnosis of myocardial infarction

Ijaz A. Khana,*, Norrapol Wattanasuwanb
a
Division of Cardiology, University of Maryland Medical Center, School of Medicine, 22 South Greene Street–S3B06, Baltimore, Maryland 21201, USA
b
Division of Cardiology, Saint James Hospital, Pontiac, Illinois, USA

Received 15 July 2004; accepted 16 October 2004

Available online 19 February 2005

Abstract

An ideal cardiac biochemical marker should have not only high sensitivity but also high specificity to myocardial infarction. The creatine
kinase-MB, a relatively specific cardiac marker, could be elevated in situations other than acute myocardial infarction, such as renal failure,
muscular injury, and myopathy. Although these are more specific than creatine kinase-MB, cardiac troponins have also been reported to be
elevated in conditions other than acute myocardial infarction, such as chronic renal failure, acute myocarditis, cardiomyopathy, congestive
heart failure, pulmonary embolism, rhabdomyolysis, sepsis, and left ventricular hypertrophy. With the ongoing research in this field, future
holds hopes of finding an ideally specific marker of myocardial infarction, but until then biochemical markers should be used in conjunction
with clinical assessment and electrocardiography in making the diagnosis of myocardial infarction, and the patients should not be treated
merely on the basis of elevated serum levels of cardiac biochemical markers.
D 2005 Elsevier Ireland Ltd. All rights reserved.

Keywords: Biochemical markers; Cardiac markers; Myocardial injury; Myocardial infarction; Myocardial necrosis

1. Introduction there should be a direct relation between the plasma level of

the marker and the extent of myocardial injury. The marker
Coronary artery disease, especially acute coronary event should persist in serum for a sufficient length of time to
is not only the number one killer in Western countries, but it provide a convenient diagnostic time. Finally, the measure-
is also the most frequent cause accounted for hospital- ment of the marker should be easy, inexpensive and rapid.
ization. In patients with chest pain, one of the most Conventionally, serum creatine kinase and its isoenzyme
important processes during the initial period of hospital- creatine kinase-MB have been the commonly use cardiac
ization is to determine whether acute myocardial infarction markers [2–4]. However, over the last decade, there have
has definitely occurred. For years, clinicians have been been many new developments in this field. Although, most
searching for diagnostic tools that would help in identifying of the new cardiac markers of acute myocardial infarction
patients with acute myocardial infarction. According to the seem to have better quality with higher sensitivity and
World Health Organization criteria for diagnosis of acute specificity in solving the diagnostic purpose, controversial
myocardial infarction, elevation of serum cardiac markers is issues still surround these new markers in many situations,
one of the three diagnostic criteria being used for this as none of these markers fulfill the criteria of an ideal
purpose [1]. The optimal and ideal cardiac marker should be cardiac marker.
present in high concentration in myocardium and should be
absent from non-myocardial tissues. It should be rapidly
released into the blood at the time of myocardial injury and 2. Early diagnosis of acute myocardial infarction

In general, serial measurement of serum cardiac markers

* Corresponding author. Tel.: +1 410 328 2251; fax: +1 410 328 2255. has a very high sensitivity in detecting acute myocardial
E-mail address: ikhan@medicine.umaryland.edu (I.A. Khan). infarction. Over 24 h and measured 8 h apart, the serum
0167-5273/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.ijcard.2004.10.031
 I.A. Khan, N. Wattanasuwan / International Journal of Cardiology 104 (2005) 238–240 239

creatine kinase-MB has an average sensitivity close to 100% kinase-MB subform demonstrated better sensitivity than
[3]. Similarly, the cardiac troponins I and T have sensitivity myoglobin for early detection of acute myocardial infarc-
of 97–100% and 86–100%, respectively, when serially tion. Measured at 2 h, 4 h and 6 h from the onset of chest
measured [3–6]. The sensitivities of troponins are somewhat pain, the sensitivities of creatine kinase-MB subform and
varied depending on the cut-off value used. However, in this myoglobin for the diagnosis of acute myocardial infarction
era of cost efficient management when physicians need the were 21%, 46%, 91% and 26%, 42%, 78%, respectively.
best quality diagnostic test, the major issue is no longer Another study has shown equivalent early sensitivities of
about the sensitivity of the serially measured biochemical myoglobin, creatine kinase-MB subform, cardiac troponin I,
markers, which certainly will require hospitalization, rather and cardiac troponin T in establishing the diagnosis of acute
it is the sensitivity of the early measurement of biochemical myocardial infarction [3].
markers that could correctly triage the patient presenting
with acute chest pain in the emergency department.
The most important but frequently neglected factor that 3. Late diagnosis of acute myocardial infarction
determines the early sample sensitivity of each serum
cardiac marker lies in the time interval between the Although myoglobin and creatine kinase-MB subform
symptom onset and the sampling time. Among all of the serve very well as cardiac markers for early diagnosis of
cardiac markers being widely studied and used, myoglobin acute myocardial infarction, these markers are not the
and creatine kinase-MB subforms seem to have the most optimal because to their rapid clearance from the serum.
rapid release and the highest sensitivity for the diagnosis of The serum level of these biochemical markers may not be
acute myocardial infarction from the early blood sample of sufficient for a valid measurement in patients presenting to
patients presenting to the hospital within 4–6 h from the hospital more than 6 h from the symptom onset. On the
symptom onset [7,8]. Gibler et al. [7] have shown 62% other hand, the markers that rise in the later hours, such as
sensitivity of serum myoglobin in diagnoses of acute creatine kinase-MB, cardiac troponins I and T, and lactic
myocardial infarction on the blood sample drawn at dehydrogenase will stay longer in the serum [12]. In
presentation and 100% on the second blood sample repeated general, elevated serum myoglobin level can return to its
at 3 h. In another study by D’Costa et al. [8], the sensitivity normal range within 24 h and elevated serum creatine
of serum myoglobin in diagnoses of acute myocardial kinase-MB within up to 48–72 h, whereas, cardiac troponins
infarction was 43% on the first blood sample and 100% on and lactic dehydrogenase will take 1–2 weeks to return to
the second blood sample repeated at 2 h after the patient the normal ranges. Because of the higher specificity of
presented to the hospital. The sensitivity of cardiac troponin cardiac troponins over creatine kinase-MB and lactic
I and creatine kinase-MB in the early measurement were dehydrogenase, cardiac troponins are better biochemical
about 79% and 45%, respectively. One-third of the patients markers for the diagnosis acute myocardial infarction in
studied presented to the hospital within 3 h from the patients who present to hospital beyond 6 h after the onset
symptom onset. Wu et al. [9] compared the early sample of chest pain.
sensitivity of myoglobin, creatine kinase-MB and cardiac
troponin I in a head-to-head comparison for the early
diagnosis of acute myocardial infarction. In this study of 4. Diagnosis of early recurrent myocardial infarction
three markers, myoglobin had the highest sensitivity of
about 50% when blood sample was collected between 0–6 h On the contrary, the prolonged elevation of cardiac
after the onset of chest pain. troponin I and cardiac troponin T levels when acute
Besides myoglobin, creatine kinase-MB subform is myocardial infarction has occurred, diminishes their accu-
another biochemical marker that has shown high sensitivity racy for the detecting early recurrent myocardial infarction.
for the early detection of acute myocardial infarction [10]. In Whereas, the pattern of re-elevation in the level of short-
the initial hours after the onset of myocardial infarction, the lived biochemical markers, such as myoglobin, creatine
amount of creatine kinase-MB released from the myocar- kinase-MB and creatine kinase-MB subform can be used as
dium is minimal, often not enough to exceed the upper limit an indicator of early recurrent myocardial infarction.
of the normal range. Creatine kinase-MB2 is the only form
of creatine kinase-MB present in myocardial tissue. On its
release into the blood, the creatine kinase-MB2 changes into 5. Clinical assessment
a different subform, creatine kinase-MB1. An absolute value
of creatine kinase-MB2 N1 U/L or a ratio of creatine kinase- In general, any ideal diagnostic test needs to have not
MB2 to creatine kinase-MB1 of 1.5 or higher provides only high sensitivity but also high specificity to the
improved sensitivity for the diagnosis of acute myocardial condition being tested. Many of the cardiac markers,
infarction within 6 h after the onset of symptoms as including myoglobin, creatine kinase and lactic dehydrogen-
compared with the conventional assays for creatine kin- ase, are also present in tissues other than myocardium,
ase-MB. In a study by Zimmerman et al. [11], creatine because of which their specificities are considered as in the
240 I.A. Khan, N. Wattanasuwan / International Journal of Cardiology 104 (2005) 238–240

lower range. The creatine kinase-MB was developed to be a [6] Cummins B, Auckland ML, Cummins P. Cardiac-specific troponin-I
more cardiac specific marker but several reports have shown radioimmunoassay in the diagnosis of acute myocardial infarction.
Am Heart J 1987;113:1333 – 44.
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