Cardiac biomarkers some up  frequently, but to be honest these questions have generally been referring only to troponin. Observe:

  • Question 10 from the second paper of 2011 (troponin)
  • Question 8 from the second paper of 2006 (troponin again)
  • Question 27 from the second paper of 2010 (in general)
  • Question 3 from the first paper of 2003 (troponin vs CK MB)
  • Question 14 from the second paper of 2012 (BNP)

Only Question 27 from the second paper of 2010 takes a broad overview of the cardiac biomarkers. The college answer to that question is a table of advantages and disadvantages, comparing oldies like CRP and ESR with CK, troponin with some exciting novel biomarkers.  Since this 2010 paper, none of these exciting novel biomarkers have become commonplace.

Anyway. The college answer to Question 27 consists of a table, listing the advantages and disadvantages of cardiac biomarkers. My response to such things has traditionally been to offer a similar table, but with more detail. This is not necessarily better. To inundate the CICM trainee with excessive tabulated data is sadistic overkill, equivalent to the difference between the fifty-first and the fifty-second stab wound (i.e. is that really necessary?). However, one can conceive of circumstances when such a table might be helpful. And, in contrast to the college model answer, references are offered.

Without further ado, the table is offered below. The treatment of this list is similar to the treatment of the biomarkers of sepsis in their on respective chapter. The cardiac biomarkers are listed in order of apprearance, i.e. the biomarkers which entered routine use in the 1950s are listed first, and all the novel exotic markers are listed last. The chronology of cardiac biomarker development was sourced from the excellent 2014 article by Kent Lewandrowski for Clinics in Laboratory Medicine. For the older biomarker enzymes such as AST, CK and LDH, the best reference is the review article by Sobel and Shell (1972). For more modern techniques, the single best resource for this would have to be the paper by  Anthony McLean et al (2012). Unless otherwise stated, this is the main source for the information offered below. If for some reason a berserk excess of tabulated biomarker information is called for, one may want to spend some time with this 2006 article in Circulation.


Cardiac Biomarkers



  • Erythrocyte sedimentation rate; the rate at which EDTA-treated diluted RBCs clump together in a vertical test tube.
  • Elevated in inflammatory conditions, mainly because of the increased amount of fibrinogen, which is an acute phase reactant.
  • Myocardial infarction and myocardial necrosis cause an elevated ESR, more so than mere angina pectoris (Riseman and Brown, 1937)



  • Takes about one hour to perform
  • Completely non-specific.
  • Old-school: as sophistication of laboratories has increased, the demand for ESR testing has diminished
  • Varies with age, temperature, test tube position... Unreliable
  • Non-cardiac causes of elevation:
    • Sepsis
    • Malignancy (eg. multiple myeloma)
    • Inflammatory disease, eg. RA/PMR
    • Chronic renal failure
    • Vasculitis, eg. temporal arteritis





  • Cheap
  • Easy to perform
  • Widely available
  • Peaks late; it can therefore be used to detect an infarction which has occurrsed many days ago (in contrast to CK MB, which is gone within two days).
  • As a part of a package of tests, it may improve the predictive value of risk analysis tools (Ridker et al, 1998)
  • Angina alone will not cause an elevation of CRP (de Beer et al, 1982)


  • A nonspecific marker of inflammation
  • Non-cardiac causes of elevation:
    • Surgery, trauma
    • Burns
    • Sepsis
    • Rheumatological disease
  • Unreliable in patients with a dysfunctional liver




  • Aspartate aminotransferase (AST), formerly SGOT (serum glutamic oxaloacetic transaminase) is a 45 kD protein which is released from necrotic tissue.
  • High concentrations are present in liver, kidney, skeletal muscle and myocardium.
  • AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate. Vitamin B6 is required as a co-factor for this process.


  • Rises up to 20 times the normal level within 48 hours of an MI (LaDue, 1957)
  • Starts going up about 8 hours after the onset of chest pain
  • Does not rise with angina (only MI)
  • Does not rise with inflammatory states, and is therefore better than ESR or CRP.


  • Also present in red blood cells: haemolysis will lead to spurious elevation
  • Not cardio-specific
  • Does not rise unless myocardial necrosis has occurred (Dewar et al, 1959)




  • CK (creatine kinase) is the enzyme which catalyses the conversion of creatine into  phosphocreatine using one molecule of ATP. This reversible reaction can then be used to create ATP out of phosphocreatine and ADP.
  • All muscle tissue is rich in CK, but all cells possess some CK, particularly specialised tissues such as retina, pancreas, placenta, the intestinal brush border, and many others (Wallimann and Hemmer, 1994)


  • Does not rise unless there has been myocardial damage. Normal levels were always found in patients with congestive heart failure, rapid supraventricular arrhythmias, and acute coronary insufficiency without evidence of infarction (Vincent et al, 1965)
  • Rapidly increasing levels: rises before AST, and peaks 15-20 hours post infarction.
  • Usually normal in sepsis, malignancy and renal failure.


  • Early peak and rapid clearance do not permit diagnosis in a delayed presentation of MI
  • Not specific for the myocardium: released from any infarcted or damaged muscle




  • Lactate dehydrogenase catalyzes the conversion of lactate to pyruvate, and back from pyruvate into lactate. It is one of the most ancient enzymes, with all animals and plants having some version of it.
  • There are numerous isoenzymes, and they are not completely tissue-specific. Howeve, LDH1 is apparently very specific for the heart


  • Elevated early: usually already raised in the first blood sample taken from the patient.
  • Sensitivity of LDH1 in myocardial infarction exceeds 95% (Sobel et al, 1972)


  • It is rare to find a laboratory which will do LDH isoenzymes.
  • LDH isonezyme assays frequently disagree between themselves.
  • Rapid drop in levels prevents delayed diagnosis
  • Total LDH (without isoenzyme breakdown) is highly non-specific.
  • In patients with haemolysis due to artifical valves, LDH is chronically elevated
  • LDH may become elevated in tachycardias and other non-ischaemic states of cardiac strain




  • The myocardium-specific isoenzyme of CK.
  • Released into the circulation along with other CK isoforms during a myocardial infarction


  • Before there were serial troponins, there was CK-MB. It was used in the 1990s as a highly specific (not low-sensitivity) test for MI (Gibler et al, 1990)
  • Sensitivity improved in mid-1990s until rapid assays achieved 95.7% sensitivity and 963.9% specificity  (Puleo et al, 1994)


  • The older assays for CK-MB may have some cross-reactivity with other isoforms, generating false positives -eg. when measuring CK-MB and Ck-BB in combination (Tseng, 1981)
  • The sensitivity and specificity is still lower than that of the troponin.
  • Since this has ben superseded by troponin, its availability has declined to virtually zero.




  • Non-specific muscle protein, released during any even causing muscle damage
  • Myocardial infarction with ensuing necrosis results in myoglobin leak.
  • The myoglobin can rise before CK-MB or total CK: at "zero hour" (i.e. on presentation) the myoglobin is raised in about 50% of patients, whereas the other markers you had to wait for (Gibler et al, 1987)


  • Early sensitivity of myoglobin in patients presenting within 4 hours is quite good, apparently equivalent to the early troponin assays (Mair et al, 1995)


  • Poor specificity for the myocardium: wil be elevated in numerous disease states
  • In the ICU, all manner of non-cardiac illnesses and interventions will result in a raised myoglobin
  • Early peak (4 hours following  chest pain) doe snot permit delayed diagnosis
  • If troponin is available, there is no advantage to the use of myoglobin (as troponin also allows early detection, and is more myocardium-sensitive)

Troponin-T and Troponin-I



  • Troponin is an enzyme involved in the excitation-contraction coupling of the myocardium.
  • Troponin T serves to attach the troponin complex to actin and tropomyosin.
  • Myocardiac damage (for example infarction) causes the release of troponin.
  • There is a cytosolic pool (which is released early in the infarct) and a structural pool (which is slowly released over days as the damaged myocardium decomposes).


  • Its a sensitive and specific marker of myocardial ischaemia.
  • It is more sensitive and specific than AST, CK and CK-MB (which are also found is skeletal muscle)
  • It is an independent predictor of 30-day mortality in STEMI 
  • It is associated with a poorer outcome in the critically ill patients.
  • Troponin levels can be used to monitor for myocardial ischaemia in critically ill patients when history and examination are unreliable.


  • A reliance on biomarkers may become unhealthy if it takes focus off clinical examination and history.
  • It is not quantitatively validated outside the setting of ACS / AMI, but only qualitatively: i.e. a "positive" troponin is associated with worse outcomes in noncardiac critical illness, but we don't know whether a higher troponin is associated with a proportionally higher mortality.
  • Troponin levels can be raised for a variety of non-cardiac reasons:
    • Myocardial ischaemia
    • Renal failure
    • Sepsis
    • Atrial fibrillation
    • Post-cardioversion
    • Cardiac trauma
    • Pulmonary embolism
    • Acute stroke or intracranial haemorrhage
    • Severe burns




  • Copeptin is also known as C-terminal provasopressin.
  • It is a 39-amino acid glycopeptide of unknown function in the circulation
  • Copeptin is derived from a larger precursor peptide (preprovasopressin) along with  neurophysin II and vasopressin.



  • Not specific for the myocardium. In fact, its whorishly indiscriminate. Recently people have been trying to promote copeptin as a biomarker in all sorts of other illnesses, such as sepsis, stroke, pancreatitis, and so forth (Reinstadler et al, 2015)
  • The positive predictive value of copeptin used alone  as a diagnostic confirmation of  MI is "unacceptably low" according to a recent meta-analysis (Raskalova et al, 2014)




  • Human-type Cytoplasmic Fatty Acid Binding Protein is a low molecular weight protein present in the myocardium.
  • It is released early in AMI, and has been proposed as a biomarker of early myocardial injury.






  • BNP (brain natriuretic peptide) is a 32-amino acid peptide released by the human atria and ventricles in response to distending pressure. In spite of its name, its presence in the human brain is rather minimal- it was first identified in porcine brain tissue, where for some reason it is concentrated. BNP is a peptide which has natriuretic and diuretic actions in the renal tubule, and is though to be a part of the natural homeostatic mechanisms which work in defence of normal intravascular volume.
  • Thus, a raised BNP, suggesting increased atrial stretch, may be a serum marker which may differentiate cardiac failure and pulmonary oedema from respiratory infection in situations when both are equally likely on the basis of history and examination.








This article has a nice graph of cardiac biomarker concentrations over time after an infarct:
Wu et al; National Academy of Clinical Biochemistry Standards of Laboratory Practice: Recommendations for the Use of Cardiac Markers in Coronary Artery Diseases. Clinical Chemistry 45:7 1104 –1121 (1999)

McLean, Anthony S., and Stephen J. Huang. "Cardiac biomarkers in the intensive care unit." Ann Intensive Care 2.8 (2012): 1-11.

Lewandrowski, Kent B. "Cardiac markers of myocardial necrosis: a history and discussion of milestones and emerging new trends." Clinics in laboratory medicine 34.1 (2014): 31-41.

The ECS and AHA statement referred to in the college answer is this article published in Circulation in 2007:

(Kristian Thygesen et al; Universal Definition of Myocardial Infarction. Circulation 2007, 116:2634-2653


This article from Current Opinion in Critical care (2004) discusses the various causes of raised troponin among ICU patients:

Ammann et al,Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes. Journal of the American College of Cardiology Volume 41, Issue 11, 4 June 2003, Pages 2004–2009


The fact that troponin rise among the critically ill population is associated with a poorer prognosis is supported by this study:

Gunnewiek et al. Cardiac troponin elevations among critically ill patients. Current Opinion in Critical Care: October 2004 - Volume 10 - Issue 5 - pp 342-346

Farthing, Don E., Christine A. Farthing, and Lei Xi. "Inosine and hypoxanthine as novel biomarkers for cardiac ischemia: From bench to point-of-care." Experimental Biology and Medicine (2015): 1535370215584931.

Bedell, Susanna E., and Booker T. Bush. "Erythrocyte sedimentation rate. From folklore to facts." The American journal of medicine 78.6 (1985): 1001-1009.

LaDue, John S. "Laboratory aids in diagnosis of myocardial infarction: Changes in muscle enzymes, erythrocyte sedimentation rate, and C-reactive protein in myocardial infarction." Journal of the American Medical Association 165.14 (1957): 1776-1781.

Riseman, Joseph EF, and Morton G. Brown. "THE SEDIMENTATION RATE IN ANGINA PECTORIS AND CORONARY THROMBOSIS." The American Journal of the Medical Sciences 194.3 (1937): 392-399.

LEVINGER, ERNEST L., H. Y. M. A. N. Levy, and SAMUEL K. ELSTER. "Study of C-reactive protein in the sera of patients with acute myocardial infarction." Annals of internal medicine 46.1 (1957): 68-78.

Ridker, Paul M., Robert J. Glynn, and Charles H. Hennekens. "C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction." Circulation 97.20 (1998): 2007-2011.

De Beer, F. C., et al. "Measurement of serum C-reactive protein concentration in myocardial ischaemia and infarction." British heart journal 47.3 (1982): 239-243.

Dewar, H. A., N. R. Rowell, and A. J. Smith. "Serum glutamic oxalacetic transaminase in acute myocardial infarction." British medical journal 2.5105 (1958): 1121.

Vincent, William R., and Elliot Rapaport. "Serum creatine phosphokinase in the diagnosis of acute myocardial infarction." The American journal of cardiology 15.1 (1965): 17-26.

Smith, Alistair F. "Diagnostic value of serum-creatine-kinase in a coronary-care unit." The Lancet 290.7508 (1967): 178-182.

Roberts, Robert, et al. "Specificity of elevated serum MB creatine phosphokinase activity in the diagnosis of acute myocardial infarction." The American journal of cardiology 36.4 (1975): 433-437.

Wallimann, Theo, and Wolfram Hemmer. "Creatine kinase in non-muscle tissues and cells." Cellular Bioenergetics: Role of Coupled Creatine Kinases. Springer US, 1994. 193-220.

Sobel, Burton E., and William E. Shell. "Serum enzyme determinations in the diagnosis and assessment of myocardial infarction." Circulation 45.2 (1972): 471-482.

Gibler, W. Brian, et al. "Early detection of acute myocardial infarction in patients presenting with chest pain and nondiagnostic ECGs: serial CK-MB sampling in the emergency department." Annals of emergency medicine 19.12 (1990): 1359-1366.

Tsung, S. H. "Several conditions causing elevation of serum CK-MB and CK-BB." American journal of clinical pathology 75.5 (1981): 711-715.

Puleo, Peter R., et al. "Use of a rapid assay of subforms of creatine kinase MB to diagnose or rule out acute myocardial infarction." New England journal of medicine 331.9 (1994): 561-566.

Mair, Johannes, et al. "Equivalent early sensitivities of myoglobin, creatine kinase MB mass, creatine kinase isoform ratios, and cardiac troponins I and T for acute myocardial infarction." Clinical chemistry 41.9 (1995): 1266-1272.

Gibler, W. Brian, et al. "Myoglobin as an early indicator of acute myocardial infarction." Annals of emergency medicine 16.8 (1987): 851-856.

Stone, M. J., et al. "Serum myoglobin level as diagnostic test in patients with acute myocardial infarction." British heart journal 39.4 (1977): 375-380.

Khan, Sohail Q., et al. "C-Terminal provasopressin (copeptin) as a novel and prognostic marker in acute myocardial infarction leicester acute myocardial infarction peptide (LAMP) study." Circulation 115.16 (2007): 2103-2110.

Reinstadler, Sebastian Johannes, et al. "Copeptin Testing in Acute Myocardial Infarction: Ready for Routine Use?." Disease markers (2015).

Reichlin, Tobias, et al. "Incremental value of copeptin for rapid rule out of acute myocardial infarction." Journal of the American College of Cardiology 54.1 (2009): 60-68.

Raskovalova, Tatiana, et al. "Diagnostic accuracy of combined cardiac troponin and copeptin assessment for early rule-out of myocardial infarction: a systematic review and meta-analysis." European Heart Journal: Acute Cardiovascular Care (2013): 2048872613514015.

Okamoto, Fumio, et al. "Human heart-type cytoplasmic fatty acid-binding protein (H-FABP) for the diagnosis of acute myocardial infarction. Clinical evaluation of H-FABP in comparison with myoglobin and creatine kinase isoenzyme MB." Clinical chemistry and laboratory medicine 38.3 (2000): 231-238.

Slot, MHE Bruins, et al. "Diagnostic value of a heart-type fatty acid-binding protein (H-FABP) bedside test in suspected acute coronary syndrome in primary care." International journal of cardiology 168.2 (2013): 1485-1489.

Orihuela, C. J., et al. "The Heart-Type Fatty Acid-Binding Protein (h-Fabp) Is Associated With Higher Icu Mortality In Severe Septic Patients." Am J Respir Crit Care Med 191 (2015): A6257.