View source for Cardiac marker

{{Short description|Biomarkers relevant to heart function}}
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{{Infobox diagnostic
| Name = Cardiac marker
| Image = AMI_bloodtests_engl.png
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| Caption = Kinetics of cardiac markers [[Troponin]] and [[CK-MB]] in myocardial infarction with or without reperfusion treatment.
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'''Cardiac markers''' are [[Biomarker (medicine)|biomarkers]] measured to evaluate heart function. They can be useful in the early prediction or diagnosis of disease.<ref>{{cite journal |vauthors=Rao SP, Miller S, Rosenbaum R, Lakier JB |title=Opportunities for microRNAs in the Crowded Field of Cardiovascular Biomarkers |journal=Annual Review of Pathology: Mechanisms of Disease |volume=14  |pages=211–238 |year=2019 |doi= 10.1146/annurev-pathmechdis-012418-012827|pmid=30332561 |pmc=6442682}}</ref> Although they are often discussed in the context of [[myocardial infarction]], other conditions can lead to an elevation in cardiac marker level.<ref name=":0" /><ref name=":1" />

Cardiac markers are used for the diagnosis and risk stratification of patients with chest pain and suspected acute coronary syndrome and for management and prognosis in patients with diseases like acute heart failure.

Most of the early markers identified were [[enzyme]]s, and as a result, the term "cardiac enzymes" is sometimes used. However, not all of the markers currently used are enzymes. For example, in formal usage, troponin would not be listed as a cardiac enzyme.<ref name="pmid10468091">{{cite journal |vauthors=Rao SP, Miller S, Rosenbaum R, Lakier JB |title=Cardiac troponin I and cardiac enzymes after electrophysiologic studies, ablations, and defibrillator implantations |journal=Am. J. Cardiol. |volume=84 |issue=4 |pages=470, A9 |date=August 1999 |pmid=10468091 |doi= 10.1016/S0002-9149(99)00337-9}}</ref>

==Applications of measurement==
Measuring cardiac biomarkers can be a step toward making a diagnosis for a condition. Whereas cardiac imaging often confirms a diagnosis, simpler and less expensive cardiac biomarker measurements can advise a physician whether more complicated or invasive procedures are warranted. In many cases medical societies advise doctors to make biomarker measurements an initial testing strategy especially for patients at low risk of cardiac death.<ref name="ASNCfive">{{Citation |author1 = American Society of Nuclear Cardiology |author1-link = American Society of Nuclear Cardiology |title = Five Things Physicians and Patients Should Question |publisher = American Society of Nuclear Cardiology |work = Choosing Wisely: an initiative of the [[ABIM Foundation]] |url = http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_Amer_Soc_Nuc_Cardio.pdf |access-date = August 17, 2012 |archive-url = https://web.archive.org/web/20120416220538/http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_Amer_Soc_Nuc_Cardio.pdf |archive-date = 2012-04-16 }}</ref><ref name="ACCcarradio">{{Cite journal | last1 = Hendel | first1 = R. C. | last2 = Berman | first2 = D. S. | last3 = Di Carli | first3 = M. F. | last4 = Heidenreich | first4 = P. A. | last5 = Henkin | first5 = R. E. | last6 = Pellikka | first6 = P. A. | last7 = Pohost | first7 = G. M. | last8 = Williams | first8 = K. A. | author9 = American College of Cardiology Foundation Appropriate Use Criteria Task Force | author10 = American Society of Nuclear Cardiology | doi = 10.1016/j.jacc.2009.02.013 | last11 = American College Of | first11 = R. | last12 = American Heart | first12 = A. | author13 = American Society of Echocardiology | author14 = Society of Cardiovascular Computed Tomography | author15 = Society for Cardiovascular Magnetic Resonance | last16 = Society Of Nuclear | first16 = M. | title = ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 Appropriate Use Criteria for Cardiac Radionuclide Imaging | journal = Journal of the American College of Cardiology | volume = 53 | issue = 23 | pages = 2201–2229 | year = 2009 | pmid =  19497454| doi-access =  }}</ref>

Many acute cardiac marker IVD products are targeted at nontraditional markets, ''e.g.'', the hospital ER instead of traditional hospital or clinical laboratory environments. Competition in the development of cardiac marker diagnostic products and their expansion into new markets is intense.<ref>{{cite web |title= Cardiac Marker Diagnostic Testing Markets |publisher=TriMark Publications, LLC |date=November 2011 |url= http://www.trimarkpublications.com/products/Cardiac-Marker-Diagnostic-Testing-Markets.html}}</ref>

Recently, the intentional destruction of myocardium by [[alcohol septal ablation]] has led to the identification of additional potential markers.<ref name="pmid18769631">{{cite journal |author=Lewis GD |title=Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury |journal=J. Clin. Invest. |volume=118 |issue=10 |pages=3503–12 |date=October 2008 |pmid=18769631 |pmc=2525696 |doi=10.1172/JCI35111 |author2=Wei R |author3=Liu E |display-authors=3 |last4=Yang |first4=Elaine |last5=Shi |first5=Xu |last6=Martinovic |first6=Maryann |last7=Farrell |first7=Laurie |last8=Asnani |first8=Aarti |last9=Cyrille |first9=Marcoli}}</ref>

==Types==
Types of cardiac markers include the following:

{| class="wikitable"
|-
! Test
! [[Sensitivity and specificity]]
! Approximate peak
! Description
|-
| [[Troponin test]]
| The most sensitive and specific test for [[myocardium|myocardial]] damage. Because it has increased specificity compared with CK-MB, troponin is composed of 3 proteins- Troponin C, Cardic troponin I, and Cardiac troponin T. Troponin I especially has a high affinity for myocardial injury.
| 12 hours
|  Troponin is released during MI from the cytosolic pool of the myocytes. Its subsequent release is prolonged with degradation of actin and myosin filaments. Isoforms of the protein, T and I, are specific to myocardium.  Differential diagnosis of troponin elevation includes acute infarction, severe pulmonary embolism causing acute right heart overload, heart failure, myocarditis. Troponins can also calculate infarct size but the peak must be measured in the 3rd day. After myocyte injury, troponin is released in 2–4 hours and persists for up to 7 days.
Normal value are - Troponin I <0.3&nbsp;ng/ml and Troponin T <0.2&nbsp;ng/ml.
In patients with non-severe asymptomatic [[Aortic stenosis|aortic valve stenosis]] and no overt [[coronary artery disease]], the increased [[troponin T]] (above 14 pg/mL) was found associated with an increased 5-year event rate of [[Coronary ischemia|ischemic cardiac events]] ([[myocardial infarction]], [[percutaneous coronary intervention]], or [[coronary artery bypass surgery]]).<ref name=":0">{{Cite journal |last1=Hadziselimovic |first1=Edina |last2=Greve |first2=Anders M. |last3=Sajadieh |first3=Ahmad |last4=Olsen |first4=Michael H. |last5=Kesäniemi |first5=Y. Antero |last6=Nienaber |first6=Christoph A. |last7=Ray |first7=Simon G. |last8=Rossebø |first8=Anne B. |last9=Wachtell |first9=Kristian |last10=Nielsen |first10=Olav W. |date=April 2023 |title=Association of high-sensitivity troponin T with outcomes in asymptomatic non-severe aortic stenosis: a post-hoc substudy of the SEAS trial |url=|journal=eClinicalMedicine |volume=58 |article-number=101875 |doi=10.1016/j.eclinm.2023.101875 |issn=2589-5370 |pmc=10006443 |pmid=36915288}}</ref>
|-
| [[CPK-MB test|Creatine Kinase (CK-MB) test]]
| It is relatively specific when skeletal muscle damage is not present.
| 10–24 hours
| The CK-MB isoform of [[creatine kinase]] is expressed in heart muscle. It resides in the cytosol and facilitates movement of high energy phosphates into and out of mitochondria. Since it has a short duration, it cannot be used for late diagnosis of acute MI but can be used to suggest infarct extension if levels rise again. This is usually back to normal within 2–3 days. Normal range - 2-6&nbsp;ng/ml
|-
| [[Lactate dehydrogenase]] (LDH)
| LDH is not as specific as troponin.
| 72 hours
| Lactate dehydrogenase catalyses the conversion of [[pyruvic acid|pyruvate]] to [[Lactic acid|lactate]]. LDH-1 isozyme is normally found in the heart muscle and LDH-2 is found predominantly in blood serum. A high LDH-1 level to LDH-2 suggest MI. LDH levels are also high in tissue breakdown or hemolysis. It can mean [[cancer]], [[meningitis]], [[encephalitis]], or [[HIV]]. This is usually back to normal 10–14 days.
|-
| [[Aspartate transaminase]] (AST)
| 
|
| This was the first used.<ref name="pmid14324110">{{cite journal |vauthors=NISSEN NI, RANLOV P, WEIS-FOGH J |title=Evaluation of Four Different Serum Enzymes in the Diagnosis of Acute Myocardial Infarction |journal=Br Heart J |volume=27 |issue= 4|pages=520–6 |date=July 1965 |pmid=14324110 |pmc=503341 |doi= 10.1136/hrt.27.4.520|url=}}</ref> It is not specific for heart damage, and it is also one of the [[liver function tests|liver transaminases]].
|-
| [[Myoglobin]] (Mb)
| low specificity for [[myocardial infarction]]
| 2 hours
| Myoglobin is used less than the other markers. Myoglobin is the primary oxygen-carrying pigment of muscle tissue. It is high when muscle tissue is damaged but it lacks specificity. It has the advantage of responding very rapidly,<ref name="urlUse of Cardiac Markers in the Emergency Department: - eMedicine">{{cite web |url=http://emedicine.medscape.com/article/811905-overview |title=Use of Cardiac Markers in the Emergency Department: - eMedicine |access-date=2009-01-06}}</ref> rising and falling earlier than CK-MB or troponin. It also has been used in assessing reperfusion after [[thrombolysis]].<ref name="pmid9323061">{{cite journal |author=Christenson RH |title=Assessment of coronary reperfusion after thrombolysis with a model combining myoglobin, creatine kinase-MB, and clinical variables. TAMI-7 Study Group. Thrombolysis and Angioplasty in Myocardial Infarction-7 |journal=Circulation |volume=96 |issue=6 |pages=1776–82 |date=September 1997 |pmid=9323061 |doi= 10.1161/01.cir.96.6.1776|url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=9323061 |author2=Ohman EM |author3=Topol EJ |display-authors=3 |last4=Peck |first4=S |last5=Newby |first5=LK |last6=Duh |first6=SH |last7=Kereiakes |first7=DJ |last8=Worley |first8=SJ |last9=Alosozana |first9=GL|url-access=subscription }}</ref>
|-
| [[Ischemia-modified albumin]] (IMA)
| low specificity
|
| IMA can be detected via the albumin cobalt binding (ACB) test, a limited available FDA approved assay.  Myocardial ischemia alters the N-terminus of albumin reducing the ability of cobalt to bind to albumin.  IMA measures ischemia in the blood vessels and thus returns results in minutes rather than traditional markers of necrosis that take hours.  [[ACB test]] has low specificity therefore generating high number of false positives and must be used in conjunction with typical acute approaches such as ECG and physical exam.  Additional studies are required.
|-
| [[Pro-brain natriuretic peptide]]
|
|
| This is increased in patients with heart failure. It has been approved as a marker for acute congestive heart failure. Patients with < 80 have a much higher rate of symptom-free survival within a year. Generally, pt with CHF will have > 100. In patients with non-severe asymptomatic [[Aortic stenosis|aortic valve stenosis]], increased age- and sex-adjusted [[N-terminal prohormone of brain natriuretic peptide|N-terminal pro-brain natriuretic peptide]] ([[NT-proBNP]]) levels alone and combined with a 50% or greater increase from baseline had been found associated with increased event rates of aortic valve stenosis related events ([[Cardiac death|cardiovascular death]], hospitalization with [[heart failure]] due to progression of [[Aortic stenosis|aortic valve stenosis]], or [[aortic valve replacement]] surgery).<ref name=":1">{{Cite journal |last1=Hadziselimovic |first1=Edina |last2=Greve |first2=Anders M. |last3=Sajadieh |first3=Ahmad |last4=Olsen |first4=Michael H. |last5=Kesäniemi |first5=Y. Antero |last6=Nienaber |first6=Christoph A. |last7=Ray |first7=Simon G. |last8=Rossebø |first8=Anne B. |last9=Willenheimer |first9=Ronnie |last10=Wachtell |first10=Kristian |last11=Nielsen |first11=Olav W. |date=2022-04-01 |title=Association of Annual N-Terminal Pro-Brain Natriuretic Peptide Measurements With Clinical Events in Patients With Asymptomatic Nonsevere Aortic Stenosis: A Post Hoc Substudy of the SEAS Trial |url=https://jamanetwork.com/journals/jamacardiology/fullarticle/2788912 |journal=JAMA Cardiology |language=en |volume=7 |issue=4 |pages=435–444 |doi=10.1001/jamacardio.2021.5916 |issn=2380-6583 |pmc=8851368 |pmid=35171199}}</ref>
|-
|  [[Glycogen phosphorylase isoenzyme BB]]
| 0.854 and 0.767<ref>{{Cite journal  | last1 = Lippi | first1 = G. | last2 = Mattiuzzi | first2 = C. | last3 = Comelli | first3 = I. | last4 = Cervellin | first4 = G. | title = Glycogen phosphorylase isoenzyme BB in the diagnosis of acute myocardial infarction: a meta-analysis. | journal = Biochem Med (Zagreb) | volume = 23 | issue = 1 | pages = 78–82 | year = 2013 | doi =  10.11613/bm.2013.010| pmid = 23457768 | pmc=3900091}}</ref>
| 7 hours
|
Glycogen phosphorylase isoenzyme BB (abbreviation: GPBB) is one of the three isoforms of [[glycogen phosphorylase]]. This isoform of the enzyme exists in cardiac (heart) and brain tissue. Because of the blood–brain barrier, GP-BB can be seen as being specific to heart muscle. GP-BB is one of the "new cardiac markers" which are considered to improve early diagnosis in acute coronary syndrome. During the process of ischemia, GP-BB is converted into a soluble form and is released into the blood. A rapid rise in blood levels can be seen in myocardial infarction and unstable angina. GP-BB is elevated 1–3 hours after process of ischemia.
|}

==Limitations==
[[Image:Reference ranges for blood tests - by units.png|thumb|right|[[Reference ranges for blood tests]], measured in units, including several cardiac markers.]]
Depending on the marker, it can take between 2 and 24 hours for the level to increase in the blood. Additionally, determining the levels of cardiac markers in the laboratory - like many other lab measurements - takes substantial time. Cardiac markers are therefore not useful in diagnosing a [[myocardial infarction]] in the acute phase. The clinical presentation and results from an [[ECG]] are more appropriate in the acute situation.{{citation needed|date=March 2021}}

However, in 2010, research at the [[Baylor College of Medicine]] revealed that, using diagnostic nanochips and a swab of the cheek, cardiac biomarker readings from saliva can, with the ECG readings, determine within minutes whether someone is likely to have had a heart attack{{Citation needed|date=April 2017}}.
{{clear}}
{{Gallery
|title=Comparison of cardiac markers over time
|width=160
|height=170
|align=center
|File:CardiacMarkerComparison.JPG|Comparison of cardiac marker in the first hours after chestpain onset and the relative concentration.
|File:CardiacMarkerComparison2.JPG|Comparison of cardiac marker in the first hours after chestpain onset and the multiples of the cutoff.
|File:AMI bloodtests engl.png|Kinetics of cardiac markers in myocardial infarction with or without reperfusion treatment.
}}

==See also==
* [[myocardial infarction#Cardiac biomarkers|Myocardial markers]] in myocardial infarction
* {{section link|Reference ranges for blood tests|Cardiac tests}}

==References==
{{reflist|2}}

==Further reading==
* {{cite journal |vauthors=Ross G, Bever F, Uddin Z, Devireddy L, Gardin J | title = Common scenarios to clarify the interpretation of cardiac markers | journal = J Am Osteopath Assoc | volume = 104 | issue = 4 | pages = 165–76 | year = 2004 | pmid = 15127984}}''[https://web.archive.org/web/20061005154846/http://www.jaoa.org/cgi/content/full/104/4/165 Full text]''

==External links==
* [https://web.archive.org/web/20060710094720/http://classes.kumc.edu/son/nurs420/unit5/cardiac_enzymes.htm Quick overview, with graph]
* [http://www.emedicine.com/emerg/topic932.htm eMedicine -- more detailed]

{{Abnormal clinical and laboratory findings}}
{{Blood tests}}
{{Authority control}}

[[Category:Biomarkers]]
[[Category:Chemical pathology]]
[[Category:Diagnostic cardiology]]