Cardiac bio-markers

DIAGNOSTIC SERUM CARDIAC MARKERS  AND AMI

WHY BIO MARKERS?

¢ Distinguish cardiac ischemia from MI.

¢ Among chest pain in emergency room:

        10% were suffered from acute MI

        20% were unstable angina;

        >30% non-cardiac origin

         The remainder: Pain of cardiac origin with or without ischemia

DISTINGUISHING CARDIAC ISCHEMIA FROM MI

¢ History and physical examination finding are crucial, and yet they alone are seldom helpful in this regard

¢ ECG: provides a positive specific diagnosis in only about 5% of patient with chest pain and 40% of patient with acute MI.

¢ Cardiac biomarkers: evidences of myocardial necrosis for MI

   The best way to distinguish cardiac ischemia from MI is to combine History (chest pain), ECG and evidence of myocardial necrosis (biomarkers).

WHAT ARE THE BIO-MARKERS?

¢ Variety of macromolecules, including enzymes, myogloin, and contractile proteins.

¢ Commonly used markers:

   Kinase and its isoenzyme

   Tropnin T and I

   Lactate dehydrogenase (LDH) isoenzyme

   Myoglobin.

   BNP

   C-Reactive protein

CARDIAC TROPONIN I/T

¢ Troponin is the regulatory protein of striated muscle

¢ Three subunits: C, I, and T. 

¢ Tropnin I and T are found on myocaridum, yet Tropnin T are also found on skeletal muscle, while Tropnin I is only expressed in myocardium.

¢ Tropnin C, however, does not play any significant role in clinical diagnosis.

CARDIAC TROPONIN T (CTNT) 

¢ Cardiac troponin T(cTNT): released when myocardium being damaged.

¢ Excellent sensitivity and specificity, it is one of the early indicator for AMI.

¢ Normal Range: < 0.2 μg/L

Clinical significance:

¢ Diagnosing AMI

¢ Diagnosing minor myocardial damage in unstable angina.

¢ Prediction indicator for adverse cardiovascular event of patients on dialysis.

¢ Indicator for assessing myocardial damage after PCI and PTCA, or other myocardial damage, eg. trauma, drug, etc

 

            Sensitivity: 100%, Specificity: 96%

CARDIAC TROPONIN I (CTNI)

¢ Cardiac troponin I(cTnI), is present solely in myocardium, and released when myocardium being damaged.

¢ Normal Range: < 0.2 μg/L

¢ It has the same characteristic as cTNT except that it is less sensitive in early stage, but it is somewhat more specific than cTNT.

CREATINE KINASE (CK) AND ITS ISOENZYMES 

¢ The use of CK and its isoenzymes were shown to be highly sensitive, specific, and cost-effective for diagnosing myocardial infarction and remained the standard over the past three decades.

¢ CK splits creatine phosphate in the presence of ADP to yield creatine and ATP. CK is released when tissue damage occur.

¢ CK is rich everywhere in the body, therefore it is not specific for heart.

¢ Three isoenzymes: located in the cytoplasm of cells are CK-MM, CK-MB, and CK-BB.

¢ CK-MB are most important for heart.

¢ Normal range for CK:

    Males, 38-174 U/L;

    Females, 26-140 U/L      (method-dependent)

¢ Increased in myocardial infarction, myocarditis, muscle damage and any other situations with muscle necrosis.

    

                  Sensitivity: 73%, Specificity: 85%

¢ Normal range for CK-MB:

   Serum enzyme activity, <12 U/L;

   or <5% of total CK,

   or <5μg/L mass units

¢ For cardiac markers, CK-MB is much more sensitive and specific than CK.

 

               Sensitivity: 88%, Specificity: 93%

 

MYOGLOBULIN

¢ Myoglobulin(Mb) exists in striate muscles and cardiac muscle.

¢ It is a protein combined oxgen in muscles. Like hemoglobulin, it can combine and release oxgen from muscle. When muscle necrosis occurs, it is released from muscles immediately.

¢ Specificity for myocardial infarction: very low.

¢ Normal ranges in serum: <85μg/L

¢ It can appear in serum very early after chest pain in the patient with myocardial infarction.

 

             Sensitivity: 59%, Specificity: 95%

 

LACTATE DEHYDROGENASE ISOENZYMES

¢ 5 isoenzymes: LDH1, LDH2, LDH3, LDH4 and LDH5.

¢ In patient with myocardial infarction, it appears in serum later but persist longer than CK-MB.

¢ It has be replaced with cTnI and T.

¢ Normal range in serum: LDH1/LDH2<0.85

 

B-type NATRIURETIC PEPTIDE

p  The natriuretic peptide family consists of three peptides:

   atrial natriuretic peptide (ANP)

   brain (or B-type) natriuretic peptide (BNP)

   C-type natriuretic peptide (CNP).

p  These neurohormones are released in response to hemodynamic stress and are involved in the regulation of intravascular volume homeostasis

p  N-terminal proBNP (NT-proBNP) is a cleavage product of the precursor protein B-type natriuretic peptide (BNP). 

 

BNP): from ventricle

Ø  C-type NP (CNP): from VEC

C-REACTIVE PROTEIN

¢ C-reactive protein (CRP)

¢ Normal Range: <3mg/L

¢ Low specificity, increases in inflammatory state

RATIONALE FOR SELECTING AN EARLY
DIAGNOSTIC CARDIAC MARKER

¢ In selecting a marker for early diagnosis of myocardial infarction upon admission to the emergency department, CK-MB and myoglobulin appear the essential choices. CKMB is more specific than myoglobulin;  myoglobulin appears a little earlier than CK-MB.

¢ For diagnosis of patients persenting 10 H or later after onset of symptoms, cTn I and T is preferred over CK-MB and myoglobulin. CTn I and T are more sensitive and specific.

PLASMA TEMPORAL PROFILES OF CARDIAC
DIAGNOSTIC MARKERS

Case Study:

Male/45 Chest pain 2 hours Which biomarker will be abnormal?

(1)cTNT

(2)cTNI

(3)Hemoglobin

(4)CK-MB

Female/70 chest pain 7 days,which biomarker will be abnormal?

(1)cTNT

(2)cTNI

(3)Hemoglobin

(4)CK-MB

How do cardiac biomarkers change after venous thrombolysis?