Cardiac Biomarkers

By : dr. samer zahran

Key wordsmyocardium : heart musclecoronary arteries : three major blood vessels

supplying blood and oxygen to the heart musclesangina :-. chest pain due to inadequate supply of

oxygen to heart musclenecrosis :- death of tissueplaque :- accumulated deposits of fat and other

substances in the blood vessels causing roughened and narrowed interior surface

Pectoris: - chest

• Atherosclerosis :- fatty accumulation causing hardening and plugging in blood vessels

• Thrombosis :- formation or development of a blood clot (thrombus) in a blood vessel

• Infarction :- dead muscle tissue often due to decreased blood flow from clogged coronary arteries

Atherosclerosis is hardening, roughing, and narrowing of the blood vessels due to fatty plaque accumulation. This culminates in plugging of the vessel, or a thrombosis or blood clot, due to activation of platelets and clotting of blood as it flows past the roughened lining of the vessel.

Cardiovascular DiseasesCongenital Heart diseases ( VSD, ASD)Congestive heart failure

cardiomyopathies inflammatory heart diseases cardiac conduction

dysfunctions/arrhythmia

Risk Factors for Cardiovascular Disease:-

1. Smoking

2. Hyperlipidemia

3. Hypertension

4. Diet and nutrition/weight

5. Diabetes Mellitus ( strong relationship )

6. Physical activity level

7. Family history

8. Gender ( men tend to be more affected )

9. Lifestyle ( Regular exercise )

The heart muscle, or myocardium, receives its blood flow from three coronary arteries rather than from the blood it constantly pumps through its chambers and out to the circulation for the rest of the body. If blood flow from the coronary arteries to the heart muscle is restricted, not enough oxygen reaches the heart. This is termed ischemia. It can cause chest pain or angina. If blood flow to a portion of the heart muscle is stopped entirely, it can cause cell death, necrosis, and heart attack, or acute myocardial infarction (AMI). The precipitating event that leads to blocking of blood flow is a clot or dislodged plaque particle that prevents blood flow to tissue.

Diagnosis of heart diseasesBecause a single, diagnostic laboratory test that

will quickly and accurately assess cardiac function does not exist, a combination of cardiac markers is required.

The search for cardiac marker that would be useful in evaluating many types of heart conditions.

The following features would be required for an ideal marker.

Features of an ideal markerHigh concentration in myocardiumAbsence from non-myocardial tissuesHigh sensitivity and specific in circulationRapid release into blood following myocardial injuryRemains in blood several days to allow detectionBlood levels correlate with extent of myocardial injury &

prognosisRapid, simple and automated commercial assays

availableRole designed for marker in dx & mgt based on clinical

studies & peer reviewed literature

Markers of myocardial infarction:- Enzymes ( AST, LDH, CK) Proteins ( Myoglobin, Troponin,Myosin)

Markers of inflammation and coagulation disorders

Hs-CRPFibrinogenD-Dimer

Markers of congestive heart failureBNP

What is Myocardial Infarction?Myocardial ischemia results from the reduction of

coronary blood flow to an extent that leads to insufficiency of oxygen supply to myocardial tissue

When this ischemia is prolonged & irreversible, myocardial cell death & necrosis occurs , this is defined as:

myocardial infarction:- is the death & necrosis of myocardial cells as a

result of coronary prolonged & irreversible ischemia

Markers of myocardial infarction:- A. Enzymes

1. AST (Aspartate Transaminase) :- lacks cardiac specificity Presently has no clinical significance for AMI

diagnosis Rises 6–8 h ,peak 18–24 h, N- 4 to 5 d

2. LD ( Lactate Dehydrogenase)Not specific for diagnosis of cardiac diseasesmyocytes ,skeletal muscles , liver, kidney, platelets & RBCs5 major LD isoenzymes, LD1–LD5 LD1 and LD2 isoenzymes being most indicative of cardiac involvement. (LD1 > LD2) (Total activity)LD →24–48 h, peak-3–6 d & N in 8–14 d

3. Creatine Kinase (CK):- Cytosolic enzyme3 major isoenzymes- CK- MM, MB & BB

CK-MB (CK2) is the benchmark and gold standard for the cardiac markers.Ck-MB ( 3-20 % of total CK) in the heart.Valuable tool for diagnosis of AMI because of its relatively high specificity for cardiac injury

It takes at least 4-6 h from the onset of the chest pain before CK-MB activities increases to significant levels in the blood.

Peak levels occur at 12-24 h and return to baseline levels with 2-3 days.

False positive results may be caused by clinical conditions such as muscle diseases and acute or chronic

Advantages: - useful for early diagnosis of MI

- useful for diagnosis reinfarctionDisadvantages: not used for delayed admission (more than 2 days) not 100% specific (elevated in skeletal muscle

damage)

CK-MB Mass :-Ck-MB activity assays have been recently replaced by CK-

MB Mass assays that measure the protein concentration of CK-MB rather than its catalytic activity.

Immunoassay technique using monoclonal antibodies Fewer interference and higher sensitivityOne hour earlier than activity – based method can detect

an increased concentration of serum CK-MB. So, useful for diagnosis of early cases & reinfarction BUT: not for diagnosis of delayed admission cases & less specific than troponin I CK-MB mass / CK activity ratio

if the ratio exceeds 3, it is indicative of AMI rather than skeletal muscle damage.

B. Cardiac Proteins:-

1. Myoglobin an oxygen binding heme protein 5 – 10 % of all cytoplasmic proteins released from striated muscles( cardiac and skeletal ) when damaged ( Not specific)More sensitive than CK and CK-MB activities during the first hours after chest pain onsetStart to rise within 1-4 hours and is detected in AMI patients between 6 and 9 hours from chest pain.Return to baseline 18-24 hours.

CK-MB determination are preferable over myoglobin in patients who admitted later than 10-12 hours after chest pain onset because myoglobin may have already returned to reference ranges.

The rapid disappearance of myoglobin from serum allows it to be used as an indicator of reinfarction in patients with recurrent chest pain after AMI.

2. Troponins Are contractile proteins found within muscle fibers

that help regulate contractions. There are three troponins that work as a complex.

They are troponin C (calcium-binding component), troponin I (inhibitory component), and troponin T (tropomyosin-binding component).

During the process of muscle necrosis, troponins I and T are released from the dying muscle fibers into the bloodstream

Increases in the concentration of troponins I and T above the reference levels in serum indicate heart muscle fiber damage and necrosis

Serum troponins generally are not elevated with angina

Troponins released from eart muscle remain in the bloodstream from 1 to 14 days after onset of AMI, making them the preferred marker for detection of an AMI.

Troponins, as cardiac markers, appear to have many advantages:-

quick release following heart muscle damage

longevity in the bloodstream following the heart attack.

Troponin T allows for both early and late diagnosis of AMI

cTnI & cTnT are used as biomarkers for MI diagnosis

Cardiac troponins (cTn) are different from skeletal muscle tropnins So, more specific for MI diagnosis

cTnI: 100 % cardiac specific With greater sensitivity for diagnosing minor damage

of MI Appears in blood within 6 hours after onset of infarction peak: around 24 hours Disappears from blood after about one week (stays

longer) So, useful for diagnosis of delayed admission

cases Prognostic marker (relation between level in blood &

extent of cardiac damage)

TEST ONSET PEAK DURATION

CK/CK-MB 4-8 hours 18-24 hours 36-48 hours

Troponins 3-12 hours 18-24 hours Up to 10 days

Myoglobin 1-4 hours 6-7 hours 24 hours

LDH 6-12 hours 24-48 hours 6-8 days

Cardiac Myosin light Chain ( MLC):- • Not specific for cardiac injury than CK-MB • Released from reversible ischemic tissue • Limited clinical significance as a routine cardiac

markers.

Markers of inflammation and coagulation disorders1. HS-CRPis a predictor of acute coronary syndrome riskThe increase in acute coronary syndrome is

minimal.Hs-CRP assay allow the detection of the small

increases in cardiac diseases.A positive association between hs-CRP and the

prevalence of coronary artery disease.

2. Fibrinogen :-Soluble glycoprotein produced in the liverInvolved in platelets aggregation and coagulation.Acute phase protein produced in response to

inflammation.A Relationship between elevated level of fibrinogen

and risk of cardiovascular diseases has been established.

3. D-Dimer :-The end product of the ongoing process of

thrombus formation and dissolution that occur at the site of active palques in acute coronary syndromes.

Because this process precedes myocardial cell damage and release of protein contents, it can be used for early detection

Lack specificity ( increased in other conditions that cause thrombus)

Remain elevated for days.

Markers of congestive heart failureBrain-type, or B natriuretic peptide (BNP):- Peptide hormone secreted primarily by cardiac

ventricles.Act on the renal glomerulus to stimulate urinary

excretion of sodium and to increase urine flow without affecting the glomerular filtration rate, blood pressure or renal blood flow. ( Fluid homeostasis )

Increased in diseases characterized by an expanded fluid volume(Renal Failure, hepatic cirrhosis)or stimulation of peptide production ( ventricular hypertrophy)

plasma level of BNP is elevated in patients with heart failure.

elevated level of BNP was found to be highly sensitive (96%) and specific (96%) for the diagnosis of CHF.

However, BNP should not be used alone or indiscriminately as a screening tool. Instead, the results of BNP measurements need to be evaluated in light of a clinical assessment in patients who have suspected heart failure.

Thank you