Acute coronary syndrome

Dr LM Murray

Chemical Pathology

Block SA13 - 2014

Acute myocardial infarction (MI)

• MI is still the leading cause of death in many

countries

• It is characterized by severe chest pain, and

takes place when there is interrupted blood

supply to myocytes and necrosis follows

Coronary artery disease

• Clinical presentation: Angina pectoris:

– Chest pain: dull or stabbing pain, radiating to the arm or jaw

– Associated with shortness of breath, diaphoresis, nausea and vomiting

• Clinical classification of angina:

– Stable angina: pain occurs only with exertion

– Unstable angina: pain occurs at rest

– Myocardial infarction: pain persists without interruption and irreversible myocyte damage has occurred

Causes of coronary artery disease

Type Comments

Atherosclerosis or

ischemic heart disease (IHD)

Most common. Risk factors:

HT, ↑ Chol, DM, smoking and family

history

Spasm Most prevalent in Japanese.

Mediated by histamine, serotonin,

catecholamine and endothelium-

derived factors

Emboli Rare, may occur from

vegetations in patients with endocarditis

Congenital 1-2% of population,

mostly asymptomatic

Atherosclerosis

• Affects medium and large vessels

• Inflammatory process that begins early in life

and results in the deposition of lipid, fibrin

and calcium in the intimal layers of the

arteries; which harden, narrow and eventually

occlude the vessel

• Exact mechanism is unclear

Response to injury theory• Endothelium is damaged by oxidized lipoprotein,

infectious agents, ↑ glucose, homocysteine, smoking or HT ??

• LDL migrates into intima

• LDL oxidizes produces VCAM-1 and MCP-1

• Attracts monocytes into intima Macrophages

• Macrophages take up oxidezed LDL Foam cells

• Growth factors and cytokines produced proliferation of smooth muscle cells and secrete collagen cap formation covering lipids

• This plaques grows and eventually blocks the lumen

• ↓ blood flow leads to ischemia

Risk factors for IHD• Primary

– Genetic predisposition

– HT

– Smoking

– Hyperlipidaemia

• Life style factors

– Nutrition

• Fat

• Antioxidants

• Salt intake

• Environmental influence in

early life

• Secondary

– Age

– Male sex

– Lack of exercise

– Obesity

– DM

– Stress

– Alcohol

– Ethnicity

– Socioeconomic factors

– Homocysteine

– CRP (C-reactive protein)

Acute coronary syndrome

• Definition: ACS is used when symptoms and signs are

indicative of myocardial ischemia

• Classification:

– MI with typical ST segment elevation (STEMI)

– MI without ST segment elevation (NSTEMI)

– Unstable angina

• It is vital to be able to diagnose MI early to start

thrombolytic treatment and improve patient survival

WHO criteria for MI diagnosis

• Include two of the three criteria:

– History of chest pain

– ECG changes

– Elevated troponin or CK-MB

Biochemical diagnosis of acute MI

• Injured myocardial cells leak enzymes and

proteins and these enzymes and proteins (or

cardiac biomarkers) are measured to

determine if a MI is present

Characteristics of cardiac markers

Cardiac

marker

Rise (hour) Peak (hour) Time to

return to

normal (day)

CK 3-8 10-24 3-4

CK-MB 3-8 10-24 2-3

LD1 8-12 72-144 8-14

Myoglobin 1-3 6-9 1

Troponin I 3-8 24-48 4-10

Troponin T 3-8 24-48 4-10

Time course of cardiac enzymes after

acute MI

CK-MB

• The pattern of CK-MB release may be influenced by:

– The size of the infarct

– Concomitant skeletal muscle injury

– Composition of myocardium

– Reperfusion (after thrombolytic therapy or spontaneous)

Cardiac marker

Rise (hour) Peak (hour) Time to return to normal (day)

CK 3-8 10-24 3-4

CK-MB 3-8 10-24 2-3

• Injury to skeletal muscle may ↑ the absolute amount

of CKMB but the relative concentration is usually <5

%

• Measurement of CK-MB mass is more specific for MI

than CK-MB activity measurement.

• Sensitivity of CK-MB:

– On admission: 17-62 %

– 3 hrs: 92-100 %

• The sensitivity of CK-MB improves with serial

measurements at 0, 3, 6, and 9 hours after

presentation

Troponins

• Troponin consists of

three proteins T, C

and I where it is a

regulator complex of

muscle

• Troponin T and I are

very cardiac specific

• Sensitivity of troponin I and T for MI diagnosis 100% by 12 hours after onset of pain

• Disadvantages of Troponins

– Troponin T is cleared by the kidneys, thus may be ↑ in renal failure

– Not good at detection of MI in early hours

– But more sensitive troponin assays are developed which could diagnose MI within 3 hours after chest pain onset.

• Elevated troponin are seen in other conditions

indicative of myocardial damage, where it is a poor

prognostic sign

– Sepsis Pulmonary Embolism

– Hypothyroidism Cardiac failure

– Pericarditis Myocarditis

Cardiac marker

Rise (hour) Peak (hour) Time to return to normal (day)

Troponin I 3-8 24-48 4-10

TroponinT 3-8 24-48 4-10

• Increase in troponin

after

• A: Acute Myocardial

infarction

• B: Minor Myocardial

infarction

• C: Myocarditis

• www.circ.ahajournal.org

Myoglobin

• Myoglobin is an oxygen-carrying haem protein present in skeletal and cardiac muscle

• Due to is small size it is released earlier than other proteins from damaged cells

• Useful biomarker to diagnose early MI

• A negative result will exclude MI, but a positive result needs to be confirmed

Cardiac marker

Rise (hour) Peak (hour) Time to return to normal (day)

Myoglobin 1-3 6-9 1

Important clinical facts

• CK-MB and troponins do not start to rise until

3-8 hours after infarction, thus not useful to

diagnose early MI

• A negative myoglobin test in the early hours

will exclude MI

• By 12 hours, troponins are 100 % sensitive

thus important in late diagnosis of MI

• Acute IM presenting within 12 hours are treated with thrombolytic treatment

• To assess if thrombolytic treatment has been successful we need to look at the increased release of cardiac markers, wash out phenomenon.

• Myoglobin is the best reperfusion marker

• Diagnosing myocardial ischemia after cardiac and non-cardiac surgery can be done with troponins as CK and CK-MB are released by injured skeletal tissue

• A high troponin in patients with unstable angina predicts higher mortality

Investigation of patients suspected of

heart failure

• CXR

• ECG

• Laboratory:

– FBC: exclude anaemia

– UCE: ↑/ ↓ Potassium, ↓ Sodium, renal function

– Mg: ↓ Mg due to long term diuretic use

– LFT and thyroid function test

– BNP or NT-pro BNP

• BNP (Brain naturetic peptide) is released in

heart failure due to ↓ left ventricular function

which leads to ↓ cardiac output

• Both BNP and NT-proBNP (fragment of

proBNP) are elevated in heart failure.

• Many laboratories measure NT-proBNP

because is more stable in vitro (tube)

• Thus if BNP or NT-proBNP is negative heart

failure can be excluded

• BNP and NT-proBNP is a prognostic marker in

heart failure as well

References

1. Swaminathan R (ed). Handbook of Clinical Biochemistry, 2th Ed 2011. World Scientific New Jersey: p 299-354.

2. Marshall WJ, Bangert SK (eds). Clinical Chemistry, 6th Ed 2008. Mosby Edinburgh: p 271-293.

3. McPhee SJ, Hammer GD (eds). Pathophysiology of Disease: An Introduction to Clinical Medicine, 6th

Ed 2010. McGraw Hill Medical New York: p 275-278.

4. www.circ.ahajournal.org