Cardiovascular disorders

Dr. Tranum Kaur

Suggested readings:
• Chapter 7 from Clinical Biochemistry by Nessar Ahmad (2nd
edition)
• Chapter 12 from Clinical Biochemistry by Peter Rae, Mike
Crane and Rebecca Pattenden (10th edition)

https://heartfoundation-prod.azurewebsites.net/getmedia/4b728949-b047-4fad-8276-070e737a0a3d/Heart-attack.jpg
 Define Define the term enzyme and biomarker

Discuss how measurement of enzyme activities and

Discuss
Learning
biomarker can be used to detect disease

outcomes: Distinguish between a heart attack (acute myocardial

Distinguish infarction) and chest pain (angina)

Diagnose acute myocardial infarction with the use of

Diagnose electrocardiogram (ECG) and cardiac biomarkers
 Cardiovascular disorders

• 17.9 million people die each year from CVDs, an estimated 31% of all
deaths worldwide (WHO).

• Myocardial Infarction (MI) can be defined pathologically as

myocardial necrosis due to prolonged ischemia.

• MI can be recognized with combination of clinical features,

biochemical biomarkers, imaging, and ECG.
Biochemical tests in myocardial infarction and ischemia

• Proteins of major diagnostic interest include Troponin I and troponin T

• Enzymes such as creatinine kinase (CK), CK-MB

aspartate aminotransferases (AST) and lactate dehydrogenase (LDH)

• Myoglobin
 What is an enzyme and
its clinical significance?

• An enzyme is a protein that function as a

biological catalyst for a specific chemical
reaction.

• The amount of enzyme present in clinical

sample such as blodd is proportional to
its activity.

Source: Chapter 7, Figure 7.1, page 158, Clinical biochemistry (2nd edition) textbook by Nessar Ahmed.
Amount of NAD+ produced or NADP+ determine enzyme activities

Source: Chapter 7, Figure 7.2, page 159, Clinical biochemistry (2nd edition) textbook by Nessar Ahmed.
 Watch and Learn Series

• Introducing spectrophotometry:
https://www.youtube.com/watch?v=B3gvQlMqYTc
Provided by De Montfort University HALS OER project

• How the spectrophotometer works:

https://www.youtube.com/watch?v=ZlWjAfJ4n
Provided by De Montfort University HALS OER project
What is a biomarker and what is its purpose?
• Biomarker is a biological molecule whose concentration in the blood
changes in response to specific disease.

• Examples – enzyme or protein whose concentration changes

significantly in response to a disease state.

• A biomarker can be used to monitor the presence or progress of a

diseases. or predict outcome in response to its treatment.
Source: Chapter 7, Clinical biochemistry (2nd edition) textbook by Nessar Ahmed.
 Cardiac diseases

• Heart disease occurs as a result of blockage of the blood vessels

supplying oxygen to the heart muscle.

• Prolonged ischemia or deficiency of oxygen can result in irreversible

cell damage and cell death can occur – this is known as infarction and
is followed by cellular breakdown and necrosis.

• Myocardial infarction (MI) and acute myocardial infarction (AMI) are

associated with cardiac pain and death of cardiac tissue (myocardial
cell necrosis).
Source: Chapter 7, Clinical biochemistry (2nd edition) textbook by Nessar Ahmed.
 Development of heart disease

Cartoon showing the stages in the development of a plaque

Source: Chapter 7, Figure 7.6, page 164, Clinical biochemistry (2nd edition) textbook by Nessar Ahmed.
 STEMI Versus NSTEMI
• ST elevation myocardial infarction (STEMI) is indicated by combination
of ST elevation on the ECG reading and changes in cardiac biomarkers.

• Non-ST elevation myocardial infarction (NSTEMI) is classified by

changes in cardiac biomarkers, but ECG readings do NOT show an ST
elevation and sometimes no change at all, or only an ST depression or
changes in the T wave.

Source: Chapter 7, Clinical biochemistry (2nd edition) textbook by Nessar Ahmed.

 Acute coronary syndrome

• Acute coronary syndrome – comprises of unstable angina, non-ST segment

elevation MI and ST segment elevation MI.

• Troponin measurements reveals an important biochemical changes in MI

along with:
- symptoms of ischemia
- ECG changes indicative of new ischemia
-Pathological Q wave in the ECG
-Imaging evidence of new loss of viable myocardium
-Identification of an intracoronary thrombus by angiography or autopsy.
Source: Chapter 7, Clinical biochemistry (2nd edition) textbook by Nessar Ahmed.
 Patterns of biochemical markers in the first
few days after a MI

- The biphasic response of

troponins with a rapid
rise and prolonged
elevation

- Rapid rise and fall of CK

and CK-MB activity
should be particularly
noted.

Source: Lecture Notes: Chapter 12, Clinical Biochemistry, 8e. By G. Beckett, S. Walker, P. Rae & P. Ashby. Published 2010
 Table. Time-course of plasma biochemical marker elevation after myocardial infarction

Abnormal activity Peak value of Duration of abnormality

Enzyme
detectable (h) abnormality (h) (days)

Troponin T or I 4–6 12–24 3–10

CK-MB 3–10 12–24 1.5–3

isoenzyme

Total CK 5–12 18–30 2–5

‘Heart- 8–16 30–48 5–14

specific’ LDH

Source: Lecture Notes: Chapter 12, Clinical Biochemistry, 8e. By G. Beckett, S. Walker, P. Rae & P. Ashby. Published 2010
 Troponin as cardiac biomarker

Trimeric troponin
complex; its three
subunit have
separate functions:

T - is responsible
for binding the
complex to
tropomyosin

I - inhibits muscle
contraction

C - binds calcium

Cartoon showing the organization of the troponin-tropomyosin complex in a cardiac muscle fiber

Source: Chapter 7, Figure 7.7, page 164, Clinical biochemistry (2nd edition) textbook by Nessar Ahmed.
 Troponin as an important cardiac biomarker
• Troponin complex is exclusively present in striated muscle fibres
and regulates the calcium-mediated interactions of actin and
myosin.

• It comprises equimolar quantities of the structurally unrelated

proteins troponin T, troponin I and troponin C.

• Sensitive Immunoassays for cardiac troponin T and I being specific

to cardiac damage have become biochemical gold standard for
detecting myocardial necrosis.
Watch and Learn Series
• Introduction to CVD: https://youtu.be/vx0bCEM_-jQ

• Mayo clinic 1 min: https://www.youtube.com/watch?v=Oqt9TgWcrxI

• What happens during a heart attack?

https://youtu.be/3_PYnWVoUzM

• New blood test speeds up heart attack diagnosis (cardiac troponin)

https://www.youtube.com/watch?v=MSZuFfigzGQ
Creatine Kinase (CK) in the diagnosis of myocardial infarction

• There are three principal CK isoenzymes, each comprising two polypeptide

chains, either B or M; these give the dimers BB, MB and MM

• CK1 or CK-MM found mainly in skeletal muscle. CK-MB may rise to 5–15% in
some patients with muscle disease, and also in athletes in training

• CK 2 or CKMB found predominately in cardiac muscle. It comprises 70–80%

CK-MM and 20–30% CK-MB. As a general rule, cardiac muscle is the only
tissue with more than 5% CK-MB.

• CK 3 or CKBB found mainly in smooth muscle. Other organs, such as brain,

contain less CK, often CK-BB. However, CK-BB rarely appears in plasma and is
not of diagnostic importance.
Source: Chapter 7, page 166, Clinical biochemistry (2nd edition) textbook by Nessar Ahmed.
 B-type natriuretic peptide (BNP) in the diagnosis of MI

• BNP is a neurohormone secreted by cardiac myocytes in response to

volume expansion and pressure overload.

• In heart failure the level of BNP increases, enabling differentiation of

cardiac and pulmonary causes of breathlessness.

• It has an evolving role in the diagnosis of heart failure in both primary

care and the emergency setting, since it costs considerably less than
echocardiography, and the result can be available much more rapidly.

Source: Chapter 7, page 170, Clinical biochemistry (2nd edition) textbook by Nessar Ahmed.
 Electrocardiogram (ECG)

• Myocardial damage can be detected by measuring the release of

cardiac biomarkers into the blood.

• The cardiac muscle in the atria of heart contract and then as they
relax the muscular walls of the ventricles begin their contraction.

• ECG is a record of this sequence of electrical events.

Source: Chapter 7, Clinical biochemistry (2nd edition) textbook by Nessar Ahmed.

 What does this ECG tell us?

https://wikem.org/wiki/File:PathoQ.png

Let’s Watch and Learn: Cardiac conduction system and its relationship with ECG
https://youtu.be/v3b-YhZmQu8
 ECG recordings

Various types of
abnormal traces

Normal heart rhythm

Source: Chapter 7, Figure 7.5, page 163, Clinical biochemistry (2nd edition) textbook by Nessar Ahmed.
 Case Study

• A well-trained marathon runner collapsed as he was approaching the

finishing line. An ECG was normal, but CK was elevated at 9500 U/L
(reference range 30–200 U/L), and the CK-MB was 14% of the total CK
(normally <6%). Troponin was undetectable. Comment on these
results.

Source: Lecture Notes: Clinical Biochemistry, 8e. By G. Beckett, S. Walker, P. Rae & P. Ashby. Published 2010
 Key Points
• The diagnosis of acute myocardial infarction is made on the basis of a rise
and/or fall in troponin above a defined level plus one of: symptoms of
ischaemia; ECG evidence of new ischaemia; development of pathological Q
waves on the ECG; or myocardial imaging information.

• Highly sensitive assays for troponin are becoming available and have
advantages. However, they are less specific and may be raised in conditions
other than myocardial injury.

• In myocardial infarction, biochemical markers usually become raised after a

lag period of 4–6 h after the onset of symptoms, reach a peak at 18–30 h
and have returned to normal within 3–7 days.

Clinical Biochemistry Lecture Notes, Tenth Edition. Peter Rae, Mike Crane and Rebecca Pattenden
Thank You!

Any questions?