Biomarkers

Question 1

What is the ideal cardiac biomarker?

Answer 1

• Highs sensitivity= high analytical sensitivity and abundant in cardiac tissue
• High specificity= absent from non-myocardial tissue, not detectable in blood from non-diseased subjects
• Release= rapid release for early diagnosis, long half-life for late diagnosis
• Analytical= cost-effective, short turnaround time, precise, accurate
• Clinical= evidence for improved patient outcomes

Question 2

What is a cardiovascular risk calculator?

Answer 2

• Used widely for estimating risk in patients without known CV disease
• Not applicable in high risk groups (known CV disease, FH, diabetes, CKD)
• 10-year risk
• Total cholesterol, HDL cholesterol

Question 3

Examples of individual biomarkers

Answer 3

-ApoB:ApoA1 ratio
-Lp(a)=LDL-apo(a)
Measures the amount of protein

Question 4

Examples of inflammatory markers

Answer 4

• Myeloperoxidase (MPO)
• Matrix metalloproteinases (MMP)
• Interleukin 18
• Pregnancy associated plasma protein alpha
• Placental Growth Factor
• hsCRP= high-sensitivity CRP

Question 5

Describe high-sensitivity C-Reactive Protein

Answer 5

Less than 1.0= low risk
1.0-3.0= intermediate risk
More than 3.0= high risk
Units (mg/L)

Question 6

What are the problems with hs-CRP?

Answer 6

High intra-individual variability= may require several measurements
Can be incorporated into multiple risk factor calculators- some doubt as to whether superior to traditional CV risk factors

Question 7

Describe Homocysteine

Answer 7

• Intermediate in the synthesis of amino-acids: cysteine and methionine
• Linked to atherosclerosis through vascular wall damage
• May be elevated in B-vitamin deficiency: Vit B6,9,12
• Very high CV risk in individuals with classical homocystinuria (autosomal recessive)
• Relationship between carrier mutation status and CV risk is more controversial
• Tends to be measured when CV disease presents in young patients in the absence of unusual risk factors

Question 8

Describe high sensitivity Troponin 1

Answer 8

• Protein specific to cardiac muscle
• Established use in diagnosis of myocardial infarction
• More recently has been demonstrated to predict long term CV risk
• Appears to be superior to hsCRP
• Remains unclear as to whether would significantly improve risk calculation using traditional risk factors alone

Question 9

What is myocardial injury?

Answer 9

• Coronary heart disease
• Ischaemia
• Trauma, hypoxaemia, anaemia, ventricular tachyarrhythmias, cardiomyopathy

Question 10

What is Acute Coronary Syndrome?

Answer 10

• Myocardial infraction is one cause of clinical presentation
• Presents with chest pain/discomfort, caused by acute ischaemia (secondary to coronary heart disease)
• Includes acute MI (STEMI, NSTEMI), unstable angina

Question 11

What is the definition of MI?

Answer 11

Detection of a rise and/or fall of cTn values with at least one value above the 99th percentile URL (upper reference limit) and

• Symptoms of acute myocardial ischaemia
• New ischaemic ECG changes
• Imaging evidence of new loss of viable myocardium
• Identification of a coronary thrombus by angiography

Question 12

Name biomarkers of myocardial injury

Answer 12

• Myoglobin
• Total creatinine kinase
• CK-MB
• Lactate dehydrogenase
• Cardiac troponin

Question 13

Describe myoglobin

Answer 13

Rapid response
Not specific to heart
Not useful for late presentation

Question 14

Describe Total creatinine kinase

Answer 14

Rapid repsonse
Not specific to heart
Cheap

Question 15

Describe CK-MB

Answer 15

Rapid response
More specific to heart than total CK
Relatively expensive

Question 16

Describe Lactate dehydrogenase

Answer 16

Slow response
Previously used for late presentation
Present in most tissues

Question 17

Describe cardiac troponin

Answer 17

Rapid response
Sensitive- smaller MI
Best specificity for cardiac tissue
Suitable for late presentation

Question 18

What is the troponin complex?

Answer 18

• 1:1:1 complex of 3 regulatory proteins= TnT, TnI, TnC
• Exclusively present in straited muscle
• Regulates the interaction between actin and myosin
• Cardiac specific forms exist- cTnI, cTnT

Question 19

What do clinical assays measure?

Answer 19

• Have improved over last 20 years to provide ever-lower analytical sensitivity
• Latest assays termed hs
• Detectable in those without myocardial damage

Question 20

What are major implications of cardiac troponin?

Answer 20

• Changed definition of MI- central role for blood test
• Higher detection rate of MI
• Improved outcomes for MI patients especially women
• Early rule-out protocols
• Greater risk of false positives
• Threshold for acute MI fallen to 34 ng/L men, 16 ng/L women

Question 21

What is heart failure?

Answer 21

Clinical syndrome in which the heart is unable to maintain a cardiac output that satisfies the metabolic demands of the body
Reduced volume and dilated ventricle

Question 22

What are the causes of myocardial heart failure?

Answer 22

• Ischaemic heart disease (35-40%)
• Idiopathic dilated cardiomyopathy (30-34%)
• Cardiomyopathy (undilated): hypertrophic/ obstructive, restrictive (amyloidosis, sarcoidosis)
• Congenital heart disease (ASD, VSD)

Question 23

What are the causes of valvular heart failure?

Answer 23

Stenosis/ regurg of mitral, tricuspid, aortic or pulmonary valves