Cardiac biomarkers Flashcards

1
Q

What is CVD?

A

Conditions that are cause by atherosclerosis, the narrowing of the artery lumen due to lipid/protein deposition in the arterial wall

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2
Q

What can CVD progress to?

A

coronary heart disease (ischaemic heart disease and coronary artery disease), where the coronary circulation can’t meet oxygen demands of the heart

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3
Q

What is a stable angina?

A

Stable angina describes the narrowing of coronary artery

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4
Q

What are acute coronary syndromes?

A

Range of disorders that are caused by sudden obstruction of coronary arteries due to plaque rupture. 3 catagories:

  • unstable angina
  • acute myocardial infarction: NSTEMI and STEMI
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5
Q

Match the following causes of ACS

  1. Unstable angina
  2. Acute myocardial infarction
  3. NSTEMI
  4. STEMI

A. Non-ST elevation MI
B. Narrowing of arteries causing myocardial ischaemia at rest
C. Blockage in coronary arteries causing cardiac ischaemia+necrosis
D. ST elevation MI

A

1B
2C
3A
4D

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6
Q

How do you differentiate between the two acute myocardial infarctions?

A

Based on ECG findings

  • STEMI; a major blockage in coronary artery causing elevated ST segment
  • NSTEMI: non complete blockage of CA/complete blockage of minor artery causing changes to ECG but no ST elevation
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7
Q

What cellular damage cause necrosis in the heart?

A

Damage to myocytes results in necoris - marker for necrosis

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8
Q

What is the current cardiac biomarker? and how does it compare to previous ones?

A

The previous were non-specific, e.g. LDH, AST/ALT, CK, CK-MB and myoglobin

Troponin is the current marker as it is more specific.

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9
Q

What is troponin and its physiological function?

A

A protein complex made up of 3 units troponin T, I and C. Control the interaction between actin and myosin to control striated muscle contraction

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10
Q

Match the following

  1. Troponin I
  2. Troponin C
  3. Troponin T

A. Bind tropomyosin
B. ATPase inhibitor of actin-myosin interaction
C. Binds calcium

A

1B
2C
3A

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11
Q

What is the detection method of troponin and how does it work?

A

Uses immunoassay, which is possible because they differ in AA composition. Thus allowing us to distinguish between them.

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12
Q

What causes variability to troponin immunoassays?

A

Assays are not standardised so they give variable results.

- Variability is due to lack of reference material and use of different antibodies + cut-offs

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13
Q

Upon admission what is the process of diagnosing ACS?

A

ECG is the first line test.

  • Persistent ST-elevation shows STEMI
  • ST/T abnormalities or normal/undeteremined ECG require cardiac marker testing

Cardiac markers
- used to determine NSTEMI or unstable angina

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14
Q

What is the clinical utility for troponin?

A

cTnT and cTnI are biomarkers of cardiac muscle necrosis

  • As oxygen availability decreases there is an increase in troponin causing arrest of muscle contraction
  • Thus myocytes cant incuce contraction for heart beat
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15
Q

What makes troponin an ideal marker?

A

High specificity for myocardial damage (cardiac tissue damage)

  • Gold standard for MI
  • Increase occurs 1hr within MI
  • Peaks at 18-24hrs
  • Elevated for 2 weeks
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16
Q

What is the definition of diagnosing MI?

A

“Detection of a rise or fall of cardiac biomarker (preferably cardiac troponin) with at least one value above 99th percentile upper reference limits…”.

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17
Q

What are some interferences of troponin release/other causes?

A
  • Any tissue damage to the heart, e.g. heart failure

Elevated in:

  • hypothyroidism
  • drug toxicity
  • pulmonary embolism
  • tachyarrythmias
  • hypertensive crisis
  • chronic or acute renal dysfunction
  • rhabdomyolysis
18
Q

What is a rise or fall in troponin?

A

99th centile

- Meaning a value +/- 3SD from mean

19
Q

What is one major flaw of cTn assays causing potentially significant rises in troponin?

A

The analytical sensitivity

- Lowest amount of troponin can be reliably quantified by standard troponin assays is higher than the 99th percentile

20
Q

What do the high sensitivity troponin assays mean?

A

Improved analytical sensitivity of assay allowing the detection of smaller but potentially more significant changes in troponin that may indicate MI

21
Q

What is NICE definition of high sensitivity troponin assays

A

high sensitivity troponin tests are those that have a coefficient of variation of 10% or less at the 99th percentile (upper limit) and able to detect cardiac troponin in at least 50% of the reference population

22
Q

How is the rise and fall detected in omitted patients?

A

1st sample upon admission (0hrs) followed by sampling at various times
- Hs-cTn have recorded earlier detection of increased troponin, and thus, may require less frequent time intervals

23
Q

How can change in troponin be measured?

A
  • Delta changes of 20-100% used to define a change
  • Delta changes will depend on troponin conc of 1st sample
  • Some suggest the use of absolute change as a better discriminator
24
Q

What are the NICE guidelines for troponin measurements intervals?

A
  • Roche hs-TnT and abbotts hs-TnI for early rule out of NSTEMI in suspected ACS
  • Sample at 0hrs and 3hrs
  • ESC guidelines also recommend to test at 0hrs and 3hrs
25
Q

Comment on the current NICE guidelines for testing patients?

A
  • several hs-Tn assays as options to rule out NSTEMI
  • Use gender specific 99th centiles
  • A single sample on presentation using threshold near limit of detection. If positive does not rule in NSTEMI
  • Multiple sampling strategies using second sample at 30min ->3hrs and use 99th percentile threshold

High risk
- Hs-Tn
Low risk
- If first troponin test is + then use hs-Tn to to rule out NSTEMI

26
Q

What are some newer cardiac markers?

A

Ischaemia modified albumin (IMA)

  • Marker of cardiac ischaemia
  • Role in MI diagnosis

Heart type fatty acid binding protein

  • Early AMI/ACS biomarker used in conjunction with troponin
  • combined with troponin for rapid MI exclusion

Copeptin

  • role as early rule out marker for AMI
  • data show that troponin and copeptin can be used as early ACS exclusion
27
Q

What is heart failure?

A

Failure of the heart ot provide sufficient cardiac output to meet needs of tissue

28
Q

Symptoms of HF

A

Non-specific: dysnopea, peripheral oedema, fatigu

29
Q

What causes HF?

A

Structural/functional cardiac disease, e.g. ischaemic heart disease, coronary artery disease, previous MU, arrythmias, cardiomyopathy, valve defects

30
Q

What is the pathogenesis of HF?

A

RAAS forms a worsening cycle.

  1. HF causes reduced BP/cardiac output
  2. RAAS activation causing fluid retention and vasoconstriction causing fluid overload (increases burden on heart)
31
Q

What is the problem with non-cardiac biomarker based diagnosisi of HF?

A

using a transthoracic 2D echocardiography to identify valve abnormalities and left ventricular ejection fraction (LVEF) is very expensive

32
Q

What is a good cardiac marker for HF?

A
Natriuretic peptides (vasoactive hormones)
- Three in the produced in the heart: ANP (atria), BNP (ventricles), CNP (vasculature, paracrine vasodilator effects)
33
Q

What receptors do natriuretic peptides act on?

A

Natriuretic peptide receptors (NPRs)

  • NPRA: mediates action of ANP/BNP
  • NPRB: mediates action of CNP
  • NPRC: clears NPs from circulatio
34
Q

Where are the different natriuretic peptides secreted?

A

ANP+BNP- synthesised and secreted from storage granules in the heart in response to cardiac stretch

35
Q

What are the actions of ANP and BNP?

A
  • Oppose those of RAAS
  • Net increase of GFR
  • dilate afferent arteriole and constricts efferent arterioles
  • inhibits Na resorption in CD
  • inhibits aldosterone secretion
  • suppress salt appetite and ADH secretion
  • suppress sympathetic catceholamine release
36
Q

How is natriuretic peptides used in HF?

A

Plasma conc of natriuretic peptides increase in HF. Can be used to rule out/in HF in primary care

37
Q

What assays are available to measure natriuretic peptides?

A

BNP and N-terminal proBNP assays

38
Q

What is the difference between BNP and NT-proBNP?

A

BNP is the active form, which occurs at a higher concentration than NT-proBNP. But NT-proBNP has a longer half life and correlate better to GFR.

  • BNP: EDTA plasma (labile)
  • NT-proBNP: serum/plasma (stable)
39
Q

What constitutes a raised BNP?

A

BNP: 100-400ng/L

NT-proBNP: 400-2000ng/L

40
Q

What are some positive interferences of BNP measurements?

A
  • ischaemia/tachycardia
  • left ventricular hypertrophy
  • ACS
  • ventricular overload
  • Hypoxaemia
  • renal dysfunction
  • sepsis
  • old age
  • exercise
  • cirrhosis
41
Q

What are some negative interferences of BNP measurements?

A
  • obesity
  • diuretics
  • ACEi
  • angiotensin receptor blockers
  • aldosterone antagonist
42
Q

What are the NICE BNP/NT-proBNP guidelines?

A

Recommend the measurement of BNP or NT-pro BNP if acute heart failure is suspected, which if positive can be followed by an echocardiography.