Biomarkers Flashcards
What is the ideal cardiac biomarker?
- 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
What is a cardiovascular risk calculator?
- 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
Examples of individual biomarkers
-ApoB:ApoA1 ratio
-Lp(a)=LDL-apo(a)
Measures the amount of protein
Examples of inflammatory markers
- Myeloperoxidase (MPO)
- Matrix metalloproteinases (MMP)
- Interleukin 18
- Pregnancy associated plasma protein alpha
- Placental Growth Factor
- hsCRP= high-sensitivity CRP
Describe high-sensitivity C-Reactive Protein
Less than 1.0= low risk
1.0-3.0= intermediate risk
More than 3.0= high risk
Units (mg/L)
What are the problems with hs-CRP?
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
Describe Homocysteine
- 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
Describe high sensitivity Troponin 1
- 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
What is myocardial injury?
- Coronary heart disease
- Ischaemia
- Trauma, hypoxaemia, anaemia, ventricular tachyarrhythmias, cardiomyopathy
What is Acute Coronary Syndrome?
- 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
What is the definition of MI?
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
Name biomarkers of myocardial injury
- Myoglobin
- Total creatinine kinase
- CK-MB
- Lactate dehydrogenase
- Cardiac troponin
Describe myoglobin
Rapid response
Not specific to heart
Not useful for late presentation
Describe Total creatinine kinase
Rapid repsonse
Not specific to heart
Cheap
Describe CK-MB
Rapid response
More specific to heart than total CK
Relatively expensive
Describe Lactate dehydrogenase
Slow response
Previously used for late presentation
Present in most tissues
Describe cardiac troponin
Rapid response
Sensitive- smaller MI
Best specificity for cardiac tissue
Suitable for late presentation
What is the troponin complex?
- 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
What do clinical assays measure?
- Have improved over last 20 years to provide ever-lower analytical sensitivity
- Latest assays termed hs
- Detectable in those without myocardial damage
What are major implications of cardiac troponin?
- 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
What is heart failure?
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
What are the causes of myocardial heart failure?
- Ischaemic heart disease (35-40%)
- Idiopathic dilated cardiomyopathy (30-34%)
- Cardiomyopathy (undilated): hypertrophic/ obstructive, restrictive (amyloidosis, sarcoidosis)
- Congenital heart disease (ASD, VSD)
What are the causes of valvular heart failure?
Stenosis/ regurg of mitral, tricuspid, aortic or pulmonary valves
