Laboratory Investigation of Cardiac Disease Flashcards
What are the characteristics of ideal biomarkers?
What do we mean by cardiovascular disease?
It is the umbrella term for a number of linked pathologies
- Coronary heart disease, cerebrovascular disease (stroke), peripheral arterial disease, peripheral arterial disease, rheumatic and congenital heart disease, venous thromboembolism (DVT, lymphatic disease
What are the two main causes of death of cardiovascular diseases?
Myocardial infarctions and heart failure
How does a myocardial infarction begin?
Begins as a disorder of the coronary vessels when there is development of atheroscleorosis and plaque formation
- Long process (decades before patients have symptoms and show signs of disease)
How are plaques formed?
- Inflammation in the vessels activates endothelial cells lining the blood vessel
- LDL particles penetrate the endothelium and are retained in the intima where they undergo oxidative modification
- Oxidative LDL will release pro-inflammatory lipids which will stimulate the endothelila cells to express adhesion molecules
- Circulating monocytes (rolling hypothesis) will adhere to adhesion molecules (VCAM-1) expressed by endothelial cells
- Monocytes will move through the endothelial spaces due to increased permeabillity and endothelial dysfunction of the intima
- Onoce monocytes migrate into the intima they will start to differentiate into macrophages
- These macrophages will gain upregulation of receptors on macrophage surface allowing further LDL uptake
- Eventually there will be the formation of foam cells which will accumulate from macrophages (build up cholesterol and become calcified)
- Macrophages will release their own inflammatory mediators attracting more macrophages to the site
What can happen if there is significant build up and deposition of cholesterol in the coronary vessels?
- Atheromatous plaque forms
- If the plaque ruptures it will induce thrombosis which will eventually cause a blocked artery
- ICSCHAEMIA = NECROSIS = Myocardial infarction
What are some causes of chest pain?
- Some causes of chest pain are as the follows
- Broken rib
- Collapsed lung
- Nerve infection (shingles)
- ‘Pulled’ muscle
- Infection
- Heart burn (hernia)
- Pericarditis
- Blood clot in the lungs
- Angina
- Myocardial Infarction
What is the assesment of Ischaemic Heart Disease?
- Medical History
- Risk factors
- Presenting signs and symptoms
- ECG
- Biomarkers!
- Imaging/scans
What can biomarkers of cardiac dysfunction contribute to?
- Rule in/ out an acute MI
- Confirm an old MI
- Help to define therapy
- Monitor success of therapy
- Diagnosis of heart failure
- Risk stratification of death
What is the effect of ischaemia on extent on myocardial injury?
- Irreversible injury will require 30 minutes of ischaemia
- High risk that 80% of cardiac cells die within 3 hours and almost 100% by 6 hours
- Cellular contents leaks out through membrane dependant on size and solubillity
- (Ions leak out first, then proteins and enzymes)
- Concentration gradient from inside to outside important (high gradient improves detection of early damage)
- Cellular contents leaks out through membrane dependant on size and solubillity
What are markers of myocardial damage?
There is a peak in these markers 7-36 hours following a myocardial infarction
- Troponin T and Troponin I (heart muscle specific marker)
-
Creatine kinase
- Increases by 90% in MIs, also released from skeletal muscle
- Heart specific isoforms of creatine phosphokinase
-
Myoglobin raised early
- Less specific for heart damage
What are the types of troponin?
3 types
- Troponin T (tropomyosin binding)
- Troponin I (inhibits actomyosin ATPase)
- Troponin C (calcium binding)
- Cardiac troponin T and I differ in skeletal muscle compared to cardiac
- Poses an advantage that they are highly specific cardiac markers opposed to creatine kinase
What are the uses of cardiac troponin?
- An index of cardiac damage
- Blood levels related to severity of cardiac damage
- Predicts major cardiac events like myocardial infarction
How do we measure troponins?
- Troponins are a protein
- To detect this we use ELISA
- Two different antibodies measure the protein of interest (troponin) in the blood with a signal
What is heart failure? What are the causes of heart failure?
A complex clincial syndrome that can result from any structural or functional cardiac disorder that impairs the abillity of the ventricle to fill or eject with blood.
Causes of Heart Failure
- Coronary artery disease
- Chronic hypertension
- Cardiomyopathy
- Heart Valve disease
- Arrhythmias
- Infective endocarditis
- Pulmonary hypertension
- Alcohol and Drugs
What are the different types of natriuretic peptides?
ANP, BNP and CNP
*all are released as high molecular weight precursor forms as an active component
What is the best natriuretic peptide marker for heart failure?
- Plasma BNP
- N-terminal precursor form is what is commonly used in clinics for detection of heart failure
What is the advantage of using the N-terminal precursor form of BNP?
- Longer half life
- Higher plasma concentration
- Less sensitive to rapid fluctuations
What are some conditions investigated for possible use of plasma BNP?
- Assessment of severity of congestive heart failure
- Screening for mild heart failure
- Monitor response to treatment in congestive heart failure
- Prognostic outcome/risk stratification
