Investigation of cardiac disease Flashcards
What are the biochemical tests in clinical medicine?
• Screening to look for subclinical conditions and identifying patients at risk
○ Look at cholesterol levels
• Diagnosis of normal vs abnormal levels
• Monitoring the course of disease
• Clinical management and treatment/response
• Prognosis and risk stratification
What are the analytical characteristics of ideal biomarkers?
○ Measure by cost effective methods
○ Simple to perform
○ Rapid turnaround time
○ Sufficient precision and accuracy
What are the clinical characteristics of ideal biomarkers?
○ Early detection of disease ○ Sensitivity vs specificity ○ Validated decision limits ○ Selection of therapy ○ Risk stratification ○ Prognostic value ○ Ability to improve patient outcome
What cardiovascular disease causes the most death in men and women?
• Coronary heart disease(CHD) causes the most deaths in men and women
What are the steps involved in the development of atheromatous plaques?
- Initial lesions occur in which there is endothelial dysfunction
- Then we get development of fatty streaks which calcify and harden
- Then we have extensive lipid accumulation
- We have further hardening and plaque eventually becomes fibrotic
- The plaque can break through the endothelium and the lumen of the vessel to initiate thrombosis and coagulation resulting in occlusion of the vessel
Steps involved in the initiation of atherosclerosis
- LDL penetrates endothelium and is retained in the intima where it undergoes oxidative modification.
- Proinflammatory lipids released from LDL stimulates endothelial cells to express adhesion molecules
- Circulating monocytes adhere to endothelial cells expressing VCAM-1 and other adhesion molecules respond to chemokines and migrate into the intima
- Monocytes which migrate into the intima can differentiate into macrophages
a. These are important for monocyte differentiation and they can upregulate receptors on the surface of macrophages which cause more uptake of LDL - Eventually we have foam cells which start to accumulate from macrophages and they build up and start to get calcified as well as the same time a pro-inflammatory response occurs within the vasculature in terms of macrophages releasing other kinds of interferons and cytokines which exacerbate the response
a. Influx of T cells that contribute to inflammatory response
What are the consequences of coronary thrombosis?
- If you have a significant build up of cholesterol eventually it results in an atheroma that induces thrombosis, you end up with a blocked artery.
- Significant ischemia will occur and so there is decreased oxygen to that part of the heart.
- Results in death - necrosis within that area of the heart.
- If fibrinolysis does not occur to restore flow naturally, a myocardial infarction will occur.
What can plaque ruptures lead to?
• Rupture of an atheroma can result in clot formation to result in a myocardial infarction.
Why is it vital to understand the cause of the chest pain?
To be able to treat the patient, provide a prognosis and further management.
Assessment of IHD
- Medical history
- Risk factors
- Presenting signs and symptoms
- ECG
- Biomarkers
- Imaging/ scans
What can biochemical markers of cardiac dysfunction/damage 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 does irreversible injury typically require ?
• Irreversible injury typically requires 30 minutes of ischaemia
What happens when myocardial injury occurs to cellular content?
• Cellular content leak out through membrane dependent on size and solubility
What content is released first in myocardial injury and what is it followed by and what does this information help indicate?
- Ions are released first and then macromolecules will be released within a few hours
- This information helps indicate when MI occurred
Markers of myocardial damage
- Creatine Kinase
- Troponin
- CPK-MB
- Heart specific torponin-T and troponin-I
Why is creatine kinase a less specific indicator of myocardial damage?
Creatine kinase increased in 90% of MI’s but it’s a less specific indicator as its also released from skeletal muscle
When do myoglobin levels increase in myocardial damage?
• Myoglobin levels raised early but less specific for heart damage
What component is the troponin complex part of?
○ Component of thin filament
What type of muscle is troponin found in?
In striated muscle
What are the 3 types of troponin?
- Troponin T
- Troponin I
- Troponin C
Function of Troponin T
Tropomyosin binding
Function of troponin I
Inhibits actomyosin
Function of troponin C
Calcium binding
What do cardiac troponin T and I differ from?
• Cardiac troponin T and I differ significantly from troponin T and I found in skeletal muscle
What are the advantages of cardiac troponin?
- An index of cardiac damage
- Blood levels related to severity of cardiac damage
- Predicts major adverse cardiac events such as myocardial infarction
What is ELISA?
Test to measure troponin
What are the steps involved in ELISA?
○ Two different antibodies measuring the protein of interest in blood
○ Produces a signal
○ Results are usually rapid -dipstick test to see if you have the biomarker of interest above a single point to give a positive result to allow diagnosis and therapy options.
What is the definition of heart failure?
Heart failure is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricles to fill with or eject blood.
What are major causes of heart failure?
- Coronary artery disease
- Chronic hypertension
- Cardiomyopathy
- Heart valve disease
- Arrhythmias - AF, VT
- Infective endocarditis
- Pulmonary hypertension - PE, COPD
- Alcohol and drugs (e.g. cocaine)
What do we use natriuretic peptides as markers for?
Natriuretic peptides used as markers of cardiac overload in terms of trying to pump fluid around the heart.
What are natriuretic peptides markers of?
• They are markers of stretch, not markers of damage or necrosis.
When are natriuretic peptide markers released?
• These peptides are Released when there is excessive stretching of the heart and they are useful as they are specific for diagnosing heart failure and prognosis and management.
What are the different types of molecules classified into?
There are a few different types of these molecules and they are classified into; ANP, BNP and CNP.
What is the source of ANP?
The atrium
What is the source of BNP?
The ventricles
What is the source of CNP?
The endothelial cells
What are all ANP, BNP and CNP synthesised as?
○ All of these peptides are synthesised as high molecular weight precursor forms.
What are the main effect of ANP, BNP and CNP?
○ The main effects of these peptides are natriuretic, vasorelaxant and RAAS inhibition.
What is the secretion stimulus for ANP?
○ Secretion stimulus for ANP is atrial stretch
What is the secretion stimulus for BNP?
○ Secretion stimulus for BNP is ventricular dilation
What is the function of booth ANP and BNP?
○ Function of both ANP and BNP is endocrine
What peptide is used clinically for heart failure?
• BNP is used clinically for heart failure
What terminal precursor is useful and why?
• N terminal precursor forms of BNP are useful because they have:
○ Longer half life
○ Higher plasma concentrations
○ Less sensitive to rapid fluctuations in comparison to active component
