Laboratory Investigation of Cardiac Disease Flashcards
Analytical Characteristics of ideal biomarkers
Analytical Characteristics
- Measurable by cost-effective method
- Simple to perform
- Rapid turnaround time
- Sufficient precision & accuracy
Clinical Characteristics of ideal biomarkers
Clinical Characteristics
- Early detection of disease
- Sensitivity vs specificity
- Validated decision limits
- Selection of therapy
- Risk stratification
- Prognostic value
- Ability to improve patient outcome
Cardiovascular Disease - list linked pathologies
Umbrella term for a number of linked pathologies including:
coronary heart disease (CHD) cerebrovascular disease peripheral arterial disease rheumatic and congenital heart diseases venous thromboembolism lymphatic disease
Atherogenesis can be divided into five key steps,
describe effect
Atherogenesis can be divided into five key steps, which are
1) endothelial dysfunction,
2) formation of lipid layer or fatty streak within the intima,
3) migration of leukocytes and smooth muscle cells into the vessel wall,
4) foam cell formation
5) degradation of extracellular matrix.
- Via these consecutive steps, an atherosclerotic plaque is formed.
The formation of the plaque can be divided into three major stages
The formation of the plaque can also be divided into three major stages namely
1) the fatty streak, which represents the initiation
2) plaque progression, which represents adaption
3) plaque disruption, which represents the clinical complication of atherosclerosis
Initiation of atherosclerosis
Endothelial activation:
LDL penetrates endothelium + retained in intima = oxidative modification
Proinflammatory lipids released from LDL stimulate endothelial cells to express adhesion molecules
Circulating monocytes adhere to endothelial cells expressing VCAM-1 + other adhesion molecules
.. respond to chemokines and migrate into intima
Consequences of coronary thrombosis
Ischaemia
Necrosis
Myocardial infarction
Angina cause
Plaque w/fibrous cap
Acute coronary syndrome cause
Plaque w/fibrous cap - ruptures
Heart attack cause
Blood clot forms around rupture = artery blocked
Some causes of chest pain
Broken rib Collapsed lung Nerve infection (shingles) “Pulled” muscle Infection Heart burn (hernia) Pericarditis Blood clot in the lungs (PE) Angina Myocardial infarction
Assessment of ischemic heart disease (IHD)
Medical history Risk factors Presenting signs and symptoms ECG Biomarkers Imaging/scans
Biochemical markers of cardiac dysfunction/damage can 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
30 minutes of ischaemia effect
Irreversible injury typically requires 30 minutes of ischaemia
Cellular content leak dependent on what
Cellular content leak out through membrane dependent on size and solubility
What improves detection of early damage
Concentration gradient from inside to outside important (high gradient improves detection of early damage)
Markers of myocardial damage
7-36 h peak after MI
Heart muscle specific markers troponin-T and troponin-I
Creatine kinase (↑ 90% MIs, but less specific as also released from skeletal muscle)
Heart specific isoforms of creatine phosphokinase (CPK-MB
Myoglobin raised early but less specific for heart damage
The troponin complex - define
The troponin complex is a component of the thin filaments in striated muscle complexed to actin
Troponin types
Troponin T (tropomyosin binding)
• Troponin I (inhibits actomyosin ATPase)
• Troponin C (calcium binding)
The troponins are three different proteins structurally unrelated with each other
Cardiac troponin T and I differ significantly from troponin T and I found in skeletal muscle
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
Heart Failure - define
“a complex clinical syndrome
that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood”
Some 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 (eg cocaine)
Signs and symptoms of congestive heart failure
Shortness of breath Swelling of feet/legs Chronic lack of energy Difficulty sleeping at night due to breathing problems Swollen/tender abdomen with loss of appetite Cough with frothy sputum Increased urination at night Confusion/impaired memory
Clinical utilisation of cardiac biomarker testing in heart failure
Initial evaluation of heart failure
Screening for cardiac dysfunction
Guiding management of heart failure
Assessment of prognosis and survival
Natriuretic peptides function
Natriuretic peptides as markers of cardiac overload
ANP Source Main effects Secretion stimulus Function
Synthesised as HMW precursor forms
Source = Atrium
Main effects = CNS effects
Secretion stimulus = atrial stretch
Function = endocrine
BNP Source Main effects Secretion stimulus Function
Synthesised as HMW precursor forms
Source = ventricle
Main effects = vasorelaxant
Secretion stimulus = ventricular dilatation
Function = endocrine
CNP Source Main effects Secretion stimulus Function
Synthesised as HMW precursor forms
Source = endothelial
Main effects =
Natriuretic
Vasorelaxant
RAAS inhibition
Secretion stimulus = ?
Function = paracrine
Assays available for what forms of peptides
Assays available for the active peptides and the N-terminal precursor forms of BNP
Advantages of N-terminal precursor forms of BNP
Longer half-life
Higher plasma concentrations
Less sensitive to rapid fluctuations
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
