Lecture 8: Biomarkers of Atherosclerosis Flashcards
What is a biomarker?
A characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathologic processes, or pharmacologic responses to a therapeutic intervention
What are the clinical manifestations of atherosclerosis?
- Stroke
- Angina
- Ischemic neuropathy
- Acute limb ischemia
What is the use of biomarkers for atherosclerosis?
- Detect patients at risk before they develop clinical manifestations of disease
- Identify patients who are candidates for preventative therapies
- Assess response to therapy
- Suggest specific therapies for individual patients
What are the common lipid biomarkers used for atherosclerosis?
Measured: total cholesterol, HDL, triglycerides
Calculated: LDL, non-HDL cholesterol
How is LDL cholesterol determined in clinical practice?
- Calculated value
- Direct LDL-C
- Sequential ultracentrifugation - only for research purposes
If LDL and non-HDL are discordant, which predicts the risk of atherosclerosis?
non-HDL
All biomarkers are causal factors for the development of atherosclerosis. T/F?
Which biomarkers play a causal role in atherosclerosis?
False.
Lp(a) and LDL cholesterol.
ApoB is a superior biomarker of cardiovascular risk than LDL cholesterol. Why or why not?
ApoB is better than LDL because it captures greater information about atherogenic particles and is not affected by heterogeneity of particle cholesterol content.
With the same concentration of LDL-C, a higher ApoB indicates higher particle number and hence a higher risk. When LDL-C and ApoB are discordant, risk tracks with ApoB.
What are the clinical manifestations of atherosclerosis?
- Stroke
- Angina
- Ischemic neuropathy
- Acute limb ischemia
What are the different lipoprotein biomarkers?
- Apolipoprotein B-100 (ApoB)
- Apolipoprotein A-1 (ApoA-1)
- Lipoprotein(a) (Lp(a))
What biomarker is a predictor of CVD?
Lp(a)
When is it helpful to measure Lp(a)?
- Family history of early onset AS
- Recurrent CV events despite appropriate medical therapy
- Familial hypercholesterolemia (FH)
- Intermediate risk for AS disease in whom the decision to treat is uncertain
What are some assays used to measure Lp(a)?
- Apo(a) Isoform Sensitive Assay
- Apo(a) Isoform Insensitive Assay
What is the difference between the two assays used to measure Lp(a)
Sensitive:
1. Antibodies against repetitive KIV₂
2. Small Apo(a) isoform is associated with increased Lp(a) conc. and CV risk while large Apo(a) isoform is associated with decreased Lp(a) conc. and decreased CV risk
Insensitive:
1. Antibodies against unique kringle (KV)
2. Each apo(a) molecule is only recognized once, which allows the measurement of Lp(a) in molar units
What are the most important markers of inflammation?
- C-reactive protein
- Lipoprotein-associated phospholipase A2
What is CRP and what does it tell us about a patient?
It is an acute phase reactant that is synthesized in the liver in response to IL6.
It is not a causal factor in AS but is associated with CVD.
What is lipoprotein-associated phospholipase A2 and what does it tell us about a patient?
It is an enzyme that generates lysophosphatidylcholine and oxidized free fatty acids.
It is associated with vascular inflammation and CVD events.
Which biomarkers do not play a causal role in AS?
CRP
Myeloperoxidase
Lp-PLA2
HDL cholesterol
What is the benefit of measuring polygenic risk scores?
Only need to be measured once as it is stable throughout life.
What does the Framingham Risk Score comprise of? (6)
Age
Total cholesterol
HDL
Diabetes
Smoker
Systolic blood pressure (SBP)
How do we know the risk of a patient by using the Framingham Risk Score?
If the 10 year risk is:
<10%, risk category is low
10-20%, risk category is intermediate
>20%, risk category is high
Multiply by 2 if there is a family history of CVD
