Lecture 8: Biomarkers of Atherosclerosis

Question 1

What is a biomarker?

Answer 1

A characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathologic processes, or pharmacologic responses to a therapeutic intervention

Question 2

What are the clinical manifestations of atherosclerosis?

Answer 2

1. Stroke
2. Angina
3. Ischemic neuropathy
4. Acute limb ischemia

Question 3

What is the use of biomarkers for atherosclerosis?

Answer 3

1. Detect patients at risk before they develop clinical manifestations of disease
2. Identify patients who are candidates for preventative therapies
3. Assess response to therapy
4. Suggest specific therapies for individual patients

Question 4

What are the common lipid biomarkers used for atherosclerosis?

Answer 4

Measured: total cholesterol, HDL, triglycerides
Calculated: LDL, non-HDL cholesterol

Question 5

How is LDL cholesterol determined in clinical practice?

Answer 5

1. Calculated value
2. Direct LDL-C
3. Sequential ultracentrifugation - only for research purposes

Question 6

If LDL and non-HDL are discordant, which predicts the risk of atherosclerosis?

Answer 6

non-HDL

Question 7

All biomarkers are causal factors for the development of atherosclerosis. T/F?

Which biomarkers play a causal role in atherosclerosis?

Answer 7

False.

Lp(a) and LDL cholesterol.

Question 8

ApoB is a superior biomarker of cardiovascular risk than LDL cholesterol. Why or why not?

Answer 8

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.

Question 9

What are the clinical manifestations of atherosclerosis?

Answer 9

1. Stroke
2. Angina
3. Ischemic neuropathy
4. Acute limb ischemia

Question 10

What are the different lipoprotein biomarkers?

Answer 10

1. Apolipoprotein B-100 (ApoB)
2. Apolipoprotein A-1 (ApoA-1)
3. Lipoprotein(a) (Lp(a))

Question 11

What biomarker is a predictor of CVD?

Answer 11

Lp(a)

Question 12

When is it helpful to measure Lp(a)?

Answer 12

1. Family history of early onset AS
2. Recurrent CV events despite appropriate medical therapy
3. Familial hypercholesterolemia (FH)
4. Intermediate risk for AS disease in whom the decision to treat is uncertain

Question 13

What are some assays used to measure Lp(a)?

Answer 13

1. Apo(a) Isoform Sensitive Assay
2. Apo(a) Isoform Insensitive Assay

Question 14

What is the difference between the two assays used to measure Lp(a)

Answer 14

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

Question 15

What are the most important markers of inflammation?

Answer 15

1. C-reactive protein
2. Lipoprotein-associated phospholipase A2

Question 16

What is CRP and what does it tell us about a patient?

Answer 16

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.

Question 17

What is lipoprotein-associated phospholipase A2 and what does it tell us about a patient?

Answer 17

It is an enzyme that generates lysophosphatidylcholine and oxidized free fatty acids.

It is associated with vascular inflammation and CVD events.

Question 18

Which biomarkers do not play a causal role in AS?

Answer 18

CRP
Myeloperoxidase
Lp-PLA2
HDL cholesterol

Question 19

What is the benefit of measuring polygenic risk scores?

Answer 19

Only need to be measured once as it is stable throughout life.

Question 20

What does the Framingham Risk Score comprise of? (6)

Answer 20

Age
Total cholesterol
HDL
Diabetes
Smoker
Systolic blood pressure (SBP)

Question 21

How do we know the risk of a patient by using the Framingham Risk Score?

Answer 21

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