Novel Circulating Risk Factors (Biomarkers) for Atherosclerosis

Question 1

Biomarkers of CAD

What are 5 known biomarkers of CAD?

Answer 1

1. C-reactive protein
2. Homocysteine
3. Inflammatory cytokines/molecules in serum
4. Asymmetric dimethlyarginine (ADMA)
5. Oxidative stress markers

Question 2

Biomarkers of CAD

Can serum levels of certain novel inflammatory markers predict furture MI and CV death?

Answer 2

yes, CRP is the strongest example

Question 3

Biomarkers of CAD

What did the AHA and CDC establish clinical guidelines for in Jan. 2003?

Answer 3

treatment of high levels of CRP for prevetion of CV disease

Question 4

CRP

What is CRP?

Answer 4

23 kDa protein porduced by liver cells

Question 5

CRP

What is the half-life of CRP?

Answer 5

18-20 hours in blood serum

Question 6

CRP

CRP is part of which type of immune response?

Answer 6

acute-phase reactant of innate immune response to infection of tissue damage

Question 7

CRP

What plasma inflammatory cytokines increase liver production of CRP?

Answer 7

TNF-alpha and IL-6

Question 8

CRP

What is considered normal CRP blood levels?

Answer 8

very low = 0.5 mg/L
- normal is less than 10 mg/L

Question 9

CRP

When can CRP levels drastically increase?

Answer 9

during massive bacterial infection or trauma
- can be 1000-fold making levels 500 mg/L

Question 10

CRP

T/F: CV event-free survival decreases with increasing population-based quintiles of CRP.

Answer 10

TRUE

Question 11

CRP

T/F: CV event-free survival decreases with increasing 3 simple clinical cut points of CRP.

Answer 11

TRUE

Question 12

CRP and Aspirin

What can be determined from comparing the 1st quintile participants with non-significant MI risk to 4th quintile participants with significant MI risk?

Answer 12

both groups saw decreases in risk with the use of aspirin
- 1st quintile = 14% decrease in risk
- 4th quintile = 55% decrease in risk

Question 13

CRP and Aspirin

Study conclusion.

Answer 13

the reduction associated with the use of aspirin in the risk of a first MI appears to be directly related to the level of CRP, rasining the possibility that anti-inflammatory agents may have clinical benefits in preventing CVD.

Question 14

CRP and statin

What was the short term effect of cerivastatin on CRP in Hypercholesterolemic patients?

Answer 14

decrease of about 10 - 12% of CRP

Question 15

CRP and statin

What were the long term effects of Pravastatin on plasma CRP?

Answer 15

decreased CRP is not related to decreased LDL

Question 16

CRP and Obesity

CRP and Obesity Hypothesis

Answer 16

BMI, fat mass, and body weight correlate to plasma CRP level

Question 17

CRP and Obesity

What does it mean if the CRP and Obesity Hypothesis is true?

Answer 17

weight (fat loss) should be associated with reductions in serum CRP

Question 18

Effect of Weight Loss on CRP

What was the n value?

Answer 18

61 obese postmenopausal women

Question 19

Effect of Weight Loss on CRP

Mean BMI?

Answer 19

35.6 kg/m2

Question 20

Effect of Weight Loss on CRP

What was the n value of conclusize participants?

Answer 20

25 women completed 1200 cal/day diet for 40 days

Question 21

Effect of Weight Loss on CRP

What was the average weight loss?

Answer 21

• 31.9 lbs (-15%)
• 22.9 lbs of fat loss

Question 22

Effect of Weight Loss on CRP

What was the decrease in plasma CRP levels?

Answer 22

32% decrease

Question 23

Effect of Weight Loss on CRP

Which of the following correlated to decrease in CRP after weight loss?
1. body weight
2. fat-free mass (lean body mass)
3. fat mass
4. HDL

Answer 23

1, 3, 4

Question 24

CRP and Exercise

What was the effect of 12 weeks of exercise on CRP in CAD patients with high baseline CRP?

Answer 24

45% decrease in plasma CRP

Question 25

CRP and Exercise

How did short term moderate aerobic exercise affect healthy sedentary older adults with moderate of low CRP at baseline?

Answer 25

there was no alteration of serum CRP

Question 26

CRP and Exercise

Key point?

Answer 26

CRP may need to be higher or weight loss may be necessary for a reduction after exercise training

Question 27

Possible Treatment for elevated CRP

Is aspirin useful?

Answer 27

yes

Question 28

Possible Treatment for elevated CRP

Are statins useful?

Answer 28

yes

Question 29

Possible Treatment for elevated CRP

Is weight loss useful?

Answer 29

yes

Question 30

Possible Treatment for elevated CRP

Is aerobic exercise training useful?

Answer 30

maybe, might need to be combined with weight loss

Question 31

Serum CRP Clinical Cutpoints for Treatment

low risk CRP level cutpoint?

Answer 31

1 mg/L

Question 32

Possible Treatment for elevated CRP

moderate risk CRP level cutpoint?

Answer 32

3 mg/L

Question 33

Possible Treatment for elevated CRP

high risk CRP level cutpoint?

Answer 33

10 mg/L

Question 34

Possible Treatment for elevated CRP

What does a CRP level of greater than 10 mg/L signify?

Answer 34

indicates possible acute infection, trauma or other source of inflammation
- results should be discarded and test should be repeated in 2-3 weeks

Question 35

Jupiter Trial

What is JUPITER’s purpose?

Answer 35

Because 50% of all CV events occur in patients with normal or low levels of LDL-C, it was designed to determine whether hs-CRP could identify whether statin therapy could prevent CV events among them

Question 36

Jupiter Trial

What was the inclusion criteria?

Answer 36

• normal LDL (less than 130 mg/L)
• high CRP (greater than 2 mg/L)

Question 37

Jupiter Trial

Follow-up after 5 years on?

Answer 37

non-fatal MI, fatal MI, all-cause mortality

Question 38

Jupiter Trial

Conclusion

Answer 38

in this trial of apparently healthy person without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidience of major cardiovascular events