Novel Circulating Risk Factors (Biomarkers) for Atherosclerosis Flashcards
Biomarkers of CAD
What are 5 known biomarkers of CAD?
- C-reactive protein
- Homocysteine
- Inflammatory cytokines/molecules in serum
- Asymmetric dimethlyarginine (ADMA)
- Oxidative stress markers
Biomarkers of CAD
Can serum levels of certain novel inflammatory markers predict furture MI and CV death?
yes, CRP is the strongest example
Biomarkers of CAD
What did the AHA and CDC establish clinical guidelines for in Jan. 2003?
treatment of high levels of CRP for prevetion of CV disease
CRP
What is CRP?
23 kDa protein porduced by liver cells
CRP
What is the half-life of CRP?
18-20 hours in blood serum
CRP
CRP is part of which type of immune response?
acute-phase reactant of innate immune response to infection of tissue damage
CRP
What plasma inflammatory cytokines increase liver production of CRP?
TNF-alpha and IL-6
CRP
What is considered normal CRP blood levels?
very low = 0.5 mg/L
- normal is less than 10 mg/L
CRP
When can CRP levels drastically increase?
during massive bacterial infection or trauma
- can be 1000-fold making levels 500 mg/L
CRP
T/F: CV event-free survival decreases with increasing population-based quintiles of CRP.
TRUE
CRP
T/F: CV event-free survival decreases with increasing 3 simple clinical cut points of CRP.
TRUE
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?
both groups saw decreases in risk with the use of aspirin
- 1st quintile = 14% decrease in risk
- 4th quintile = 55% decrease in risk
CRP and Aspirin
Study conclusion.
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.
CRP and statin
What was the short term effect of cerivastatin on CRP in Hypercholesterolemic patients?
decrease of about 10 - 12% of CRP
CRP and statin
What were the long term effects of Pravastatin on plasma CRP?
decreased CRP is not related to decreased LDL
CRP and Obesity
CRP and Obesity Hypothesis
BMI, fat mass, and body weight correlate to plasma CRP level
CRP and Obesity
What does it mean if the CRP and Obesity Hypothesis is true?
weight (fat loss) should be associated with reductions in serum CRP
Effect of Weight Loss on CRP
What was the n value?
61 obese postmenopausal women
Effect of Weight Loss on CRP
Mean BMI?
35.6 kg/m2
Effect of Weight Loss on CRP
What was the n value of conclusize participants?
25 women completed 1200 cal/day diet for 40 days
Effect of Weight Loss on CRP
What was the average weight loss?
- 31.9 lbs (-15%)
- 22.9 lbs of fat loss
Effect of Weight Loss on CRP
What was the decrease in plasma CRP levels?
32% decrease
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
1, 3, 4
CRP and Exercise
What was the effect of 12 weeks of exercise on CRP in CAD patients with high baseline CRP?
45% decrease in plasma CRP
CRP and Exercise
How did short term moderate aerobic exercise affect healthy sedentary older adults with moderate of low CRP at baseline?
there was no alteration of serum CRP
CRP and Exercise
Key point?
CRP may need to be higher or weight loss may be necessary for a reduction after exercise training
Possible Treatment for elevated CRP
Is aspirin useful?
yes
Possible Treatment for elevated CRP
Are statins useful?
yes
Possible Treatment for elevated CRP
Is weight loss useful?
yes
Possible Treatment for elevated CRP
Is aerobic exercise training useful?
maybe, might need to be combined with weight loss
Serum CRP Clinical Cutpoints for Treatment
low risk CRP level cutpoint?
1 mg/L
Possible Treatment for elevated CRP
moderate risk CRP level cutpoint?
3 mg/L
Possible Treatment for elevated CRP
high risk CRP level cutpoint?
10 mg/L
Possible Treatment for elevated CRP
What does a CRP level of greater than 10 mg/L signify?
indicates possible acute infection, trauma or other source of inflammation
- results should be discarded and test should be repeated in 2-3 weeks
Jupiter Trial
What is JUPITER’s purpose?
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
Jupiter Trial
What was the inclusion criteria?
- normal LDL (less than 130 mg/L)
- high CRP (greater than 2 mg/L)
Jupiter Trial
Follow-up after 5 years on?
non-fatal MI, fatal MI, all-cause mortality
Jupiter Trial
Conclusion
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
