This document discusses the use of C-reactive protein (CRP) and low-density lipoprotein (LDL) cholesterol levels to predict cardiovascular risk. It summarizes a study that found CRP to be a stronger predictor of future cardiovascular events than LDL, with CRP and LDL providing complementary and non-correlated information. The document concludes that measuring both CRP and LDL provides superior risk detection compared to either marker alone, and that patients with high CRP but low LDL (<160 mg/dl) should be considered at increased risk.

1. What Do You Do With A Patient
Who Has High CRP and Low LDL?
Editorial Slides
VP Watch – November 27, 2002 - Volume 2, Issue 47

2.  More than 200 risk factors have been
suggested for atherosclerotic
cardiovascular disease.
 However, only hypercholesterolemia,
hypertension, diabetes, and smoking,
are traditionally considered as modifiable
major risk factors for CAD.

3.  During the last decade, atherosclerosis has
found a new face as an inflammatory disease,
with a its metabolic aspect (e.g.
hypercholesterolemia) as a background
component.
 A composite marker that reflects the combined
metabolic and inflammatory aspects of
atherosclerosis, and their interactions, is now
wanted more than ever.

4.  Cholesterol screening was the first
screening tests used for CAD risk
assessment and still is the major routine
clinical test.
 LDL cholesterol is the focus of current
national guidelines for the determination of
the risk of atherosclerotic cardiovascular
disease. 11

5.  Results of Framingham study showed
that more than 35% of CAD events occur
in people with total cholesterol of less
than 200 mg/dl. 10
 Based on this result, most of the cases
of acute MI occur in people with less
than average cholesterol levels which is
around 200-240mg/dl in the USA.

6.  Ridker et al showed that CRP
predicts adverse cardiovascular
events in asymptomatic healthy
populations. 4,5,14,15
 They also showed that CRP can
predict future incidence of diabetes
in apparently healthy people. 4,5,14,15

7.  As reported in VP Watch of this week, Ridker
and his colleagues showed that CRP is a stronger
predictor of future cardiovascular events than LDL
cholesterol. 12
 They measured CRP and LDL at base line in
(all of) 27,939 apparently healthy American
women, who were then followed for a mean of
eight years for the occurrence of myocardial
infarction, ischemic stroke, coronary
revascularization, or death from cardiovascular
causes. 12

8.  Seventy seven percent of all events (MI,
ischemic stroke, coronary revascularization, or
death from cardiovascular causes) occurred
among women with (normal) LDL below 160
mg/dl, and 46% occurred among those with
LDL levels below (current treatment target)
130 mg/dl. 12
 CRP and LDL levels were minimally
correlated, which shows that each biologic
marker was detecting a different group of
people at risk. 12
Results

9. 0
0.5
1
1.5
2
2.5
3
3.5
4
1 2 3 4 5
LDL
CRP
Quintile
RelativeRisk
All Cardiovascular Events
Age-Adjusted Relative Risk of Future Cardiovascular Events, According to Base-
Line CRP and LDL Cholesterol Levels.
Adopted from: Ridker et al. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the
prediction of first cardiovascular events. N Engl J Med. 2002 Nov 14;347(20):1557-65.

10.  Increasing levels of CRP were
associated with increased risk of
cardiovascular events at all levels of
estimated 10-year risk based on the
Framingham risk score. 12
 Increasing CRP were associated with
increased risk of cardiovascular events
at LDL cholesterol levels below 130,
130-160, and above 160 mg/dl. 12
Results

11. Advantages of measuring CRP: 13
 stable over long periods
 has no diurnal variation
 can be measured inexpensively with available high-sensitivity
assays
 Not directly related to lipid metabolism
 More importantly, CRP predicts incidence
of diabetics and insulin resistance
syndrome as it does cardiovascular events,
which means it can be considered as a
cumulative risk marker of metabolic as well
as inflammatory aspects of atherosclerosis.

12. Conclusion:
 CRP is a stronger predictor of future
cardiovascular events than LDL.
 CRP and LDL are minimally correlated.
The combined evaluation of both CRP
and LDL is superior as a method of risk
detection to measurement of either
biologic marker alone.

13.  CRP now has the final verdict
to be considered as a major
risk factor/marker for
prediction of adverse
cardiovascular events.
Conclusion:

14. Questions:
 What do you do with a patient who
has high CRP and low LDL
(<160mg/dl)?
• What are the other useful
combinations of risk markers
(factors), like CRP and LDL in this
study, for risk assessment?

15. Questions:
 Do you agree that CRP, LDL, and
Coronary Calcium Score jointly can
provide a more powerful predictive
value for risk assessment?

16. Questions:
 What is the difference in value of CRP
in primary versus secondary
prevention?
 And which one of the following should
be used for patient follow up and
monitoring their response to treatment?
CRP, LDL, Calcium Score, or all?

17. 1) Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med 1999;340:115-126
2) Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995;91:2844-2850.
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4) Wilson PWF, D’Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation. 1998; 97: 1837–1847.
5) Pekkanen J, Linn S, Heiss G, Suchindran CM, Leon A, Rifkind BM, Tyroler HA; Ten-year mortality from cardiovascular disease in relation to
cholesterol level among men with and without preexisting cardiovascular disease. N Engl J Med. 1990 Jun 14;322(24):1700-7.
6) Speidl et al. High-sensitivity C-reactive protein in the prediction of coronary events in patients with premature coronary artery disease. Am Heart J.
2002 Sep;144(3):449-55.
7) Anderson JL, Carlquist JF, Muhlestein JB, Horne BD, Elmer SP; Evaluation of C-reactive protein, an inflammatory marker, and infectious serology
as risk factors for coronary artery disease and myocardial infarction.J Am Coll Cardiol. 1998 Jul;32(1):35-41.
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myocardial infarction. Circulation. 1998; 97: 2007–2011.
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healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study,
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10) Castelli WP. Lipids, risk factors and ischaemic heart disease. Atherosclerosis 1996;124(Suppl):S1-9.
11) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the Third Report of the National
Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult
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12) Ridker et al. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl
J Med. 2002 Nov 14;347(20):1557-65.
13) Ockene IS, Matthews CE, Rifai N, Ridker PM, Reed G, Stanek E. Variability and classification accuracy of serial high-sensitivity C-reactive protein
measurements in healthy adults. Clin Chem 2001;47:444-50
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References