SHAPE Society

1. CRP + Calcium Score; More Powerful
Together
Provided by:
M. Leila Rasouli, M.D.
Division of Cardiology, Harbor UCLA Medical Center
Editorial Slides
VP Watch – October 30, 2002 - Volume 2, Issue 43

2. Computed Tomographic
Coronary Artery Calcium (CAC)
• A manifestation of subclinical
atherosclerosis
• A Recent meta-analysis reported a pooled
4-fold relative risk (RR) for CAC as a
predictor of myocardial infarction (MI) or
coronary death.1

3. High-sensitivity C-Reactive
Protein (CRP)
• A measure of chronic inflammation
• Serum levels of CRP in highest tertile predict future
coronary events in asymptomatic men2
and
postmenopausal women.3,4
• Elevated CRP levels impart an approximately 2-fold
risk of coronary events after adjustment for
demographic and risk factors.

4. South Bay Heart Watch (SBHW)
• As reported in VP Watch of this week, a
prospective cohort study designed to appraise the
value of coronary calcium and both traditional &
non-tradidtional risk factors for cardiovascular
outcomes in asymptomatic adults
• Objective of investigation: To evaluate
prospectively the combined use of CT coronary
calcium scores & high-sensitivity CRP in
predicting cardiovascular events in SBHW cohort
of nondiabetics

5. Methods
• SBHW cohort: n=1461. Asymptomatic
participants ≥ 45 yo with multiple cardiac risk
factors
• Study inclusion criteria: SBHW cohort who
were nondiabetic5
and CRP ≤10 mg/L
• Exclusion criteria: Participants with
ECG/clinical evidence of infarction,
revascularization, or typical angina

6. Methods
• Enrollment: between December 1990 –December
1992
• Final N= 967
• Baseline and follow-up risk factor screening, CT for
CAC, and CRP measurement conducted
• Follow-up: 6.4 ± 1.3 years

7. Methods
• Study end points: 1)nonfatal MI or
coronary death, 2 )any cardiovascular
event (MI, coronary death, coronary
revascularization, or stroke)
• Statistical Analysis: t-test, Cox regression
analyses, all analyses conducted at .05
significance level and used SAS software

8. Results
• 50 participants experienced MI/coronary
death endpoint
• Participants with MI/coronary death had
higher systolic BP and lower HDL
cholesterol
• 104 participants experienced any
cardiovascular event (CV)
• Participants with any CV event were older,
less likely to smoke, took ASA, had higher
BP and BMI, and lower HDL

9. Results
• Median calcium score was 5 times greater
in participants who had an event than in
those who did not (p<0.0001)
• Significantly larger CRP values for those
who experienced end points (p=0.002)

10. Results
• Calcium score was a statistically
significant predictor of both end points
(p<0.005)
• CRP was a marginally significant predictor
of MI/coronary death (p=0.09) &
statistically significant predictor of any CV
event (p=0.03)

11. Results
• Risk group analysis defined by tertiles
for CAC (<3.7, 3.7-142.1, >142.1) and
the 75th
percentile for CRP (>4.05
mg/L) indicated increasing risk with
increasing CAC and CRP

12. Results
• RR for medium-calcium/low CRP risk
group to high-calcium/high CRP risk group
ranged from 1.8-6.1 for MI/coronary death
(p=0.003)
• For any CV event: RR ranged from 2.8-7.5
(p<0.001)

13. 6.1
4.3
1.7
4.9
1.8 1
0
2
4
6
8
High Medium Low
Low
High
Relative risks of nonfatal MI or coronary death associated with high (>
75th percentile = 4.05 mg/L) and low (<4.05 mg/L) levels of CRP and high
(> 142.1), medium (3.7 to 142.1) and low (< 3.7) tertiles of calcium scores.

14. 7.5
3.4
1.64.4
2.8
1
0
2
4
6
8
High Medium Low
Low
High
Relative risks of nonfatal MI, coronary death, PTCA, CABG, or stroke
associated with high (> 75th percentile = 4.05 mg/L) and low (<4.05
mg/L) levels of CRP and high (> 142.1, medium (3.7 to 142.1) and low (<
3.7) tertiles of calcium scores.

15. Discussion
• Risk-adjusted analysis revealed CAC and CRP
are associated with ischemic cardiovascular
events in previously asymptomatic nondiabetic
adults
• Lack of interaction in nondiabetics between CRP
levels and CAC along with the complementary
predictive power of the 2 tests suggests that
they assess different aspects/mechanisms that
result in CV events

16. Limitations
• Participants homogeneous (older men)
• Statistical analyses could not control for all
possible relevant confounders (ie physical
activity)
• CRP levels in the study were greater than
those derived from a meta-analysis based
on 14 population-based studies.4

17. Conclusion
• Combined use of calcium scores and CRP
improves risk stratification in non-diabetic
patients.
• Use of combined testing with CT and CRP
appears to complementary.

18. Question
• What is the exact role of both calcification
and CRP in the development of
atherosclerosis and cardiovascular
events?
– Only markers of disease?
– CRP is a marker but calcification is a risk
factor?
– Calcification is a marker but CRP is a risk
factor?
– Both are risk factors?

19. References
1) O’Malley PG, Taylor AJ, Jackson JL, et al. Prognostic value of coronary
electron-beam computed tomography for coronary heart disease events in
asymptomatic populations. Am J Cardiol. 2000;85:945-948.
2) Koenig W, Sund M, Frohlich M, et al. C-reactive protein, a sensitive marker of
inflammation, predicts future risk of coronary heart disease in initially healthy
middle-aged men:results from the MONICA. Circulation 1999;99:237-242.
3) Ridker PM, Hennekens CH, Buring JE, et al. C-reactive protein and other
markers of inflammation in the prediction of cardiovascular disease in
women. N Engl J Med. 2000;342:836-843.
4) Danesh J, Whincup P, Walker M, et al. Low grade inflammation and coronary
heart disease: prospective study and updated meta-analyses. BMJ.
2000;321:199-204.
5) Le T, Wong N, Detrano R, et al. The relationship between clinical coronary
events and coronary artery calcium as detected by electron beam computed
tomography in diabetes. Diabetologia 1999;42:A231.