SHAPE Society

1. Inflammation is NOT specific to
culprit lesions.
PRO
Gerard Pasterkamp,
UMC Utrecht

2. First:
What is the definition of the
vulnerable plaque?
First:
What is the definition of the
culprit lesion?
Lesion that is pathological
substrate of clinical
syndrome?
Lesion that is
pathological substrate of
plaque rupture?
Lesion that hides
inflammatory cells?

3. 74 coronary arteries
3 random (non ruptured)
sections per artery
Nr cross-sections revealing
plaque inflammation
50 femoral arteries
6 sites per artery
Arteriosclerosis, Thrombosis, and Vascular
Biology. 1999;19:54-58

4. Vink et al. J Anatomy 2001

5. Radial artery

6. Specificity: Proportion of negatives that
are correctly identified by the test
Sensitivity: proportion of positives that are
correctly identified by the test
For diagnosis we do not need “spec” and
“sens”, but we need the probability of the test
giving the correct diagnosis.

7. Values for diagnostic testing:
Positive predictive value:: proportion of patients
with positive test results who are correctly
diagnosed
Negative predictive value:: proportion of patients
with negative test results who are correctly
diagnosed

8. Inflammation
Culprit lesion + -
+ 5 0 5
- 195 400 595
200 400
Specificity: 5/5 = 1.0 PPV: 5/200 = 0.025
Sensitivity: 400/595= 0.67 NPV: 400/400 = 1.0

9. Inflammation culprit lesion MI?

10. Inflammation specific for culprit
lesion (MI)?
Inflammation specific for culprit
lesion (plaque rupture)?
NO
We do not know
Not in cross-sectional post mortem studies, but maybe over time?

11. Inflammation: local arterial system
The number of inflammatory lesions observed
during catheterization: a predictive marker
for adverse outcomes?

12. METHODS:
• Post mortem
• 30 pairs of left and right femoral arteries
equally present left and right systemically
influenced
unilateral prevalence locally determined

13. Plaque vulnerability:
• 60 arteries (30 pairs), 6 cross sections per artery
• (Immuno)histochemistry
– smooth muscle cells (SMC)
– collagen
– macrophages
– T lymphocyes
• Plaque “vulnerable” if:
1. Heavy staining macrophages or T lymphocytes
2. Absent/minor staining of SMC and collagen

14. y = 1.2x - 2.7
r2
= 0,71
0
10
20
30
40
50
0 10 20 30 40 50
plaque area left (mm2
)
plaquearearight(mm2
)

15. Right No
Vulnerable
Plaque
Right ≥1
Vulnerable
Plaque
Left No Vulnerable
Plaque
9 (30%) 5 (17%)
Left ≥1 Vulnerable
Plaque
5 (17%) 11 (37%)
Agreement 67%, kappa = 0.35 (p=0.05)
Vulnerable plaque: atheroma ≥40% and
a thin cap with inflammation
Plaque vulnerability

16. 1. Large lipid pool
2. Inflammatory cells in cap
Vulnerable Plaque

17. Right No
Atheroma ≥40%
Right ≥1
Atheroma ≥40%
Left No
Atheroma ≥40%
5 (17%) 4 (13%)
Left
≥1 Atheroma ≥40%
3 (10%) 18 (60%)
Agreement 77%, kappa = 0.43 (p=0.02)
Atheroma ≥40%: atheroma occupying ≥40%
of total plaque area
Large atheroma

18. Right No
Vulnerable Cap
Right ≥1
Vulnerable Cap
Left No Vulnerable Cap 1 (3%) 5 (17%)
Left ≥1 Vulnerable Cap 11 (37%) 13 (43%)
Agreement 47%, kappa = −0.21 (p=0.19)
Vulnerable cap: a thin cap with at least moderate
inflammation irrespective of atheroma size
Thin cap with inflammation

19. Conclusion
• Association plaque size left and right arteries
• 32/42 (76%) similarity in presence or absence
significant correlation PA and VA
• plaque vulnerability:
– large lipid pool: moderate agreement left and right
– thin cap with inflammation: left independent of right
Vink et al. J Am Coll Cardiol 2001;38:718-723

20. Conclusion:
• Inflammation (cells) as a diagnostic marker
probably probably has a very low positive
predictive value for the culprit lesion (lesion that
may lead to clinical syndrome).
• Thus far, local segmental sampling for the
presence of inflammation does not seem strongly
representative for inflammatory responses
throughout the arterial system (cave: cross-
sectional studies in 2D).