Inflammation is NOT specific to culprit lesions.

PRO

Gerard Pasterkamp,

UMC Utrecht

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?

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

Vink et al. J Anatomy 2001

Radial artery

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.

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

InflammationCulprit 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

Inflammation culprit lesion MI?

Inflammation specific for culprit lesion (MI)?

Inflammation specific for culprit lesion (plaque rupture)?

NO

We do not knowNot in cross-sectional post mortem studies, but maybe over time?

Inflammation: local arterial system

The number of inflammatory lesions observed during catheterization: a predictive marker

for adverse outcomes?

METHODS:

• Post mortem• 30 pairs of left and right femoral arteries

equally present left and right systemically influenced

unilateral prevalence locally determined

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 lymphocytes2. Absent/minor staining of SMC and collagen

y = 1.2x - 2.7r2 = 0,71

0

10

20

30

40

50

0 10 20 30 40 50plaque area left (mm2)

plaq

ue a

rea

righ

t (m

m2 )

Right NoVulnerable

Plaque

Right 1Vulnerable

PlaqueLeft No VulnerablePlaque 9 (30%) 5 (17%)

Left 1 VulnerablePlaque 5 (17%) 11 (37%)

Agreement 67%, kappa = 0.35 (p=0.05)

Vulnerable plaque: atheroma 40% anda thin cap with inflammation

Plaque vulnerability

1. Large lipid pool

2. Inflammatory cells in cap

Vulnerable Plaque

Right NoAtheroma 40%

Right 1Atheroma 40%

Left NoAtheroma 40% 5 (17%) 4 (13%)

Left1 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

Right NoVulnerable Cap

Right 1Vulnerable 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 moderateinflammation irrespective of atheroma size

Thin cap with inflammation

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

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).