1. Editorial Slides
VP Watch, March 4, 2002, Volume 2, Issue 9
Positive Remodeling, A Surrogate Marker of
Plaque Inflammation and Vulnerability?
By: Gerard Pasterkamp, M.D., Ph.D.
Inter University Cardiology Institute of the Netherlands
2. Determinants of Atherosclerotic
Luminal Narrowing
In the long term:
i. Plaque formation
ii. The mode of geometrical remodelling
a) Expansive remodeling prevents whereas
b) Constrictive remodeling accelerates luminal
narrowing
Acutely:
>> plaque rupture/erosion with subsequent
thrombus formation.
* In some cases, plaque rupture goes silent and the healing process results in
fibrous cap formation and further luminal narrowing.
3. Seymour Glagov:
Compensatory Enlargement of Human
Atherosclerotic Coronary Arteries
”Positive Remodeling”
<50%
stenosis
<80%
stenosis
Luminal area is not endangered until more than 40% of internal
elastic lamina is destructed and occupied by plaque.
Coronary artery disease is a disease
of arterial wall not lumen.
7. Previous studies demonstrated that:
a. Histologically: an association between expansive
remodeling and markers for plaque vulnerability in
unruptured plaques. 1,2
b. Clinically: an association between expansive
remodeling and unstable clinical syndromes. 3,4
8. As highlighted in VP Watch,
Varnava et al. studied the
associaton between de novo
atherosclerotic remodeling and
histological markers for plaque
vulnerability in plaques (n=108)
obtained from patients (n=88)
that died of coronary artery
disease.
9. Results:
64/108 plaques revealed expansive
remodelling.
44/108 revealed constrictive remodelling.
Lipid core was larger in expansively
remodelled plaques (39+/-21 % versus 22+/-
23%).
Macrophage count was higher in expansively
remodelled segments.
10. Conclusion:
I. In patients that died acutely of coronary
artery disease, expansive remodeling is
associated with a vulnerable plaque
phenotype.
II. This observation may explain why acute
coronary syndromes often originate from
locations with minor luminal stenosis (but
with outward remodelled plaques).
11. Questions:
1. Studies are cross-sectional, thus no causal
of prognostic inferences are allowed.
The question is what is the predictive value
of the remodelling mode for the occurrence
of plaque rupture and an acute
cardiovascular event?
To answer this, serial (IVUS) studies are
necessary.
12. Questions:
2. Remodelling is a double edged sword: in
the long term expansive remodeling
prevents luminal narrowing by plaque
formation. In the short term these plaques
are more prone to rupture giving rise to an
acute cardiovascular event. How can we induce
expansive remodeling without destabilizing the
plaques?
To answer this, good animal models are needed that
develop both types of geometrical remodeling
13. Questions:
3. In this study, positive (expansive)
remodeling was present in 72%, however
negative (constrictive) remodeling was
also present in 50%, the question is how
these two correlate with each other?
4. If expansive remodeling correlate with
macrophage count and thin cap and can be a
surrogate marker of vulnerability, what is the
predictive value of constrictive remodeling
(stenosis in angiography) in predicting presence
of expansive remodeling and vulnerability to
rupture in other plaques in the same patient?
15. 1- Atherosclerotic arterial remodeling and the localization of macrophages and matrix
metalloproteases 1, 2 and 9 in the human coronary artery; Atherosclerosis 2000;
150(2):245-253 ; Gerard Pasterkamp, Arjan H. Schoneveld, Dirk Jan Hijnen, Dominique P.
V. de Kleijn, Hans Teepen, A. C. van der Wal and Cornelius Borst
2- Relation of arterial geometry to luminal narrowing and histologic markers for plaque
vulnerability: the remodeling paradox, J American Coll Cardio 1998; 32(3):655-662
Gerard Pasterkamp, Arjan H. Schoneveld, Allard C. van der Wal, Christian C.
Haudenschild, Ruud J. G. Clarijs, Anton E. Becker, Berend Hillen and Cornelius Borst
3- Coronary artery disease: arterial remodelling and clinical presentation Heart 1999; 82:
461-464. P C Smits, G Pasterkamp, M A Quarles van Ufford, F D Eefting, P R Stella, P P T
de Jaegere, and C Borst
4- Extent and Direction of Arterial Remodeling in Stable Versus Unstable Coronary
Syndromes
: An Intravascular Ultrasound Study; Paul Schoenhagen, Khaled M. Ziada, Samir R.
Kapadia, Timothy D. Crowe, Steven E. Nissen, and E. Murat Tuzcu; Circulation 2000 101:
598 - 603.
5 Compensatory Enlargement of Human Atherosclerotic Coronary Arteries. Seymour Glagov:
New England Journal of Medcine 1987 May 28;316(22):1371-5
References