Statistical modeling in pharmaceutical research and development.
Definitions of artereial remodeling
1. Definitions of arterial remodeling in
post mortem and Intravascular
ultrasound research
G. Pasterkamp
Experimental Cardiology, UMC and
Interuniversity cardiology Institute of the
Netherlands, Utrecht, The Netherlands
2. Arterial remodeling
Gradual Luminal narrowing
Expansive
remodeling
Constrictive
remodeling
Glagov et al. New Engl J Med 1987;316:1371-1375
Pasterkamp et al. Circulation 1995;91:1444-1449
3. Background
In international literature, the modes of
arterial geometrical remodeling are
differentially defined resulting in
different prevalence numbers.
The current presentation will show and
discuss the most widely used definitions
4. L = Lesion
R1 = most proximal site
R2 = proximal reference with normal lumen and least
amount of plaque
R3 = distal reference with normal lumen and least
amount of plaque
lumen
plaque
LR2 R3R1
5. Definition 1
Remodeling Index (RI)= VA L / ( (VA R2 + VA R3)/2)
lumen
plaque
LR2 R3R1
Expansive remodeling when RI >1.05
Intermediate remodeling when RI >0.95 or < 1.05
Constrictive remodeling when RI <0.95
Smits et al. Heart 1999;82:461-464
von Birgelen et al. J Am Coll Cardiol 2001;37:1864-1870.
Schoenhagen et al. Circulation 1999;101:598-603
6. Definition 2
RI= VA L / ( (VA R2 + VA R3)/2)
lumen
plaque
LR2 R3R1
Expansive remodeling when RI >1.0
Constrictive remodeling when RI <1.0
Dangas et al. Circulation 1999;99:3149-3154.
Nakamura et al. J Am Coll Cardiol. 2001 Jan;37(1):63-9
Okura et al. J Am Coll Cardiol 2001;37:1031-1035.
7. Definition 3
lumen
plaque
LR2 R3R1
Expansive remodeling when VA L > VA R2 and VA L > VA R3
Constrictive remodeling when VA L < VA R2 and VA L < VA R3
Other values: intermediate remodeling
Nishioka et al. J Am Coll Cardiol 1996;27:1571-1576
Wexberg et al. J Am Coll Cardiol 2000;36:1860-1869.
8. Definition 4
lumen
plaque
Expansive/no remodeling when VA L / VA R2 > 0.78
Constrictive remodeling when VA L / VA R2 < 0. 78
Mintz et al Circulation 1997;95:1791-1798.
Upper limit of normal tapering over 10 mm never exceeds
21% of vessel area reference limit at 0.78
LR2 R3R1
9. Definition 5
RI= VA L / ( VA R1)
lumen
plaque
LR2 R3R1
Expansive remodeling when RI >1.0
Constrictive remodeling when RI <1.0
Taylor et al. J Am Coll Cardiol 1999 Sep;34(3):760-7
10. Definition 6
RI = VA L / VA R2 (site with
least amount of plaque
lumen
plaque
LR2 R3R1
Expansive remodeling when RI > 1.05
Constrictive remodeling when RI < 0.95
Other values: intermediate remodeling
Pasterkamp et al. J Am Coll Cardiol 1995;26:422-428.
(Only applied peripheral arteries)
11. Remodeling definitions lead to large variations
in prevalence numbers.
expansive
remodeling
intermediate
remodeling
constrictive
remodeling
definition
remodeling
Mintz et al 512 (85%) 91 (15%) 4
Nishioka et al 19 (53%) 7 (20%) 9 (27%) 3
Smits et al 24 (35%) 16 (23%) 29 (42%) 1
Wexberg et al 70 (29%) 110 (45%) 64 (26%) 3
Dangas et al. 269 (42%) 377 (58%) 2
Nakamura et al. 68 (54%) 57 (46%) 2
Okura et al. 59 (55%) 49 (45%) 2
Von Birgelen et al. 38 (48%) 22 (28%) 19 (24%) 1
Pasterkamp et al. 226 (37%) 383 (63%) 2
Schoenhagen et al. 70 (53%) 26 (20%) 35 (27%) 1
12. Which definition is best?
All studies are cross-sectional
The reference is not free of atherosclerotic disease
The reference may have been remodeled in either
direction
We do not know which definition gives us the best
estimate of the prevalence of the different remodeling
modes.
13. Which definitions make sense?
• Definitions 1-4 share the same receipt, only
the tresholds differ.
• Definition 5 may be used in casuistic studies,
but in larger studies on prevalence this
definition should not be used (it will, by definition,
approximate the 50% for each remodeling mode)
• Definition 6 can only be used in non tapering
vessels.
14. Conclusion
• The prevalence of constrictive and expansive
remodeling differs widely in literature due to
the application of different definitions.
• Without serial studies, there is no gold
standard for the reference site.
• The definition of the remodeling modes merit
careful consideration when prevalences are
mentioned.