SHAPE Society

1. Editorial Slides
VP Watch – October , 2002 - Volume 2, Issue 36
Influence of Statin Therapy on Progression ofInfluence of Statin Therapy on Progression of
Coronary CalcificationCoronary Calcification
Paolo Raggi, MD, FACP, FACCPaolo Raggi, MD, FACP, FACC
Professor of Medicine and Director of Preventive Cardiology and Non-InvasiveProfessor of Medicine and Director of Preventive Cardiology and Non-Invasive
ImagingImaging
Department of Medicine, Section of CardiologyDepartment of Medicine, Section of Cardiology
Tulane University School of Medicine, New Orleans, LA, USATulane University School of Medicine, New Orleans, LA, USA

2. The Importance of Halting
Atherosclerotic Disease
• Regression of atherosclerotic disease has been
demonstrated to occur using invasive coronary
angiography in long-term follow up studies 1-3
• The minor regression of luminal stenosis
demonstrated in those studies was associated
with a very significant reduction in risk of
cardiovascular events 1-3

3. The Importance of Halting
Atherosclerotic Disease
• Coronary angiography is expensive and
invasive and therefore it is not a practical tool
to assess effectiveness of therapy.
• In observational studies several investigators
have shown that statin therapy can slow
progression of coronary calcification, a very
sensitive marker of atherosclerosis. 4-6

4. Calcium progression influenced by lipid levels*
*
Callister, NEJM 1998

5. Can Calcification be Removed from the
Atherosclerotic Plaque?
• Plaque calcification appears to depend on active processes
of mineralization with deposition of hydroxyapatite crystals
in the plaque. 7
• Many enzymes normally found in bone tissue can be found
in the context of the atherosclerotic plaque. 7
• Vascular cells can express phenotypic changes and behave
similarly to osteoblastic and osteoclastic cells. 8
• Osteoblasts cultured in the presence of ox-LDL loose bone
forming potential. 9

6. Can Calcification be Removed from the
Atherosclerotic Plaque?
• Therefore, active calcium removal from the plaque might be
possible.
• However, since calcification indicates the presence of plaque
even the simple halting of progression might be extremely
beneficial.
• In a recent prospective study Achenbach et al investigated
whether statin therapy in hyperlipemic patients can slow or
reverse coronary calcification measured by means of
sequential Electron Beam Tomography (EBT) imaging.10

7. • As reported in VP Watch of this week, in a
recent prospective study Achenbach et al
investigated whether statin therapy in
hyperlipemic patients can slow or reverse
coronary calcification measured by means of
sequential Electron Beam Tomography
(EBT) imaging.10

8. EBT 2EBT 2EBT 1EBT 1
Does the initiation of lipid-lowering therapy in
hyperlipidemic patients significantly delay the
progression of coronary calcification?
72 Patients LDL-Cholesterol > 130 mg/dl
No treatment with lipid-lowering drugs
No prior coronary intervention or CABG
Sinus rhythm
Calcium volume scores used for sequential analysis
1 year
NO
THERAPY
1 year
CERIVASTATIN
0.3 mg/d
Achenbach S et al Circulation 2002; 106:1077-82
EBT 3

9. 72 patients
11 women / 61 men; mean age: 61 years (36-79 years)
6 patients excluded: 4 discontinued medication
1 pancreatic cancer
1 lost to follow-up
YEAR 1 YEAR 2
NO TREATMENT CERIVASTATIN 0.3 mg/d
CHOLESTEROL (mg/dl) 244 ± 32 188 ± 28 -23%*
LDL-CHOL. (mg/dl) 164 ± 30 107 ± 21 -35%*
HDL-CHOL. (mg/dl) 51 ± 12 52 ± 12 +2%
n = 66
* p < 0.001

10. VOLUME
SCORE
EBT 1 EBT 2 EBT 3
287±346 353±421 374±441
NO TREATMENT CERIVASTATIN 0.3 mg/d
+25%* +8.8%*
*p < 0.0001

11. Conclusions:
• This was the first study to employ a prospective
design to follow progression of coronary calcification
in patients exposed to treatment with statins
• It demonstrated that the findings of prior
observational studies were credible:
-the plaque calcification process can be
significantly slowed with statin therapy
- EBT is a useful non-invasive tool for the
follow up of progression of cardiovascular
calcification

12. Conclusions:
• Reversal of coronary calcification was not
demonstrable in the entire group
• Nonetheless, the average calcium volume score
change in 32 pts achieving LDL<100 mg/dl was
slightly negative (-3.4%)
• It remains to be demonstrated that slowing of coronary
calcification is associated with reduced risk of events

13. References
1. Brown G et al. New Engl J Med 1990;323:1289–98
2. Watts GF et al. Lancet 1992;339:563–9
3. Jukema JW et al. Circulation 1995;91:2528–40.
4. Callister et al, NEJM 1998;339:1972-78
5. Budoff et al, AJC 2000;86:8-11
6. Schmermund et al, ATVB 2001;21:421-426
7. Bostrom K, et al. Bone morphogenetic protein expression in human atherosclerotic
lesions. J Clin Invest 1993;91:1800-1809
8. Bostrom K. Cell differentiation in vascular calcification. Z Kardiol 2000;89:II69-II74
9. Parhami F, et al. Arterioscler Thromb Vasc Biol 1997;17:680-687
10. Achenbach S. et al Circulation 2002; 106:1077-82