Editorial Slides VP Watch – October , 2002 - Volume 2, Issue 36

Influence of Statin Therapy on Progression of Influence of Statin Therapy on Progression of Coronary CalcificationCoronary Calcification

Paolo Raggi, MD, FACP, FACCPaolo Raggi, MD, FACP, FACCProfessor of Medicine and Director of Preventive Cardiology and Non-Invasive Professor of Medicine and Director of Preventive Cardiology and Non-Invasive

ImagingImagingDepartment 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

The Importance of HaltingAtherosclerotic 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

The Importance of HaltingAtherosclerotic 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

Calcium progression influenced by lipid levels*

* Callister et al, NEJM 1998

Budoff et al, AJC 2001

Schmermund et al, ATVB 2001

Callister, NEJM 1998

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

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

• 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

EBT 2EBT 1

Does the initiation of lipid-lowering therapy in hyperlipidemic patients significantly delay the progression of coronary calcification?

72 Patients LDL-Cholesterol > 130 mg/dlNo treatment with lipid-lowering drugsNo prior coronary intervention or CABGSinus rhythmCalcium volume scores used for sequential analysis

1 year

NOTHERAPY

1 year

CERIVASTATIN 0.3 mg/d

Achenbach S et al Circulation 2002; 106:1077-82

EBT 3

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 2NO 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

VOLUME SCORE

EBT 1 EBT 2 EBT 3

287±346 353±421 374±441NO TREATMENT CERIVASTATIN 0.3 mg/d

+25%* +8.8%**p < 0.0001

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

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

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;17:680-68710. Achenbach S. et al Circulation 2002; 106:1077-82