No abstract

Background-Recent clinical trials have suggested that intensive versus standard lipid-lowering therapy provides for additional benefit. Electron-beam computed tomography provides the opportunity to quantify the progression of coronary artery calcification (CAC) in serial measurements. Methods and Results-In a multicenter, randomized, double-blind trial, 471 patients (age 61Ϯ8 years) who had no history of coronary artery disease and no evidence of high-grade coronary stenoses (Ͼ50% diameter reduction) were randomized if they had Ն2 cardiovascular risk factors and moderate calcified coronary atherosclerosis as evidenced by a CAC score Ն30. Patients were assigned to receive 80 mg or 10 mg of atorvastatin per day over 12 months. Progression of CAC volume scores could be analyzed in 366 patients. After pretreatment with 10 mg of atorvastatin for 4 weeks, 12 months of study medication reduced LDL cholesterol from 106Ϯ22 to 87Ϯ33 mg/dL in the group randomized to receive 80 mg of atorvastatin (PϽ0.001), whereas levels remained stable in the group randomized to receive 10 mg (108Ϯ23 at baseline, 109Ϯ28 mg/dL at the end of the study, PϭNS). The mean progression of CAC volume scores, corrected for the baseline CAC volume score, was 27% (95% CI 20.8% to 33.1%) in the 80-mg atorvastatin group and 25% (95% CI 19.1% to 30.8%) in the 10-mg atorvastatin group (Pϭ0.65). CAC progression showed no relationship with on-treatment LDL cholesterol levels. Conclusions-We did not observe a relationship between on-treatment LDL cholesterol levels and the progression of calcified coronary atherosclerosis. Over a period of 12 months, intensive atorvastatin therapy was unable to attenuate CAC progression compared with standard atorvastatin therapy. The possibility remains that the time window was too short to demonstrate an effect. (Circulation. 2006;113:427-437.)

No abstract

We thank Drs Romanens and Miserez for their interest in our study. 1 We completely agree with their conclusion that our study cannot be used to argue against the predictive ability of coronary artery calcification (CAC) scores regarding cardiovascular events. The predictive ability of CAC has been demonstrated in numerous studies (please see References 14 and 23 in our article for further reading), and it should be viewed independent of the progression of CAC over 12 months under the effects of lipid-lowering therapy with different intensity.The statistical power calculations underlying our study were performed considering the primary end point of the study, that is, the percent change of total CAC volume scores between baseline and final determination (after 12 months of atorvastatin treatment). Accordingly, the expected standard deviation of the change of CAC volume scores was considered. The standard deviation of the absolute CAC volume scores could be neglected because these were largely unrelated to the study end point.It is true that in the end, the standard deviation of the change of CAC volume scores in our study was somewhat greater than the expected 30%. It was 46.5% in the group receiving 10 mg atorvastatin and 35.9% in the group receiving 80 mg atorvastatin. This does not, however, explain the neutral finding. Rather, the study had been planned assuming a positive linear relation between the percent change of total CAC volume scores and the percent change of low-density lipoprotein cholesterol (LDL-C) values. However, the clear relation suggested by Callister et al 2 was not observed (see Figure 6 in our article). Indeed, the percent change of total CAC volume scores was independent of LDL-C values or percent change of LDL-C values during the study. This "neutral" finding has been confirmed in other randomized trials of lipid-lowering therapy versus placebo 3,4 and more intensive versus standard lipid-lowering therapy. 5 Because CAC progression seems to be unrelated to LDL-C values at least during the first years of therapy, it does not appear to be a suitable measurement for assessing lipid-lowering treatment effects. On the other hand, the predictive value of crosssectional measurements of CAC has been demonstrated repeatedly, and CAC progression does portend its own risk independent of statin therapy and on-treatment LDL-C values. 3,6 Despite many questions that remain to be addressed, the current evidence suggests that with measuring CAC, we have a parameter at hand that is complementary to the information derived from risk factor analysis and lipid-lowering therapy rather than being competitive in its prognostic ability.

No abstract