Response to Letter Regarding Article, “Effect of Intensive Versus Standard Lipid-Lowering Treatment With Atorvastatin on the Progression of Calcified Coronary Atherosclerosis Over 12 Months: A Multicenter, Randomized, Double-Blind Trial”

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.

Cardiovascular residual risk assessment in patients undergoing therapy: A combined structural and functional approach

“…Several randomized double-blind trials have evaluated changes in CAC in response to aggressive versus less aggressive LDL lowering (Table 1). Despite signifi cant differences in achieved LDL, the treatment and control groups in all studies had almost identical CAC progression [12][13][14]. The consistent, but misguided, interpretation has been that CAC progression is not useful in tracking the effects of treatment because CAC progression should have paralleled LDL reduction.…”

Coronary Risk Assessment and Arterial Age Calculation Using Coronary Artery Calcium Scoring and the Framingham Risk Score

“…82 A large cohort of patients (n = 4,609) referred by primary physicians for CAC Score measurements with repeat screening was analyzed. 80,[86][87][88][89] The largest trial, the St. Francis Heart Study, did find a significant reduction in cardiovascular events, despite no significant change in CAC Score progression. 83 Similarly, the National Institutes of Health MESA Study has obtained a second CAC Score on a large cohort of patients, and is following for cardiovascular events.…”

“…All achieved a significant improvement in LDL lowering, but none found a statistically significant alteration of temporal progression of CAC Score. 80,[86][87][88][89] The largest trial, the St. Francis Heart Study, did find a significant reduction in cardiovascular events, despite no significant change in CAC Score progression. 87 Further analysis did show that progression of CAC Score along with baseline CAC Scores was the strongest predictor of subsequent cardiovascular events in these baseline asymptomatic patients.…”

High- vs. Low-Intensity Statin Therapy and Changes in Coronary Artery Calcification Density after One Year

“…In mid- to long-term follow-up, statin therapy increases the CAC score as documented by serial non-contrast cardiac CT, suggesting that the plaque-stabilizing effect of statins may be reflected in a higher CAC score [ 8 , 9 ]. However, with a one-year follow-up, randomized controlled trials failed to detect an influence of HIST vs. low-to-intermediate-intensity statin therapy (LIST) on the progression of the Agatston and CAC volume score [ 10 , 11 , 12 , 13 ].…”