High coronary plaque load: a heavy burden.

Hydroxymethylglutaryl (HMG) CoA-reductase inhibitors, or statins, play an important role in the primary and secondary prevention of coronary heart disease. By inhibiting the enzyme HMG-CoA reductase, statins lower the production of cholesterol in the liver, resulting in lower LDL cholesterol levels. Besides lowering cholesterol levels, statin therapy slows down plaque progression and in some patients even causes plaque regression. In the beginning of the 1990s, the first trials were initiated to assess the effect of statin therapy on plaque dynamics. Randomized trials, such as MARS and REGRESS, used (quantitative) invasive coronary angiography (ICA) to assess luminal stenosis characteristics. Since ICA only allows assessment of the coronary lumen, differences in minimal lumen diameters (MLDs) and mean segment diameters (MSDs) between baseline and follow-up were assessed as a measurement of coronary plaque change. These early studies demonstrated that moderate dose statin therapy on average reduces plaque progression. Importantly, this was associated with a reduction of major adverse cardiovascular events (MACEs). Of note, it was shown that the beneficial effect of statin therapy is more pronounced in more severe lesions. A relative shortcoming of these studies was the inability of ICA to visualize true coronary atherosclerotic burden. Around the same time as the first angiographic studies with statin therapy were executed, a novel method for the assessment of coronary plaque burden was designed; intracoronary ultrasound (ICUS), nowadays known as intravascular ultrasound (IVUS). This invasive method uses ultrasound to create two-dimensional tomographic images of the coronary lumen and vessel wall morphology. Since then IVUS is frequently used for coronary plaque assessment and has been widely validated for serial plaque imaging. IVUS is able to visualize true atherosclerotic burden with a high resolution and could be of value, not only for prognostic implications, but also to provide novel insights into the mechanisms of plaque dynamics in patients receiving statin therapy. In the future, non-invasive, serial assessment of coronary atherosclerosis could be feasible using quantitative computed tomography coronary angiography (QCT). Figure 1 demonstrates the difference in coronary plaque assessment between ICA, IVUS, and QCT. Puri et al. have now presented the results of a novel substudy of the SATURN trial. In this study, 1039 patients underwent serial IVUS before and after 24 months of statin therapy. Patients were randomized to the highest dose of either rosuvastatin (40 mg) or atorvastatin (80 mg), which is currently the most intensive statin regiment used in clinical practice. Serial IVUS was performed in a single coronary artery, without significant luminal stenosisor previous revascularization. The authors investigated the prognostic influence of baseline percentage atheroma volume (PAV) on: (i) MACEs; (ii) lipid levels at baseline and follow-up; and (iii) coronary plaque progression. It was demonstrated that PAV at baseline is associated with the occurrence of MACEs during 2 years of follow-up. The incidence of MACEs in patients in the lowest quartile of PAV was 5.1% and was significantly increased stepwise per PAV quartile (5.1, 5.7, 7.9, and 12%, respectively, P 1⁄4 0.001). This relationship remained significant after correction for baseline risk factors. Of particular interest, neither LDL cholesterol levels at baseline nor those after high dose statin treatment could independently predict MACEs. Thereafter, the correlation between PAV at baseline and plaque progression on IVUS was assessed. As expected, patients with PAV above the median demonstrated a greater reduction in PAV at 12 months follow-up. Accordingly, in these patients, lumen volume was significantly more increased after therapy compared with patients with PAV below the median. However, no significant differences in vessel wall volume were observed between the two groups. Thus, patients with heavydiseaseburden atbaseline benefit relativelymore from aggressive/high dose statin therapy with regard to plaque regression, compared with patients with a light disease burden, confirming the older ICA results with modest dose statin therapy. One of the most striking results of this study is the fact that LDL levels at baseline or after statin treatment showed no predictive value for MACEs. This could lead to doubt about the beneficial effect of LDL-lowering therapy. However, as also discussed by the authors, there is overwhelming evidence for the beneficial effects