Early decrease in carotid plaque lipid content as assessed by magnetic resonance imaging during treatment of rosuvastatin

Ruixue Du, Jianming Cai, Xue-Qiao Zhao, Qing-Jun Wang, Dan-Qing Liu, Wen-Xiu Leng, Peng Gao, Hong-Mei Wu, Lin Ma, Ping Ye, Ruixue Du, Jianming Cai, Xue-Qiao Zhao, Qing-Jun Wang, Dan-Qing Liu, Wen-Xiu Leng, Peng Gao, Hong-Mei Wu, Lin Ma, Ping Ye

Abstract

Background: Statin therapy has shown to deplete atherosclerotic plaque lipid content and induce plaque regression. However, how early the plaque lipid depletion can occur with low-density lipoprotein cholesterol (LDL-C) lowering in humans in vivo has not been fully described.

Methods: We enrolled 43 lipid treatment naïve subjects with asymptomatic carotid atherosclerosis and LDL-C ≥ 100 and ≤ 250 mg/dl. Rosuvastatin 5-20 mg/day was used to lower LDL-C levels to < 80 mg/dl. Lipid profile and carotid MRI scans were obtained at baseline, 3, 12, and 24 months. Carotid plaque lipid-rich necrotic core (LRNC) and plaque burden were measured and compared between baseline and during treatment.

Results: Among the 32 subjects who completed the study, at 3 months, an average dose of rosuvastatin of 11 mg/day lowered LDL-C levels by 47% (125.2 ± 24.4 mg/dl vs. 66.7 ± 17.3 mg/dl, p < 0.001). There were no statistically significant changes in total wall volume, percent wall volume or lumen volume. However, LRNC volume was significantly decreased by 7.9 mm3, a reduction of 7.3% (111.5 ± 104.2 mm3 vs. 103.6 ± 95.8 mm3, p = 0.044). Similarly, % LRNC was also significantly decreased from 18.9 ± 11.9% to 17.9 ± 11.5% (p = 0.02) at 3 months. Both LRNC volume and % LRNC continued to decrease moderately at 12 and 24 months, although this trend was not significant.

Conclusions: Among a small number of lipid treatment naïve subjects, rosuvastatin therapy may induce a rapid and lasting decrease in carotid plaque lipid content as assessed by MRI.

Trial registration: ClinicalTrials.Gov numbers NCT00885872.

Figures

Figure 1
Figure 1
REACH study recruitment, enrollment and completion.
Figure 2
Figure 2
Reduction in LRNC and % LRNC during the 24 months of rosuvastatin therapy. The time course of plaque LRNC reduction over 24 months suggested that LRNC (red rhombuses) significantly decreased by 7.9 mm3, a reduction of 7.3% at 3 months, and continue to decrease moderately at 12 and 24 months. †p < 0.05 when compared to baseline. There were no statistically significant differences when LRNC at 12 months compared to that at 3 months, and at 24 months vs. at 12 months. The decrease of % LRNC (green squares) displayed the same trend. *p < 0.05 when compared to baseline. Bars around the estimates are standard error bars. LRNC = lipid-rich necrotic core.
Figure 3
Figure 3
Representative MRIs showing plaque lipid depletion in right common carotid artery over 2 years. The lumen in red, outer wall boundary in blue and lipid content in yellow of the carotid artery were identified and outlined in post-contrast T1W images. LRNC demonstrate isointense on pre-contrast T1W images and TOF, and was detected as non-enhanced areas (relative to surrounding tissues) on CET1W images with the corresponding pre-contrast T1W images used as reference. Regression in LRNC at the same location was found between the baseline, 3 months, 12 months and 24 months MRI scans. MRI = magnetic resonance imaging; LRNC = lipid-rich necrotic core; TOF = time-of-flight; T1W = T1-weighted; T2W = T2-weighted; PDW = proton-density-weighted; CET1W = contrast enhanced T1-weighted.
Figure 4
Figure 4
Associations between changes of LRNC volume at 24 months and LRNC volume at baseline. Spearman rank correlation showed that magnitude of LRNC decrease over 24 months was significantly correlated with the LRNC volume at baseline (r = - 0.53, p = 0.002).

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