Carotid plaque regression following 6-month statin therapy assessed by 3T cardiovascular magnetic resonance: comparison with ultrasound intima media thickness

Abstract

Background: Cardiovascular magnetic resonance (CMR) allows volumetric carotid plaque measurement that has advantage over 2-dimensional ultrasound (US) intima-media thickness (IMT) in evaluating treatment response. We tested the hypothesis that 6-month statin treatment in patients with carotid plaque will lead to plaque regression when measured by 3 Tesla CMR but not by IMT.

Methods: Twenty-six subjects (67 ± 2 years, 7 females) with known carotid plaque (> 1.1 mm) and coronary or cerebrovascular atherosclerotic disease underwent 3T CMR (T1, T2, proton density and time of flight sequences) and US at baseline and following 6 months of statin therapy (6 had initiation, 7 had increase and 13 had maintenance of statin dosing). CMR plaque volume (PV) was measured in the region 12 mm below and up to 12 mm above carotid flow divider using software. Mean posterior IMT in the same region was measured. Baseline and 6-month CMR PV and US IMT were compared. Change in lipid rich/necrotic core (LR/NC) and calcification plaque components from CMR were related to change in PV.

Results: Low-density lipoprotein cholesterol decreased (86 ± 6 to 74 ± 4 mg/dL, p = 0.046). CMR PV decreased 5.8 ± 2% (1036 ± 59 to 976 ± 65 mm3, p = 0.018). Mean IMT was unchanged (1.12 ± 0.06 vs. 1.14 ± 0.06 mm, p = NS). Patients with initiation or increase of statins had -8.8 ± 2.8% PV change (p = 0.001) while patients with maintenance of statin dosing had -2.7 ± 3% change in PV (p = NS). There was circumferential heterogeneity in CMR plaque thickness with greatest thickness in the posterior carotid artery, in the region opposite the flow divider. Similarly there was circumferential regional difference in change of plaque thickness with significant plaque regression in the anterior carotid region in region of the flow divider. Change in LR/NC (R = 0.62, p = 0.006) and calcification (R = 0.45, p = 0.03) correlated with PV change.

Conclusions: Six month statin therapy in patients with carotid plaque led to reduced plaque volume by 3T CMR, but ultrasound posterior IMT did not show any change. The heterogeneous spatial distribution of plaque and regional differences in magnitude of plaque regression may explain the difference in findings and support volumetric measurement of plaque. 3T CMR has potential advantage over ultrasound IMT to assess treatment response in individuals and may allow reduced sample size, duration and cost of clinical trials of plaque regression.

Figure 1

Ultrasound and CMR images. A. B-mode ultrasound of the common carotid artery demonstrating plaque. Automated software detection is used to measure mean posterior IMT. B. Oblique sagittal spin echo of the carotid artery showing the reference flow divider (white arrow). C. Multicontrast CMR T1/T2/proton density spin echo and time of flight gradient echo images of the same axial slice. Luminal/adventitial borders are outlined to measure plaque area/volume.

Figure 2

CMR Plaque volume. A. All subjects, B. Statin increase group, C. Statin maintain group. Overall there was reduction in CMR PV. Reduction was significant only in the statin increase group.

Figure 3

Ultrasound IMT. A. All subjects, B. statin increase group, C. statin maintain group. There was no significant change from baseline-6 months.

Figure 4

CMR plaque volume reduction. A. Statin increase group (red represents statin naïve subjects, black represents statin intensification subjects), B. statin maintain group. Blue line represents mean for the group.

Figure 5

Circumferential plaque distribution. A. T1 images showing circumferential heterogeneity in plaque thickness. Angular designation is shown in the first image, with the most medial point arbitrarily designated as 360 degrees. B-D. Regional plaque thickness on CMR at baseline and 6 months. Note significant regional variation in plaque thickness (+p < 0.05 versus 241-300 degrees at both 0 and 6 month periods, #p < 0.05 versus 301-360 degrees at both 0 and 6 month periods) with greater plaque thickness at 241-300 and 301-360 degree regions. In all subjects, significant change in plaque thickness was only seen in 61-120 degree region (B); in statin increase patients, significant change was seen in 61-120 and 301-360 degree regions (C). There was no significant regional change in thickness in statin maintain patients (D).