Page 16 - Read Online

Page 8 of 15 Miura et al. Vessel Plus 2019;3:1 I http://dx.doi.org/10.20517/2574-1209.2018.69

beneficial and preventive effects against the progression of CA IMT [13-15] . According to meta-analyses of 7
[13]
clinical trials of statins, statin treatments contributed to a mean of -0.012 mm/year reduction in CA IMT .
In the subsequent meta-analyses of 11 clinical trials of statins, the mean differences of changes in carotid
[14]
IMT between statin and placebo therapies were -0.040 mm/25.6 months (P < 0.001) . As regards dosages,
intensive lipid-lowering treatments may result in a more regression of CA IMT compared with moderate
[67]
lipid-lowering treatments in patients with familial hypercholesterolemia .
Statin and CA plaque volume
[17]
Ainsworth et al. used 3-dimensional ultrasound scans and evaluated CA plaque volume after 3 months
treatment with randomly assigned placebo or 80 mg/day of atorvastatin in 38 patients with asymptomatic >
60% CA stenosis: atorvastatin treatments decreased the plaque volume, although placebo treatments caused a
[16]
tendency for the plaque volume to increase. Corti et al. used magnetic resonance imaging (MRI), and found
that 2 years simvastatin treatments induced a significant regression in an asymptomatic plaque in both aorta
and CA in hypercholesterolemic patients. In regard to dosages, the same group investigated effects of doses
of 20 or 80 mg/day simvastatin treatments for a mean follow-up of 18.1 months on CA plaques in 51 patients,
[68]
and showed no differences in vessel wall changes between the two dosages . In another clinical trial, 43
patients with asymptomatic 16%-79% CA stenosis were treated with randomly assigned low (5 mg/day) or high
(40 or 80 mg/day) dosages of rosuvastatin for 2 years, and showed no changes in CA plaque volume between
[69]
the 2 treatment groups on duplex ultrasound . In the trial, however, all plaques with a lipid-rich necrotic
[69]
core at baseline were decreased by a mean of 41% with the statin treatments . It was also demonstrated in
patients with 24 statin-naïve newly diagnosed stable coronary artery diseases that 3 months open-label statin
[70]
treatments induced a 3.1% reduction in the carotid plaque index (normalized vessel wall area) .
Statin and CA plaque vulnerability
The relationships between statin treatments and CA plaque vulnerability were investigated previously [18,19] .
[18]
Tang et al. estimated the extent of inflammations in CA plaques using ultra-small supermagnetic iron
oxide enhanced carotid MRI, which visualizes the infiltrations of macrophages in human CA atheroma
in vivo, and reported that 3 months treatments with a high dose (80 mg/day), but not a low dose (10 mg/day)
[19]
of atorvastatin decreased intra-plaque inflammations. Mujaj et al. reported that high-dosage statins have
beneficial influences on the compositions of CA atherosclerosis: that is, statins shifted vulnerable plaques
[71]
with a lipid core to more stable calcified plaques. Lenglet et al. revealed that statin treatment reduced
serum levels of neutrophilic products, receptor activator of NF-κB ligand/osteoprotegerin ratio, osteopontin,
and MMP-9 /pro-MMP-9 activity in severe CA stenosis patients having no history of ischemic stroke.
Moreover, CA plaques on statin therapy exhibited an increase in collagen, and reduced levels of neutrophil
[71]
infiltration and MMP-9 compared with untreated patients with asymptomatic severe CA stenosis .
Statin in CEA and CAS
Statin therapy is reported to reduce perioperative risks of ischemic stroke, and to improve clinical outcomes
[72]
[72]
in patients with CA stenosis undergoing CEA and CAS . McGirt et al. investigated effects of statin
treatment on the incidences of perioperative strokes and mortality in 1,566 patients with CA stenosis
undergoing CEA, and showed that statins had a benefit to reduce perioperative strokes, TIAs and all-
cause mortality related to CEA. In the report, the usage of statins independently reduced the odds of stroke
[72]
threefold (OR, 0.35) and death fivefold (OR, 0.20) .

Periprocedural usage of statins may be more beneficial in patients with CA stenosis undergoing CAS, as
high-pressure balloons and stents are applied during CAS and therefore thromboses and inflammations
[73]
are likely to be developed within the vessel walls after CAS. Tanemura et al. investigated the association
between cerebral embolisms related to CAS and CA plaque characteristics using 3-dimensional T1-weighted
gradient echo MRI, and revealed that vulnerable and large CA plaques had high risks for cerebral embolisms