Stabilization of Carotid Atheroma Assessed by Quantitative Ultrasound Analysis in Nonhypercholesterolemic Patients With Coronary Artery Disease

Kumamoto University, Kumamoto, Kumamoto, Japan
Journal of the American College of Cardiology (Impact Factor: 16.5). 12/2005; 46(11):2022-30. DOI: 10.1016/j.jacc.2005.04.070
Source: PubMed


Several large clinical trials have demonstrated that lipid-lowering therapy with statins reduces cardiovascular events (1, 2 and 3). Stabilization rather than regression of vulnerable atheroma is considered the major contributor to this beneficial effect (4). Recent detailed animal studies support the plaque stabilization hypothesis (5); however, clinical evidence of plaque stabilization is uncertain and there are no practical indexes to assess the effectiveness of plaque stabilization therapy. Hence it is difficult for physicians to verify achievement of plaque stabilization and to be able to assess the efficacy of the treatment given their patients. Some hope in this area derives from recent technologic advances that can assist in the evaluation of atherosclerotic plaque vulnerability, such as plaque temperature (6), intravascular angioscopy (7), intravascular ultrasound (8), and optical-coherence tomography (9), but these methods are generally complicated, invasive, expensive, and hardly repeatable. Because plaque stabilization is a promising clinical strategy to prevent cardiovascular complications in patients with established coronary artery disease (CAD) (4), practical and feasible examinations to identify vulnerable plaques and to evaluate the effects of treatment on plaque stabilization are needed.

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    • "Treatment with statins has already shown to influence plaque composition and its ultrasound appearance [6, 7]. As perioperative beta-blockade became standard therapy in the prevention of cardiovascular (CV) events in patients undergoing vascular surgery, the question about their mechanisms of action was raised. "
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    ABSTRACT: The presence of echolucent carotid plaques as defined by low ultrasound grey-scale median (GSM) is associated with a higher risk of stroke and myocardial infarction. Betablockers have shown possible anti-atherosclerotic effects. The aim of the present study was to determine if there is an association between carotid plaque GSM and treatment with betablockers. The GSM of the carotid plaques of 350 patients who underwent carotid endarterectomy (CEA) for asymptomatic (n = 113) or symptomatic (n = 237) carotid disease was measured. Patients were divided in two groups based on the absence/presence of an on-going long-term (i.e. at least 6 months) oral treatment with betablockers at the time of CEA. The prevalence and type of preoperative neurological symptoms were similar in the two groups. Patients with betablockers had more frequently arterial hypertension (P < .0001), diabetes (P = .035) and a higher BMI (P = .0004), while patients without betablockers were most frequently smokers (P = .017). Patients with betablockers revealed to have higher GSM (37.79 ± 25 vs 32.61 ± 23.50 P = .036). Echogenic plaques (i.e. with GSM > 30) showed to be more frequent in patients with betablockers also after correction for age, gender, the occurrence of preoperative symptoms, diabetes, hypertension, smoking and statins use (P = .024). These results suggest the use of standardized ultrasound techniques as an important tool in evaluating the effect of anti-atherosclerotic medications and underline the need of.further prospective randomized studies on larger patient cohorts in order to confirm these results.
    Full-text · Article · Aug 2014 · BMC Cardiovascular Disorders
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    • "As for evaluating the therapeutic effects of irbesartan, the beneficial effects of ARBs on plaque morphology have been confirmed by ultrasound [26], cardiac computed tomography (CT), and magnetic resonance imaging (MRI) [27]. However, few challenges in the use of molecular imaging for evaluating the therapeutic effects of ARBs on atherosclerosis remain. "
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    ABSTRACT: To investigate the effects of irbesartan on inflammation and apoptosis in atherosclerotic plaques by histochemical examination and molecular imaging using (14)C-FDG and (99m)Tc-annexin A5. Irbesartan has a peroxisome proliferator-activated receptor gamma (PPARγ) activation property in addition to its ability to block the AT1 receptor. Accordingly, irbesartan may exert further anti-inflammatory and anti-apoptotic effects in atherosclerotic plaques. However, such effects of irbesartan have not been fully investigated. Molecular imaging using (18)F-FDG and (99m)Tc-annexin A5 is useful for evaluating inflammation and apoptosis in atherosclerotic plaques. Female apoE(-/-) mice were treated with irbesartan-mixed (50 mg/kg/day) or irbesartan-free (control) diet for 12 weeks (n = 11/group). One week after the treatment, the mice were co-injected with (14)C-FDG and (99m)Tc-annexin A5, and cryostat sections of the aortic root were prepared. Histochemical examination with Movat's pentachrome (plaque size), Oil Red O (lipid deposition), Mac-2 (macrophage infiltration), and TUNEL (apoptosis) stainings were performed. Dual-tracer autoradiography was carried out to evaluate the levels of (14)C-FDG and (99m)Tc-annexin A5 in plaques (%ID×kg). In vitro experiments were performed to investigate the mechanism underlying the effects. Histological examination indicated that irbesartan treatment significantly reduced plaque size (to 56.4%±11.1% of control), intra-plaque lipid deposition (53.6%±20.2%) and macrophage infiltration (61.9%±20.8%) levels, and the number of apoptotic cells (14.5%±16.6%). (14)C-FDG (43.0%±18.6%) and (99m)Tc-annexin A5 levels (45.9%±16.8%) were also significantly reduced by irbesartan treatment. Irbesartan significantly suppressed MCP-1 mRNA expression in TNF-α stimulated THP-1 monocytes (64.8%±8.4% of un-treated cells). PPARγ activation was observed in cells treated with irbesartan (134%±36% at 3 µM to 3329%±218% at 81 µM) by a PPARγ reporter assay system. Remissions of inflammation and apoptosis as potential therapeutic effects of irbesartan on atherosclerosis were observed. The usefulness of molecular imaging using (18)F-FDG and (99m)Tc-annexin A5 for evaluating the therapeutic effects of irbesartan on atherosclerosis was also suggested.
    Full-text · Article · Feb 2014 · PLoS ONE
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    • "Although the patients enrolled in the ENHANCE study had relatively low levels of carotid artery intima-media thickening and a correlation between carotid artery intima-media thickening change and cardiovascular outcome was not investigated, adding ezetimibe to statin did not reduce carotid artery intima-media thickness. On the other hand, others have shown that statins cause carotid intima-media thickness to regress [45,46]. According to these and the present findings, quadruple-dose statin might be more favourable than a combination of ezetimibe and statin at least from the viewpoint of an anti-atherogenic effect. "
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    ABSTRACT: Statins are frequently administered to reduce low-density lipoprotein cholesterol (LDL-C) and vascular inflammation, because LDL-C and high sensitive C-reactive protein (hs-CRP) are associated with high risk for cardiovascular events. When statins do not reduce LDL-C to desired levels in high-risk patients with coronary artery disease (CAD), ezetimibe can be added or the statin dose can be increased. However, which strategy is more effective for treating patients with CAD has not been established. The present study compares anti-inflammatory effects and lipid profiles in patients with CAD and similar LDL-C levels who were treated by increasing the statin dose or by adding ezetimibe to the original rosuvastatin dose to determine the optimal treatment for such patients. 46 patients with high-risk CAD and LDL-C and hs-CRP levels of >70 mg/dL and >1.0 mg/L, respectively, that were not improved by 4 weeks of rosuvastatin (2.5 mg/day) were randomly assigned to receive 10 mg (R10, n = 24) of rosuvastatin or 2.5 mg/day of rosuvastatin combined with 10 mg/day of ezetimibe (R2.5/E10, n = 22) for 12 weeks. The primary endpoint was a change in hs-CRP. Baseline characteristics did not significantly differ between the groups. At 12 weeks, LDL-C and inflammatory markers (hs-CRP, interleukin-6, tumour necrosis factor-alpha and pentraxin 3) also did not significantly differ between the two groups (LDL-C: R10 vs. R2.5/E10: -19.4 ± 14.2 vs. -22.4 ± 14.3 mg/dL). However, high-density lipoprotein cholesterol (HDL-C) was significantly improved in the R10, compared with R2.5/E10 group (4.6 ± 5.9 vs. 0.0 ± 6.7 mg/dL; p < 0.05). Both enhanced therapies exerted similar anti-inflammatory effects under an equal LDL-C reduction in patients with high-risk CAD despite 2.5 mg/day of rosuvastatin. However, R10 elevated HDL-C more effectively than R2.5/E10. Trial registration
    Full-text · Article · Feb 2013 · Lipids in Health and Disease
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