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In the last years, the concepts of plaque vulnerability, composition of the plaque, and ­cerebrovascular events have been vastly studied. The gray scale median (GSM) score has been proposed with the intent of identifying asymptomatic patients at high risk of stroke. Several studies demonstrated the relationship between carotid plaque echolucency ­evaluated by GSM, hs-CRP, carotid plaque infiltration by macrophage, neovascularization, plaque rupture, embolic load to the brain, and eventually risk of stroke. The GSM analysis has been included in the current guidelines for treatment of patients with carotid stenoses, both with endovascular and surgical approach.

AIMS: The time course of atherosclerosis burden in distinct vascular territories remains poorly understood. We longitudinally evaluated the natural history of atherosclerotic progression in two different arterial territories using high spatial resolution magnetic resonance imaging (HR-MRI), a powerful, safe, and non-invasive tool. METHODS AND RESULTS: We prospectively studied a cohort of 30 patients (mean age 68.3, n = 9 females) with high Framingham general cardiovascular disease 10-year risk score (29.5%) and standard medical therapy with mild-to-moderate atherosclerosis intra-individually at the level of both carotid and femoral arteries. A total of 178 HR-MRI studies of carotid and femoral arteries performed at baseline and at 1- and 2-year follow-up were evaluated in consensus reading by two experienced readers for lumen area (LA), total vessel area (TVA), vessel wall area (VWA = TVA - LA), and normalized wall area index (NWI = VWA/TVA). At the carotid level, LA decreased (-3.19%/year, P = 0.018), VWA increased (+3.83%/year, P = 0.019), and TVA remained unchanged. At the femoral level, LA remained unchanged, VWA and TVA increased (+5.23%/year and +3.11%/year, both P < 0.01), and NWI increased for both carotid and femoral arteries (+2.28%/year, P = 0.01, and +1.8%/year, P = 0.033). CONCLUSION: The atherosclerotic burden increased significantly in both carotid and femoral arteries. However, carotid plaque progression was associated with negative remodelling, whereas the increase in femoral plaque burden was compensated by positive remodelling. This finding could be related to anatomic and flow differences and/or to the distinct degree of obstruction in the two arterial territories.

Heme oxygenase-1 (HO-1, encoded by the HMOX1 gene) and inducible nitric oxide synthase (iNOS) have been implicated in vascular disease; however the role of these genes remains unclear. Therefore, we studied the mechanism by which iNOS-derived nitric oxide (NO) affects the intimal hyperplasia (IH) formation in relation to HO-1. We show, in a model of balloon injury in rats, that the suppression of vascular smooth muscle cells (VSMC) proliferation by NO required HO-1, while induction of apoptosis of the VSMC by NO does not involve HO-1. To better clarify the molecular mechanism of this finding, we used Hmox1+/+ and Hmox1-/- VSMC exposed to NO. In Hmox1+/+ VSMC, NO is antiproliferative (up to 34% inhibition) and it is associated to an increase of apoptosis (up to 35%) due to a decrease of X-linked inhibitor of apoptosis protein (XIAP) expression level and to the activation of caspase-3. In the absence of HO-1 (Hmox1-/- VSMC) apoptosis was significantly greater (69% p

Stenting of carotid artery disease has emerged as a potential alternative to carotid endarterectomy (CEA), the current gold standard treatment for carotid artery lesions.1, 2, 3, 4 After the initial experience with an unacceptably high rate of neurologic complications, the results have now improved, and, as a consequence, several trials have been planned to compare carotid angioplasty/stenting (CAS) with CEA.5

To the Editor: Dr Reiter analyzed the relationship between carotid plaque morphology and the risk of stroke after carotid artery stenting (CAS), showing that the grayscale median (GSM) is not associated with adverse outcome.1 In the ICAROS Study, we demonstrated that GSM is a predictor of stroke during CAS.2 Dr Cremonesi, with one of the biggest CAS experiences, has already demonstrated Dr Reiter’s findings. They treated patients with a GSM

The effectiveness of carotid endarterectomy (CEA) in the prevention of stroke in symptomatic and asymptomatic patients with carotid stenosis has been demonstrated by several randomized studies (Ferguson et al. 1999; Halliday et al. 2004; MRC European Carotid Surgery Trial 1991; ECACAS 1995). Carotid artery stenting (CAS) is an alternative technique that gives favorable results when associated with the use of brain protection devices (BPD) (Cremonesi et al. 2003).

Stroke is the third leading cause of death and the first cause of disability, which burdens society with the need to supply extensive resources for assistance and rehabilitation. The prevention of stroke has consequently become of utmost importance in modern healthcare. Years ago, several randomized controlled trials (RCT) demonstrated the efficacy of carotid endarterectomy (CEA) in the prevention of stroke in patients with carotid atherosclerosis. 1–4 However, the subsequent introduction of carotid artery stenting (CAS) stressed the need for a critical revision to the management strategy for patients with carotid plaques. One issue that deserves the highest consideration is the indication for treatment. In this article, we analyzed the conventional and emerging parameters used to select surgical or endovascular treatment of carotid artery stenoses, namely, the therapeutic options, risk factors influencing outcome, and evidence supporting various management approaches for patients with carotid disease.

Ischemia-reperfusion injury, a clinical problem during cardiac surgery, involves worsened adenosine trisphosphate (ATP) generation and damage to the heart. We studied carbon monoxide ( CO) pretreatment, proven valuable in rodents but not previously tested in large animals, for its effects on pig hearts subjected to cardiopulmonary bypass with cardioplegic arrest. Hearts of CO-treated pigs showed significantly higher ATP and phosphocreatine levels, less interstitial edema, and apoptosis of cardiomyocytes and required fewer defibrillations after bypass. We conclude that treatment with CO improves the energy status, prevents edema formation and apoptosis, and facilitates recovery in a clinically relevant model of cardiopulmonary bypass surgery.

Carotid artery stenting (CAS) is used widely to treat carotid lesions. Indication to CAS is mostly based, both in trial and in clinical practice, on the percentage of stenosis and the presence or absence of preprocedural neurologic symptoms, whereas the features of the plaque are somehow disregarded and ignored. The most severe complication of CAS is stroke, related to cerebral embolization from carotid plaque. Several studies showed that echolucent plaques generate a higher number of embolic particles following carotid stenting. Echolucency can be measured using the gray scale median, which is an objective and quantitative computer-assisted grading of the echogenicity of carotid plaques. As previously demonstrated in the ICAROS study, carotid plaque echolucency is an independent risk factor for stroke in carotid stenting. Carotid plaque echolucency is one of the parameters that should be mandatory to be considered for indication to treatment.