Beneficial changes of serum calcification markers and contralateral carotid plaques echogenicity after combined carotid artery stenting plus intensive lipid-lowering therapy in patients with bilateral carotid stenosis.

OBJECTIVES/DESIGN In symptomatic patients treated with ipsilateral carotid artery stenting (CAS) plus intensive lipid lowering, we assessed the changes of osteopontin (OPN), osteoprotegerin (OPG) and the Gray-Scale Median (GSM) score contralateral to symptomatic carotid stenosis. MATERIALS/METHODS Forty-six symptomatic patients (group A) with significant carotid stenosis (North American Symptomatic Carotid Endarterectomy Trial (NASCET): >70%) underwent ipsilateral CAS. Those patients had simultaneously contralateral low-grade carotid stenosis (NASCET: 30-69%). Group B included 67 symptomatic patients with low-grade bilateral carotid stenosis (NASCET: 30-69%), but without indications for revascularisation. All patients were treated with atorvastatin (10-80mg) to target low-density lipoprotein (LDL)<100mgdl(-1). Blood samples and plaques' GSM score contralateral to brain infarct were assayed at baseline and after 6 months. RESULTS At baseline, there were no significant differences between groups (p>0.05). Six-month atorvastatin treatment equivalently improved lipid profile in both groups (p<0.05). The parameters hsCRP, OPN and OPG were significantly down-regulated within both groups, but to a greater extent in group A (p<0.05). Besides this, contralateral GSM score was significantly improved from baseline in both groups (p<0.01), but that increment was more pronounced in group A (vs. group B; p=0.041). These changes were inversely correlated with changes in OPN (p=0.014), OPG (p=0.011) and LDL (p=0.041). CONCLUSION Ipsilateral CAS plus intensive lipid-lowering therapy was associated with enhanced contralateral carotid plaque stability and attenuated inflammatory burden and calcification inhibitors to a greater extent than atorvastatin therapy alone in patients with bilateral carotid stenosis.

[1]  William Insull,et al.  Bilateral Symmetry of Human Carotid Artery Atherosclerosis , 2002, Stroke.

[2]  C. Baracchini,et al.  Progression of atherosclerosis in asymptomatic carotid arteries after contralateral endarterectomy: a 10-year prospective study. , 2007, Journal of vascular surgery.

[3]  Mark Fisher,et al.  Carotid Plaque Pathology: Thrombosis, Ulceration, and Stroke Pathogenesis , 2005, Stroke.

[4]  P. Allan,et al.  Fate of the non‐operated carotid artery after contralateral endarterectomy , 1995, The British journal of surgery.

[5]  P. Rothwell,et al.  Risk of Coronary and Other Nonstroke Vascular Death in Relation to the Presence and Extent of Atherosclerotic Disease at the Carotid Bifurcation , 2006, Stroke.

[6]  Martin J Graves,et al.  Assessment of Inflammatory Burden Contralateral to the Symptomatic Carotid Stenosis Using High-Resolution Ultrasmall, Superparamagnetic Iron Oxide–Enhanced MRI , 2006, Stroke.

[7]  R Eugene Zierler,et al.  Carotid artery stenosis: gray-scale and Doppler US diagnosis--Society of Radiologists in Ultrasound Consensus Conference. , 2003, Radiology.

[8]  R. Vito,et al.  Markers of inflammation collocate with increased wall stress in human coronary arterial plaque , 2009, Biomechanics and modeling in mechanobiology.

[9]  M. Davidson,et al.  A review of lipid management in primary and secondary prevention. , 2009, Journal of cardiopulmonary rehabilitation and prevention.

[10]  Spyretta Golemati,et al.  The relationship between serum levels of vascular calcification inhibitors and carotid plaque vulnerability. , 2008, Journal of vascular surgery.

[11]  G. Sangiorgi,et al.  Role of Inflammation in Atherosclerosis* , 2007, Journal of Nuclear Medicine.

[12]  A. Arauz,et al.  Carotid plaque inflammation detected by 18F-fluorodeoxyglucose-positron emission tomography Pilot study , 2007, Clinical Neurology and Neurosurgery.

[13]  Stefan Puchner,et al.  Increasing carotid plaque echolucency is predictive of cardiovascular events in high-risk patients. , 2008, Radiology.

[14]  W. Sheu,et al.  The short-/intermediate-term changes in novel vascular inflammatory markers after angioplasty plus stenting in patients with symptomatic advanced systemic arterial diseases. , 2004, Atherosclerosis.

[15]  W. Poewe,et al.  Osteoprotegerin Is a Risk Factor for Progressive Atherosclerosis and Cardiovascular Disease , 2004, Circulation.

[16]  K. Yokote,et al.  NK‐104, a 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitor, reduces osteopontin expression by rat aortic smooth muscle cells , 2001, British journal of pharmacology.

[17]  D. Charlesworth,et al.  Variability in measurement of internal carotid artery stenosis by arch angiography and duplex ultrasonography--time for a reappraisal? , 2001, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[18]  C. Liapis,et al.  Cardiorespiratory capacity is associated with favourable cardiovascular risk profile in patients with Type 2 diabetes. , 2009, Journal of diabetes and its complications.

[19]  T. Rand,et al.  Grading of Internal Carotid Artery Stenosis: Can CTA Overcome the Confusion? , 2006, Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists.

[20]  A. Dahl,et al.  Soluble CD36 in Plasma Is Increased in Patients With Symptomatic Atherosclerotic Carotid Plaques and Is Related to Plaque Instability , 2008, Stroke.

[21]  H. Weintraub,et al.  Identifying the vulnerable patient with rupture-prone plaque. , 2008, The American journal of cardiology.

[22]  J. Granada,et al.  The effect of percutaneous coronary intervention on inflammatory response and endothelial progenitor cell recruitment , 2008, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[23]  W. Insull The pathology of atherosclerosis: plaque development and plaque responses to medical treatment. , 2009, The American journal of medicine.

[24]  L. Liaw,et al.  Osteopontin: A Multifunctional Molecule Regulating Chronic Inflammation and Vascular Disease , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[25]  J. Golledge,et al.  Osteoprotegerin and Osteopontin Are Expressed at High Concentrations Within Symptomatic Carotid Atherosclerosis , 2004, Stroke.

[26]  A. Nicolaides,et al.  ESVS guidelines. Invasive treatment for carotid stenosis: indications, techniques. , 2009, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[27]  B. Perler The effect of statin medications on perioperative and long-term outcomes following carotid endarterectomy or stenting. , 2007, Seminars in vascular surgery.

[28]  C. Liapis,et al.  Intensive lipid-lowering therapy ameliorates novel calcification markers and GSM score in patients with carotid stenosis. , 2008, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[29]  D. Mikhailidis,et al.  Pleiotropic effects of statins--clinical evidence. , 2009, Current pharmaceutical design.

[30]  M. Järvilehto,et al.  Vasa vasorum hypoxia: initiation of atherosclerosis. , 2009, Medical hypotheses.

[31]  M. Hori,et al.  Statin therapy increases carotid plaque echogenicity in hypercholesterolemic patients. , 2008, Ultrasound in medicine & biology.

[32]  B. Lal,et al.  Pixel distribution analysis of B-mode ultrasound scan images predicts histologic features of atherosclerotic carotid plaques. , 2002, Journal of vascular surgery.