Ultrasound Assessment of Carotid Plaque Echogenicity Response to Statin Therapy: A Systematic Review and Meta-Analysis

Objective: To evaluate in a systematic review and meta-analysis model the effect of statin therapy on carotid plaque echogenicity assessed by ultrasound. Methods: We have systematically searched electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to April, 2015, for studies evaluating the effect of statins on plaque echogenicity. Two researchers independently determined the eligibility of studies evaluating the effect of statin therapy on carotid plaque echogenicity that used ultrasound and grey scale median (GSM) or integrated back scatter (IBS). Results: Nine out of 580 identified studies including 566 patients’ carotid artery data were meta-analyzed for a mean follow up of 7.2 months. A consistent increase in the echogenicity of carotid artery plaques, after statin therapy, was reported. Pooled weighted mean difference % (WMD) on plaque echogenicity after statin therapy was 29% (95% CI 22%–36%), p < 0.001, I2 = 92.1%. In a meta-regression analysis using % mean changes of LDL, HDL and hsCRP as moderators, it was shown that the effects of statins on plaque echogenicity were related to changes in hsCRP, but not to LDL and HDL changes from the baseline. The effect of statins on the plaque was progressive; it showed significance after the first month of treatment, and the echogenicity continued to increase in the following six and 12 months. Conclusions: Statin therapy is associated with a favorable increase of carotid plaque echogenicity. This effect seems to be dependent on the period of treatment and hsCRP change from the baseline, independent of changes in LDL and HDL.

[1]  A. Schmermund,et al.  High dose and long-term statin therapy accelerate coronary artery calcification. , 2015, International journal of cardiology.

[2]  P. Ibrahimi,et al.  Vulnerable plaques in the contralateral carotid arteries in symptomatic patients: a detailed ultrasound analysis. , 2014, Atherosclerosis.

[3]  P. Thompson,et al.  A systematic review of the time course of atherosclerotic plaque regression. , 2014, Atherosclerosis.

[4]  P. Ibrahimi,et al.  Coronary and carotid atherosclerosis: how useful is the imaging? , 2013, Atherosclerosis.

[5]  R. Nohara,et al.  Effect of long-term intensive lipid-lowering therapy with rosuvastatin on progression of carotid intima-media thickness--Justification for Atherosclerosis Regression Treatment (JART) extension study. , 2013, Circulation journal : official journal of the Japanese Circulation Society.

[6]  Per Wester,et al.  Coronary and carotid atherosclerosis: similarities and differences. , 2013, Atherosclerosis.

[7]  S. Peters,et al.  Effect of rosuvastatin on the echolucency of the common carotid intima-media in low-risk individuals: the METEOR trial. , 2012, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[8]  C. Cannon,et al.  The controversies of statin therapy: weighing the evidence. , 2012, Journal of the American College of Cardiology.

[9]  R. Sacco,et al.  The short-term effect of atorvastatin on carotid plaque morphology assessed by computer-assisted gray-scale densitometry: a pilot study , 2011, Neurological research.

[10]  Paul Welsh,et al.  Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. , 2011, JAMA.

[11]  A. Nicolaides,et al.  Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification. , 2010, Journal of vascular surgery.

[12]  A. Nicolaides,et al.  The effect of statins on carotid plaque morphology: a LDL-associated action or one more pleiotropic effect of statins? , 2010, Atherosclerosis.

[13]  C. Liapis,et al.  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. , 2010, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[14]  Yasuo Ohashi,et al.  Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials , 2010, The Lancet.

[15]  C. Liapis,et al.  Aggressive lipid-lowering is more effective than moderate lipid-lowering treatment in carotid plaque stabilization. , 2009, Journal of vascular surgery.

[16]  Hiroshi Kanai,et al.  Evaluation of plaque stabilization by fluvastatin with carotid intima- medial elasticity measured by a transcutaneous ultrasonic-based tissue characterization system. , 2009, Journal of atherosclerosis and thrombosis.

[17]  T. Iwama,et al.  Effects of Atorvastatin on Carotid Atherosclerotic Plaques: A Randomized Trial for Quantitative Tissue Characterization of Carotid Atherosclerotic Plaques with Integrated Backscatter Ultrasound , 2009, Cerebrovascular Diseases.

[18]  J. Ioannidis,et al.  The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration , 2009, Annals of Internal Medicine [serial online].

[19]  A. Alexandrov,et al.  Update on Ultrasound Techniques for the Diagnosis of Cerebral Ischemia , 2009, Cerebrovascular Diseases.

[20]  B. Coll,et al.  Carotid intima-media thickness measurements: Techniques and clinical relevance , 2008, Current atherosclerosis reports.

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

[22]  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.

[23]  J. Obata,et al.  Rapid Stabilization of Vulnerable Carotid Plaque Within 1 Month of Pitavastatin Treatment in Patients With Acute Coronary Syndrome , 2008, Journal of Cardiovascular Pharmacology.

[24]  S. Momjian,et al.  Correlation of Cerebrovascular Symptoms and Microembolic Signals With the Stratified Gray-Scale Median Analysis and Color Mapping of the Carotid Plaque , 2006, Stroke.

[25]  S. Achenbach,et al.  Effect of Intensive Versus Standard Lipid-Lowering Treatment With Atorvastatin on the Progression of Calcified Coronary Atherosclerosis Over 12 Months: A Multicenter, Randomized, Double-Blind Trial , 2006, Circulation.

[26]  Matthew A Silva,et al.  Statin-related adverse events: a meta-analysis. , 2006, Clinical therapeutics.

[27]  T. Hirai,et al.  Stabilization of carotid atheroma assessed by quantitative ultrasound analysis in nonhypercholesterolemic patients with coronary artery disease. , 2005, Journal of the American College of Cardiology.

[28]  R. Cianci,et al.  Carotid Plaque Reduction After Medical Treatment , 2005 .

[29]  R. Cianci,et al.  Images in cardiovascular medicine. Carotid plaque reduction after medical treatment. , 2005, Circulation.

[30]  P. Touboul,et al.  Statins in Stroke Prevention and Carotid Atherosclerosis: Systematic Review and Up-to-Date Meta-Analysis , 2004, Stroke.

[31]  K. Slim,et al.  Methodological index for non‐randomized studies (MINORS): development and validation of a new instrument , 2003, ANZ journal of surgery.

[32]  Ali F Aburahma,et al.  Prospective controlled study of the natural history of asymptomatic 60% to 69% carotid stenosis according to ultrasonic plaque morphology. , 2002, Journal of vascular surgery.

[33]  Børge G Nordestgaard,et al.  Macrophages are associated with lipid-rich carotid artery plaques, echolucency on B-mode imaging, and elevated plasma lipid levels. , 2002, Journal of vascular surgery.

[34]  J. Liao,et al.  Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[35]  A. Nicolaides,et al.  Histological verification of computerised carotid plaque characterisation. , 1996, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[36]  J. Seeger,et al.  The relationship between carotid plaque composition, plaque morphology, and neurologic symptoms. , 1995, The Journal of surgical research.

[37]  J. Seeger,et al.  The relationship between carotid plaque composition and neurologic symptoms. , 1987, The Journal of surgical research.