Prevalence and risk factors of carotid vessel wall inflammation in coronary artery disease patients: FDG-PET and CT imaging study.

OBJECTIVES We investigated the prevalence and clinical risk factors of carotid vessel wall inflammation by means of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in a population consisting of coronary artery disease (CAD) patients. BACKGROUND The atherosclerotic disease process is characterized by infiltration and retention of oxidized lipids in the artery wall, triggering a disproportionate inflammatory response. Efforts have been made to use noninvasive imaging to quantify this inflammatory response in the vessel wall. Recently, carotid FDG-PET has been shown to reflect the metabolic rate of glucose, a process known to be enhanced in inflamed tissue. METHODS Carotid inflammation was quantified in 82 CAD patients (age 62 ± 10 years) as the maximum target-to-background ratio ((wholevessel)TBR(max)). Furthermore, we assessed the maximal standardized uptake value values ((wholevessel)SUV(max)), the single hottest segment (SHS), and the percent active segments (PAS) of the FDG uptake in the artery wall, measured by FDG-PET. RESULTS Whole-vessel TBR(max) >1.8 was present in 67%, >2.0 in 39%, >2.2 in 23%, and >2.4 in 12% of the population. Multiple linear regression analysis with backward elimination revealed that body mass index (BMI) ≥30 kg/m2 (p < 0.0001), age >65 years (p = 0.01), smoking (p = 0.02), and hypertension (p = 0.01) were associated with (wholevessel)TBR(max). The number of components of the metabolic syndrome was also associated with (wholevessel)TBR(max) (p = 0.02). In similar analyses, (wholevessel)SUV(max) was associated with BMI ≥30 kg/m2 (p < 0.0001), age >65 years (p = 0.004), male gender (p = 0.02), and hypertension (p = 0.04); SHS with BMI ≥30 kg/m2 (p < 0.0001), age >65 years (p = 0.02), smoking (p = 0.04), and hypertension (p = 0.05); PAS with BMI ≥30 kg/m2 (p = 0.001), smoking (p = 0.03), and hypertension (p = 0.01). CONCLUSIONS Carotid inflammation as revealed by FDG-PET is highly prevalent in the CAD population and is associated with obesity, age over 65 years, history of hypertension, smoking, and male gender. Artery wall FDG uptake increased when components of the metabolic syndrome clustered.

[1]  R. Virmani,et al.  Activated inflammatory cells are associated with plaque rupture in carotid artery stenosis. , 1997, Surgery.

[2]  Diederik F Van Wijk,et al.  Mycophenolate mofetil attenuates plaque inflammation in patients with symptomatic carotid artery stenosis. , 2010, Atherosclerosis.

[3]  Joel Karp,et al.  Consensus recommendations for the use of 18F-FDG PET as an indicator of therapeutic response in patients in National Cancer Institute Trials. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[4]  Paul M. Ridker,et al.  Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein , 2009 .

[5]  Victor M Montori,et al.  Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. , 2007, Journal of the American College of Cardiology.

[6]  Sungeun Kim,et al.  Serum adipocyte fatty acid-binding protein is associated independently with vascular inflammation: analysis with (18)F-fluorodeoxyglucose positron emission tomography. , 2011, The Journal of clinical endocrinology and metabolism.

[7]  Ahmed Tawakol,et al.  Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography , 2005, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[8]  Masatoshi Ishibashi,et al.  Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. , 2006, Journal of the American College of Cardiology.

[9]  V. Fuster,et al.  Imaging atherosclerotic plaque inflammation by fluorodeoxyglucose with positron emission tomography: ready for prime time? , 2010, Journal of the American College of Cardiology.

[10]  Paul Kinahan,et al.  Analytic 3D image reconstruction using all detected events , 1989 .

[11]  B. Spiegelman,et al.  Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. , 1993, Science.

[12]  B. Howard,et al.  Obesity and dyslipidemia. , 2003, Endocrinology and metabolism clinics of North America.

[13]  V. Fuster,et al.  (18)Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. , 2007, Journal of the American College of Cardiology.

[14]  M. Reiser,et al.  18F-FDG PET/CT Identifies Patients at Risk for Future Vascular Events in an Otherwise Asymptomatic Cohort with Neoplastic Disease , 2009, Journal of Nuclear Medicine.

[15]  Marc Faraggi,et al.  Arterial wall uptake of fluorodeoxyglucose on PET imaging in stable cancer disease patients indicates higher risk for cardiovascular events , 2008, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[16]  H. Sillesen,et al.  Gene expression and 18FDG uptake in atherosclerotic carotid plaques , 2010, Nuclear medicine communications.

[17]  K. Walsh,et al.  Adiponectin as an anti-inflammatory factor. , 2007, Clinica chimica acta; international journal of clinical chemistry.

[18]  Neil J Stone,et al.  Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines , 2004, Circulation.

[19]  M. Komatsu,et al.  Adiponectin inversely correlates with high sensitive C-reactive protein and triglycerides, but not with insulin sensitivity, in apparently healthy Japanese men. , 2007, Endocrine journal.

[20]  P. Libby,et al.  Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. , 2008, The New England journal of medicine.

[21]  Ahmed Tawakol,et al.  In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. , 2006, Journal of the American College of Cardiology.

[22]  Diederik F Van Wijk,et al.  Novel insights into anti-inflammatory actions of HDL. , 2010, Atherosclerosis.

[23]  John S. Hill,et al.  Myeloperoxidase and C-reactive protein have combined utility for long-term prediction of cardiovascular mortality after coronary angiography. , 2010, Journal of the American College of Cardiology.

[24]  C. Block,et al.  Mechanisms linking obesity with cardiovascular disease , 2006, Nature.

[25]  J. Pickard,et al.  Imaging Atherosclerotic Plaque Inflammation With [18F]-Fluorodeoxyglucose Positron Emission Tomography , 2002, Circulation.

[26]  Paul M Ridker,et al.  Inflammation in atherosclerosis: from pathophysiology to practice. , 2009, Journal of the American College of Cardiology.

[27]  J. Kastelein,et al.  Surrogate markers in clinical trials--challenges and opportunities. , 2009, Atherosclerosis.

[28]  H. Steinmetz,et al.  Inflammation in high-grade carotid stenosis: a possible role for macrophages and T cells in plaque destabilization. , 1998, Stroke.

[29]  Sungeun Kim,et al.  Vascular Inflammation in Patients With Impaired Glucose Tolerance and Type 2 Diabetes: Analysis With 18F-Fluorodeoxyglucose Positron Emission Tomography , 2010, Circulation. Cardiovascular imaging.

[30]  Paul Zimmet,et al.  The metabolic syndrome—a new worldwide definition , 2005, The Lancet.

[31]  H. Schumacher,et al.  Immunophenotypic characterisation of carotid plaque: increased amount of inflammatory cells as an independent predictor for ischaemic symptoms. , 2001, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[32]  M. Eliasziw,et al.  Statistical methodology for the concurrent assessment of interrater and intrarater reliability: using goniometric measurements as an example. , 1994, Physical therapy.

[33]  Peter Libby,et al.  The forgotten majority: unfinished business in cardiovascular risk reduction. , 2005, Journal of the American College of Cardiology.

[34]  V. Fuster,et al.  Relationships Among Regional Arterial Inflammation, Calcification, Risk Factors, and Biomarkers: A Prospective Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Imaging Study , 2009, Circulation. Cardiovascular imaging.

[35]  George Steiner,et al.  Safety and tolerability of dalcetrapib. , 2009, The American journal of cardiology.

[36]  A. Becker,et al.  Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. , 1994, Circulation.

[37]  Eun Jeong Lee,et al.  Reversal of Vascular 18F-FDG Uptake with Plasma High-Density Lipoprotein Elevation by Atherogenic Risk Reduction , 2008, Journal of Nuclear Medicine.

[38]  T. Imaizumi,et al.  Vascular inflammation evaluated by [18F]-fluorodeoxyglucose positron emission tomography is associated with the metabolic syndrome. , 2007, Journal of the American College of Cardiology.

[39]  P. Libby,et al.  Obesity, inflammation, and atherosclerosis , 2009, Nature Reviews Cardiology.