title: Biochemical and clinical correlation of intraplaque neovascularization using contrast-enhanced ultrasound of the carotid artery.
abstract: OBJECTIVE
  Several biomarkers reflecting inflammatory or proteolytic activity have been known to represent plaque vulnerability. Moreover, a recent study confirmed that contrast-enhanced ultrasound (CEUS) can visualize intraplaque neovascularization (IPN) and demonstrate plaque vulnerability. In this study, we tried to demonstrate that IPN detected by CEUS was correlated with several well-known biomarkers and clinical outcome in patients with coronary artery disease (CAD).
  
  
  METHODS
  Patients with stable CAD were screened by conventional carotid ultrasound and patients with carotid plaque thickness more than 2 mm were performed by CEUS for the presence of IPN. Plasma levels of biomarkers and clinical outcomes were evaluated.
  
  
  RESULTS
  Among consecutive 89 patients fulfilled the inclusion criteria, 30 patients without IPN (group 1) and 59 patients with IPN (group 2) were analyzed. There were no significant difference in baseline characteristics except for mean age (62.9±10.1 yrs versus 68.4±9.6 yrs, p=0.015). On multivariate analysis, only MMP-9 (p=0.021, 95% CI 1.002-1.027) showed a significant association with IPN. But patients with IPN showed only trend for a history of cardiovascular disease (CVD) (44% versus 30%, p=0.19) and one-year cardiovascular events (CVE) (6.8% versus 3.3%, p=0.50) compared to group 1. Maximum plaque thickness (p=0.04, 95% CI 1.230-6.322) showed a significant correlation with the clinical outcome including CVD or CVE.
  
  
  CONCLUSIONS
  MMP-9 correlated with IPN on CEUS. For clinical implication, however, large prospective studies are needed.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Jong Shin
authors.initials: JS
authors.lastname: Woo
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Bu Yong
authors.initials: BY
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Hyun Hee
authors.initials: HH
authors.lastname: Jang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Hwang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Kwon
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Jin Bae
authors.initials: JB
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Xianwu
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, China.
authors.forename: Enze
authors.initials: E
authors.lastname: Jin
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University, Seoul, South Korea. Electronic address: kkabeeheart@empal.com.
authors.forename: Woo Shik
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Kwon Sam
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kyung Hee University, Seoul, South Korea. Electronic address: mylovekw@hanmail.neet.
authors.forename: Weon
authors.initials: W
authors.lastname: Kim
mesh_terms: D000367:Age Factors; D000368:Aged; D015415:Biomarkers; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging*; D059168:Carotid Intima-Media Thickness; D056668:Cathepsin L / Q000097:blood; D015897:Comorbidity; D003287:Contrast Media; D005260:Female; D005466:Fluorocarbons; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood / Q000000981:diagnostic imaging*; D010743:Phospholipids; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000000981:diagnostic imaging*; D011446:Prospective Studies; D013459:Sulfur Hexafluoride; D018615:Ultrasonography, Doppler, Color; D018617:Ultrasonography, Doppler, Pulsed
chemical_list: D015415:Biomarkers; D003287:Contrast Media; D005466:Fluorocarbons; D010743:Phospholipids; C420843:contrast agent BR1; C534281:CTSL protein, human; D056668:Cathepsin L; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D013459:Sulfur Hexafluoride; C042852:perflutren
keywords: Atherosclerosis; Biomarker; Carotid-enhanced ultrasound; Intraplaque neovascularization; Matrix metalloproteinase-9