Kevin D O'Brien1, Daniel S Hippe2, Huijun Chen3, Moni B Neradilek4, Jeffrey L Probstfield5, Suzanne Peck6, Daniel A Isquith5, Gador Canton7, Chun Yuan2, Nayak L Polissar4, Xue-Qiao Zhao5, William S Kerwin8. 1. Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: cardiac@uw.edu. 2. Department of Radiology, University of Washington, Seattle, WA, USA. 3. Center for Biomedical Imaging Research, Tsinghua University, Beijing, China. 4. The Mountain-Whisper-Light Statistics, Seattle, WA, USA. 5. Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA. 6. Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, WA, USA. 7. Department of Mechanical Engineering, University of Washington, Seattle, WA, USA. 8. Presage Biosciences, Inc., Seattle, WA, USA.
Abstract
OBJECTIVE: Plaque neovasculature is a major route for lipoprotein and leukocyte ingress into plaques, and has been identified as a risk factor for carotid plaque disruption. Vp, a variable derived from pharmacokinetic modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), correlates with plaque neovasculature density. Because lipid-lowering therapy has been associated with regression of neovasculature in animal models, we sought to determine clinical correlates of carotid plaque neovasculature (as assessed by Vp) in participants on statin therapy for established cardiovascular disease. METHODS:98 participants from an AIM-HIGH sub-study underwent DCE-MRI of their carotid arteries. Expert readers who were blinded to all clinical variables analyzed the MR images to measure carotid plaque Vp in all participants. Associations between Vp and duration of statin therapy and other clinical risk factors were analyzed. RESULTS: Prior duration of statin treatment at enrollment ranged from <1 year (21%) 1-5 years (40%) and >5 years (39%). In univariate analyses, shorter duration of statin therapy (P = 0.01), the presence of metabolic syndrome (P = 0.02), and higher body mass index (P = 0.01) and lipoprotein(a) (P = 0.01) were all significantly associated with higher baseline Vp values. In multivariate analyses, significant associations remained between shorter duration of statin therapy (P = 0.004) and lipoprotein(a) (P = 0.04). CONCLUSIONS: These are the first human, in vivo findings suggesting a relationship between duration of statin therapy and regression of carotid plaque neovasculature. Future longitudinal studies are warranted both to confirm this finding and to address whether changes in neovasculature may translate into change in risk for plaque disruption. CLINICALTRIALS. GOV IDENTIFIERS: NCT00880178, NCT01178320 and NCT00120289.
RCT Entities:
OBJECTIVE: Plaque neovasculature is a major route for lipoprotein and leukocyte ingress into plaques, and has been identified as a risk factor for carotid plaque disruption. Vp, a variable derived from pharmacokinetic modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), correlates with plaque neovasculature density. Because lipid-lowering therapy has been associated with regression of neovasculature in animal models, we sought to determine clinical correlates of carotid plaque neovasculature (as assessed by Vp) in participants on statin therapy for established cardiovascular disease. METHODS: 98 participants from an AIM-HIGH sub-study underwent DCE-MRI of their carotid arteries. Expert readers who were blinded to all clinical variables analyzed the MR images to measure carotid plaque Vp in all participants. Associations between Vp and duration of statin therapy and other clinical risk factors were analyzed. RESULTS: Prior duration of statin treatment at enrollment ranged from <1 year (21%) 1-5 years (40%) and >5 years (39%). In univariate analyses, shorter duration of statin therapy (P = 0.01), the presence of metabolic syndrome (P = 0.02), and higher body mass index (P = 0.01) and lipoprotein(a) (P = 0.01) were all significantly associated with higher baseline Vp values. In multivariate analyses, significant associations remained between shorter duration of statin therapy (P = 0.004) and lipoprotein(a) (P = 0.04). CONCLUSIONS: These are the first human, in vivo findings suggesting a relationship between duration of statin therapy and regression of carotid plaque neovasculature. Future longitudinal studies are warranted both to confirm this finding and to address whether changes in neovasculature may translate into change in risk for plaque disruption. CLINICALTRIALS. GOV IDENTIFIERS: NCT00880178, NCT01178320 and NCT00120289.
Authors: Daniel S Hippe; Binh An P Phan; Jie Sun; Daniel A Isquith; Kevin D O'Brien; John R Crouse; Todd Anderson; John Huston; Santica M Marcovina; Thomas S Hatsukami; Chun Yuan; Xue-Qiao Zhao Journal: Arterioscler Thromb Vasc Biol Date: 2018-01-04 Impact factor: 8.311
Authors: Zahi A Fayad; Filip K Swirski; Claudia Calcagno; Clinton S Robbins; Willem Mulder; Jason C Kovacic Journal: J Am Coll Cardiol Date: 2018-10-30 Impact factor: 24.094
Authors: Bram F Coolen; Claudia Calcagno; Pim van Ooij; Zahi A Fayad; Gustav J Strijkers; Aart J Nederveen Journal: MAGMA Date: 2017-08-14 Impact factor: 2.310
Authors: L Saba; W Brinjikji; J D Spence; M Wintermark; M Castillo; G J de Borst; Q Yang; C Yuan; A Buckler; M Edjlali; T Saam; D Saloner; B K Lal; D Capodanno; J Sun; N Balu; R Naylor; A V D Lugt; B A Wasserman; M E Kooi; J Wardlaw; J Gillard; G Lanzino; U Hedin; D Mikulis; A Gupta; J K DeMarco; C Hess; J V Goethem; T Hatsukami; P Rothwell; M M Brown; A R Moody Journal: AJNR Am J Neuroradiol Date: 2021-07-29 Impact factor: 4.966
Authors: Kevin D O'Brien; Daniel S Hippe; Huijun Chen; Moni B Neradilek; Jeffrey L Probstfield; Suzanne Peck; Daniel A Isquith; Gador Canton; Chun Yuan; Nayak L Polissar; Xue-Qiao Zhao; William S Kerwin Journal: Data Brief Date: 2016-01-02
Authors: Esben Laugesen; Pernille Høyem; Samuel Thrysoe; Esben Søvsø Szocska Hansen; Anders F Stegmann Mikkelsen; William S Kerwin; Per L Poulsen; Troels K Hansen; W Yong Kim Journal: J Am Heart Assoc Date: 2018-08-21 Impact factor: 5.501