Francis R Joshi1, Nikil K Rajani1, Markus Abt2, Mark Woodward3, Jan Bucerius4, Venkatesh Mani5, Ahmed Tawakol6, David Kallend2, Zahi A Fayad5, James H F Rudd7. 1. Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom. 2. Pharma Development, F. Hoffmann-La Roche AG, Basel, Switzerland. 3. George Institute for Global Health, University of Sydney, Sydney, Australia; University of Oxford, Oxford, United Kingdom. 4. Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Nuclear Medicine, and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, the Netherlands; Department of Nuclear Medicine, University Hospital RWTH Aachen, Aachen, Germany. 5. Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York. 6. Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts. 7. Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom. Electronic address: jhfr2@cam.ac.uk.
Abstract
BACKGROUND: Atherosclerosis is an inflammatory condition with calcification apparent late in the disease process. The extent and progression of coronary calcification predict cardiovascular events. Relatively little is known about noncoronary vascular calcification. OBJECTIVES: This study investigated noncoronary vascular calcification and its influence on changes in vascular inflammation. METHODS: A total of 130 participants in the dal-PLAQUE (Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging) study underwent fluorodeoxyglucose positron emission tomography/computed tomography at entry and at 6 months. Calcification of the ascending aorta, arch, carotid, and coronary arteries was quantified. Cardiovascular risk factors were related to arterial calcification. The influences of baseline calcification and drug therapy (dalcetrapib vs. placebo) on progression of calcification were determined. Finally, baseline calcification was related to changes in vascular inflammation. RESULTS: Age >65 years old was consistently associated with higher baseline calcium scores. Arch calcification trended to progress more in those with calcification at baseline (p = 0.055). There were no significant differences between progression of vascular calcification with dalcetrapib compared to that with placebo. Average carotid target-to-background ratio indexes declined over 6 months if carotid calcium was absent (single hottest slice [p = 0.037], mean of maximum target-to-background ratio [p = 0.010], and mean most diseased segment [p < 0.001]), but did not significantly change if calcification was present at baseline. CONCLUSIONS: Across multiple arterial regions, higher age is consistently associated with higher calcium scores. The presence of vascular calcification at baseline is associated with progressive calcification; in the carotid arteries, calcification appears to influence vascular inflammation. Dalcetrapib therapy did not affect vascular calcification.
BACKGROUND: Atherosclerosis is an inflammatory condition with calcification apparent late in the disease process. The extent and progression of coronary calcification predict cardiovascular events. Relatively little is known about noncoronary vascular calcification. OBJECTIVES: This study investigated noncoronary vascular calcification and its influence on changes in vascular inflammation. METHODS: A total of 130 participants in the dal-PLAQUE (Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging) study underwent fluorodeoxyglucose positron emission tomography/computed tomography at entry and at 6 months. Calcification of the ascending aorta, arch, carotid, and coronary arteries was quantified. Cardiovascular risk factors were related to arterial calcification. The influences of baseline calcification and drug therapy (dalcetrapib vs. placebo) on progression of calcification were determined. Finally, baseline calcification was related to changes in vascular inflammation. RESULTS: Age >65 years old was consistently associated with higher baseline calcium scores. Arch calcification trended to progress more in those with calcification at baseline (p = 0.055). There were no significant differences between progression of vascular calcification with dalcetrapib compared to that with placebo. Average carotid target-to-background ratio indexes declined over 6 months if carotid calcium was absent (single hottest slice [p = 0.037], mean of maximum target-to-background ratio [p = 0.010], and mean most diseased segment [p < 0.001]), but did not significantly change if calcification was present at baseline. CONCLUSIONS: Across multiple arterial regions, higher age is consistently associated with higher calcium scores. The presence of vascular calcification at baseline is associated with progressive calcification; in the carotid arteries, calcification appears to influence vascular inflammation. Dalcetrapib therapy did not affect vascular calcification.
Authors: Nicholas R Evans; Jason M Tarkin; Mohammed M Chowdhury; Elizabeth A Warburton; James H F Rudd Journal: Curr Atheroscler Rep Date: 2016-06 Impact factor: 5.113
Authors: Mohammed M Chowdhury; Lukasz P Zieliński; James J Sun; Simon Lambracos; Jonathan R Boyle; Seamus C Harrison; James H F Rudd; Patrick A Coughlin Journal: Eur J Vasc Endovasc Surg Date: 2017-12-07 Impact factor: 7.069
Authors: Nicholas R Evans; Jason M Tarkin; John R Buscombe; Hugh S Markus; James H F Rudd; Elizabeth A Warburton Journal: Nat Rev Neurol Date: 2017-10-06 Impact factor: 42.937
Authors: Diana Carmona-Fernandes; Sofia C Barreira; Natacha Leonardo; Renata I Casimiro; Alice M Castro; Pedro Oliveira Santos; António N Fernandes; Filipe Cortes-Figueiredo; Carolina A Gonçalves; Rafael Cruz; Mariana L Fernandes; Margarida Ivo; Luis M Pedro; Helena Canhão; João Eurico Fonseca; Maria José Santos Journal: Front Med (Lausanne) Date: 2021-05-20
Authors: Mohammed M Chowdhury; Gregory C Makris; Jason M Tarkin; Francis R Joshi; Paul D Hayes; James H F Rudd; Patrick A Coughlin Journal: PLoS One Date: 2017-09-08 Impact factor: 3.240