Author + information
- Received September 4, 2015
- Accepted October 7, 2015
- Published online January 5, 2016.
- Francis R. Joshi, MBBS∗,
- Nikil K. Rajani, MA∗,
- Markus Abt, PhD†,
- Mark Woodward, PhD‡,§,
- Jan Bucerius, MD, PhD‖,¶,#,
- Venkatesh Mani, PhD‖,
- Ahmed Tawakol, MD∗∗,
- David Kallend, MBBS†,
- Zahi A. Fayad, PhD‖ and
- James H.F. Rudd, MD, PhD∗∗ ()
- ∗Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom
- †Pharma Development, F. Hoffmann-La Roche AG, Basel, Switzerland
- ‡George Institute for Global Health, University of Sydney, Sydney, Australia
- §University of Oxford, Oxford, United Kingdom
- ‖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
- ∗∗Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. James H.F. Rudd, Division of Cardiovascular Medicine, University of Cambridge, Box 110, ACCI Level 6, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom.
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.
- carotid arteries
- positron emission tomography
Dr. Kallend’s present address is The Medicines Company, Zürich, Switzerland. This study was supported by F. Hoffmann-La Roche AG and U.S. National Institutes of Health/National Heart, Lung, and Blood Institute grant R01 HL071021 (Dr. Fayad), and some editorial assistance was provided by Prime Healthcare. Dr. Joshi is supported by British Heart Foundation Research Fellowship award FS/12/29/29463 and a Raymond and Beverly Sackler PhD studentship. Dr. Rudd is supported in part by the National Institute for Health Research Cambridge Biomedical Research Centre. Dr. Abt is an employee of and holds stock options in F. Hoffmann-La Roche AG. Prof. Woodward has received honoraria and research funding from F. Hoffmann-La Roche AG and honoraria from Novartis. Dr. Tawakol has received honoraria from F. Hoffmann-La Roche AG, Bristol-Myers Squibb, and Novartis; research grants from Takeda, Actelion, F. Hoffmann-La Roche AG/Genentech, Merck, Bristol-Myers Squibb, GlaxoSmithKline, and VBL Therapeutics; and has consulted for Roche, Takeda, AstraZeneca, Amgen, and Actelion. Dr. Kallend is a former employee of F. Hoffmann-La Roche AG and holds stock options in The Medicines Company. Prof. Fayad has received research grants from F. Hoffmann-La Roche AG, GlaxoSmithKline, Merck, VBL Therapeutics, Novartis, Bristol-Myers Squibb, and Via Pharmaceuticals; and honoraria from F. Hoffmann-La Roche AG. Dr. Rudd has received honoraria from F. Hoffmann-La Roche AG. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received September 4, 2015.
- Accepted October 7, 2015.
- American College of Cardiology Foundation