Invited Editorial
Can Imaging Improve our Understanding of
Cardiovascular Pathophysiology?
Marc R Dweck MD PhD1,2
Fabien Hyafil MD PhD3
AUTHOR AFFILIATIONS
1Translation Molecular Imaging Institute, Icahn School of Medicine at Mount-Sinai, New York
2British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
3 Department of Nuclear Medicine, Bichat University Hospital, Assistance Publique –Hôpitaux de Paris, Département Hospitalo-Universitaire FIRE, Inserm 1148, Paris, France
Word Count: 1494
References:13
CORRESPONDING AUTHOR
Marc Dweck, MD PhD
Chancellor’s Building
University of Edinburgh
49 Little France Crescent
EH16 4SB
Email:
FINANCIAL SUPPORT
MRD is supported by the British Heart Foundation (FS/14/78/31020) and is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA).
CONFLICTS OF INTEREST
None
Recent advances in non-invasiveimaging technology now allow us to simultaneously investigate cardiovascular anatomy, soft tissue characteristics and disease activity as pathological processes occur in the body. Moreover this can be performed at different anatomical locations so that the interplay between different organ systems can be interrogated. This offers us a powerful tool with which to improve our understanding of the mechanisms underlying cardiovascular disease and the adverse events that ensue.
This is the focus of the manuscript by Figueroa and colleagues in the current edition of Circulation Cardiovascular Imaging,1where the authors have used both anatomical computed tomography (CT) assessments and positron emission tomography (PET) measures of disease activity to investigate the relationship between visceral adiposity, vascular inflammation and cardiovascular events. Recently the view on adipose visceral tissue has evolved from a passive lipid storage compartment towards an active endocrine organ able to secrete large amounts of bioactive factors and pro-inflammatory cytokines, which might play a role in the progression of atherosclerosis2 The current study is therefore both timely and of clinical relevance, especially given the worldwide epidemic in obesity rates and the acceptance that obesity represents a major modifiable risk factor for coronary artery disease.3
The strength and originality of this work is that the Authors have tested their hypothesis in a large cohort of more than 400 patients imaged with 18F-fluorodeoxyglucose (FDG) PET with a median follow-up of 4 years for the development of cardiovascular events. This builds upon this research group’s extensive experience and expertise in evaluating vascular inflammation with FDG-PET that has provided a series of key pathological insights. Ultimately they have here demonstrated that CT measures of visceral fat demonstrate an association with vascular inflammation (the modest correlation is perhaps not unexpected given the multitude of factors with pro-inflammatory effects), and that patients with a combination of both elevated visceral fat and vascular inflammation have an increased rate of subsequent vascular events. Importantly the imaging assessment of visceral fat providedincremental information to simpler and cheaper assessments such as the body mass index, which did not demonstrate the same associations and predictive capability.This therefore adds credence to the growing argument that visceral fat is an important player in the progression of systemic atherosclerosis and worthy of study beyond more generalized measures of systemic adiposity. Moreover it adds support to the expanding body of evidence indicating that assessments of vascular inflammation with 18F-FDG are of prognostic value. The authors are to be congratulated on these two important additions to the literature.
Whilst such retrospective studies are of undoubted value in establishing potential pathological associations,there are limitations to the conclusions they allow us to draw. For example the correlation between visceral adiposity and vascular inflammation cannot establish causality. Therefore whilst it is interesting to speculate that visceral fat directly secretes factors that promote vascular inflammation, progression and adverse events, this conclusion cannot be established directly from this data. Moreover as the authors clearly acknowledge the study of cancer patients will always be prone to referral bias limiting generalizability.The major value of these retrospective observational data is therefore in generating novel hypotheses,to then be tested in prospective and definitive mechanistic studies.
The design of definitive mechanistic imaging studies is challenging and has been limited by concerns regarding the radiation exposure associatedwith multiple time-point studies. Perhaps the best model focuses on imaging a chosen parameter both before and afteran intervention, allowing the effect of that intercessionto be assessed in isolation. Indeed this approach has been used by the authors’research group and others to investigate the impact of drug therapy on atherosclerotic plaque anatomy and activity. Statins for example have been demonstrated to reduce both carotid atherosclerotic plaque burden,4,5 and plaque composition6 on magnetic resonance(MR) as well as reducing vascular 18F-FDG uptake on PET.7Other medication such cholesterol ester transfer protein (CETP) inhibitors have by comparison failed to reduce 18F-FDG activity mirroring the similarly disappointing effects of these drugs on clinical outcomes.8,9The recent emergence of hybrid PET/MR systems offers major potential in this field allowing combined, detailed assessment of large vessel plaque burden (MR), composition(MR) and activity(PET) at radiation doses considerably lower than possible with PET/CT (3-4mSv per scan).10As a consequence multiple time point studies become feasible. How could this technology be used to build upon the important study by Figueroa and colleagues and further investigate the relationship between visceral fat and atherosclerosis? One possibility would be to image patients before and after gastric banding. This operation results in major weight loss in patients with multiple risk factors for atherosclerosis and can be performed laparoscopically. A multiple time-point PET/MR study could be used to simultaneously assess the effect of this intervention on visceral fat, atherosclerotic burden, plaque composition and 18F-FDG activity. Given the excellent reproducibility of both MR11 and PET12 assessments few patients would be required to demonstrate an effect and depending on the timing of the scans valuable insights might be gained into both the acute effects of surgery and the long-term effects of weight loss on systemic atherosclerosis. Large bore scanners would be preferential, as ultimately would more specific markers of vascular inflammation than 18F-FDG. Moreover it would be interesting to compare the activity of visceral fat with brown fat, the metabolic activity of which has also been studied using 18F-FDG.13As we enter a new era of powerful non-invasive molecular imaging the availability of imaging systems will increase as will the range of tracers at our disposal, costs will come down and the scope for such studies will expand. There is therefore real excitement that non-invasive imaging can greatly contribute to our future understanding of cardiovascular disease in humans.
References
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