Systemic atherosclerotic plaque vulnerability in patients with Coronary Artery Disease with a single Whole Body [FDG]PET-CT scan

Document Type: Original Article

Authors

1 Wales Research and Diagnostic Positron Emission Tomography Imaging Centre (PETIC), University Hospital of Wales, Cardiff University, Cardiff, Wales, UK

2 Severnside Alliance for Translational Research, School of Medicine, Cardiff University, Cardiff, Wales, UK

3 Department of Radiology, University Hospital of Wales, Cardiff, Wales, UK

Abstract

Objective(s): Cardiovascular disease is a leading cause of morbimortality with over half cardiovascular events occurring in the asymptomatic population by traditional risk stratification. This preliminary study aimed to evaluate systemic plaque vulnerability in patients with prior Coronary Artery Disease (CAD) with a single Whole Body [FDG] PET-CT scan in terms of plaque inflammation and calcifications.
Methods: Twenty-two patients referred for oncological evaluation and with prior history of advanced CAD or age and gender matched controls without cardiovascular disease, underwent a Whole Body PET-CT scan 90 min after injection of 18F-FDG. A total of 975 transaxial PET images were retrospectively analysed to assess plaque inflammation using a standardized method of analysis with averaged Target-to-Background Ratios (TBRs) at different levels, in the thoracic and abdominal aorta, carotids, LAD, common iliac and femoral arteries, and were correlated with calcium scores from the CT images.
Results: TBRs from the thoracic aorta were higher in male patients than controls (1.49±0.11, p<0.05) and a gradient was observed (ascending > descending > aortic arch), and were also higher in the carotids in female patients (1.43±0.07) versus controls (p<0.05). A tendency for higher levels of plaque inflammation in the abdominal aorta was noted in all groups, but no significant FDG uptake was found either in the iliac or femoral arteries in any group. Plaque inflammation was also higher in the LAD in males but with large variations. Higher levels of calcifications were noted in the LAD, infra-renal abdominal aorta and common iliac arteries, but without significant correlation with plaque inflammation except sporadic overlapping. 
Conclusion: Patients with advanced CAD are at risk for vulnerable inflamed atheromas in other territories such as the thoracic aorta and carotid arteries, underpinning the systemic nature of the atherosclerotic disease. Coexistence with calcifications is rare, suggesting a different functional status of the plaques and different stages of the disease. Evaluation of subclinical systemic plaque vulnerability in CAD with a Whole Body [FDG] PET-CT scan is feasible and a potentially useful biomarker to assess subclinical vascular risk for risk stratification and treatment optimization, but further studies are needed.

Keywords


1. Strong JP, Malcom GT, Newman WP, Oalmann MC.  Early lesions of atherosclerosis in childhood and youth: natural history and risk factors.  J Am Coll Nutr 1992; 11 Suppl: 51S-54S.

2. Libby P. Inflammation in atherosclerosis.  Nature 2002; 420: 19-26.

 3. Falk E, Sha P, Fuster V. Coronary plaque disruption.  Circulation 1995; 92: 657-671.

4. Libby P, Theroux P.  Pathophysiology of Coronary Artery Disease.  Circulation 2005; 28, 111 (25): 3481-3488.

5.  Aziz K, Berger K, Claycombe K, Huang R, Patel R, Abela GS. Noninvasive Detection and Localization of Vulnerable Plaque and Arterial Thrombosis.  Circulation 2008; 117: 2061-2070.

6. Ogawa M, Ishino S, Mukai T, Asano D, Teramoto M, Watanabe H, et al.  (18)F-FDG accumulation in atherosclerotic plaques: immunohistochemical and PET imaging study. J Nucl Med 2004; 45: 1245-1250.

7. Rudd J, Warburton E, Fryer T.  Imaging atherosclerotic plaque inflammation with [18F]-fluordeoxyglucose positron emission tomography.  Circulation 2002; 105: 2708-2711.

8.  Naghavi, Libby P, Falk K, Cassells SW, Litovsky S, Rumberger J, et al.  From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I and Part II.  Circulation 2003; 7, 108 (14): 1664-1678.

9. Ambrose JA, Fuster V.  The risk of coronary occlusion is not proportional to the prior severity of coronary stenosis.  Heart 1998; 79: 3-4.

10. Falk E, Sillesen H, Muntendam P, Fuster V.  The High Risk Plaque Initiative: primary prevention of atherothrombotic events in the asymptomatic population. Curr Atheroscler Rep 2001; 13: 359-366.

11. Crea F, Libby P.  Acute coronary Syndromes: the way forward from mechanisms to precision treatment.  Circulation (2017); 136: 1155-1156.

12. Fuster V, Vahl T.  The role of non-invasive imaging in promoting cardiovascular health.  J Nucl Cardiol 2010; 17: 781-790.

13. Owe D, Lindsay A, Choudhury R, Fayad Z.  Imaging of atherosclerosis.  Ann Rev Med 2011; 62: 25-40.

14. Rudd H, Myers K, Bansilal S, Machac J, Woodward M et al.  Relationships among regional arterial inflammation, calcification, risk factors and biomarkers: a prospective Fluorodeoxyglucose Tomography/Computed Tomography imaging study.  Circ Cardiovasc Imag 2009; 2: 107-115.

15. Tahara N, Kai H, Ishibashi M, Nakaura H, Kaida H, Baba K et al.  Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography.  J Am Coll Cardiol 2006; 48 (9): 1825-1831.

16. Hacker M. Monitoring anti-inflammatory therapies in patients with atherosclerosis: PET emerges as the method of choice.  Eur J Nucl Med Mol Imag 2012; 39: 2396-2398.

17. Tawakol A, Migrino RQ, Bashian GG, Bedri S, Bermylen D, Cury RC et al.  In vivo 18F-fluordeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients.  J Am Coll Cardiol 2006; 48: 1818-1824.

18. Graebe M, Pedersen S, Borgwardt L, Hojgaard L, Sillesen H, Kjaer.  A Molecular pathology in vulnerable carotid plaques: correlation with [18]-fluorodeoxyglucose positron emission tomography (FDG-PET). Eur J Vasc Endovasc Surg 2009; 37: 714-721.

19. Menezes L, Kotze C, Agu O, Richards T, Brooks J, Goh VJ et al.  Investigating vulnerable atheroma using combined 18F-FDG PET-CT angiography of carotid plaque with immuno-histochemical validation.  J Nucl Med 2011; 52: 1698-1703.

20. Rudd J, Myers K, Bansilal S, Machac J, Pinto CA, Tong C et al.  Atherosclerosis Inflammation Imaging with 18F-FDG PET: carotid, iliac and femoral uptake, reproducibility, quantification methods and recommendations.  J Nucl Med 2008; 49: 871-878.

21. Warboys C, Amini N, de Luca A, Evans P.  The role of blood flow in determining the sites of atherosclerotic plaques.  F1000 Medicine Reports 2011; 3-5.

22. Rominger A, Saam S, Wolpers S, Cyran CC, Schmidt M, Foerster S et al.  FDG PET-CT identifies patients at risk for future cardiovascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med 2009; 50: 1611-1620.

23. Bucerius J, Duivenvoorden R, Mani V, Moncrieff C, Rudd JH, Calcagno C et al.  Prevalence and risk factors of carotid vessel wall inflammation in coronary artery disease patients.  J Am Coll Cardiol Cardiovasc Imag 2011; 4 (11): 1196-1205.

24. Rogers I, Nasir K, Figueroa A, Cury RC, Hoffmann U, Vermylen DA et al.  Feasibility of FDG imaging of the coronary arteries.  Comparison between acute coronary syndrome and stable angina.  J Am Coll Cardiol Imag 2010; 3: 388-397.

25. Sen S, Wu K, McNamara R, Lima J, Piantadosi S, Oppenheimer SM.  Distribution, severity and risk factors for aortic atherosclerosis in cerebral ischemia.  Cerebrovasc Dis 2000; 10: 102-109.

26. Krozon I, Tunick P. Aortic atherosclerosis disease and stroke.  Circulation 2006; 114 (1): 63-75.

27. Bucerius J, Dijkgraaf I, Mottaghy F, Schurgers L. Target identification for the diagnosis and intervention of vulnerable atherosclerotic plaques beyond 18F-fluorodeoxyglucose positron emission tomography imaging: promising tracers on the horizon. Eur J of Nucl Med Mol Imag 2019; 46: 251-265.

28. Cherry SR, Jones T, Karp JS, Qi J, Moses WW, Badawi RD.  Total Body PET: maximizing sensitivity to create new opportunities for clinical research and patient care.  J Nucl Med 2018; 59 (1): 3-12.

29. Wong N, Lopez V, Allison M, Detrano LC, Blumenthal RS, Folson AR.  Abdominal carotid calcium and multisite atherosclerosis: The multiethnic study of atherosclerosis.  Atherosclerosis 2011; 214: 436-441.

30. Brown ER, Kronmal RA, Bluemke DA, Guerci AD, Carr JJ, Goldin J, Detrano R.  Coronary calcium coverage score: determination, correlates, and predictive accuracy in the Multi-Ethnic Study of Atherosclerosis. Radiology 2011; 247 (3): 669-675.

31. Gottlieb I, Miller JM, Arbab-Zadeh A, Dewey M, Clouse ME, Sara L et al.  The absence of coronary calcification does not exclude obstructive coronary artery disease or the need for revascularization in patients referred for conventional coronary angiography. J Am Coll Cardiol 2010; 55: 627-634.

32. Villines TC, Hulten EA, Shaw LJ, Goyal M, Dunning A, Achenbach S et al.  Prevalence and severity of coronary artery disease and adverse events among symptomatic patients with coronary artery calcification scores of zero undergoing coronary computed tomography angiography: results from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter registry.  J Am Coll Cardiol 2011; 58 (24): 2533-2540.

33. Ben-Haim S, Kupzov E, Tamir A, Israel O.  Evaluation of 18F-FDG uptake and arterial wall calcifications using 18F-FDG PET/CT. J Nucl Med 2004; 45: 1816-1821.