The online version of this article (doi:10.1186/1476-9255-9-26) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
KEY conceived, designed, and coordinated the study, acquired and interpreted data, performed the statistical analyses, and drafted the manuscript. EL participated in the design and coordination of the study, and acquired data. ETO and DNR participated in the design and coordination of the study, acquired and interpreted data, monitored participants, and helped draft the manuscript. MH and SB participated in the design and coordination of the study, acquired PET-CT images, assisted with PET-CT image analysis, and helped draft the manuscript. VGD-R participated in the design and conduct of the study, acquired, analyzed, interpreted carotid ultrasound images, and helped draft the manuscript. All authors read and approved the final manuscript.
Persistent vascular inflammation has been implicated as an important cause for a higher prevalence of cardiovascular disease (CVD) in HIV-infected adults. In several populations at high risk for CVD, vascular 18Fluorodeoxyglucose (18FDG) uptake quantified using 3D-positron emission-computed tomography (PET-CT) has been used as a molecular level biomarker for the presence of metabolically active proinflammatory macrophages in rupture-prone early atherosclerotic plaques. We hypothesized that 18FDG PET-CT imaging would detect arterial inflammation and early atherosclerosis in HIV-infected adults with modest CVD risk.
We studied 9 HIV-infected participants with fully suppressed HIV viremia on antiretroviral therapy (8 men, median age 52 yrs, median BMI 29 kg/m2, median CD4 count 655 cells/μL, 33% current smokers) and 5 HIV-negative participants (4 men, median age 44 yrs, median BMI 25 kg/m2, no current smokers). Mean Framingham Risk Scores were higher for HIV-infected persons (9% vs. 2%, p < 0.01). 18FDG (370 MBq) was administered intravenously. 3D-PET-CT images were obtained 3.5 hrs later. 18FDG uptake into both carotid arteries and the aorta was compared between the two groups.
Right and left carotid 18FDG uptake was greater (P < 0.03) in the HIV group (1.77 ±0.26, 1.33 ±0.09 target to background ratio (TBR)) than the control group (1.05 ± 0.10, 1.03 ± 0.05 TBR). 18FDG uptake in the aorta was greater in HIV (1.50 ±0.16 TBR) vs control group (1.24 ± 0.05 TBR), but did not reach statistical significance (P = 0.18).
Carotid artery 18FDG PET-CT imaging detected differences in vascular inflammation and early atherosclerosis between HIV-infected adults with CVD risk factors and healthy HIV-seronegative controls. These findings confirm the utility of this molecular level imaging approach for detecting and quantifying glucose uptake into inflammatory macrophages present in metabolically active, rupture-prone atherosclerotic plaques in HIV infected adults; a population with increased CVD risk.
Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, Mohler ER, Najjar SS, Rembold CM, Post WS: Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr. 2008, 21: 93-111. 10.1016/j.echo.2007.11.011. CrossRefPubMed
O'Byrne D, Devaraj S, Islam KN, Collazo R, McDonald L, Grundy S, Jialal I: Low-density lipoprotein (LDL)-induced monocyte-endothelial cell adhesion, soluble cell adhesion molecules, and autoantibodies to oxidized-LDL in chronic renal failure patients on dialysis therapy. Metabolism. 2001, 50: 207-215. 10.1053/meta.2001.19486. CrossRefPubMed
McNeely MJ, McClelland RL, Bild DE, Jacobs DR, Tracy RP, Cushman M, Goff DC, Astor BC, Shea S, Siscovick DS: The association between A1C and subclinical cardiovascular disease. Diab Care. 2009, 32: 1727-1733. 10.2337/dc09-0074. CrossRef
Masiá M, Bernal E, Padilla S, Graells ML, Jarrín I, Almenar MV, Molina J, Hernández I, Gutiérrez F: The role of C-reactive protein as a marker for cardiovascular risk associated with antiretroviral therapy in HIV-infected patients. Atherosclerosis. 2007, 195: 167-171. 10.1016/j.atherosclerosis.2006.09.013. CrossRefPubMed
Phillips AN, Carr A, Neuhaus J, Visnegarwala F, Prineas R, Burman WJ, Williams I, Drummond F, Duprez D, Belloso WH: Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial. Antivir Ther. 2008, 13: 177-187. PubMed
Bural GG, Torigian DA, Botvinick E, Houseni M, Basu S, Chen W, Alavi A: A pilot study of changes in 18 F-FDG uptake, calcification and global metabolic activity of the aorta with aging. Hell J Nucl Med. 2009, 12: 123-128. PubMed
Davies JR, Rudd JHF, Fryer TD, Graves MJ, Clark JC, Kirkpatrick PJ, Gillard JH, Warburton EA, Weissberg PL: Identification of culprit lesions after transient ischemic attack by combined 18 F Fluorodeoxyglucose positron-emission tomography and high-resolution magnetic resonance imaging. Stroke. 2005, 36: 2642-2647. 10.1161/01.STR.0000190896.67743.b1. CrossRefPubMed
Graebe M, Borgwardt L, Højgaard L, Sillesen H, Kjaer A: When to image carotid plaque inflammation with FDG PET/CT. Nucl Med Comm. 2010, 31: 773-779. 10.1097/MNM.0b013e32833c365e. CrossRef
Hongming Z, Abass A: 18-Fluorodeoxyglucose positron emission tomographic imaging in the detection and monitoring of infection and inflammation. Semin Nucl Med. 2002, 32: 47-59. 10.1053/snuc.2002.29278. CrossRef
Izquierdo-Garcia D, Davies JR, Graves MJ, Rudd JHF, Gillard JH, Weissberg PL, Fryer TD, Warburton EA: Comparison of methods for magnetic resonance-guided [18-F]luorodeoxyglucose positron emission tomography in human carotid arteries: reproducibility, partial volume correction, and correlation between methods. Stroke. 2009, 40: 86-93. 10.1161/STROKEAHA.108.521393. CrossRefPubMed
Kim TN, Kim S, Yang SJ, Yoo HJ, Seo JA, Kim SG, Kim NH, Baik SH, Choi DS, Choi KM: Vascular inflammation in patients with impaired glucose tolerance and type 2 diabetes: analysis with18 F-Fluorodeoxyglucose positron emission tomography. Circ Cardiovasc Imaging. 2010, 3: 142-148. 10.1161/CIRCIMAGING.109.888909. CrossRefPubMed
Moustafa RR, Izquierdo-Garcia D, Fryer TD, Graves MJ, Rudd JHF, Gillard JH, Weissberg PL, Baron J-C, Warburton EA: Carotid plaque inflammation is associated with cerebral microembolism in patients with recent transient ischemic attack or stroke: a pilot study. Circ Cardiovasc Imaging. 2010, 3: 536-541. 10.1161/CIRCIMAGING.110.938225. CrossRefPubMed
Okane K, Ibaraki M, Toyoshima H, Sugawara S, Takahashi K, Miura S, Shimosegawa E, Satomi J, Kitamura K, Satoh T: 18 F-FDG accumulation in atherosclerosis: use of CT and MR co-registration of thoracic and carotid arteries. Eur J Nucl Med Mol Imaging. 2006, 33: 589-594. 10.1007/s00259-005-0005-2. CrossRefPubMed
Rudd JHF, Myers KS, Bansilal S, Machac J, Rafique A, Farkouh M, Fuster V, Fayad ZA: 18Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. J Am Coll Cardiol. 2007, 50: 892-896. 10.1016/j.jacc.2007.05.024. CrossRefPubMed
Rudd JHF, Myers KS, Bansilal S, Machac J, Woodward M, Fuster V, Farkouh ME, Fayad ZA: Relationships among regional arterial inflammation, calcification, risk factors, and biomarkers: a prospective fluorodeoxyglucose positron-emission tomography/computed tomography imaging study. Circ Cardiovasc Imaging. 2009, 2: 107-115. 10.1161/CIRCIMAGING.108.811752. PubMedCentralCrossRefPubMed
Rudd JHF, Narula J, Strauss HW, Virmani R, Machac J, Klimas M, Tahara N, Fuster V, Warburton EA, Fayad ZA, Tawakol AA: Imaging atherosclerotic plaque inflammation by fluorodeoxyglucose with positron emission tomography: ready for prime time?. J Am Coll Cardiol. 2010, 55: 2527-2535. 10.1016/j.jacc.2009.12.061. CrossRefPubMed
Rudd JHF, Warburton EA, Fryer TD, Jones HA, Clark JC, Antoun N, Johnstrom P, Davenport AP, Kirkpatrick PJ, Arch BN: Imaging atherosclerotic plaque inflammation with [18 F]-Fluorodeoxyglucose positron emission tomography. Circulation. 2002, 105: 2708-2711. 10.1161/01.CIR.0000020548.60110.76. CrossRefPubMed
Subramanian S, Tawakol A: Molecular PET and CT imaging of inflammation and metabolism in atherosclerosis. Curr Cardiovasc Imag Rep. 2010, 3: 92-98. 10.1007/s12410-010-9014-z. CrossRef
Tahara N, Kai H, Yamagishi S-i, Mizoguchi M, Nakaura H, Ishibashi M, Kaida H, Baba K, Hayabuchi N, Imaizumi T: Vascular inflammation evaluated by [18 F]-Fluorodeoxyglucose positron emission tomography is associated with the metabolic syndrome. J Am Coll Cardiol. 2007, 49: 1533-1539. 10.1016/j.jacc.2006.11.046. CrossRefPubMed
Tawakol A, Migrino RQ, Bashian GG, Bedri S, Vermylen D, Cury RC, Yates D, LaMuraglia GM, Furie K, Houser S: In vivo 18 F-Fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol. 2006, 48: 1818-1824. 10.1016/j.jacc.2006.05.076. CrossRefPubMed
de las Fuentes L, Waggoner AD, Mohammed BS, Stein RI, Miller Iii BV, Foster GD, Wyatt HR, Klein S, Davila-Roman VG: Effect of moderate diet-induced weight loss and weight regain on cardiovascular structure and function. J Am Coll Cardiol. 2009, 54: 2376-2381. 10.1016/j.jacc.2009.07.054. PubMedCentralCrossRefPubMed
Standardization of lipid and lipoprotein measurements. . Edited by: Myers GL, Cooper GR, Henderson LO, Hassemer DJ, Kimberly MM. 1997, AACC, Washington, DC, 223-250.
Yarasheski KE, Cade WT, Overton ET, Mondy KE, Hubert S, Laciny E, Bopp C, Lassa-Claxton S, Reeds DN: Exercise training augments the peripheral insulin sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity. Am J Physiol Endocrinol Metab. 2011, 300: E243-E251. 10.1152/ajpendo.00468.2010. PubMedCentralCrossRefPubMed
Wykrzykowska J, Lehman S, Williams G, Parker JA, Palmer MR, Varkey S, Kolodny G, Laham R: Imaging of inflamed and vulnerable plaque in coronary arteries with 18 F-FDG PET/CT in patients with suppression of myocardial uptake using a low-carbohydrate, high-fat preparation. J Nucl Med. 2009, 50: 563-568. 10.2967/jnumed.108.055616. CrossRefPubMed
Subramanian S, Tawakol A, Burdo T, Abbara S, Wei J, Zanni M, Hoffmann U, Williams K, Lo J, Grinspoon S: Increased arterial inflammation in association with monocyte activation in HIV + patients (abstract # 121). 19thConference on Retroviruses and Opportunistic Infections. 2012, , Seattle, WA, 124-
- 18FDG PET-CT imaging detects arterial inflammation and early atherosclerosis in HIV-infected adults with cardiovascular disease risk factors
Kevin E Yarasheski
E Turner Overton
Dominic N Reeds
Victor G Dávila-Román
- BioMed Central
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