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Non-alcoholic fatty liver disease with reduced myocardial FDG uptake is associated with coronary atherosclerosis

  • Original Article
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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Non-alcoholic fatty liver disease (NAFLD) has a significant role in the development of coronary atherosclerosis, independent of traditional cardiovascular and metabolic risk factors. However, the role of myocardial glucose uptake in NAFLD patients who develop coronary atherosclerosis was unclear. The aim of the present study thus was to investigate the association between NAFLD with characteristic of coronary atherosclerotic plaque and myocardial glucose uptake measured by using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET).

Methods and Results

A total of 418 consecutive subjects who had undergone FDG PET/computed tomography (CT) and coronary computed tomography angiography (CCTA) were retrospectively investigated. Fatty liver was assessed by unenhanced CT. Coronary atherosclerotic plaques and stenosis on CCTA were evaluated. The metabolic parameters were measured on PET images. The ratio of the maximum myocardium FDG value to the mean standardized uptake value of liver (SUVratio) was calculated to estimate myocardial glucose uptake. The association of myocardial glucose uptake with NAFLD and coronary atherosclerosis was determined by multivariate logistic regression analysis. The proportion of low SUVratio in patients with NAFLD was significantly higher compared to those without NAFLD (45.00% vs 19.82%, P < .001). There was a significantly negative correlation between myocardial FDG uptake and hepatic steatosis in association trend analysis (P < .001). When the proportion of individuals with non-calcified plaque on CCTA is stratified by quartiles of SUVratio, patients with low quartiles of SUVratio were more likely to have higher proportion of non-calcified plaque than those with high quartiles of SUVratio (Q1 and Q2 vs Q3 and Q4, P = .003). The trend analysis presented correlated inversely relationship between non-calcified plaque and myocardial SUVratio (P = .001). Moreover, multivariate regression analysis showed that the low SUVratio was independently associated with NAFLD, non-calcified plaque, and significant stenosis after adjusting for clinically important factors.

Conclusion

We demonstrated that the presence of reduced myocardial glucose uptake in patients with NAFLD was independently associated with non-calcified plaque and significant stenosis, suggesting an increased risk of coronary atherosclerosis and future cardiovascular events.

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Abbreviations

BMI:

Body mass index

CCTA:

Coronary computed tomography angiography

CT:

Computed tomography

CVD:

Cardiovascular diseases

FDG:

Fluorodeoxyglucose

LV:

Left ventricular

NAFLD:

Non-alcoholic fatty liver disease

OR:

Odds ratio

PET:

Positron emission tomography

SUV:

Standardized uptake value

References

  1. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016;64:73-84.

    Article  Google Scholar 

  2. Lee SB, Park G-M, Lee J-Y, Lee BU, Park JH, Kim BG, et al. Association between non-alcoholic fatty liver disease and subclinical coronary atherosclerosis: An observational cohort study. J Hepatol 2018;68:1018-24.

    Article  Google Scholar 

  3. Lee HJ, Lee CH, Kim S, Hwang SY, Hong HC, Choi HY, et al. Association between vascular inflammation and non-alcoholic fatty liver disease: Analysis by (18)F-fluorodeoxyglucose positron emission tomography. Metabolism 2017;67:72-9.

    Article  CAS  Google Scholar 

  4. Sert A, Aypar E, Pirgon O, Yilmaz H, Odabas D, Tolu I. Left ventricular function by echocardiography, tissue doppler imaging, and carotid intima-media thickness in obese adolescents with nonalcoholic fatty liver disease. Am J Cardiol 2013;112:436-43.

    Article  Google Scholar 

  5. Lee YH, Kim KJ, Yoo ME, Kim G, Yoon HJ, Jo K, et al. Association of non-alcoholic steatohepatitis with subclinical myocardial dysfunction in non-cirrhotic patients. J Hepatol 2018;68:764-72.

    Article  Google Scholar 

  6. Mantovani A, Mingolla L, Rigolon R, Pichiri I, Cavalieri V, Zoppini G, et al. Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular disease in adult patients with type 1 diabetes. Int J Cardiol 2016;225:387-91.

    Article  Google Scholar 

  7. Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. J Hepatol 2016;65:589-600.

    Article  Google Scholar 

  8. Ong JP, Pitts A, Younossi ZM. Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol 2008;49:608-12.

    Article  Google Scholar 

  9. Park HE, Lee H, Choi SY, Kwak MS, Yang JI, Yim JY, et al. Clinical significance of hepatic steatosis according to coronary plaque morphology: Assessment using controlled attenuation parameter. J Gastroenterol 2019;54:271-80.

    Article  CAS  Google Scholar 

  10. Tang K, Zheng X, Lin J, Zheng M, Lin H, Li T, et al. Association between non-alcoholic fatty liver disease and myocardial glucose uptake measured by 18F-fluorodeoxyglucose positron emission tomography. J Nucl Cardiol 2018.

  11. Thomsen C, Abdulla J. Characteristics of high-risk coronary plaques identified by computed tomographic angiography and associated prognosis: A systematic review and meta-analysis. Eur Heart J Cardiovasc Imaging 2016;17:120-9.

    Article  Google Scholar 

  12. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute scientific statement: Executive Summary. Crit Pathw Cardiol 2005;4:198-203.

    Article  Google Scholar 

  13. Alberti KG, Zimmet P, Shaw J. Metabolic syndrome—A new world-wide definition. A consensus statement from the international diabetes federation. Diabet Med 2006;23:469-80.

    Article  CAS  Google Scholar 

  14. Park GM, Yun SC, Cho YR, Gil EH, Her SH, Kim SH, et al. Prevalence of coronary atherosclerosis in an Asian population: Findings from coronary computed tomographic angiography. Int J Cardiovasc Imaging 2015;31:659-68.

    Article  Google Scholar 

  15. Boyce CJ, Pickhardt PJ, Kim DH, Taylor AJ, Winter TC, Bruce RJ, et al. Hepatic steatosis (fatty liver disease) in asymptomatic adults identified by unenhanced low-dose CT. AJR Am J Roentgenol 2010;194:623-8.

    Article  Google Scholar 

  16. Park YS, Park SH, Lee SS, Kim DY, Shin YM, Lee W, et al. Biopsy-proven nonsteatotic liver in adults: estimation of reference range for difference in attenuation between the liver and the spleen at nonenhanced CT. Radiology 2011;258:760-6.

    Article  Google Scholar 

  17. Kapuria D, Takyar VK, Etzion O, Surana P, O’Keefe JH, Koh C. Association of hepatic steatosis with subclinical atherosclerosis: Systematic review and meta-analysis. Hepatol Commun 2018;2:873-83.

    Article  Google Scholar 

  18. Puchner SB, Lu MT, Mayrhofer T, Liu T, Pursnani A, Ghoshhajra BB, et al. High-risk coronary plaque at coronary CT angiography is associated with nonalcoholic fatty liver disease, independent of coronary plaque and stenosis burden: Results from the ROMICAT II trial. Radiology 2015;274:693-701.

    Article  Google Scholar 

  19. Park HE, Kwak MS, Kim D, Kim MK, Cha MJ, Choi SY. Nonalcoholic fatty liver disease is associated with coronary artery calcification development: A longitudinal study. J Clin Endocrinol Metab 2016;101:3134-43.

    Article  CAS  Google Scholar 

  20. Kim D, Choi SY, Park EH, Lee W, Kang JH, Kim W, et al. Nonalcoholic fatty liver disease is associated with coronary artery calcification. Hepatology 2012;56:605-13.

    Article  CAS  Google Scholar 

  21. Jaruvongvanich V, Sanguankeo A, Wirunsawanya K, Upala S. Nonalcoholic fatty liver disease is associated with coronary artery calcification: A systematic review and meta-analysis. Hepatology 2016;64:594a-5a.

    Article  Google Scholar 

  22. Schroeder S, Kopp AF, Baumbach A, Meisner C, Kuettner A, Georg C, et al. Noninvasive detection and evaluation of atherosclerotic coronary plaques with multislice computed tomography. J Am Coll Cardiol 2001;37:1430-5.

    Article  CAS  Google Scholar 

  23. Gronholdt ML, Dalager-Pedersen S, Falk E. Coronary atherosclerosis: Determinants of plaque rupture. Eur Heart J 1998;19:C24-9.

    PubMed  Google Scholar 

  24. Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB. Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 1997;349:462-6.

    Article  CAS  Google Scholar 

  25. Bouki KP, Katsafados MG, Chatzopoulos DN, Psychari SN, Toutouzas KP, Charalampopoulos AF, et al. Inflammatory markers and plaque morphology: An optical coherence tomography study. Int J Cardiol 2012;154:287-92.

    Article  Google Scholar 

  26. Harada K, Amano T, Uetani T, Yoshida T, Kato B, Kato M, et al. Association of inflammatory markers with the morphology and extent of coronary plaque as evaluated by 64-slice multidetector computed tomography in patients with stable coronary artery disease. Int J Cardiovasc Imaging 2013;29:1149-58.

    Article  Google Scholar 

  27. Manabe O, Kroenke M, Aikawa T, Murayama A, Naya M, Masuda A, et al. Volume-based glucose metabolic analysis of FDG PET/CT: The optimum threshold and conditions to suppress physiological myocardial uptake. J Nucl Cardiol 2017.

  28. Kobayashi Y, Kumita S, Fukushima Y, Ishihara K, Suda M, Sakurai M. Significant suppression of myocardial (18)F-fluorodeoxyglucose uptake using 24-h carbohydrate restriction and a low-carbohydrate, high-fat diet. J Cardiol 2013;62:314-9.

    Article  Google Scholar 

  29. Manabe O, Yoshinaga K, Ohira H, Masuda A, Sato T, Tsujino I, et al. The effects of 18-h fasting with low-carbohydrate diet preparation on suppressed physiological myocardial (18)F-fluorodeoxyglucose (FDG) uptake and possible minimal effects of unfractionated heparin use in patients with suspected cardiac involvement sarcoidosis. J Nucl Cardiol 2016;23:244-52.

    Article  Google Scholar 

  30. Pessin JE, Bell GI. Mammalian facilitative glucose transporter family: Structure and molecular regulation. Annu Rev Physiol 1992;54:911-30.

    Article  CAS  Google Scholar 

  31. Aerni-Flessner L, Abi-Jaoude M, Koenig A, Payne M, Hruz PW. GLUT4, GLUT1, and GLUT8 are the dominant GLUT transcripts expressed in the murine left ventricle. Cardiovasc Diabetol 2012;11:63.

    Article  CAS  Google Scholar 

  32. Yki-Jarvinen H, Westerbacka J. The fatty liver and insulin resistance. Curr Mol Med 2005;5:287-95.

    Article  CAS  Google Scholar 

  33. Lautamaki R, Borra R, Iozzo P, Komu M, Lehtimaki T, Salmi M, et al. Liver steatosis coexists with myocardial insulin resistance and coronary dysfunction in patients with type 2 diabetes. Am J Physiol Endocrinol Metab 2006;291:E282-90.

    Article  CAS  Google Scholar 

  34. Kouidhi S, Berrhouma R, Rouissi K, Jarboui S, Clerget-Froidevaux MS, Seugnet I, et al. Human subcutaneous adipose tissue Glut 4 mRNA expression in obesity and type 2 diabetes. Acta Diabetol 2013;50:227-32.

    Article  CAS  Google Scholar 

  35. Liu Q, Docherty JC, Rendell JC, Clanachan AS, Lopaschuk GD. High levels of fatty acids delay the recovery of intracellular pH and cardiac efficiency in post-ischemic hearts by inhibiting glucose oxidation. J Am Coll Cardiol 2002;39:718-25.

    Article  CAS  Google Scholar 

  36. Fillmore N, Mori J, Lopaschuk GD. Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy. Br J Pharmacol 2014;171:2080-90.

    Article  CAS  Google Scholar 

  37. Dalal JJ, Mishra S. Modulation of myocardial energetics: An important category of agents in the multimodal treatment of coronary artery disease and heart failure. Indian Heart J 2017;69:393-401.

    Article  Google Scholar 

  38. Burgeiro A, Fuhrmann A, Cherian S, Espinoza D, Jarak I, Carvalho RA, et al. Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes. Am J Physiol Endocrinol Metab 2016;310:E550-64.

    Article  Google Scholar 

  39. Ansaldo AM, Montecucco F, Sahebkar A, Dallegri F, Carbone F. Epicardial adipose tissue and cardiovascular diseases. Int J Cardiol 2019;278:254-60.

    Article  Google Scholar 

  40. Limanond P, Raman SS, Lassman C, Sayre J, Ghobrial RM, Busuttil RW, et al. Macrovesicular hepatic steatosis in living related liver donors: Correlation between CT and histologic findings. Radiology 2004;230:276-80.

    Article  Google Scholar 

  41. Lee SW, Park SH, Kim KW, Choi EK, Shin YM, Kim PN, et al. Unenhanced CT for assessment of macrovesicular hepatic steatosis in living liver donors: Comparison of visual grading with liver attenuation index. Radiology 2007;244:479-85.

    Article  Google Scholar 

  42. Pickhardt PJ, Park SH, Hahn L, Lee SG, Bae KT, Yu ES. Specificity of unenhanced CT for non-invasive diagnosis of hepatic steatosis: Implications for the investigation of the natural history of incidental steatosis. Eur Radiol 2012;22:1075-82.

    Article  Google Scholar 

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Author Contributions

KT drafted the manuscript and contributed to the data analysis. JL and XJ contributed to clinical data acquisition and PET images analysis. TL and DS contributed to CT images analysis. XZ and LW contributed to the study design and manuscript drafting. All authors read and approved the final version of the manuscript.

Disclosure

The authors have indicated that they have no financial conflict of interest.

Author information

Author notes

  1. Xiangwu Zheng and Ling Wang contributed equally to this work.

Authors and Affiliations

  1. Department of PET/CT, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Kun Tang MD, Jie Lin MD, Xiaowei Ji MD & Xiangwu Zheng MD

  2. Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Tingting Lin MD

  3. Department of Radiology, The People’s Hospital of Yuhuan, Yuhuan, 317600, Zhejiang, China

    Dongrui Sun MD

  4. Department of Nuclear Medicine, The First Affiliated Hospital of Wenzhou Medical University, Xuefu North Road, Wenzhou, 325000, Zhejiang, China

    Ling Wang MD, PhD

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  1. Kun Tang MD
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Correspondence to Ling Wang MD, PhD.

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Tang, K., Lin, J., Ji, X. et al. Non-alcoholic fatty liver disease with reduced myocardial FDG uptake is associated with coronary atherosclerosis. J. Nucl. Cardiol. 28, 610–620 (2021). https://doi.org/10.1007/s12350-019-01736-6

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  • DOI: https://doi.org/10.1007/s12350-019-01736-6

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