Yonsei Med J.  2015 Sep;56(5):1288-1295. 10.3349/ymj.2015.56.5.1288.

Nonalcoholic Fatty Liver Disease Is Associated with the Presence and Morphology of Subclinical Coronary Atherosclerosis

• Kang MK
• Kang BH
• Kim JH

• KMID: 2163620
• DOI: http://doi.org/10.3349/ymj.2015.56.5.1288

Abstract

PURPOSE
In this study, we aimed to evaluate whether nonalcoholic fatty liver disease (NAFLD) was associated with the presence and morphology of coronary atherosclerotic plaques shown by multidetector computed tomography (MDCT) in asymptomatic subjects without a history of cardiovascular disease.
MATERIALS AND METHODS
We retrospectively enrolled 772 consecutive South Korean individuals who had undergone both dualsource 64-slice MDCT coronary angiography and hepatic ultrasonography during general routine health evaluations. The MDCT studies were assessed for the presence, morphology (calcified, mixed, and non-calcified), and severity of coronary plaques.
RESULTS
Coronary atherosclerotic plaques were detected in 316 subjects (40.9%) by MDCT, and NAFLD was found in 346 subjects (44.8%) by hepatic ultrasonography. Subjects with NAFLD had higher prevalences of all types of atherosclerotic plaque and non-calcified, mixed, and calcified plaques than the subjects without NAFLD. However, the prevalence of significant stenosis did not differ between groups. After adjusting for age, smoking status, diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome, NAFLD remained a significant predictor for all types of coronary atherosclerotic plaque [odds ratio (OR): 1.48; 95% confidence interval (CI): 1.05-2.08; p=0.025] in binary logistic analysis, as well as for calcified plaques (OR: 1.70; 95% CI: 1.07-2.70; p=0.025) in multinomial regression analysis.
CONCLUSION
Our study demonstrated that NAFLD was significantly associated with the presence and the calcified morphology of coronary atherosclerotic plaques detected by MDCT. Further prospective clinical studies are needed to clarify the exact physiopathologic role of NAFLD in coronary atherosclerosis.

Keyword

Nonalcoholic fatty liver disease; subclinical coronary atherosclerosis; metabolic syndrome; multidetector computed tomography

MeSH Terms

Adult
Aged
Asian Continental Ancestry Group/statistics & numerical data
Calcinosis/ethnology/*radiography
Case-Control Studies
Coronary Angiography/*methods
Coronary Artery Disease/ethnology/pathology/*radiography
Female
Humans
Male
Middle Aged
Multidetector Computed Tomography/*methods
Non-alcoholic Fatty Liver Disease/epidemiology/*ultrasonography
Odds Ratio
Plaque, Atherosclerotic/*diagnosis/epidemiology
Prevalence
Regression Analysis
Republic of Korea/epidemiology
Retrospective Studies
Risk Factors
Ultrasonography

Reference

1. Hsiao TJ, Chen JC, Wang JD. Insulin resistance and ferritin as major determinants of nonalcoholic fatty liver disease in apparently healthy obese patients. Int J Obes Relat Metab Disord. 2004; 28:167–172.

2. Suzuki A, Angulo P, Lymp J, St Sauver J, Muto A, Okada T, et al. Chronological development of elevated aminotransferases in a nonalcoholic population. Hepatology. 2005; 41:64–71.

3. Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology. 2005; 42:44–52.

4. Chen CH, Nien CK, Yang CC, Yeh YH. Association between nonalcoholic fatty liver disease and coronary artery calcification. Dig Dis Sci. 2010; 55:1752–1760.

5. Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005; 129:113–121.

6. Adibi P, Sadeghi M, Mahsa M, Rozati G, Mohseni M. Prediction of coronary atherosclerotic disease with liver transaminase level. Liver Int. 2007; 27:895–900.

7. Hoffmann U, Moselewski F, Nieman K, Jang IK, Ferencik M, Rahman AM, et al. Noninvasive assessment of plaque morphology and composition in culprit and stable lesions in acute coronary syndrome and stable lesions in stable angina by multidetector computed tomography. J Am Coll Cardiol. 2006; 47:1655–1662.

8. Abdulla J, Asferg C, Kofoed KF. Prognostic value of absence or presence of coronary artery disease determined by 64-slice computed tomography coronary angiography a systematic review and metaanalysis. Int J Cardiovasc Imaging. 2011; 27:413–420.

9. Bamberg F, Dannemann N, Shapiro MD, Seneviratne SK, Ferencik M, Butler J, et al. Association between cardiovascular risk profiles and the presence and extent of different types of coronary atherosclerotic plaque as detected by multidetector computed tomography. Arterioscler Thromb Vasc Biol. 2008; 28:568–574.

10. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002; 106:3143–3421.

11. Osawa H, Mori Y. Sonographic diagnosis of fatty liver using a histogram technique that compares liver and renal cortical echo amplitudes. J Clin Ultrasound. 1996; 24:25–29.

12. el-Hassan AY, Ibrahim EM, al-Mulhim FA, Nabhan AA, Chammas MY. Fatty infiltration of the liver: analysis of prevalence, radiological and clinical features and influence on patient management. Br J Radiol. 1992; 65:774–778.

13. Austen WG, Edwards JE, Frye RL, Gensini GG, Gott VL, Griffith LS, et al. A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc Committee for Grading of Coronary Artery Disease, Council on Cardiovascular Surgery, American Heart Association. Circulation. 1975; 51:4 Suppl. 5–40.

14. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990; 15:827–832.

15. Ekstedt M, Franzén LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006; 44:865–873.

16. Hamaguchi M, Kojima T, Takeda N, Nagata C, Takeda J, Sarui H, et al. Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease. World J Gastroenterol. 2007; 13:1579–1584.

17. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003; 107:499–511.

18. Pai JK, Pischon T, Ma J, Manson JE, Hankinson SE, Joshipura K, et al. Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med. 2004; 351:2599–2610.

19. Lizardi-Cervera J, Chavez-Tapia NC, Pérez-Bautista O, Ramos MH, Uribe M. Association among C-reactive protein, Fatty liver disease, and cardiovascular risk. Dig Dis Sci. 2007; 52:2375–2379.

20. Rydén M, Arner P. Tumour necrosis factor-alpha in human adipose tissue--from signalling mechanisms to clinical implications. J Intern Med. 2007; 262:431–438.

21. Gupta D, Varma S, Khandelwal RL. Long-term effects of tumor necrosis factor-alpha treatment on insulin signaling pathway in HepG2 cells and HepG2 cells overexpressing constitutively active Akt/PKB. J Cell Biochem. 2007; 100:593–607.

22. Corti R, Fuster V, Badimon JJ. Pathogenetic concepts of acute coronary syndromes. J Am Coll Cardiol. 2003; 41:4 Suppl S. 7S–14S.

23. Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004; 109:23 Suppl 1. III27–III32.

24. Villanova N, Moscatiello S, Ramilli S, Bugianesi E, Magalotti D, Vanni E, et al. Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. Hepatology. 2005; 42:473–480.

25. Targher G, Bertolini L, Padovani R, Zenari L, Zoppini G, Falezza G. Relation of nonalcoholic hepatic steatosis to early carotid atherosclerosis in healthy men: role of visceral fat accumulation. Diabetes Care. 2004; 27:2498–2500.

26. Brea A, Mosquera D, Martín E, Arizti A, Cordero JL, Ros E. Nonalcoholic fatty liver disease is associated with carotid atherosclerosis: a case-control study. Arterioscler Thromb Vasc Biol. 2005; 25:1045–1050.

27. Targher G, Bertolini L, Padovani R, Poli F, Scala L, Zenari L, et al. Non-alcoholic fatty liver disease is associated with carotid artery wall thickness in diet-controlled type 2 diabetic patients. J Endocrinol Invest. 2006; 29:55–60.

28. Fracanzani AL, Burdick L, Raselli S, Pedotti P, Grigore L, Santorelli G, et al. Carotid artery intima-media thickness in nonalcoholic fatty liver disease. Am J Med. 2008; 121:72–78.

29. Wong VW, Wong GL, Yip GW, Lo AO, Limquiaco J, Chu WC, et al. Coronary artery disease and cardiovascular outcomes in patients with non-alcoholic fatty liver disease. Gut. 2011; 60:1721–1727.