Background and Aim: Association of non-alcoholic fatty liver disease (NAFLD) and liver related mortality is well-known; however; its cardiovascular risk remains questionable. The aim of this work was to highlight the association between NAFLD and the severity of coronary heart disease. Method: The study was conducted between July and December 2019 at Qena university hospital, Qena, Egypt on patients who were scheduled for coronary angiography. Liver steatosis was diagnosed using FibroScan and the severity of coronary artery occlusion was assessed by Gensini score calculation. Statistical analysis was done to study the correlation between liver steatosis and angiography findings. Result: A total of 100 patients were included, mean age 48 years (±8 SD). Correlation between coronary angiography and the baseline variables revealed statistically significant positive correlation between Gensini score and ALT (p = 0.002), FBS (p < 0.001), steatosis (p < 0.001) and diabetes (p < 0.001). Also, gradual increase in the Gensini score with higher steatosis grades was noticed, medians: 10.5, 21.7, 57.6 and 102.6 in S0, S1, S2 and S3 respectively, p = 0.01. Variables that have significantly predicted higher Gensini score in univariable regression analysis were: diabetes (OR: 55.6, CI: (41 - 70)), hypertension (OR: 19, CI: (2 - 37)), F2-F4 fibrosis (OR: 33, CI: (24 - 38)) and S2-S3 steatosis (OR: 34, (23 - 40)), while in multivariable regression; the statistically significant variables were: diabetes (OR: 23, CI: (10 - 37)), hypertension (OR: 11, CI: (4.8 - 22)) and S2-S3 steatosis (OR: 24, CI: (17 - 31)). Conclusion: NAFLD is an independent cardiovascular risk predictor with statistically significant increase in Gensini score with the higher grades of NAFLD.
KeywordsNAFLDFibroScanGensini Score
Younossi, Z.M., Stepanova, M., Afendy, M., Fang, Y., Younossi, Y., Mir, H., et al. (2011) Changes in the Prevalence of the Most Common Causes of Chronic Liver Diseases in the United States from 1988 to 2008. Clinical Gastroenterology and Hepatology, 9, 524-530.e521. https://doi.org/10.1016/j.cgh.2011.03.020
Younossi, Z.M., Koenig, A.B., Abdelatif, D., Fazel, Y., Henry, L. and Wymer, M. (2016) Global Epidemiology of Nonalcoholic Fatty Liver Disease Meta-Analytic Assessment of Prevalence, Incidence, and Outcomes. Hepatology, 64, 73-84. https://doi.org/10.1002/hep.28431
Charlton, M.R., Burns, J.M., Pedersen, R.A., Watt, K.D., Heimbach, J.K. and Dierkhising, R.A. (2011) Frequency and Outcomes of Liver Transplantation for Nonalcoholic Steatohepatitis in the United States. Gastroenterology, 141, 1249-1253. https://doi.org/10.1053/j.gastro.2011.06.061
Targher, G., Day, C.P. and Bonora, E. (2010) Risk of Cardiovascular Disease in Patients with Nonalcoholic Fatty Liver Disease. The New England Journal of Medicine, 363, 1341-1350. https://doi.org/10.1056/NEJMra0912063
Soderberg, C., Stal, P., Askling, J., Glaumann, H., Lindberg, G., Marmur, J., et al. (2010) Decreased Survival of Subjects with Elevated Liver Function Tests during a 28-Year Follow-Up. Hepatology, 51, 595-602. https://doi.org/10.1002/hep.23314
Ekstedt, M., Hagstrom, H., Nasr, P., Fredrikson, M., Stal, P., Kechagias, S., et al. (2015) Fibrosis Stage Is the Strongest Predictor for Disease-Specific Mortality in NAFLD after up to 33 Years of Follow-Up. Hepatology, 61, 1547-1554. https://doi.org/10.1002/hep.27368
Emrich, I.E., Böhm, M. and Mahfoud, F. (2019) The 2018 ESC/ESH Guidelines for the Management of Arterial Hypertension: A German Point of View. European Heart Journal, 40, 1830-1831. https://doi.org/10.1093/eurheartj/ehz381
Arnett, D.K., Khera, A. and Blumenthal, R.S. (2019) ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Part 1, Lifestyle and Behavioral Factors. JAMA Cardiology, 4, 1043-1044. https://doi.org/10.1001/jamacardio.2019.2604
Chalasani, N., Younossi, Z., Lavine, J.E., Charlton, M., Cusi, K., Rinella, M., Harrison, S.A., Brunt, E.M. and Sanyal, A.J. (2018) The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology, 67, 328-357. https://doi.org/10.1002/hep.29367
Tag-Adeen, M., Sabra, A.M., Akazawa, Y., Ohnita, K. and Nakao, K. (2017) Impact of Hepatitis C Virus Genotype-4 Eradication Following Direct Acting Antivirals Treatment on Liver Stiffness Measurement. Hepatic Medicine; Evidence and Research, 9, 45-53. https://doi.org/10.2147/HMER.S142600
Castera, L., Vergniol, J., Foucher, J., et al. (2005) Prospective Comparison of Transient Elastography, Fibrotest, APRI, and Liver Biopsy for the Assessment of Fibrosis in Chronic Hepatitis C. Gastroenterology, 128, 343-350. https://doi.org/10.1053/j.gastro.2004.11.018
Sasso, M., Miette, V., Sandrin, L. and Beaugrand, M. (2012) The Controlled Attenuation Parameter (CAP): A Novel Tool for the Non-Invasive Evaluation of Steatosis Using Fibroscan. Clinics and Research in Hepatology and Gastroenterology, 36, 13-20. https://doi.org/10.1016/j.clinre.2011.08.001
Neeland, I.J., Patel, R.S., Eshtehardi, P., Dhawan, S., McDaniel, M.C., Rab, S.T., et al. (2012) Coronary Angiographic Scoring Systems: An Evaluation of Their Equivalence and Validity. American Heart Journal, 164, 547-552e1. https://doi.org/10.1016/j.ahj.2012.07.007
Gensini, G.G. (1983) A More Meaningful Scoring System for Determining the Severity of Coronary Heart Disease. American Journal of Cardiology, 51, 606. https://doi.org/10.1016/S0002-9149(83)80105-2
European Association for the Study of the Liver, European Association for the Study of Diabetes and European Association for the Study of Obesity (2016) EASL-EASD-EASO Clinical Practice Guidelines for the Management of Nonalcoholic Fatty Liver Disease. Journal of Hepatology, 64, 1388-1402.
Liu, Y.L., Reeves, H.L., Burt, A.D., Tiniakos, D., McPherson, S., Leathart, J.B., et al. (2014) TM6SF2 rs58542926 Influence Shepatic Fibrosis Progression in Patients with Non-Alcoholic Fatty Liver Disease. Nature Communications, 5, 4309. https://doi.org/10.1038/ncomms5309
Dongiovanni, P., Petta, S., Maglio, C., Fracanzani, A.L., Pipitone, R., Mozzi, E., et al. (2015) Transmembrane 6 Superfamilymember 2 Gene Variant Disentangles Nonalcoholic Steatohepatitis from Cardiovascular Disease. Hepatology, 61, 506-514. https://doi.org/10.1002/hep.27490
Valenti, L., Alisi, A., Galmozzi, E., Bartuli, A., Del Menico, B., Alterio, A., et al. (2010) I148M Patatin-Like Phospholipasedomain-Containing 3 Gene Variant and Severity of Pediatric Nonalcoholic Fatty Liver Disease. Hepatology, 52, 1274-1280. https://doi.org/10.1002/hep.23823
Nobili, V., Donati, B., Panera, N., Vongsakulyanon, A., Alisi, A., Dallapiccola, B., et al. (2014) A 4-Polymorphism Risk Scorepredicts Steatohepatitis in Children with Nonalcoholic Fatty Liver Disease. The Journal of Pediatric Gastroenterology and Nutrition, 58, 632-636. https://doi.org/10.1097/MPG.0000000000000279
Zhou, Y.Y., Zhou, X.D., Wu, S.J., Hu, X.Q., Tang, B., Poucke, S.V., Pan, X.Y., Wu, W.J., Gu, X.M., Fu, S.W., et al. (2018) Synergistic Increase in Cardiovascular Risk in Diabetes Mellitus with Nonalcoholic Fatty Liver Disease: A Meta-Analysis. European Journal of Gastroenterology & Hepatology, 30, 631-636. https://doi.org/10.1097/MEG.0000000000001075
Targher, G., Pichiri, I., Zoppini, G., Trombetta, M. and Bonora, E. (2012) Increased Prevalence of Cardiovascular Disease in Type 1 Diabetic Patients with Non-Alcoholic Fatty Liver Disease. Journal of Endocrinological Investigation, 35, 535-540. https://doi.org/10.1111/j.1464-5491.2011.03427.x
Targher, G. and Arcaro, G. (2007) Non-Alcoholic Fatty Liver Disease and Increased Risk of Cardiovascular Disease. Atherosclerosis, 191, 235-240. https://doi.org/10.1016/j.atherosclerosis.2006.08.021
Wu, S., Wu, F., Ding, Y., Hou, J., Bi, J. and Zhang, Z. (2016) Association of Non-Alcoholic Fatty Liver Disease with Major Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis. Scientific Reports, 6, Article No. 33386. https://doi.org/10.1038/srep33386
Olubamwo, O.O., Virtanen, J.K., Voutilainen, A., Kauhanen, J., Pihlajamäkia, J. and Tuomainen, T.-P. (2018) Association of Fatty Liver Index with the Risk of Incident Cardiovascular Disease and Acute Myocardial Infarction. European Journal of Gastroenterology & Hepatology, 30, 1047-1054. https://doi.org/10.1097/MEG.0000000000001183
Chang, Y., Ryu, S., Sung, K.C., Cho, Y.K., Sung, E., Kim, H.N., Jung, H.S., Yun, K.E., Ahn, J., Shin, H., et al. (2019) Alcoholic and Non-Alcoholic Fatty Liver Disease and Associations with Coronary Artery Calcification: Evidence from the Kangbuk Samsung Health Study. Gut, 68, 1667-1675. https://doi.org/10.1136/gutjnl-2018-317666