Riesgo cardiovascular en pacientes con hígado graso no alcohólico

1. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) & European Association for the Study of Obesity (EASO). EASL- EASD-EASO Clinical Practice Guidelines for the management of nonalcoholic fatty liver disease. J. Hepatol. 64,1388–1402 (2016).

2. Lonardo, A. et al. Epidemiological modifiers of nonalcoholic fatty liver disease: focus on high- risk groups. Dig. Liver Dis. 47, 997–1006 (2015).

3. Younossi, Z. M. et al. Global epidemiology of nonalcoholic fatty liver disease- Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 64, 73–84 (2016).

4. Tilg, H., Moschen, A. R. & Roden, M. NAFLD and diabetes mellitus. Nat. Rev. Gastroenterol. Hepatol. 14, 32–42 (2017).

5. Targher, G., Day, C. P. & Bonora, E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N. Engl. J. Med. 363, 1341–1350 (2010).

6. Byrne, C. D. & Targher, G. NAFLD: a multisystem disease. J. Hepatol. 62, S47–64 (2015).

7. Adams, L. A., Anstee, Q. M., Tilg, H. & Targher, G. Non- alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut 66, 1138–1153 (2017).

8. Younossi, Z. M. et al. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology 64, 1577–1586 (2016).

9. Perseghin, G. et al. Increased mediastinal fat and impaired left ventricular energy metabolism in young men with newly found fatty liver. Hepatology 47, 51–58 (2008).

10. Rijzewijk, L. J. et al. Effects of hepatic triglyceride content on myocardial metabolism in type 2 diabetes. J. Am. Coll. Cardiol. 56, 225–233 (2010).

11. Lautamaki, R. et al. Liver steatosis coexists with myocardial insulin resistance and coronary dysfunction in patients with type 2 diabetes. Am. J. Physiol. Endocrinol. Metab. 291, E282–E290 (2006).

12. Goland, S. et al. Cardiac abnormalities as a new manifestation of nonalcoholic fatty liver disease: echocardiographic and tissue Doppler imaging assessment. J. Clin. Gastroenterol. 40, 949–955 (2006).

13. Fallo, F. et al. Non- alcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in essential hypertension. Nutr. Metab. Cardiovasc. Dis. 19, 646–653 (2009).

14. Fotbolcu, H. et al. Impairment of the left ventricular systolic and diastolic function in patients with non- alcoholic fatty liver disease. Cardiol. J. 17, 457–463 (2010).

15. Mantovani, A., Zoppini, G., Targher, G., Golia, G. & Bonora, E. Non- alcoholic fatty liver disease is independently associated with left ventricular hypertrophy in hypertensive Type 2 diabetic individuals. J. Endocrinol. Invest. 35, 215–218 (2012).

16. Bonapace, S. et al. Nonalcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in patients with type 2 diabetes. Diabetes Care 35, 389–395 (2012).

17. Hallsworth, K. et al. Cardiac structure and function are altered in adults with non- alcoholic fatty liver disease. J. Hepatol. 58, 757–762 (2013).

18. Kim, N. H. et al. Non- alcoholic fatty liver disease, metabolic syndrome and subclinical cardiovascular changes in the general population. Heart 100, 938–943 (2014).

19. Karabay, C. Y. et al. Impaired left ventricular mechanics in nonalcoholic fatty liver disease: a speckle- tracking echocardiography study. Eur. J. Gastroenterol. Hepatol. 26, 325–331 (2014).

20. VanWagner, L. B. et al. Association of nonalcoholic fatty liver disease with subclinical myocardial remodeling and dysfunction: a population- based study. Hepatology 62, 773–783 (2015).

21. Cassidy, S. et al. Cardiac structure and function are altered in type 2 diabetes and non- alcoholic fatty liver disease and associate with glycemic control. Cardiovasc. Diabetol. 14, 23 (2015).

22. Kocabay, G. et al. Left atrial deformation parameters in patients with non- alcoholic fatty liver disease: a 2D speckle tracking imaging study. Clin. Sci. 126, 297–304 (2014).

23. Graner, M. et al. Ectopic fat depots and left ventricular function in nondiabetic men with nonalcoholic fatty liver disease. Circ. Cardiovasc. Imag. 8, e001979 (2015).

24. Mantovani, A. et al. Nonalcoholic fatty liver disease is independently associated with early left ventricular diastolic dysfunction in patients with type 2 diabetes. PLoS ONE 10, e0135329 (2015).

25. Petta, S. et al. Epicardial fat, cardiac geometry and cardiac function in patients with non- alcoholic fatty liver disease: association with the severity of liver disease. J. Hepatol. 62, 928–933 (2015).

26. Sunbul, M. et al. Nonalcoholic steatohepatitis score is an independent predictor of right ventricular dysfunction in patients with nonalcoholic fatty liver disease. Cardiovasc. Ther. 33, 294–299 (2015).

27. Psychari, S. N. et al. Epicardial fat in nonalcoholic fatty liver disease: properties and relationships with metabolic factors, cardiac structure, and cardiac function. Angiology 67, 41–48 (2016).

28. Ozveren, O. et al. Doppler tissue evaluation of atrial conduction properties in patients with non- alcoholic fatty- liver disease. Ultrason. Imag. 38, 225–235 (2016).

29. Widya, R. L. et al. Association between hepatic triglyceride content and left ventricular diastolic function in a population- based cohort: the Netherlands epidemiology of obesity study. Radiology 279, 443–450 (2016).

30. Trovato, F. M. et al. Echocardiography and NAFLD (non- alcoholic fatty liver disease). Int. J. Cardiol. 221, 275–279 (2016).

31. Jung, J. Y. et al. Effect of non- alcoholic fatty liver disease on left ventricular diastolic function and geometry in the Korean general population. Hepatol.Res. 47, 522–532 (2017).

32. Simon, T. G., Bamira, D. G., Chung, R. T., Weiner, R. B. & Corey, K. E. Nonalcoholic steatohepatitis is associated with cardiac remodeling and dysfunction. Obesity 25, 1313–1316 (2017).

33. Lee, Y. H. et al. Association of nonalcoholic steatohepatitis with subclinical myocardial dysfunction in non- cirrhotic patients. J. Hepatol. 68, 764–772 (2018).

34. Sert, A. et al. Left ventricular function by echocardiography, tissue Doppler imaging, and carotid intima- media thickness in obese adolescents with nonalcoholic fatty liver disease. Am. J. Cardiol. 112,436–443 (2013).

35. Alp, H. et al. Association between nonalcoholic fatty liver disease and cardiovascular risk in obese children and adolescents. Can. J. Cardiol. 29, 1118–1125 (2013).

36. Singh, G. K. et al. Alterations in ventricular structure and function in obese adolescents with nonalcoholic fatty liver disease. J. Pediatr. 162, 1160–1168.e1 (2013).

37. Pacifico, L. et al. Left ventricular dysfunction in obese children and adolescents with nonalcoholic fatty liver disease. Hepatology 59, 461–470 (2014).

38. Bonci, E. et al. Association of nonalcoholic fatty liver disease with subclinical cardiovascular changes: a systematic review and meta- analysis. Biomed. Res. Int.2015, 213737 (2015).

39. Dhingra, R. et al. Serum gamma- glutamyl transferase and risk of heart failure in the community. Arterioscler. Thromb. Vasc. Biol. 30, 1855–1860 (2010).

40. Wannamethee, S. G., Whincup, P. H., Shaper, A. G., Lennon, L. & Sattar, N. Gamma- glutamyltransferase, hepatic enzymes, and risk of incident heart failure in older men. Arterioscler. Thromb. Vasc. Biol. 32,830–835 (2012).

41. Wang, Y. et al. Serum gamma- glutamyltransferase and the risk of heart failure in men and women in Finland. Heart 99, 163–167 (2013).

42. Valbusa, F. et al. Nonalcoholic fatty liver disease is associated with higher 1-year all- cause rehospitalization rates in patients admitted for acute heart failure. Medicine 95, e2760 (2016).

43. Valbusa, F. et al. Nonalcoholic fatty liver disease and increased risk of 1-year all- cause and cardiac hospital readmissions in elderly patients admitted for acute heart failure. PLoS ONE 12, e0173398 (2017).

44. Sato, Y. et al. Liver stiffness assessed by Fibrosis-4 index predicts mortality in patients with heart failure. Open Heart 4, e000598 (2017).

45. Otto, C. M. & Prendergast, B. Aortic- valve stenosis — from patients at risk to severe valve obstruction. N. Engl. J. Med. 371, 744–756 (2014).

46. Volzke, H. et al. Heart valve sclerosis predicts all- cause and cardiovascular mortality. Atherosclerosis 209,606–610 (2010).

47. Rossi, A. et al. Aortic and mitral annular calcifications are predictive of all- cause and cardiovascular mortality in patients with type 2 diabetes. Diabetes Care 35,1781–1786 (2012).

48. O’Neal, W. T. et al. Mitral annular calcification and incident atrial fibrillation in the Multi- Ethnic Study of Atherosclerosis. Europace 17, 358–363 (2015).

49. Markus, M. R. et al. Hepatic steatosis is associated with aortic valve sclerosis in the general population: the Study of Health in Pomerania (SHIP). Arterioscler. Thromb. Vasc. Biol. 33, 1690–1695 (2013).

50. Bonapace, S. et al. Nonalcoholic fatty liver disease is associated with aortic valve sclerosis in patients with type 2 diabetes mellitus. PLoS ONE 9, e88371 (2014).

51. Mantovani, A. et al. Heart valve calcification in patients with type 2 diabetes and nonalcoholic fatty liver disease. Metabolism 64, 879–887 (2015).

52. Newton, J. L. et al. Fatigue in non- alcoholic fatty liver disease (NAFLD) is significant and associates with inactivity and excessive daytime sleepiness but not with liver disease severity or insulin resistance. Gut 57, 807–813 (2008).

53. Liu, Y. C. et al. Influence of non- alcoholic fatty liver disease on autonomic changes evaluated by the time domain, frequency domain, and symbolic dynamics of heart rate variability. PLoS ONE 8, e61803 (2013).

54. Kumar, M. S. et al. Cardiovascular autonomic dysfunction in patients of nonalcoholic fatty liver disease. Int. J. Hepatol. 2016, 5160754 (2016).

55. Ozveren, O. et al. Deterioration of heart rate recovery index in patients with non- alcoholic fatty liver disease (NAFLD). Med. Sci. Monit. 20, 1539–1543 (2014).

56. Cho, K. I., Jo, E. A., Cho, S. H. & Kim, B. H. The influence of epicardial fat and nonalcoholic fatty liver disease on heart rate recovery in metabolic syndrome. Metab. Syndr. Relat. Disord. 15, 226–232 (2017).

57. Targher, G. et al. Non- alcoholic fatty liver disease is associated with an increased prevalence of atrial fibrillation in hospitalized patients with type 2 diabetes. Clin. Sci. 125, 301–309 (2013).

58. Targher, G. et al. Non- alcoholic fatty liver disease is associated with an increased incidence of atrial fibrillation in patients with type 2 diabetes. PLoS ONE 8, e57183 (2013).

59. Sinner, M. F. et al. Relation of circulating liver transaminase concentrations to risk of new- onset atrial fibrillation. Am. J. Cardiol. 111, 219–224 (2013).

60. Iscen, S. RBBB is associated with an increased risk of NAFLD in young healthy individuals. Int. J. Cardiol.168, 4056–4057 (2013).

61. Alonso, A. et al. Circulating levels of liver enzymes and incidence of atrial fibrillation: the Atherosclerosis Risk in Communities cohort. Heart 100, 1511–1516 (2014).

62. Targher, G. et al. Association of nonalcoholic fatty liverdisease with QTc interval in patients with type 2 diabetes. Nutr. Metab. Cardiovasc. Dis. 24, 663–669 (2014).

63. Karajamaki, A. J. et al. Non- alcoholic fatty liver disease as a predictor of atrial fibrillation in middleaged population (OPERA Study). PLoS ONE 10,e0142937 (2015).

64. Hung, C. S. et al. Nonalcoholic fatty liver disease is associated with QT prolongation in the general population. J. Am. Heart Assoc. 4, e001820 (2015).

65. Markus, M. R. et al. Association between hepatic steatosis and serum liver enzyme levels with atrial fibrillation in the general population: the Study of Health in Pomerania (SHIP). Atherosclerosis 245,123–131 (2016).

66. Mantovani, A. et al. Nonalcoholic fatty liver disease is associated with ventricular arrhythmias in patients with type 2 diabetes referred for clinically indicated24-hour holter monitoring. Diabetes Care 39, 1416–1423 (2016).

67. Mangi, M. A. et al. Association of non- alcoholic fatty liver disease with conduction defects on electrocardiogram. Cureus 9, e1107 (2017).

68. Karajamaki, A. J. et al. Presence of atrial fibrillation is associated with liver stiffness in an elderly Finnish population. PLoS ONE 12, e0173855 (2017).

69. Long, M. T. et al. Relations of liver fat with prevalent and incident atrial fibrillation in the Framingham Heart Study. J. Am. Heart Assoc. 6, e005227 (2017).

70. Mantovani, A. et al. Nonalcoholic fatty liver disease is associated with an increased risk of heart block in hospitalized patients with type 2 diabetes mellitus. PLoS ONE 12, e0185459 (2017).

71. Lip, G. Y., Tse, H. F. & Lane, D. A. Atrial fibrillation. Lancet 379, 648–661 (2012).

72. Wijarnpreecha, K., Boonpheng, B., Thongprayoon, C., Jaruvongvanich, V. & Ungprasert, P. The association between non- alcoholic fatty liver disease and atrial fibrillation: a meta- analysis. Clin. Res. Hepatol. Gastroenterol. 41, 525–532 (2017).

73. Straus, S. M. et al. Prolonged QTc interval and risk of sudden cardiac death in a population of older adults. J. Am. Coll. Cardiol. 47, 362–367 (2006).

74. Coumbe, A. G. et al. Long- term follow- up of older patients with Mobitz type I second degree atrioventricular block. Heart 99, 334–338 (2013).

75. Kwok, C. S. et al. Prolonged PR interval, first- degree heart block and adverse cardiovascular outcomes: a systematic review and meta- analysis. Heart 102,672–680 (2016).

76. Gregor, M. F. & Hotamisligil, G. S. Inflammatory mechanisms in obesity. Annu. Rev. Immunol. 29,415–445 (2011).

77. Tilg, H. & Moschen, A. R. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 52, 1836–1846 (2010).

78. Liu, Y. L. et al. TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non- alcoholic fatty liver disease. Nat. Commun. 5, 4309 (2014).

79. Anstee, Q. M. & Day, C. P. The genetics of nonalcoholic fatty liver disease: spotlight on PNPLA3 and TM6SF2. Semin. Liver Dis. 35, 270–290 (2015).

80. Kahali, B. et al. TM6SF2: catch-22 in the fight against nonalcoholic fatty liver disease and cardiovascular disease? Gastroenterology 148, 679–684 (2015).

81. Anstee, Q. M., Seth, D. & Day, C. P. Genetic factors that affect risk of alcoholic and nonalcoholic fatty liver disease. Gastroenterology 150, 1728–1744.e7 (2016).

82. Tilg, H., Moschen, A. R. & Szabo, G. Interleukin-1 and inflammasomes in alcoholic liver disease/acute alcoholic hepatitis and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Hepatology 64, 955–965 (2016).

83. Cai, D. et al. Local and systemic insulin resistance resulting from hepatic activation of IKK- beta and NF- kappaB. Nat. Med. 11, 183–190 (2005).