Highlights
- •Patients with NAFLD had alterations in cardiac remodeling.
- •Hepatic steatosis and fibrosis are associated with diastolic heart dysfunction.
- •Those without NAFLD were more likely to have higher myocardial glucose uptake.
- •Hepatic fibrosis was correlated with decreased myocardial glucose uptake.
Background & Aims
Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular
risk. Among categories of NAFLD, hepatic fibrosis is most likely to affect mortality.
Myocardial function and its energy metabolism are tightly linked, which might be altered
by an insulin resistant condition such as NAFLD. We investigated whether hepatic steatosis
and fibrosis were associated with myocardial dysfunction relative to myocardial glucose
uptake.
Methods
A total of 308 patients (190 without NAFLD, 118 with NAFLD) were studied in a tertiary
care hospital. Myocardial glucose uptake was evaluated at fasted state using [18F]-fluorodeoxyglucose-positron emission tomography (18FDG-PET). Hepatic steatosis and fibrosis were assessed by transient liver elastography
(Fibroscan®) with controlled attenuation parameter, which quantifies hepatic fat and
by surrogate indices (fatty liver index and NAFLD fibrosis score). Cardiac structure
and function were examined by echocardiogram.
Results
Compared to those without NAFLD, patients with NAFLD had alterations in cardiac remodeling,
manifested by increased left ventricular mass index, left ventricular end-diastolic
diameter, and left atrial volume index (all p <0.05). Hepatic steatosis was significantly associated with left ventricular filling
pressure (E/e’ ratio), which reflects diastolic dysfunction (p for trend <0.05). Those without NAFLD were more likely to have higher myocardial
glucose uptake compared to those with NAFLD. Significant hepatic fibrosis was also
correlated with diastolic dysfunction and impaired myocardial glucose uptake. Using
multivariable linear regression, E/e’ ratio was independently associated with hepatic
fibrosis (standardized β = 0.12 to 0.27; all p <0.05). Association between hepatic steatosis and E/e’ ratio was also significant
(standardized β = 0.10 to 0.15; all p <0.05 excluding the model adjusted for adiposity).
Conclusions
Hepatic steatosis and fibrosis are significantly associated with diastolic heart dysfunction.
This association is linked with myocardial glucose uptake evaluated by 18FDG-PET.
Lay summary
Non-alcoholic fatty liver disease is associated with an increased risk of cardiovascular
disease. More severe forms of non-alcoholic fatty liver disease, where hepatic fibrosis
occurs, are linked to increased mortality. In this study, we have shown that hepatic
steatosis and fibrosis are associated with subclinical myocardial dysfunction. This
association is linked to altered myocardial glucose uptake.
Graphical abstract
Graphical Abstract
Keywords
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References
- Nonalcoholic fatty liver disease: a systematic review.JAMA. 2015; 313: 2263-2273
- The global NAFLD epidemic.Nat Rev Gastroenterol Hepatol. 2013; 10: 686-690
- The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association.Hepatology. 2012; 55: 2005-2023
- Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.Gastroenterology. 1999; 116: 1413-1419
- Sarcopenia is associated with significant liver fibrosis independently of obesity and insulin resistance in nonalcoholic fatty liver disease: Nationwide surveys (KNHANES 2008–2011).Hepatology. 2016; 63: 776-786
- Epidemiology and natural history of nonalcoholic fatty liver disease.Semin Liver Dis. 2015; 35: 221-235
- Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease.J Hepatol. 2008; 49: 608-612
- Long-term follow-up of patients with nonalcoholic fatty liver.Clin Gastroenterol Hepatol. 2009; 7: 234-238
- Long-term follow-up of patients with NAFLD and elevated liver enzymes.Hepatology. 2006; 44: 865-873
- Alanine aminotransferase predicts coronary heart disease events: a 10-year follow-up of the Hoorn Study.Atherosclerosis. 2007; 191: 391-396
- Non-alcoholic fatty liver disease - the heart of the matter.World J Hepatol. 2015; 7: 1369-1376
- Liver steatosis coexists with myocardial insulin resistance and coronary dysfunction in patients with type 2 diabetes.Am J Physiol Endocrinol Metab. 2006; 291: E282-E290
- Cardiac abnormalities as a new manifestation of nonalcoholic fatty liver disease: echocardiographic and tissue Doppler imaging assessment.J Clin Gastroenterol. 2006; 40: 949-955
- Impairment of the left ventricular systolic and diastolic function in patients with non-alcoholic fatty liver disease.Cardiol J. 2010; 17: 457-463
- Failing mouse hearts utilize energy inefficiently and benefit from improved coupling of glycolysis and glucose oxidation.Cardiovasc Res. 2014; 101: 30-38
- Trends in prevalence and outcome of heart failure with preserved ejection fraction.N Engl J Med. 2006; 355: 251-259
- New concepts in diastolic dysfunction and diastolic heart failure: Part I: diagnosis, prognosis, and measurements of diastolic function.Circulation. 2002; 105: 1387-1393
- Outcome of heart failure with preserved ejection fraction in a population-based study.N Engl J Med. 2006; 355: 260-269
- Visceral adiposity is associated with altered myocardial glucose uptake measured by (18)FDG-PET in 346 subjects with normal glucose tolerance, prediabetes, and type 2 diabetes.Cardiovasc Diabetol. 2015; 14: 148
- Severity of coronary artery calcification by electron beam computed tomography predicts silent myocardial ischemia.Circulation. 2000; 101: 244-251
- Obesity and metabolic syndrome in Korea.Diabetes Metab J. 2011; 35: 561-566
- Standards of medical care in diabetes--2014.Diabetes Care. 2014; 37: S14-S80
- Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.J Am Soc Echocardiogr. 2005; 18: 1440-1463
- Sex differences in central hemodynamics and their relationship to left ventricular diastolic function.J Am Coll Cardiol. 2011; 57: 1226-1233
- Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings.Am J Cardiol. 1986; 57: 450-458
- Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology.Eur Heart J. 2005; 26: 1115-1140
- Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American society of echocardiography and the European association of cardiovascular imaging.J Am Soc Echocardiogr. 2016; 29: 277-314
- Non-laboratory-based self-assessment screening score for non-alcoholic fatty liver disease: development, validation and comparison with other scores.PLoS One. 2014; 9: e107584
- The relationship between type 2 diabetes mellitus and non-alcoholic fatty liver disease measured by controlled attenuation parameter.Yonsei Med J. 2016; 57: 885-892
- The utility of radiological imaging in nonalcoholic fatty liver disease.Gastroenterology. 2002; 123: 745-750
- Liver stiffness measurement in combination with noninvasive markers for the improved diagnosis of B-viral liver cirrhosis.J Clin Gastroenterol. 2009; 43: 267-271
- Controlled attenuation parameter (CAP) for detection of hepatic steatosis in patients with chronic liver diseases: a prospective study of a native Korean population.Liver Int. 2014; 34: 102-109
- Retrospective study of coronary uptake of 18F-fluorodeoxyglucose in association with calcification and coronary artery disease: a preliminary study.Nucl Med Commun. 2009; 30: 287-291
- Effect of hepatic steatosis on liver FDG uptake measured in mean standard uptake values.Radiology. 2010; 254: 917-924
- Within-patient variability of (18)F-FDG: standardized uptake values in normal tissues.J Nucl Med. 2004; 45: 784-788
- Effects of noise, image resolution, and ROI definition on the accuracy of standard uptake values: a simulation study.J Nucl Med. 2004; 45: 1519-1527
- Increased mediastinal fat and impaired left ventricular energy metabolism in young men with newly found fatty liver.Hepatology. 2008; 47: 51-58
- Cardiac structure and function are altered in adults with non-alcoholic fatty liver disease.J Hepatol. 2013; 58: 757-762
- Association of nonalcoholic fatty liver disease with subclinical myocardial remodeling and dysfunction: A population-based study.Hepatology. 2015; 62: 773-783
- Non-alcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in essential hypertension.Nutr Metab Cardiovasc Dis. 2009; 19: 646-653
- Nonalcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in patients with type 2 diabetes.Diabetes Care. 2012; 35: 389-395
- Non-alcoholic fatty liver disease, metabolic syndrome and subclinical cardiovascular changes in the general population.Heart. 2014; 100: 938-943
- Interactions of the heart and the liver.Eur Heart J. 2013; 34: 2804-2811
- Serum gamma-glutamyltransferase and the risk of heart failure in men and women in Finland.Heart. 2013; 99: 163-167
- Gamma-glutamyltransferase, hepatic enzymes, and risk of incident heart failure in older men.Arterioscler Thromb Vasc Biol. 2012; 32: 830-835
- Epicardial fat, cardiac geometry and cardiac function in patients with non-alcoholic fatty liver disease: association with the severity of liver disease.J Hepatol. 2015; 62: 928-933
- Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart.Nat Clin Pract Cardiovasc Med. 2005; 2: 536-543
- Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis.Free Radic Biol Med. 2012; 52: 59-69
- Relationship between high-sensitivity C-reactive protein levels and liver histology in subjects with non-alcoholic fatty liver disease.J Hepatol. 2006; 45 ([Author reply 881-882]): 879-881
- Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor?.Eur Heart J. 2012; 33: 1190-1200
- Angiotensin-II type 1 receptor-mediated Janus kinase 2 activation induces liver fibrosis.Hepatology. 2014; 60: 334-348
- Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications.Eur Heart J. 2015; 36: 2555-2564
- The ubiquitin proteasome system in human cardiomyopathies and heart failure.Am J Physiol Heart Circ Physiol. 2013; 304: H1283-H1293
- Sarcopaenia is associated with NAFLD independently of obesity and insulin resistance: Nationwide surveys (KNHANES 2008–2011).J Hepatol. 2015; 63: 486-493
- Hepatokines as a link between obesity and cardiovascular diseases.Diabetes Metab J. 2015; 39: 10-15
- Fetuin-A: the missing link in lipid-induced inflammation.Nat Med. 2012; 18: 1182-1183
- Fetuin-A as a predicator of sarcopenic left ventricular dysfunction.Sci Rep. 2015; 5: 12078
- Mortality rate in patients with diastolic dysfunction and normal systolic function.Arch Intern Med. 2011; 171: 1082-1087
- Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review.Eur J Heart Fail. 2016; 18: 242-252
- Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden.Am J Cardiol. 2002; 90: 1284-1289
- Long-term prognostic significance of left atrial volume in acute myocardial infarction.J Am Coll Cardiol. 2004; 44: 327-334
- Left atrial remodelling in patients with myocardial infarction complicated by heart failure, left ventricular dysfunction, or both: the VALIANT Echo study.Eur Heart J. 2009; 30: 56-65
- Left atrial volume index: relation to long-term clinical outcome in type 2 diabetes.J Am Coll Cardiol. 2013; 62: 2416-2421
- Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease.J Hepatol. 2003; 39: 239-244
- Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection.Am J Gastroenterol. 2002; 97: 2614-2618
- Reliability of transient elastography for the detection of fibrosis in non-alcoholic fatty liver disease and chronic viral hepatitis.J Hepatol. 2011; 54: 64-71
- Controlled attenuation parameter (CAP) for the diagnosis of steatosis: a prospective study of 5323 examinations.J Hepatol. 2014; 60: 1026-1031
- Controlled attenuation parameter for non-invasive assessment of hepatic steatosis in Chinese patients.World J Gastroenterol. 2014; 20: 4702-4711
Article info
Publication history
Published online: November 23, 2017
Accepted:
November 13,
2017
Received in revised form:
October 24,
2017
Received:
April 25,
2017
See Editorial, pages 640–642Identification
Copyright
© 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
