Skip to main content
Top
Published in: Digestive Diseases and Sciences 7/2020

01-07-2020 | Coronary Heart Disease | Original Article

Impact of NAFLD on the Incidence of Cardiovascular Diseases in a Primary Care Population in Germany

Authors: Christian Labenz, Yvonne Huber, Maurice Michel, Michael Nagel, Peter R. Galle, Karel Kostev, Jörn M. Schattenberg

Published in: Digestive Diseases and Sciences | Issue 7/2020

Login to get access

Abstract

Background

Patients with NAFLD are considered at a high risk of cardiovascular events due to underlying metabolic risk factors. Currently, data related to the impact of NAFLD on cardiovascular risk in the general population are lacking.

Aims

The aim of this study was to investigate the role of NAFLD on risk of myocardial infarction (MI), coronary heart disease (CHD), atrial fibrillation (AF), and stroke in primary care in Germany.

Methods

The study included patients diagnosed with NAFLD in primary care between 2010 and 2015. NAFLD cases (n = 22,048) were matched to a cohort without NAFLD (n = 22,048) based on age, sex, treating physician, type 2 diabetes, arterial hypertension, and hyperlipidemia. The primary outcome of the study was the incidence of MI, CHD, AF, and stroke.

Results

Within 10 years of the index date, 12.8% of patients with NAFLD and 10.0% of controls were diagnosed with CHD (p < 0.001). Additionally, frequency of MI was significantly higher in NAFLD (2.9% vs. 2.3%, p < 0.001). On regression analysis, HR for incidence of MI was 1.34 (p = 0.003) in all NAFLD patients and 1.35 (p = 0.013) for men. Incidence of AF was significantly higher in patients with NAFLD. On regression analysis, HR for incidence of AF was 1.15 (p = 0.005). NAFLD was not associated with a higher incidence of stroke (HR 1.09, p = 0.243).

Conclusions

NAFLD constitutes an independent risk factor for CHD, MI, and AF in primary care in Germany. Identification of patients with NAFLD in primary care will allow specifically managing and modifying underlying risk factors to improve the overall prognosis.
Literature
1.
go back to reference Younossi Z, Tacke F, Arrese M, et al. Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology. 2019;69:2672–2682.CrossRef Younossi Z, Tacke F, Arrese M, et al. Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology. 2019;69:2672–2682.CrossRef
2.
go back to reference Schuppan D, Schattenberg JM. Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches. J Gastroenterol Hepatol. 2013;28:68–76.CrossRef Schuppan D, Schattenberg JM. Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches. J Gastroenterol Hepatol. 2013;28:68–76.CrossRef
3.
go back to reference Estes C, Anstee QM, Arias-Loste MT, et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030. J Hepatol. 2018;69:896–904.CrossRef Estes C, Anstee QM, Arias-Loste MT, et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030. J Hepatol. 2018;69:896–904.CrossRef
4.
go back to reference Schattenberg JM, Schuppan D. Nonalcoholic steatohepatitis: the therapeutic challenge of a global epidemic. Curr Opin Lipidol. 2011;22:479–488.CrossRef Schattenberg JM, Schuppan D. Nonalcoholic steatohepatitis: the therapeutic challenge of a global epidemic. Curr Opin Lipidol. 2011;22:479–488.CrossRef
5.
go back to reference Schattenberg JM, Loomba R. Refining noninvasive diagnostics in nonalcoholic fatty liver disease: closing the gap to detect advanced fibrosis. Hepatology. 2019;69:934–936.CrossRef Schattenberg JM, Loomba R. Refining noninvasive diagnostics in nonalcoholic fatty liver disease: closing the gap to detect advanced fibrosis. Hepatology. 2019;69:934–936.CrossRef
6.
go back to reference Liebig S, Stoeckmann N, Geier A, et al. Multicenter validation study of a diagnostic algorithm to detect NASH and fibrosis in NAFLD patients with low NAFLD fibrosis score or liver stiffness. Clin Transl Gastroenterol. 2019;10:e00066.CrossRef Liebig S, Stoeckmann N, Geier A, et al. Multicenter validation study of a diagnostic algorithm to detect NASH and fibrosis in NAFLD patients with low NAFLD fibrosis score or liver stiffness. Clin Transl Gastroenterol. 2019;10:e00066.CrossRef
7.
go back to reference Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15:11–20.CrossRef Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15:11–20.CrossRef
8.
go back to reference Wong RJ, Aguilar M, Cheung R, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148:547–555.CrossRef Wong RJ, Aguilar M, Cheung R, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148:547–555.CrossRef
9.
go back to reference Huber Y, Pfirrmann D, Gebhardt I, et al. Improvement of non-invasive markers of NAFLD from an individualised, web-based exercise program. Aliment Pharmacol Ther. 2019;50:930–939.CrossRef Huber Y, Pfirrmann D, Gebhardt I, et al. Improvement of non-invasive markers of NAFLD from an individualised, web-based exercise program. Aliment Pharmacol Ther. 2019;50:930–939.CrossRef
10.
go back to reference Dulai PS, Singh S, Patel J, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology. 2017;65:1557–1565.CrossRef Dulai PS, Singh S, Patel J, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology. 2017;65:1557–1565.CrossRef
11.
go back to reference Ekstedt M, Hagstrom H, Nasr P, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61:1547–1554.CrossRef Ekstedt M, Hagstrom H, Nasr P, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61:1547–1554.CrossRef
12.
go back to reference 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.CrossRef 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.CrossRef
13.
go back to reference Golabi P, Paik J, Fukui N, Locklear CT, de Avilla L, Younossi ZM. Patients with lean nonalcoholic fatty liver disease are metabolically abnormal and have a higher risk for mortality. Clin Diabetes. 2019;37:65–72.CrossRef Golabi P, Paik J, Fukui N, Locklear CT, de Avilla L, Younossi ZM. Patients with lean nonalcoholic fatty liver disease are metabolically abnormal and have a higher risk for mortality. Clin Diabetes. 2019;37:65–72.CrossRef
14.
go back to reference Labenz C, Prochaska JH, Huber Y, et al. Cardiovascular risk categories in patients with nonalcoholic fatty liver disease and the role of low-density lipoprotein cholesterol. Hepatol Commun. 2019;3:1472–1481.CrossRef Labenz C, Prochaska JH, Huber Y, et al. Cardiovascular risk categories in patients with nonalcoholic fatty liver disease and the role of low-density lipoprotein cholesterol. Hepatol Commun. 2019;3:1472–1481.CrossRef
15.
go back to reference Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013;10:330–344.CrossRef Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013;10:330–344.CrossRef
16.
go back to reference Ndumele CE, Nasir K, Conceicao RD, Carvalho JA, Blumenthal RS, Santos RD. Hepatic steatosis, obesity, and the metabolic syndrome are independently and additively associated with increased systemic inflammation. Arterioscler Thromb Vasc Biol. 2011;31:1927–1932.CrossRef Ndumele CE, Nasir K, Conceicao RD, Carvalho JA, Blumenthal RS, Santos RD. Hepatic steatosis, obesity, and the metabolic syndrome are independently and additively associated with increased systemic inflammation. Arterioscler Thromb Vasc Biol. 2011;31:1927–1932.CrossRef
17.
go back to reference Santos RD, Valenti L, Romeo S. Does nonalcoholic fatty liver disease cause cardiovascular disease? Current knowledge and gaps. Atherosclerosis. 2019;282:110–120.CrossRef Santos RD, Valenti L, Romeo S. Does nonalcoholic fatty liver disease cause cardiovascular disease? Current knowledge and gaps. Atherosclerosis. 2019;282:110–120.CrossRef
18.
go back to reference Labenz C, Huber Y, Kalliga E, et al. Predictors of advanced fibrosis in non-cirrhotic non-alcoholic fatty liver disease in Germany. Aliment Pharmacol Ther. 2018;48:1109–1116.CrossRef Labenz C, Huber Y, Kalliga E, et al. Predictors of advanced fibrosis in non-cirrhotic non-alcoholic fatty liver disease in Germany. Aliment Pharmacol Ther. 2018;48:1109–1116.CrossRef
19.
go back to reference Rathmann W, Bongaerts B, Carius HJ, Kruppert S, Kostev K. Basic characteristics and representativeness of the German Disease Analyzer database. Int J Clin Pharmacol Ther. 2018;56:459–466.CrossRef Rathmann W, Bongaerts B, Carius HJ, Kruppert S, Kostev K. Basic characteristics and representativeness of the German Disease Analyzer database. Int J Clin Pharmacol Ther. 2018;56:459–466.CrossRef
20.
go back to reference Zwiener I, Blettner M, Hommel G. Survival analysis: part 15 of a series on evaluation of scientific publications. Deutsches Arzteblatt International. 2011;108:163–169.PubMedPubMedCentral Zwiener I, Blettner M, Hommel G. Survival analysis: part 15 of a series on evaluation of scientific publications. Deutsches Arzteblatt International. 2011;108:163–169.PubMedPubMedCentral
21.
go back to reference Alexander M, Loomis AK, van der Lei J, et al. Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD: real-world study of 18 million patients in four European cohorts. BMC Med. 2019;17:95.CrossRef Alexander M, Loomis AK, van der Lei J, et al. Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD: real-world study of 18 million patients in four European cohorts. BMC Med. 2019;17:95.CrossRef
22.
go back to reference Schattenberg JM, Ekstedt M. Assessing the disease burden of non-alcoholic fatty liver disease in the real world—big data and big numbers. BMC Med. 2019;17:123.CrossRef Schattenberg JM, Ekstedt M. Assessing the disease burden of non-alcoholic fatty liver disease in the real world—big data and big numbers. BMC Med. 2019;17:123.CrossRef
23.
go back to reference Stepanova M, Younossi ZM. Independent association between nonalcoholic fatty liver disease and cardiovascular disease in the US population. Clin Gastroenterol Hepatol. 2012;10:646–650.CrossRef Stepanova M, Younossi ZM. Independent association between nonalcoholic fatty liver disease and cardiovascular disease in the US population. Clin Gastroenterol Hepatol. 2012;10:646–650.CrossRef
25.
go back to reference Targher G, Bertolini L, Poli F, et al. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes. 2005;54:3541–3546.CrossRef Targher G, Bertolini L, Poli F, et al. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes. 2005;54:3541–3546.CrossRef
26.
go back to reference Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62:S47–S64.CrossRef Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62:S47–S64.CrossRef
27.
go back to reference Golabi P, Fukui N, Paik J, Sayiner M, Mishra A, Younossi ZM. Mortality risk detected by atherosclerotic cardiovascular disease score in patients with nonalcoholic fatty liver disease. Hepatol Commun. 2019;3:1050–1060.CrossRef Golabi P, Fukui N, Paik J, Sayiner M, Mishra A, Younossi ZM. Mortality risk detected by atherosclerotic cardiovascular disease score in patients with nonalcoholic fatty liver disease. Hepatol Commun. 2019;3:1050–1060.CrossRef
28.
go back to reference Francque SM, van der Graaff D, Kwanten WJ. Non-alcoholic fatty liver disease and cardiovascular risk: pathophysiological mechanisms and implications. J Hepatol. 2016;65:425–443.CrossRef Francque SM, van der Graaff D, Kwanten WJ. Non-alcoholic fatty liver disease and cardiovascular risk: pathophysiological mechanisms and implications. J Hepatol. 2016;65:425–443.CrossRef
30.
go back to reference Petta S, Argano C, Colomba D, 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. 2015;62:928–933.CrossRef Petta S, Argano C, Colomba D, 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. 2015;62:928–933.CrossRef
31.
go back to reference Hu J, Xu Y, He Z, et al. Increased risk of cerebrovascular accident related to non-alcoholic fatty liver disease: a meta-analysis. Oncotarget. 2018;9:2752–2760.CrossRef Hu J, Xu Y, He Z, et al. Increased risk of cerebrovascular accident related to non-alcoholic fatty liver disease: a meta-analysis. Oncotarget. 2018;9:2752–2760.CrossRef
32.
go back to reference Kim SU, Song D, Heo JH, et al. Liver fibrosis assessed with transient elastography is an independent risk factor for ischemic stroke. Atherosclerosis. 2017;260:156–162.CrossRef Kim SU, Song D, Heo JH, et al. Liver fibrosis assessed with transient elastography is an independent risk factor for ischemic stroke. Atherosclerosis. 2017;260:156–162.CrossRef
33.
go back to reference Wong RJ, Liu B, Bhuket T. Significant burden of nonalcoholic fatty liver disease with advanced fibrosis in the US: a cross-sectional analysis of 2011-2014 National Health and Nutrition Examination Survey. Aliment Pharmacol Ther. 2017;46:974–980.CrossRef Wong RJ, Liu B, Bhuket T. Significant burden of nonalcoholic fatty liver disease with advanced fibrosis in the US: a cross-sectional analysis of 2011-2014 National Health and Nutrition Examination Survey. Aliment Pharmacol Ther. 2017;46:974–980.CrossRef
34.
go back to reference Mensink G, Schienkiewitz A, Haftenberger M, Lampert T, Ziese T, Scheidt-Nave C. Overweight and obesity in Germany. Bundesgesundheitsbl. 2013;56:786–794.CrossRef Mensink G, Schienkiewitz A, Haftenberger M, Lampert T, Ziese T, Scheidt-Nave C. Overweight and obesity in Germany. Bundesgesundheitsbl. 2013;56:786–794.CrossRef
35.
go back to reference Hebebrand J, Dabrock P, Lingenfelder M, Mand E, Rief W, Voit W. Ist Adipositas eine Krankheit? Interdisziplinäre Perspektiven. Dtsch Arztebl International. 2004;101:A-2468. Hebebrand J, Dabrock P, Lingenfelder M, Mand E, Rief W, Voit W. Ist Adipositas eine Krankheit? Interdisziplinäre Perspektiven. Dtsch Arztebl International. 2004;101:A-2468.
Metadata
Title
Impact of NAFLD on the Incidence of Cardiovascular Diseases in a Primary Care Population in Germany
Authors
Christian Labenz
Yvonne Huber
Maurice Michel
Michael Nagel
Peter R. Galle
Karel Kostev
Jörn M. Schattenberg
Publication date
01-07-2020
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 7/2020
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-019-05986-9

Other articles of this Issue 7/2020

Digestive Diseases and Sciences 7/2020 Go to the issue