Risk of cardiovascular events in patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis
Tóm tắt
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent disease and has been repeatedly associated with an increased risk of cardiovascular disease. However, the extent of such association is unclear. We conducted a systematic review and meta-analysis of the literature to evaluate the risk of myocardial infarction (MI), ischaemic stroke (IS), atrial fibrillation (AF), and heart failure (HF) in NAFLD patients.
According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed and EMBASE, from inception to 6 March 2021, and included all studies reporting the incidence of MI, IS, AF, and HF in patients with and without NAFLD. Random-effect fmodels were used to estimate pooled odds ratio (OR), 95% confidence intervals (CI), and 95% prediction intervals (PI); subgroup analyses, meta-regressions, and sensitivity analyses were additionally performed. Among 3254 records retrieved from literature, 20 studies were included. Non-alcoholic fatty liver disease was associated with an increased risk of MI (OR: 1.66, 95% CI: 1.39–1.99, 95% PI: 0.84–3.30), IS (OR: 1.41, 95% CI: 1.29–1.55, 95% PI 1.03–1.93), AF (OR: 1.27, 95% CI: 1.18–1.37, 95% PI: 1.07–1.52), and HF (OR: 1.62, 95% CI: 1.43–1.84, 95% CI: 1.04–2.51). We identified significant subgroup differences according to geographical location, study design, NAFLD definition, and risk of bias; meta-regressions identified mean age, male sex, and study-level characteristics as potential moderators of the risk of MI and IS.
Non-alcoholic fatty liver disease was associated with increased risk of MI, IS, AF, and HF. Age, sex, and study characteristics may moderate the strength of this association. Further studies are required to evaluate specific cardiovascular prevention strategies in patients with NAFLD.
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Tài liệu tham khảo
Powell, 2021, Non-alcoholic fatty liver disease, The Lancet, 397, 2212, 10.1016/S0140-6736(20)32511-3
Younossi, 2016, Global epidemiology of nonalcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes, Hepatology, 64, 73, 10.1002/hep.28431
Chalasani, 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, 10.1002/hep.29367
2020, The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017, Lancet Gastroenterol Hepatol, 5, 245, 10.1016/S2468-1253(19)30349-8
Paik, 2019, Mortality related to nonalcoholic fatty liver disease is increasing in the United States, Hepatol Commun, 3, 1459, 10.1002/hep4.1419
Kasper, 2021, NAFLD and cardiovascular diseases: a clinical review, Clin Res Cardiol, 110, 921, 10.1007/s00392-020-01709-7
Lonardo, 2016, Non-alcoholic fatty liver disease and risk of cardiovascular disease, Metabolism, 65, 1136, 10.1016/j.metabol.2015.09.017
Stahl, 2019, Nonalcoholic fatty liver disease and the heart: JACC state-of-the-art review, J Am Coll Cardiol, 73, 948, 10.1016/j.jacc.2018.11.050
Tang, 2017, Gut microbiota in cardiovascular health and disease, Circ Res, 120, 1183, 10.1161/CIRCRESAHA.117.309715
Tang, 2019, Intestinal microbiota in cardiovascular health and disease: JACC state-of-the-art review, J Am Coll Cardiol, 73, 2089, 10.1016/j.jacc.2019.03.024
Targher, 2016, Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis, J Hepatol, 65, 589, 10.1016/j.jhep.2016.05.013
Hu, 2018, Increased risk of cerebrovascular accident related to non-alcoholic fatty liver disease: a meta-analysis, Oncotarget, 9, 2752, 10.18632/oncotarget.22755
Mantovani, 2019, Association between non-alcoholic fatty liver disease and risk of atrial fibrillation in adult individuals: an updated meta-analysis, Liver Int, 39, 758, 10.1111/liv.14044
Page, 2021, The PRISMA 2020 statement: an updated guideline for reporting systematic reviews, BMJ, 372, n71, 10.1136/bmj.n71
Moon, 2017, Hepatic FDG uptake is associated with future cardiovascular events in asymptomatic individuals with non-alcoholic fatty liver disease, J Nucl Cardiol, 24, 892, 10.1007/s12350-015-0297-y
Pisto, 2014, Fatty liver predicts the risk for cardiovascular events in middle-aged population: a population-based cohort study, BMJ Open, 4, e004973, 10.1136/bmjopen-2014-004973
Labenz, 2020, Impact of NAFLD on the incidence of cardiovascular diseases in a primary care population in Germany, Dig Dis Sci, 65, 2112, 10.1007/s10620-019-05986-9
Yang, 2020, The association between nonalcoholic fatty liver disease and stroke: results from the Korean Genome and Epidemiology Study (KoGES), Int J Environ Res Public Health, 17, 9568, 10.3390/ijerph17249568
Lee, 2021, Nonalcoholic fatty liver disease and the risk of atrial fibrillation stratified by body mass index: a nationwide population-based study, Sci Rep, 11, 3737, 10.1038/s41598-021-83367-x
Baratta, 2020, Nonalcoholic fatty liver disease and fibrosis associated with increased risk of cardiovascular events in a prospective study, Clin Gastroenterol Hepatol, 18, 2324, 10.1016/j.cgh.2019.12.026
Wong, 2016, Long-term clinical outcomes after fatty liver screening in patients undergoing coronary angiogram: a prospective cohort study, Hepatology, 63, 754, 10.1002/hep.28253
Allen, 2019, Women with nonalcoholic fatty liver disease lose protection against cardiovascular disease: a longitudinal cohort study, Am J Gastroenterol, 114, 1764, 10.14309/ajg.0000000000000401
Käräjämäki, 2015, Non-alcoholic fatty liver disease as a predictor of atrial fibrillation in middle-aged population (OPERA study), PLoS One, 10, e0142937, 10.1371/journal.pone.0142937
Hamaguchi, 2007, Nonalcolholic fatty liver disease is a novel predictor cardiovascular disease, World J Gastroenterol, 13, 1579, 10.3748/wjg.v13.i10.1579
Meyersohn, 2020, Association of Hepatic Steatosis With Major Adverse Cardiovascular Events, Independent of Coronary Artery Disease, Clin Gastroenterol Hepatol
Alexander, 2019, Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults, BMJ, 367, l5367, 10.1136/bmj.l5367
Xu, 2021, Severity of nonalcoholic fatty liver disease and risk of future ischemic stroke events, Stroke, 52, 103, 10.1161/STROKEAHA.120.030433
Sinn, 2020, Non-alcoholic fatty liver disease and the incidence of myocardial infarction: a cohort study, J Gastroenterol Hepatol, 35, 833, 10.1111/jgh.14856
Long, 2017, Relations of liver fat with prevalent and incident atrial fibrillation in the Framingham Heart Study, J Am Heart Assoc, 6, e005227, 10.1161/JAHA.116.005227
Targher, 2013, Non-alcoholic fatty liver disease is associated with an increased incidence of atrial fibrillation in patients with type 2 diabetes, PLoS One, 8, e57183, 10.1371/journal.pone.0057183
VanWagner, 2020, Longitudinal association of non-alcoholic fatty liver disease with changes in myocardial structure and function: the CARDIA study, J Am Heart Assoc, 9, e014279, 10.1161/JAHA.119.014279
Ichikawa, 2021, Prognostic value of non-alcoholic fatty liver disease for predicting cardiovascular events in patients with diabetes mellitus with suspected coronary artery disease: a prospective cohort study, Cardiovasc Diabetol, 20, 8, 10.1186/s12933-020-01192-4
El Azeem, 2013, Association between nonalcoholic fatty liver disease and the incidence of cardiovascular and renal events, J Saudi Heart Assoc, 25, 239, 10.1016/j.jsha.2013.07.004
Lee, 2021, Metabolic Dysfunction-Associated Fatty Liver Disease and Incident Cardiovascular Disease Risk: A Nationwide Cohort Study, Clinical Gastroenterology and Hepatology : The Official Clinical Practice Journal of the American Gastroenterological Association, 19, 2138, 10.1016/j.cgh.2020.12.022
Targher, 2007, Non-alcoholic fatty liver disease, the metabolic syndrome and the risk of cardiovascular disease: the plot thickens, Diabet Med, 24, 1, 10.1111/j.1464-5491.2007.02025.x
Sonmez, 2015, Low- and high-density lipoprotein subclasses in subjects with nonalcoholic fatty liver disease, J Clin Lipidol, 9, 576, 10.1016/j.jacl.2015.03.010
Francque, 2016, Non-alcoholic fatty liver disease and cardiovascular risk: pathophysiological mechanisms and implications, J Hepatol, 65, 425, 10.1016/j.jhep.2016.04.005
Villanova, 2005, Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease, Hepatology, 42, 473, 10.1002/hep.20781
Musso, 2008, Association of liver disease with postprandial large intestinal triglyceride-rich lipoprotein accumulation and pro/antioxidant imbalance in normolipidemic non-alcoholic steatohepatitis, Ann Med, 40, 383, 10.1080/07853890801946515
Ichikawa, 2021, Incremental prognostic value of non-alcoholic fatty liver disease over coronary computed tomography angiography findings in patients with suspected coronary artery disease, Eur J Prev Cardiol, 10.1093/eurjpc/zwab120
Trovato, 2016, Echocardiography and NAFLD (non-alcoholic fatty liver disease), Int J Cardiol, 221, 275, 10.1016/j.ijcard.2016.06.180
Hallsworth, 2013, Cardiac structure and function are altered in adults with non-alcoholic fatty liver disease, J Hepatol, 58, 757, 10.1016/j.jhep.2012.11.015
Simon, 2017, Nonalcoholic steatohepatitis is associated with cardiac remodeling and dysfunction, Obesity (Silver Spring), 25, 1313, 10.1002/oby.21879
VanWagner, 2015, Association of nonalcoholic fatty liver disease with subclinical myocardial remodeling and dysfunction: a population-based study, Hepatology, 62, 773, 10.1002/hep.27869
Itier, 2021, Non-alcoholic fatty liver disease and heart failure with preserved ejection fraction: from pathophysiology to practical issues, ESC Heart Fail, 8, 789, 10.1002/ehf2.13222
Fracanzani, 2016, Epicardial adipose tissue (EAT) thickness is associated with cardiovascular and liver damage in nonalcoholic fatty liver disease, PLoS One, 11, e0162473, 10.1371/journal.pone.0162473
Liu, 2019, Association of epicardial adipose tissue with non-alcoholic fatty liver disease: a meta-analysis, Hepatol Int, 13, 757, 10.1007/s12072-019-09972-1
Wong, 2017, Epicardial fat and atrial fibrillation: current evidence, potential mechanisms, clinical implications, and future directions, Eur Heart J, 38, 1294
2016, EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease, J Hepatol, 64, 1388, 10.1016/j.jhep.2015.11.004