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Sonaglioni A, Cerini F, Fagiani V, Nicolosi GL, Rumi MG, Lombardo M, Muti P. Effect of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) on Left Ventricular Mechanics in Patients Without Overt Cardiac Disease: A Systematic Review and Meta-Analysis. J Clin Med 2025; 14:2690. [PMID: 40283520 PMCID: PMC12028084 DOI: 10.3390/jcm14082690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2025] [Revised: 04/10/2025] [Accepted: 04/12/2025] [Indexed: 04/29/2025] Open
Abstract
Background: Over the last two decades, a fair number of echocardiographic studies have investigated the influence of metabolic dysfunction-associated steatotic liver disease (MASLD) on myocardial strain and strain rate parameters assessed by speckle tracking echocardiography (STE) in individuals without overt heart disease, reporting not univocal results. We aimed at analyzing the main findings of these studies. Methods: All studies examining conventional echoDoppler parameters by transthoracic echocardiography (TTE) and left ventricular (LV) mechanics [LV-global longitudinal strain (GLS), LV-global strain rate in systole (GSRs), in early diastole (GSRe) and late diastole (GSRl)] by STE in MASLD patients without known heart disease vs. healthy individuals, were searched on PubMed, Embase and Scopus databases. The primary endpoint was to quantify the effect of MASLD on LV-GLS in individuals without overt cardiac disease. Continuous data [LV-GLS, LV-GLSRs, LV-GLSRe, LV-GLSRl and left ventricular ejection fraction (LVEF)] were pooled as the standardized mean difference (SMD) comparing MASLD cohorts with healthy controls. Results: A total of 11 studies were included, totaling 1348 MASLD patients and 6098 healthy controls. Overall, MASLD showed a medium effect on LV-GLS (SMD -0.6894; 95%CI -0.895, -0.472, p < 0.001) and LV-GLSRs (SMD -0.753; 95%CI -1.501, -0.006, p = 0.048), a large effect on LV-GLSRe (SMD -0.837; 95%CI -1.662, -0.012, p = 0.047) and a small and not statistically significant effect on LV-GLSRl (SMD -0.375; 95%CI -1.113, 0.363, p = 0.319) and LVEF (SMD -0.134; 95%CI -0.285, 0.017, p = 0.083). The overall I2 statistic was 86.4%, 89.4%, 90.9%, 89.6% and 72.5% for LV-GLS, LV-GLSRs, LV-GLSRe, LV-GLSRl and LVEF studies, respectively, indicating high between-study heterogeneity. Egger's test for LV-GLS studies gave a p value of 0.11, 0.26, 0.40, 0.32 and 0.42 for LV-GLS, LV-GLSRs, LV-GLSRe, LV-GLSRl and LVEF studies, respectively, thus excluding publication bias. Meta-regression analysis excluded any correlation between potential confounders and LV-GLS in MASLD individuals (all p > 0.05). Sensitivity analysis confirmed the robustness of study results. Conclusions: MASLD has a medium effect on LV-GLS, independently of demographics, anthropometrics and the cardiovascular disease burden. STE analysis may allow early detection of subclinical LV systolic dysfunction in MASLD patients, potentially identifying those who may develop heart failure later in life.
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Affiliation(s)
| | - Federica Cerini
- Hepatology Unit, IRCCS MultiMedica, 20123 Milan, Italy; (F.C.); (M.G.R.)
- Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023–2027, University of Milan, 20122 Milan, Italy
| | - Valeria Fagiani
- Department of Emergency, Fondazione IRCSS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy;
| | | | - Maria Grazia Rumi
- Hepatology Unit, IRCCS MultiMedica, 20123 Milan, Italy; (F.C.); (M.G.R.)
- Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023–2027, University of Milan, 20122 Milan, Italy
| | | | - Paola Muti
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy;
- IRCCS MultiMedica, 20138 Milan, Italy
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Savzikhanova RR, Subkhangulova DO, Khazova EV. Hepatocardial relationships in non-alcoholic fatty liver disease: issues of epidemiology, diagnosis, prognosis. KAZAN MEDICAL JOURNAL 2024; 105:1003-1014. [DOI: 10.17816/kmj624813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
World statistics indicate a steady increase in the prevalence of non-alcoholic fatty liver disease, which correlates with the pandemics of obesity and diabetes, which are quite common in Russia. The commonality of cardiometabolic risk factors, the high global prevalence of non-alcoholic fatty liver disease and atherosclerotic cardiovascular diseases generates the interest of researchers in studying hepatocardial relationships. Currently, non-alcoholic fatty liver disease is positioned as a hepatic manifestation of a multisystem disorder, heterogeneous in underlying causes, manifestations, course and outcomes. The purpose of this review was to analyze hepatocardial relationships based on publications. 76 sources on the epidemiology of non-alcoholic fatty liver disease, published from 2011–2023 in journals indexed in Pubmed and eLibrary, were analyzed. Age and gender aspects of the development of non-alcoholic fatty liver disease were considered. The pathogenetic mechanisms of hepatocardial relationships, which were closely related to systemic inflammation, insulin resistance, metabolic syndrome and its components, were highlighted. The criteria and methods for diagnosing non-alcoholic fatty liver disease and metabolic-associated liver disease were outlined. Recent studies demonstrated the presence of hepatocardial connections, characterized by an increased risk of developing atherosclerosis, cardiomyopathy and rhythm disturbances, changes in the structural and functional parameters and geometry of the heart, as well as diastolic dysfunction, which may precede and/or contribute to the development of chronic heart failure in patients with non-alcoholic fatty liver disease. The article presents data on non-alcoholic fatty liver disease as a new factor associated with the development of adverse cardiovascular events to a greater extent than the outcome of liver diseases themselves, which confirms the need for primary and secondary prevention of cardiovascular diseases in this cohort of patients.
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Affiliation(s)
| | | | - Elena V. Khazova
- Kazan State Medical University
- Kazan (Volga Region) Federal University
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Giangregorio F, Mosconi E, Debellis MG, Provini S, Esposito C, Garolfi M, Oraka S, Kaloudi O, Mustafazade G, Marín-Baselga R, Tung-Chen Y. A Systematic Review of Metabolic Syndrome: Key Correlated Pathologies and Non-Invasive Diagnostic Approaches. J Clin Med 2024; 13:5880. [PMID: 39407941 PMCID: PMC11478146 DOI: 10.3390/jcm13195880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 09/26/2024] [Accepted: 09/27/2024] [Indexed: 10/20/2024] Open
Abstract
Background and Objectives: Metabolic syndrome (MetS) is a condition marked by a complex array of physiological, biochemical, and metabolic abnormalities, including central obesity, insulin resistance, high blood pressure, and dyslipidemia (characterized by elevated triglycerides and reduced levels of high-density lipoproteins). The pathogenesis develops from the accumulation of lipid droplets in the hepatocyte (steatosis). This accumulation, in genetically predisposed subjects and with other external stimuli (intestinal dysbiosis, high caloric diet, physical inactivity, stress), activates the production of pro-inflammatory molecules, alter autophagy, and turn on the activity of hepatic stellate cells (HSCs), provoking the low grade chronic inflammation and the fibrosis. This syndrome is associated with a significantly increased risk of developing type 2 diabetes mellitus (T2D), cardiovascular diseases (CVD), vascular, renal, pneumologic, rheumatological, sexual, cutaneous syndromes and overall mortality, with the risk rising five- to seven-fold for T2DM, three-fold for CVD, and one and a half-fold for all-cause mortality. The purpose of this narrative review is to examine metabolic syndrome as a "systemic disease" and its interaction with major internal medicine conditions such as CVD, diabetes, renal failure, and respiratory failure. It is essential for internal medicine practitioners to approach this widespread condition in a "holistic" rather than a fragmented manner, particularly in Western countries. Additionally, it is important to be aware of the non-invasive tools available for assessing this condition. Materials and Methods: We conducted an exhaustive search on PubMed up to July 2024, focusing on terms related to metabolic syndrome and other pathologies (heart, Lung (COPD, asthma, pulmonary hypertension, OSAS) and kidney failure, vascular, rheumatological (osteoarthritis, rheumatoid arthritis), endocrinological, sexual pathologies and neoplastic risks. The review was managed in accordance with the PRISMA statement. Finally, we selected 300 studies (233 papers for the first search strategy and 67 for the second one). Our review included studies that provided insights into metabolic syndrome and non-invasive techniques for evaluating liver fibrosis and steatosis. Studies that were not conducted on humans, were published in languages other than English, or did not assess changes related to heart failure were excluded. Results: The findings revealed a clear correlation between metabolic syndrome and all the pathologies above described, indicating that non-invasive assessments of hepatic fibrosis and steatosis could potentially serve as markers for the severity and progression of the diseases. Conclusions: Metabolic syndrome is a multisystem disorder that impacts organs beyond the liver and disrupts the functioning of various organs. Notably, it is linked to a higher incidence of cardiovascular diseases, independent of traditional cardiovascular risk factors. Non-invasive assessments of hepatic fibrosis and fibrosis allow clinicians to evaluate cardiovascular risk. Additionally, the ability to assess liver steatosis may open new diagnostic, therapeutic, and prognostic avenues for managing metabolic syndrome and its complications, particularly cardiovascular disease, which is the leading cause of death in these patients.
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Affiliation(s)
- Francesco Giangregorio
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Emilio Mosconi
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Maria Grazia Debellis
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Stella Provini
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Ciro Esposito
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Matteo Garolfi
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Simona Oraka
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Olga Kaloudi
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Gunel Mustafazade
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Raquel Marín-Baselga
- Department of Internal Medicine, Hospital Universitario La Paz, Paseo Castellana 241, 28046 Madrid, Spain;
| | - Yale Tung-Chen
- Department of Internal Medicine, Hospital Universitario La Paz, Paseo Castellana 241, 28046 Madrid, Spain;
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Fu Z, Wang Y, Wang Y, Shi S, Li Y, Zhang B, Wu H, Song Q. Linking abnormal fat distribution with HFpEF and diastolic dysfunction: a systematic review, meta-analysis, and meta-regression of observational studies. Lipids Health Dis 2024; 23:277. [PMID: 39217346 PMCID: PMC11365188 DOI: 10.1186/s12944-024-02266-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 08/19/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND The global prevalence of obesity has escalated into a formidable health challenge intricately linked with the risk of developing cardiac diastolic disfunction and heart failure with preserved ejection fraction (HFpEF). Abnormal fat distribution is potentially strongly associated with an increased risk of cardiac diastolic dysfunction, and we aimed to scrutinize and elucidate the correlation between them. METHODS Following the Cochrane Handbook and PRISMA 2020 guidelines, we systematically reviewed the literature from PubMed, Embase, and Web of Science. We focused on studies reporting the mean and standard deviation (SD) of abnormal fat in HFpEF or cardiac diastolic dysfunction patients and the Pearson/Spearman correlation coefficients for the relationship between abnormal fat distribution and the risk of developing cardiac diastolic dysfunction. Data were standardized to the standard mean difference (SMD) and Fisher's z value for meta-analysis. RESULTS After progressive filtering and selection, 63 studies (43,113 participants) were included in the quantitative analyses. Abnormal fat distribution was significantly greater in participants with cardiac diastolic dysfunction than in controls [SMD 0.88 (0.69, 1.08)], especially in epicardial adipose tissue [SMD 0.99 (0.73, 1.25)]. Abnormal fat distribution was significantly correlated with the risk of developing cardiac diastolic dysfunction [E/E': 0.23 (0.18, 0.27), global longitudinal strain: r=-0.11 (-0.24, 0.02)]. Meta-regression revealed sample size as a potential heterogeneous source, and subgroup analyses revealed a stronger association between abnormal fat distribution and the risk of developing cardiac diastolic dysfunction in the overweight and obese population. CONCLUSION Abnormal fat distribution was significantly associated with the risk of developing cardiac diastolic dysfunction. TRIAL REGISTRATION CRD42024543774.
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Affiliation(s)
- Zhenyue Fu
- Department of General Internal Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Yajiao Wang
- Department of General Internal Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yuxin Wang
- Department of General Internal Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Shuqing Shi
- Department of General Internal Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yumeng Li
- Department of General Internal Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Bingxuan Zhang
- Department of General Internal Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Huaqin Wu
- Department of Cardiovascular, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qingqiao Song
- Department of General Internal Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
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Koch DG, Rockey DC, Litwin SS, Tedford RJ. H2FPEF Scores Are Increased in Patients with NASH Cirrhosis and Are Associated with Post-liver Transplant Heart Failure. Dig Dis Sci 2024; 69:3061-3068. [PMID: 38782854 PMCID: PMC11341588 DOI: 10.1007/s10620-024-08438-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 04/09/2024] [Indexed: 05/25/2024]
Abstract
INTRODUCTION Patients with cirrhosis are at risk for cardiac complications such as heart failure, particularly heart failure with preserved ejection fraction (HFpEF) due to left ventricular diastolic dysfunction (LVDD). The H2FPEF score is a predictive model used to identify patients with HFpEF. Our primary aim was to assess the H2FPEF score in patients with cirrhosis and determine its potential to identify patients at risk for heart failure after liver transplant. METHODS This was a cohort study of patients undergoing liver transplant for cirrhosis from January 2010 and October 2018 who had a pre-transplant transthoracic echocardiogram. RESULTS 166 cirrhosis subjects were included in the study. The majority were men (65%) and Caucasian (85%); NASH was the most common cause of cirrhosis (41%) followed by alcohol (34%). The median H2FPEF score was 2.0 (1.0-4.0). Patients with NASH cirrhosis had higher H2FPEF scores (3.22, 2.79-3.64) than those with alcohol induced cirrhosis (1.89, 1.5-2.29, p < 0.001) and other causes of cirrhosis (1.73, 1.28-2.18, p < 0.001). All subjects with a H2FPEF score > 6 had NASH cirrhosis. There was no association between the H2FPEF scores and measures of severity of liver disease (bilirubin, INR, or MELD score). Patients with heart failure after liver transplant had higher H2FPEF scores than those without heart failure (4.0, 3.1-4.9 vs. 2.3, 2.1-2.6, respectively; p = 0.015), but the score did not predict post-transplant mortality. CONCLUSION H2FPEF scores are higher in cirrhosis patients with NASH and appear to be associated with post-transplant heart failure, but not death.
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Affiliation(s)
- David G Koch
- MUSC Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, 25 Courtenay Dr., Charleston, SC, 29425, USA.
| | - Don C Rockey
- MUSC Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, 25 Courtenay Dr., Charleston, SC, 29425, USA
| | - Sheldon S Litwin
- Division of Cardiology, Medical University of South Carolina, Charleston, USA
| | - Ryan J Tedford
- Division of Cardiology, Medical University of South Carolina, Charleston, USA
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Westcott F, Dearlove DJ, Hodson L. Hepatic fatty acid and glucose handling in metabolic disease: Potential impact on cardiovascular disease risk. Atherosclerosis 2024; 394:117237. [PMID: 37633797 DOI: 10.1016/j.atherosclerosis.2023.117237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 08/09/2023] [Accepted: 08/10/2023] [Indexed: 08/28/2023]
Abstract
The prevalence of metabolic diseases, including type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing. Although invariably associated with obesity, the importance of fat deposition in non-adipose tissue organs has yet to be fully explored. Pathological ectopic fat deposition within the liver (known as (MASLD)) has been suggested to underlie the development of T2DM and is now emerging as an independent risk factor for cardiovascular disease (CVD). The process of hepatic de novo lipogenesis (DNL), that is the synthesis of fatty acids from non-lipid precursors (e.g. glucose), has received much attention as it sits at the intersect of hepatic glucose and fatty acid handling. An upregulation of the DNL pathway has been suggested to be central in the development of metabolic diseases (including MASLD, insulin resistance, and T2DM). Here we review the evidence to determine if hepatic DNL may play a role in the development of MASLD and T2DM and therefore underlie an increased risk of CVD.
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Affiliation(s)
- Felix Westcott
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, UK
| | - David J Dearlove
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, UK
| | - Leanne Hodson
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, UK; Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
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Kim G, Yu TY, Jee JH, Bae JC, Kang M, Kim JH. Association between nonalcoholic fatty liver disease and left ventricular diastolic dysfunction: A 7-year retrospective cohort study of 3,380 adults using serial echocardiography. DIABETES & METABOLISM 2024; 50:101534. [PMID: 38608865 DOI: 10.1016/j.diabet.2024.101534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 04/05/2024] [Accepted: 04/08/2024] [Indexed: 04/14/2024]
Abstract
AIM Left ventricular diastolic dysfunction (LVDD) has been observed in people with nonalcoholic fatty liver disease (NAFLD) in cross-sectional studies but the causal relationship is unclear. This study aimed to investigate the impact of NAFLD and the fibrotic progression of the disease on the development of LVDD, assessed by serial echocardiography, in a large population over a 7-year longitudinal setting. METHODS This retrospective cohort study included the data of 3,380 subjects from a medical health check-up program. We defined subjects having NAFLD by abdominal ultrasonography and assessed significant liver fibrosis by the aspartate transaminase (AST) to platelet ratio index (APRI), the NAFLD fibrosis score (NFS), and the fibrosis-4 (FIB-4) index. LVDD was defined using serial echocardiography. A parametric Cox proportional hazards model was used. RESULTS During 11,327 person-years of follow-up, there were 560 (16.0 %) incident cases of LVDD. After adjustment for multiple risk factors, subjects with NAFLD showed an increased adjusted hazard ratio (aHR) of 1.21 (95 % confidence interval [CI]=1.02-1.43) for incident LVDD compared to those without. The risk of LV diastolic dysfunction increased progressively with increasing degree of hepatic steatosis (P< 0.001). Compared to subjects without NAFLD, the multivariable-aHR (95 % CI) for LVDD in subjects with APRI < 0.5 and APRI ≥ 0.5 were 1.20 (1.01-1.42) and 1.36 (0.90-2.06), respectively (P= 0.036), while other fibrosis prediction models (NFS and FIB-4 index) showed insignificant results. CONCLUSIONS This study demonstrated that NAFLD was associated with an increased risk of LVDD in a large cohort. More severe forms of hepatic steatosis and/or significant liver fibrosis may increase the risk of developing LVDD.
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Affiliation(s)
- Gyuri Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Tae Yang Yu
- Division of Endocrinology and Metabolism, Department of Medicine, Wonkwang Medical Center, Wonkwang University School of Medicine, Iksan, Republic of Korea
| | - Jae Hwan Jee
- Department of Health Promotion Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Ji Cheol Bae
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea
| | - Mira Kang
- Department of Health Promotion Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Jae Hyeon Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea; Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Republic of Korea.
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Desai R, Alvi AT, Vasavada A, Pulakurthi YS, Patel B, Mohammed AS, Doshi S, Ogbu I. Sex and racial disparities in non-alcoholic fatty liver disease-related cardiovascular events: National inpatient sample analysis (2019). World J Cardiol 2024; 16:137-148. [PMID: 38576521 PMCID: PMC10989223 DOI: 10.4330/wjc.v16.i3.137] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Revised: 01/15/2024] [Accepted: 02/18/2024] [Indexed: 03/21/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) increases cardiovascular disease (CVD) risk irrespective of other risk factors. However, large-scale cardiovascular sex and race differences are poorly understood. AIM To investigate the relationship between NAFLD and major cardiovascular and cerebrovascular events (MACCE) in subgroups using a nationally representative United States inpatient sample. METHODS We examined National Inpatient Sample (2019) to identify adult hospitalizations with NAFLD by age, sex, and race using ICD-10-CM codes. Clinical and demographic characteristics, comorbidities, and MACCE-related mortality, acute myocardial infarction (AMI), cardiac arrest, and stroke were compared in NAFLD cohorts by sex and race. Multivariable regression analyses were adjusted for sociodemographic characteristics, hospitalization features, and comorbidities. RESULTS We examined 409130 hospitalizations [median 55 (IQR 43-66) years] with NFALD. NAFLD was more common in females (1.2%), Hispanics (2%), and Native Americans (1.9%) than whites. Females often reported non-elective admissions, Medicare enrolment, the median age of 55 (IQR 42-67), and poor income. Females had higher obesity and uncomplicated diabetes but lower hypertension, hyperlipidemia, and complicated diabetes than males. Hispanics had a median age of 48 (IQR 37-60), were Medicaid enrollees, and had non-elective admissions. Hispanics had greater diabetes and obesity rates than whites but lower hypertension and hyperlipidemia. MACCE, all-cause mortality, AMI, cardiac arrest, and stroke were all greater in elderly individuals (P < 0.001). MACCE, AMI, and cardiac arrest were more common in men (P < 0.001). Native Americans (aOR 1.64) and Asian Pacific Islanders (aOR 1.18) had higher all-cause death risks than whites. CONCLUSION Increasing age and male sex link NAFLD with adverse MACCE outcomes; Native Americans and Asian Pacific Islanders face higher mortality, highlighting a need for tailored interventions and care.
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Affiliation(s)
- Rupak Desai
- Independent Researcher, Atlanta, GA 30079, United States
| | - Ali Tariq Alvi
- Department of Internal Medicine, HCA Florida Westside Hospital, Plantation, FL 33324, United States
| | - Advait Vasavada
- Department of Internal Medicine, M.P. Shah Medical Coll, Jamnagar 361008, India
| | | | - Bhavin Patel
- Department of Internal Medicine, Trinity Health Oakland Hospital, Pontiac, MI 48341, United States
| | - Adil Sarvar Mohammed
- Department of Internal Medicine, Central Michigan University College of Medicine, Saginaw, MI 48602, United States
| | - Shreyans Doshi
- Department of Internal Medicine, UCF College of Medicine HCA GME Consortium, Gainesville, FL 32605, United States
| | - Ikechukwu Ogbu
- Department of Internal Medicine, Mountainview Hospital, Las Vegas, NV 89108, United States.
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Terzi FVDO, Camargo GC, Parente DB, Pittella AM, Silva-Junior G, de Novaes GG, Oliveira Neto JA, Barroso JM, Pinheiro MVT, Xavier de Brito AS, de Oliveira RS, Rodrigues RS, de Mello Perez R, de Sousa AS, Moll-Bernardes RJ. How Cardiac Fibrosis Assessed via T1 Mapping Is Associated with Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease. J Clin Med 2023; 12:7381. [PMID: 38068433 PMCID: PMC10707357 DOI: 10.3390/jcm12237381] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 11/18/2023] [Accepted: 11/23/2023] [Indexed: 01/03/2025] Open
Abstract
(1) Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Although cardiovascular and NAFLD risk factors overlap, an independent association between these conditions may exist. Hepatic and cardiac fibrosis are important markers of mortality, but the correlation between these markers in patients with NAFLD has not been well studied. Our main objective was to determine the degree of myocardial fibrosis in patients with NAFLD and its correlation with the severity of liver fibrosis. (2) Methods: In this cross-sectional study, patients with NAFLD were allocated to two groups according to the stage of liver fibrosis assessed using MRI: no or mild fibrosis (F0-F1) and significant fibrosis (F2-F4). Framingham risk scores were calculated to evaluate cardiovascular risk factors, and patients underwent multiparametric cardiac and abdominal MRIs. (3) Results: The sample comprised 44 patients (28 with no or mild liver fibrosis and 16 with significant liver fibrosis). The mean age was 57.9 ± 12 years, and 41% were men. Most patients had high cardiac risk factors and carotid disease. Relative to patients with no or mild liver fibrosis, those with significant fibrosis had a higher median calcium score (p = 0.05) and increased myocardial extracellular volume (ECV; p = 0.02). Liver fibrosis correlated with cardiac fibrosis, represented by the ECV (r = 0.49, p < 0.001). The myocardial ECV differentiated patients with and without significant liver fibrosis (AUC = 0.78). (4) Conclusion: This study showed that diffuse myocardial fibrosis is associated with liver fibrosis in patients with NAFLD.
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Affiliation(s)
- Flavia Vernin de Oliveira Terzi
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
| | - Gabriel Cordeiro Camargo
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
| | - Daniella Braz Parente
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
- School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
| | - Ana Maria Pittella
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
| | - Gilberto Silva-Junior
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
| | - Gabrielle Gonçalves de Novaes
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
| | - Jaime Araújo Oliveira Neto
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
| | - Julia Machado Barroso
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
| | - Martha Valéria Tavares Pinheiro
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
| | - Adriana Soares Xavier de Brito
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
| | - Renée Sarmento de Oliveira
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
| | - Rosana Souza Rodrigues
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
- School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
| | - Renata de Mello Perez
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
- School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
| | - Andréa Silvestre de Sousa
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
- School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, Brazil
| | - Renata Junqueira Moll-Bernardes
- D’Or Institute for Research and Education—IDOR, Rio de Janeiro 22281-100, Brazil; (F.V.d.O.T.); (G.C.C.); (D.B.P.); (A.M.P.); (G.S.-J.); (G.G.d.N.); (J.A.O.N.); (J.M.B.); (M.V.T.P.); (A.S.X.d.B.); (R.S.d.O.); (R.S.R.); (R.d.M.P.); (A.S.d.S.)
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10
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Jiang W, Liu Z, Liu S, Du T. Associations of advanced liver fibrosis with heart failure with preserved ejection fraction in type 2 diabetic patients according to obesity and metabolic goal achievement status. Front Endocrinol (Lausanne) 2023; 14:1183075. [PMID: 37941902 PMCID: PMC10628500 DOI: 10.3389/fendo.2023.1183075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 10/06/2023] [Indexed: 11/10/2023] Open
Abstract
Background Heart failure with preserved ejection fraction (HFpEF), a major cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM), is frequently coexisted with obesity, poor glycemic, blood pressure (BP), and/or lipid control. We aimed to investigate the associations of nonalcoholic fatty liver disease (NAFLD) and its advanced fibrosis with HFpEF according to obesity, glycated hemoglobin A1c (HbA1c), BP, and low-density lipoprotein cholesterol (LDL-C) goal achievement status in T2DM patients. Methods A total of 2,418 T2DM patients who were hospitalized were cross-sectionally assessed. Liver fibrosis was evaluated by non-invasive biomarkers. Logistic regression analysis was used to evaluate the independent and combined associations of fibrosis status and diabetic care goal attainments with HFpEF risk. Results Simple steatosis was not associated with HFpEF risk compared with patients without steatosis, while advanced liver fibrosis was found to have significantly higher odds for HFpEF risk (odds ratio,1.59; 95% confidence interval, 1.22-2.08). Advanced fibrosis in NAFLD was significantly associated with an increased risk of HFpEF, regardless of obesity status, HbA1c, BP, and LDL-C goal achievement status. P values for the interactions between fibrosis status and HbA1c control status, fibrosis status and BP control status, fibrosis status and LDL-C control status, and fibrosis status and body mass index (BMI) status on HFpEF risk were 0.021, 0.13, 0.001, and 0.23, respectively. Conclusion In patients with T2DM, advanced hepatic fibrosis was significantly associated with HFpEF risk, irrespective of obesity status, HbA1c, BP, and LDL-C goal attainment status. Further, HbA1c and LDL-C goal attainment status modified this association.
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Affiliation(s)
- Wangyan Jiang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, Hubei, China
- Department of Clinical Nutrition, Deyang People’s Hospital, Deyang, Sichuan, China
| | - Zhelong Liu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, Hubei, China
| | - Shaohua Liu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, Hubei, China
| | - Tingting Du
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, Hubei, China
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11
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Yang R, Fan JG. Non-alcoholic fatty liver disease and risk of cardiovascular diseases: clinical association, pathophysiological mechanisms, and management. CARDIOLOGY PLUS 2023; 8:217-226. [DOI: 10.1097/cp9.0000000000000067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a fatty liver disease associated with metabolic dysfunction in genetically susceptible individuals due to over-nutrition and lack of exercise. With the prevalence of obesity, metabolic syndrome, and type 2 diabetes mellitus, NAFLD has become the most common cause of chronic liver disease worldwide. NAFLD shares many risk factors with cardiovascular diseases (CVDs). NAFLD is associated with increased risk of major cardiovascular events and other cardiac complications even after adjustment for traditional cardiovascular risk factors. The primary pathology of NAFLD is within the liver, but the most common cause of deaths in patients with NAFLD is CVDs. This review summarizes the epidemiological evidence for the association between NAFLD and CVD risk and the pathophysiological mechanisms underlying this association. Current treatment strategies for NAFLD and their potential impact on CVD risk are also discussed.
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Affiliation(s)
- Rong Yang
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Jian-Gao Fan
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
- Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
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12
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Goliopoulou A, Theofilis P, Oikonomou E, Anastasiou A, Pantelidis P, Gounaridi MI, Zakynthinos GE, Katsarou O, Kassi E, Lambadiari V, Tousoulis D, Vavuranakis M, Siasos G. Non-Alcoholic Fatty Liver Disease and Echocardiographic Parameters of Left Ventricular Diastolic Function: A Systematic Review and Meta-Analysis. Int J Mol Sci 2023; 24:14292. [PMID: 37762592 PMCID: PMC10532416 DOI: 10.3390/ijms241814292] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 09/15/2023] [Accepted: 09/16/2023] [Indexed: 09/29/2023] Open
Abstract
The cardiovascular implications of non-alcoholic fatty liver disease (NAFLD) have been associated with heart failure with preserved ejection fraction (HFpEF). The purpose of this review was to conduct a bibliographic search regarding the correlation between NAFLD and the echocardiographic parameters of left ventricular diastolic function. A systematic literature search was conducted in PubMed and Embase for original research data reporting on the association of NAFLD with diastolic function markers [E/e', left atrial volume index (LAVi), left ventricular mass index (LVMi)]. Meta-analysis was performed using the meta and dmetar packages in R studio v.1.4.1106, with p < 0.05 values being considered significant. Results are expressed as the standardized mean difference (SMD) for continuous variables and as the odds ratio (OR) for categorical variables, with respective 95% confidence intervals (CI). Heterogeneity between studies was expressed with index Ι2. From the preliminary search, 2619 articles were found from which 31 studies were included in the final statistical analysis. The meta-analysis of 8 studies which reported on the prevalence of diastolic dysfunction showed that it was increased in patients with NAFLD (OR: 2.07, 95% CI 1.24-3.44 with p = 0.01, I2: 80% with p < 0.01). The meta-analysis of 21 studies showed significantly higher E/e' in NAFLD patients (SMD 1.02, 95% CI 0.43-1.61 with p < 0.001, I2: 97% with p < 0.001). Individuals with NAFLD had increased LAVi (SMD: 0.87, 95% CI 0.38-1.37 with p < 0.001, I2: 96% with p < 0.001) and LVMi (SMD: 0.89, 95% CI 0.31-1.48 with p = 0.003, I2: 100% with p < 0.001). To conclude, in the meta-analysis of 31 observational studies, NAFLD patients were found to have affected left ventricular diastolic function, supporting the hypothesis of NAFLD being associated with HFpEF.
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Affiliation(s)
- Athina Goliopoulou
- 3rd Department of Cardiology, Sotiria Chest Disease Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece (P.P.)
| | - Panagiotis Theofilis
- 1st Department of Cardiology, Hippokration General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Evangelos Oikonomou
- 3rd Department of Cardiology, Sotiria Chest Disease Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece (P.P.)
| | - Artemis Anastasiou
- 3rd Department of Cardiology, Sotiria Chest Disease Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece (P.P.)
| | - Panteleimon Pantelidis
- 3rd Department of Cardiology, Sotiria Chest Disease Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece (P.P.)
| | - Maria Ioanna Gounaridi
- 3rd Department of Cardiology, Sotiria Chest Disease Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece (P.P.)
| | - Georgios E. Zakynthinos
- 3rd Department of Cardiology, Sotiria Chest Disease Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece (P.P.)
| | - Ourania Katsarou
- 3rd Department of Cardiology, Sotiria Chest Disease Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece (P.P.)
| | - Eva Kassi
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Vaia Lambadiari
- 2nd Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Medical School, 12462 Athens, Greece
| | - Dimitris Tousoulis
- 1st Department of Cardiology, Hippokration General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Manolis Vavuranakis
- 3rd Department of Cardiology, Sotiria Chest Disease Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece (P.P.)
| | - Gerasimos Siasos
- 3rd Department of Cardiology, Sotiria Chest Disease Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece (P.P.)
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13
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Siddiqui MS, Parmar D, Sheikh F, Sarin SK, Cisneros L, Gawrieh S, Momin T, Duseja A, Sanyal AJ. Saroglitazar, a Dual PPAR α/γ Agonist, Improves Atherogenic Dyslipidemia in Patients With Non-Cirrhotic Nonalcoholic Fatty Liver Disease: A Pooled Analysis. Clin Gastroenterol Hepatol 2023; 21:2597-2605.e2. [PMID: 36731585 DOI: 10.1016/j.cgh.2023.01.018] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 11/23/2022] [Accepted: 01/17/2023] [Indexed: 02/04/2023]
Abstract
BACKGROUND & AIMS Cardiovascular disease is the leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the effects of saroglitazar, a dual peroxisome proliferator-activated receptor α/γ agonist, on serum lipids in patients with NAFLD. METHODS A total of 221 patients (saroglitazar, 130; placebo, 91) with NAFLD from phase 2 and 3 double-blinded placebo-controlled randomized clinical trials were pooled to assess the impact of saroglitazar magnesium 4 mg on traditional lipids, very low density lipoprotein cholesterol (VLDL-C), and small dense LDL-C (sdLDL-C). Change from baseline in lipid parameters was performed by using analysis of covariance including treatment as fixed effect and baseline value, diabetes, hypertension, and statin use as covariates. RESULTS Treatment with saroglitazar significantly improved total cholesterol (-17 mg/dL, 95% confidence interval [CI], -24 to 9; P < .001), triglyceride (-45 mg/dL, 95% CI, -60 to 31; P < .001), low-density lipoprotein cholesterol (-8 mg/dL, 95% CI, -15 to -1; P = .01), and VLDL-C (-8 mg/dL, -14 to -3; P < .001). Saroglitazar improved serum lipids as early as 4-6 weeks of initiation of therapy, and these effects persisted for duration of therapy. Saroglitazar also improved the highly atherogenic sdLDL-C (-10 mg/dL, -17 to -2; P = .01). In subgroup analysis of patients with either diabetes or hypertension, saroglitazar significantly improved serum lipids. CONCLUSIONS Saroglitazar improved the serum atherogenic lipoprotein profile in patients with NAFLD, irrespective of comorbid conditions and statin use. Saroglitazar has the potential to not only positively affect liver disease but also reduce cardiovascular risk in patients with NAFLD. (Trials registrations: CTRI 2015/10/006236, CTRI 173300410A0106, NCT03863574, and NCT03061721).
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Affiliation(s)
| | | | | | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
| | | | - Samer Gawrieh
- Indiana University School of Medicine, Indianapolis, Indiana
| | | | - Ajay Duseja
- Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Arun J Sanyal
- Virginia Commonwealth University, Richmond, Virginia
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14
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Gohil NV, Tanveer N, Makkena VK, Jaramillo AP, Awosusi BL, Ayyub J, Dabhi KN, Nath TS. Non-alcoholic Fatty Liver Disease and Its Association With Left Ventricular Diastolic Dysfunction: A Systematic Review. Cureus 2023; 15:e43013. [PMID: 37674936 PMCID: PMC10477932 DOI: 10.7759/cureus.43013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 08/06/2023] [Indexed: 09/08/2023] Open
Abstract
The commonest cause of hepatic illness globally is non-alcoholic fatty liver disease (NAFLD). This multisystemic disease affects extrahepatic organs, including the heart. It causes cardiac remodeling and a disruption of the systolic and diastolic functioning of the left ventricle. Numerous studies have investigated the connection between NAFLD and left ventricular diastolic dysfunction (LVDD). The results, nevertheless, are often contradictory. This systematic review looked at the relationship between NAFLD and LVDD generally and among different patient groups since it is a topic of interest. A thorough search approach was used to locate relevant publications published between 2003 and 2023 using major medical databases. Studies were chosen based on the pre-established eligibility criteria; the studies selected then underwent a critical evaluation using standardized quality assessment tools. For the systematic review, 13 articles were chosen, comprising nine cross-sectional studies, three narrative reviews, and one meta-analysis. There were a total of 13,341 NAFLD patients in these studies. Data extraction and qualitative synthesis from the selected research articles were conducted to determine the relationship between NAFLD and LVDD in various patient categories. We found a significant association between NAFLD and LVDD. Therefore, patients with NAFLD should be treated early to avoid complications since they are more likely to develop cardiac dysfunction in the future.
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Affiliation(s)
- Namra V Gohil
- Internal Medicine, Medical College Baroda, Vadodara, IND
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Nida Tanveer
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Internal Medicine, University of Louisville, Louisville, USA
| | - Vijaya Krishna Makkena
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Medicine, Osmania Medical College, Hyderabad, IND
| | - Arturo P Jaramillo
- General Practice, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Babatope L Awosusi
- Pathology and Laboratory Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Javaria Ayyub
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Karan Nareshbhai Dabhi
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Tuheen Sankar Nath
- Surgical Oncology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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15
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Inciardi RM, Mantovani A, Targher G. Non-Alcoholic Fatty Liver Disease as an Emerging Risk Factor for Heart Failure. Curr Heart Fail Rep 2023; 20:308-319. [PMID: 37402108 PMCID: PMC10421789 DOI: 10.1007/s11897-023-00613-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/14/2023] [Indexed: 07/05/2023]
Abstract
PURPOSE OF THE REVIEW Non-alcoholic fatty liver disease (NAFLD) and heart failure (HF) are two chronic diseases that have become important global public health problems. This narrative review provides a comprehensive overview of the association between NAFLD and increased risk of new-onset HF, briefly discusses the putative biological mechanisms linking these two conditions, and summarizes targeted pharmacotherapies for NAFLD that might also beneficially affect cardiac complications leading to new-onset HF. RECENT FINDINGS Recent observational cohort studies supported a significant association between NAFLD and the long-term risk of new-onset HF. Notably, this risk remained statistically significant even after adjustment for age, sex, ethnicity, adiposity measures, pre-existing type 2 diabetes and other common cardiometabolic risk factors. In addition, the risk of incident HF was further increased with more advanced liver disease, especially with higher severity of liver fibrosis. There are multiple potential pathophysiological mechanisms by which NAFLD (especially in its more advanced forms) may increase the risk of new-onset HF. Because of the strong link existing between NAFLD and HF, more careful surveillance of these patients will be needed. However, further prospective and mechanistic studies are required to better decipher the existing but complex link between NAFLD and risk of new-onset HF.
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Affiliation(s)
- Riccardo M Inciardi
- ASST Spedali Civili Di Brescia, Division of Cardiology and Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Alessandro Mantovani
- Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, University of Verona, Verona, Italy
| | - Giovanni Targher
- Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, University of Verona, Verona, Italy.
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16
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Hydes TJ, Kennedy OJ, Buchanan R, Cuthbertson DJ, Parkes J, Fraser SDS, Roderick P. The impact of non-alcoholic fatty liver disease and liver fibrosis on adverse clinical outcomes and mortality in patients with chronic kidney disease: a prospective cohort study using the UK Biobank. BMC Med 2023; 21:185. [PMID: 37198624 DOI: 10.1186/s12916-023-02891-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 05/04/2023] [Indexed: 05/19/2023] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) frequently co-exist. We assess the impact of having NAFLD on adverse clinical outcomes and all-cause mortality for people with CKD. METHODS A total of 18,073 UK Biobank participants identified to have CKD (eGFR < 60 ml/min/1.73 m2 or albuminuria > 3 mg/mmol) were prospectively followed up by electronic linkage to hospital and death records. Cox-regression estimated the hazard ratios (HR) associated with having NAFLD (elevated hepatic steatosis index or ICD-code) and NAFLD fibrosis (elevated fibrosis-4 (FIB-4) score or NAFLD fibrosis score (NFS)) on cardiovascular events (CVE), progression to end-stage renal disease (ESRD) and all-cause mortality. RESULTS 56.2% of individuals with CKD had NAFLD at baseline, and 3.0% and 7.7% had NAFLD fibrosis according to a FIB-4 > 2.67 and NFS ≥ 0.676, respectively. The median follow-up was 13 years. In univariate analysis, NAFLD was associated with an increased risk of CVE (HR 1.49 [1.38-1.60]), all-cause mortality (HR 1.22 [1.14-1.31]) and ESRD (HR 1.26 [1.02-1.54]). Following multivariable adjustment, NAFLD remained an independent risk factor for CVE overall (HR 1.20 [1.11-1.30], p < 0.0001), but not ACM or ESRD. In univariate analysis, elevated NFS and FIB-4 scores were associated with increased risk of CVE (HR 2.42 [2.09-2.80] and 1.64 [1.30-2.08]) and all-cause mortality (HR 2.82 [2.48-3.21] and 1.82 [1.47-2.24]); the NFS score was also associated with ESRD (HR 5.15 [3.52-7.52]). Following full adjustment, the NFS remained associated with an increased incidence of CVE (HR 1.19 [1.01-1.40]) and all-cause mortality (HR 1.31 [1.13-1.52]). CONCLUSIONS In people with CKD, NAFLD is associated with an increased risk of CVE, and the NAFLD fibrosis score is associated with an elevated risk of CVE and worse survival.
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Affiliation(s)
- Theresa J Hydes
- Department of Cardiovascular and Metabolic Medicine, 3Rd Floor Clinical Sciences Centre, Institute of Life Course and Medical Sciences, Liverpool University Hospitals NHS Foundation Trust, University of Liverpool, Longmoor Lane, Liverpool, L9 7AL, UK.
- University Hospital Aintree, Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK.
| | - Oliver J Kennedy
- School of Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, SO17 1BJ, UK
| | - Ryan Buchanan
- School of Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, SO17 1BJ, UK
- Department of Hepatology, University Hospitals Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK
- NIHR Southampton Biomedical Research Centre, Southampton General Hospital, Southampton, SO16 6YD, UK
| | - Daniel J Cuthbertson
- Department of Cardiovascular and Metabolic Medicine, 3Rd Floor Clinical Sciences Centre, Institute of Life Course and Medical Sciences, Liverpool University Hospitals NHS Foundation Trust, University of Liverpool, Longmoor Lane, Liverpool, L9 7AL, UK
- University Hospital Aintree, Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK
| | - Julie Parkes
- School of Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, SO17 1BJ, UK
| | - Simon D S Fraser
- School of Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, SO17 1BJ, UK
| | - Paul Roderick
- School of Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, SO17 1BJ, UK
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17
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Wang S, Zhang X, Zhang Q, Zhang B, Zhao L. Is non-alcoholic fatty liver disease a sign of left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus? A systematic review and meta-analysis. BMJ Open Diabetes Res Care 2023; 11:11/1/e003198. [PMID: 36807034 PMCID: PMC9943910 DOI: 10.1136/bmjdrc-2022-003198] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 01/28/2023] [Indexed: 02/22/2023] Open
Abstract
Recent studies have associated non-alcoholic fatty liver disease (NAFLD) with impaired cardiac function. However, patients with type 2 diabetes mellitus (T2DM), a high-risk group for left ventricular diastolic dysfunction (LVDD), were not analyzed as an independent study population. A systematic review was conducted to identify all published clinical trials using the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases from inception to September 14, 2022. Observational studies that reported echocardiographic parameters in T2DM patients with NAFLD compared with those without NAFLD were included for further selection. The Agency for Healthcare Research and Quality checklist was used to appraise the study quality. Ten observational studies (all cross-sectional in design) comprising 1800 T2DM patients (1124 with NAFLD, 62.4%) were included. We found that T2DM patients with NAFLD had a significantly lower E/A ratio, higher peak A velocity, higher E/e' ratio, lower e' velocity, greater left atrial maximum volume index, and greater left ventricular mass index than non-NAFLD patients. These findings reinforced the importance of NAFLD being associated with an increased risk of LVDD in the T2DM population, and NAFLD may be a sign of LVDD in patients with T2DM.PROSPERO registration numberCRD42022355844.
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Affiliation(s)
- Sicheng Wang
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiangyuan Zhang
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Qiqi Zhang
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Boxun Zhang
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Linhua Zhao
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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18
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Sheba W, Morsy E, Altahan S, Ayaad M, Lashen SA. Nonalcoholic fatty liver disease is associated with early left ventricular diastolic dysfunction in patients with type 2 diabeteS. ALEXANDRIA JOURNAL OF MEDICINE 2022. [DOI: 10.1080/20905068.2022.2132603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
Affiliation(s)
- Walaa Sheba
- Department of Internal Medicine, Faculty of Medicine, Alexandria University, Alexandria 21521, Egypt
| | - Eman Morsy
- Department of Internal Medicine, Faculty of Medicine, Alexandria University, Alexandria 21521, Egypt
| | - Salah Altahan
- Department of Cardiology, Faculty of Medicine, Alexandria University, Alexandria, 21521 Egypt
| | - Mona Ayaad
- Department of Clinical Pathology, Faculty of Medicine, Alexandria University, Alexandria 21521, Egypt
| | - Sameh A. Lashen
- Department of Internal Medicine, Faculty of Medicine, Alexandria University, Alexandria 21521, Egypt
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19
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Potential Roles of Glucagon-Like Peptide 1 Receptor Agonists (GLP-1 RAs) in Nondiabetic Populations. Cardiovasc Ther 2022; 2022:6820377. [PMID: 36474714 PMCID: PMC9683988 DOI: 10.1155/2022/6820377] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 10/29/2022] [Accepted: 11/01/2022] [Indexed: 11/17/2022] Open
Abstract
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been observed in several large cardiovascular outcome trials to significantly reduce the incidence of major cardiovascular event (MACE) with type 2 diabetic patients. The clinical trials of GLP-1 RAs, including lixisenatide, exenatide, liraglutide, semaglutide, albiglutide, and dulaglutide, are associated with a significantly 14% lower risk of MACE in patients with T2DM and a history of CV disease, and with a nonsignificantly 6% lower risk in patients without history of CV disease. Some of the interpretation with GLP-1 RA trials suggested the possible role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in primary prevention of cardiovascular diseases in nondiabetic individual, echoed by a recent editorial redefining the role of GLP-1 RAs being beyond glycaemic control. The narrative review provides an in-depth insight into GLP-1 RA use guideline in different countries and regions of the world and examines the safety and concern of GLP-1 RA use. The narrative review draws the comparison of GLP-1 RA use between diabetic and nondiabetic individual in terms of cardiovascular and metabolic benefits and points out the direction of future clinical trials of GLP-1 RAs in nondiabetic individuals. The focus of the review is on GLP-1 RAs' preventive roles in nondiabetic individuals with cardiovascular disease, chronic kidney diseases, obesity, dyslipidaemia, hypertension, nonalcoholic fatty liver diseases, polycystic ovarian syndrome (PCOS), and perioperative complications of bariatric surgery, albeit in small studies and subset analysis of clinical trials of diabetic patients.
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20
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Chen B, Tang WHW, Rodriguez M, Corey KE, Sanyal AJ, Kamath PS, Bozkurt B, Virk HUH, Pressman GS, Lazarus JV, El-Serag HB, Krittanawong C. NAFLD in Cardiovascular Diseases: A Contributor or Comorbidity? Semin Liver Dis 2022; 42:465-474. [PMID: 36241194 DOI: 10.1055/s-0042-1757712] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases are both highly prevalent conditions around the world, and emerging data have shown an association between them. This review found several longitudinal and cross-sectional studies showing that NAFLD was associated with coronary artery disease, cardiac remodeling, aortic valve remodeling, mitral annulus valve calcifications, diabetic cardiomyopathy, diastolic cardiac dysfunction, arrhythmias, and stroke. Although the specific underlying mechanisms are not clear, many hypotheses have been suggested, including that metabolic syndrome might act as an upstream metabolic defect, leading to end-organ manifestations in both the heart and liver. Management of NAFLD includes weight loss through lifestyle interventions or bariatric surgery, and pharmacological interventions, often targeting comorbidities. Although there are no Food and Drug Administration-approved nonalcoholic steatohepatitis-specific therapies, several drug candidates have demonstrated effect in the improvement in fibrosis or nonalcoholic steatohepatitis resolution. Further studies are needed to assess the effect of those interventions on cardiovascular outcomes, the major cause of mortality in patients with NAFLD. In conclusion, a more comprehensive, multidisciplinary approach to diagnosis and management of patients with NAFLD and cardiovascular diseases is needed to optimize clinical outcomes.
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Affiliation(s)
- Bing Chen
- Department of Gastroenterology and Nutrition, Geisinger Medical Center, Danville, Pennsylvania
| | - W H Wilson Tang
- Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio
| | - Mario Rodriguez
- John T. Milliken Department of Medicine, Division of Cardiovascular disease, Barnes-Jewish Hospital/Washington University in St. Louis School of Medicine, St. Louis, Missouri
| | - Kathleen E Corey
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
| | - Biykem Bozkurt
- Winters Center for Heart Failure Research, Cardiovascular Research Institute (B.B.), Baylor College of Medicine, DeBakey VA Medical Center, Houston, Texas
| | - Hafeez Ul Hassan Virk
- Harrington Heart & Vascular Institute, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Gregg S Pressman
- Division of Cardiovascular Diseases, Einstein Medical Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Jeffrey V Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain.,Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas.,Veterans Affairs Health Services Research and Development Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
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21
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Mitrovic B, Gluvic ZM, Obradovic M, Radunovic M, Rizzo M, Banach M, Isenovic ER. Non-alcoholic fatty liver disease, metabolic syndrome, and type 2 diabetes mellitus: where do we stand today? Arch Med Sci 2022; 19:884-894. [PMID: 37560721 PMCID: PMC10408022 DOI: 10.5114/aoms/150639] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 06/02/2022] [Indexed: 08/11/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), metabolic syndrome (MetS), and type 2 diabetes (T2DM) are metabolic disorders that belong to a highly prevalent disease cluster with a significant impact on public health worldwide. MetS is a complex condition characterized by metabolism perturbations that include glucose intolerance, insulin resistance, dyslipidaemia, associated pro-inflammatory state, and arterial hypertension. Because the components of MetS commonly co-occur, the management of these disorders cannot be considered separate issues. Thus NAFLD, recognized as a hepatic manifestation of MetS, is frequently associated with T2DM. This review analyses the underlying connections between these diseases and the risks associated with their co-occurrence. The effective management of NAFLD associated with MetS and T2DM involves an early diagnosis and optimal treatment of each condition leading to improvement in glycaemic and lipid regulation, liver steatosis, and arterial hypertension. The net effect of such treatment is the prevention of atherosclerotic cardiovascular diseases and liver fibrosis.
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Affiliation(s)
- Bojan Mitrovic
- University Clinical-Hospital Centre Zemun-Belgrade, Clinic of Internal medicine, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Zoran M. Gluvic
- University Clinical-Hospital Centre Zemun-Belgrade, Clinic of Internal medicine, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Milan Obradovic
- Department of Radiobiology and Molecular Genetics, “VINČA” Institute of Nuclear Sciences – National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Maja Radunovic
- Faculty of Stomatology, Pancevo, University Business Academy, Novi Sad, Serbia
| | - Manfredi Rizzo
- Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Maciej Banach
- Department of Hypertension, Medical University of Lodz, Lodz, Poland
| | - Esma R. Isenovic
- Department of Radiobiology and Molecular Genetics, “VINČA” Institute of Nuclear Sciences – National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
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22
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Abstract
The heart and the liver display multifaceted, complex interactions that can be divided into cardiac effects of liver disease, hepatic effects of heart disease, and disease processes affecting both organs. In part 1 of this 2 part series, we discuss how acute and chronic heart failure can have devastating effects on the liver, such as acute cardiogenic liver injury and congestive hepatopathy. On the other hand, primary liver disease, such as cirrhosis, can lead to a plethora of cardiac insults representative in cirrhotic cardiomyopathy as systolic dysfunction, diastolic dysfunction, and electrophysiological disturbances. Nonalcoholic fatty liver disease has long been associated with cardiovascular events that increase mortality. The management of both disease processes changes when the other organ system becomes involved. This consideration is important with regard to a variety of interventions, most notably transplantation of either organ, as risk of complications dramatically rises in the setting of both heart and liver disease (discussed in part 2). As our understanding of the intricate communication between the heart and liver continues to expand so does our management.
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Affiliation(s)
- Nicholas Scalzo
- From the Department of Medicine, Section of Gastroenterology & Hepatobiliary Diseases, New York Medical College and Westchester Medical Center, Valhalla, NY
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23
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Baars T, Gieseler RK, Patsalis PC, Canbay A. Towards harnessing the value of organokine crosstalk to predict the risk for cardiovascular disease in non-alcoholic fatty liver disease. Metabolism 2022; 130:155179. [PMID: 35283187 DOI: 10.1016/j.metabol.2022.155179] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 02/25/2022] [Accepted: 03/07/2022] [Indexed: 12/13/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Importantly, NAFLD increases the risk for cardiovascular disease (CVD). A causal relationship has been substantiated. Given the pandemic proportions of NAFLD, a reliable scoring system for predicting the risk of NAFLD-associated CVD is an urgent medical need. We here review cumulative evidence suggesting that systemically released organokines - especially certain adipokines, hepatokines, and cardiokines - may serve this purpose. The underlying rationale is that these signalers directly communicate between white adipose tissue, liver, and heart as key players in the pathogenesis of NAFLD and resultant CVD events. Moreover, evidence suggests that these organ-specific cytokines are secreted in a biologically predetermined, cascade-like pattern. Consequently, upon pinpointing organokines of relevance, we sketch requirements to establish an algorithm predictive of the CVD risk in patients with NAFLD. Such an algorithm, as to be consolidated in the form of an applicable equation, may be improved continuously by machine learning. To the best of our knowledge, such an option has not yet been considered. Establishing and implementing a reliable algorithm for determining the NAFLD-associated CVD risk has the potential to save many NAFLD patients from life-threatening CVD events.
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Affiliation(s)
- Theodor Baars
- Department of Internal Medicine, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany; Section of Metabolic and Preventive Medicine, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany
| | - Robert K Gieseler
- Department of Internal Medicine, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany; Laboratory of Immunology and Molecular Biology, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany
| | - Polykarpos C Patsalis
- Department of Internal Medicine, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany; Section of Cardiology and Internal Emergency Medicine, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany
| | - Ali Canbay
- Department of Internal Medicine, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany; Section of Hepatology and Gastroenterology, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany.
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24
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Yong JN, Ng CH, Lee CWM, Chan YY, Tang ASP, Teng M, Tan DJH, Lim WH, Quek J, Xiao J, Chin YH, Foo R, Chan M, Lin W, Noureddin M, Siddiqui MS, Muthiah MD, Sanyal A, Chew NWS. Non-alcoholic fatty liver disease association with structural heart, systolic and diastolic dysfunction: a meta-analysis. Hepatol Int 2022; 16:269-281. [PMID: 35320497 DOI: 10.1007/s12072-022-10319-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 02/11/2022] [Indexed: 01/30/2023]
Abstract
OBJECTIVE Several studies have documented a relationship between non-alcoholic fatty liver disease (NAFLD) and structural heart disease, particularly diastolic function. This meta-analysis will be the first to examine the echocardiographic-derived cardiac function and structural characteristics in NAFLD patients, and its association with liver disease severity and metabolic profile. METHODS Medline and Embase were searched and pairwise meta-analysis was conducted in DerSimonian and Laird to obtain the odds ratio (OR) and mean difference (MD) for dichotomous and continuous variables, respectively, to compare the effects of NAFLD on the echocardiography parameters. RESULTS Forty-one articles involving 33,891 patients underwent echocardiography. NAFLD patients had worse systolic indices with lower ejection fraction (EF, MD: - 0.693; 95% CI: - 1.112 to - 0.274; p = 0.001), and worse diastolic indices with higher E/e' (MD: 1.575; 95% CI: 0.924 to 2.227; p < 0.001) compared to non-NAFLD patients. NAFLD patients displayed increased left ventricular mass (LVM, MD: 34.484; 95% CI: 26.236 to 42.732; p < 0.001) and epicardial adipose thickness (EAT, MD: 0.1343; 95% CI: 0.055 to 0.214; p = 0.001). An increased severity of NAFLD was associated with worse diastolic indices (decreased E/A ratio, p = 0.007), but not with systolic indices. CONCLUSIONS NAFLD is associated with impaired systolic and diastolic function with changes in cardiac structure. Concomitant metabolic risk factors and liver disease severity are independently associated with worsening systolic and diastolic function.
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Affiliation(s)
- Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Chloe Wen-Min Lee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Yu Yi Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ansel Shao Pin Tang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Margaret Teng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jingxuan Quek
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Yip Han Chin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Roger Foo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Department of Cardiology, National University Heart Centre, National University Hospital, Tower Block Level 9, 1E Kent Ridge Road, Singapore, 119228, Singapore
| | - Mark Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Department of Cardiology, National University Heart Centre, National University Hospital, Tower Block Level 9, 1E Kent Ridge Road, Singapore, 119228, Singapore
| | - Weiqin Lin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Department of Cardiology, National University Heart Centre, National University Hospital, Tower Block Level 9, 1E Kent Ridge Road, Singapore, 119228, Singapore
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Comprehensive Transplant Center, Los Angeles, CA, USA
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. .,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore. .,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore.
| | - Arun Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Nicholas W S Chew
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. .,Department of Cardiology, National University Heart Centre, National University Hospital, Tower Block Level 9, 1E Kent Ridge Road, Singapore, 119228, Singapore.
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25
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Mantovani A, Dalbeni A, Beatrice G, Cappelli D, Gomez-Peralta F. Non-Alcoholic Fatty Liver Disease and Risk of Macro- and Microvascular Complications in Patients with Type 2 Diabetes. J Clin Med 2022; 11:jcm11040968. [PMID: 35207239 PMCID: PMC8878156 DOI: 10.3390/jcm11040968] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 02/01/2022] [Accepted: 02/10/2022] [Indexed: 02/01/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. To date, NAFLD is the most frequent chronic liver disease seen day by day in clinical practice across most high-income countries, affecting nearly 25–30% of adults in the general population and up to 70% of patients with T2DM. Over the last few decades, it clearly emerged that NAFLD is a “multisystemic disease” and that the leading cause of death among patients with NAFLD is cardiovascular disease (CVD). Indeed, several observational studies and some meta-analyses have documented that NAFLD, especially its advanced forms, is strongly associated with fatal and non-fatal cardiovascular events, as well as with specific cardiac complications, including sub-clinical myocardial alteration and dysfunction, heart valve diseases and cardiac arrhythmias. Importantly, across various studies, these associations remained significant after adjustment for established cardiovascular risk factors and other confounders. Additionally, several observational studies and some meta-analyses have also reported that NAFLD is independently associated with specific microvascular conditions, such as chronic kidney disease and distal or autonomic neuropathy. Conversely, data regarding a potential association between NAFLD and retinopathy are scarce and often conflicting. This narrative review will describe the current evidence about the association between NAFLD and the risk of macro- and microvascular manifestations of CVD, especially in patients with T2DM. We will also briefly discuss the biological mechanisms underpinning the association between NAFLD and its advanced forms and macro- and microvascular CVD.
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Affiliation(s)
- Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy; (G.B.); (D.C.)
- Correspondence: (A.M.); (F.G.-P.)
| | - Andrea Dalbeni
- Section of General Medicine C and Liver Unit, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy;
| | - Giorgia Beatrice
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy; (G.B.); (D.C.)
| | - Davide Cappelli
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy; (G.B.); (D.C.)
| | - Fernando Gomez-Peralta
- Endocrinology and Nutrition Unit, Segovia General Hospital, 40002 Segovia, Spain
- Correspondence: (A.M.); (F.G.-P.)
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26
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Fudim M, Zhong L, Patel KV, Khera R, Abdelmalek MF, Diehl AM, McGarrah RW, Molinger J, Moylan CA, Rao VN, Wegermann K, Neeland IJ, Halm EA, Das SR, Pandey A. Nonalcoholic Fatty Liver Disease and Risk of Heart Failure Among Medicare Beneficiaries. J Am Heart Assoc 2021; 10:e021654. [PMID: 34755544 PMCID: PMC8751938 DOI: 10.1161/jaha.121.021654] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) and heart failure (HF) are increasing in prevalence. The independent association between NAFLD and downstream risk of HF and HF subtypes (HF with preserved ejection fraction and HF with reduced ejection fraction) is not well established. Methods and Results This was a retrospective, cohort study among Medicare beneficiaries. We selected Medicare beneficiaries without known prior diagnosis of HF. NAFLD was defined using presence of 1 inpatient or 2 outpatient claims using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), claims codes. Incident HF was defined using at least 1 inpatient or at least 2 outpatient HF claims during the follow-up period (October 2015-December 2016). Among 870 535 Medicare patients, 3.2% (N=27 919) had a clinical diagnosis of NAFLD. Patients with NAFLD were more commonly women, were less commonly Black patients, and had a higher burden of comorbidities, such as diabetes, obesity, and kidney disease. Over a mean 14.3 months of follow-up, patients with (versus without) baseline NAFLD had a significantly higher risk of new-onset HF in unadjusted (6.4% versus 5.0%; P<0.001) and adjusted (adjusted hazard ratio [HR] [95% CI], 1.23 [1.18-1.29]) analyses. Among HF subtypes, the association of NAFLD with downstream risk of HF was stronger for HF with preserved ejection fraction (adjusted HR [95% CI], 1.24 [1.14-1.34]) compared with HF with reduced ejection fraction (adjusted HR [95% CI], 1.09 [0.98-1.2]). Conclusions Patients with NAFLD are at an increased risk of incident HF, with a higher risk of developing HF with preserved ejection fraction versus HF with reduced ejection fraction. The persistence of an increased risk after adjustment for clinical and demographic factors suggests an epidemiological link between NAFLD and HF beyond the basis of shared risk factors that requires further investigation.
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Affiliation(s)
- Marat Fudim
- Division of Cardiology Duke University Medical Center Durham NC.,Duke Clinical Research Institute Durham NC
| | - Lin Zhong
- Division of Cardiology University of Texas Southwestern Medical Center Dallas TX
| | - Kershaw V Patel
- Department of Cardiology Houston Methodist DeBakey Heart and Vascular Center Houston TX
| | - Rohan Khera
- Division of Cardiology Yale Medical Center New Haven CT
| | | | - Anna Mae Diehl
- Division of Gastroenterology Duke University Medical Center Durham NC
| | | | - Jeroen Molinger
- Division of Cardiology Duke University Medical Center Durham NC
| | - Cynthia A Moylan
- Division of Gastroenterology Duke University Medical Center Durham NC.,Durham Veterans Affairs Medical Center Durham NC
| | - Vishal N Rao
- Division of Cardiology Duke University Medical Center Durham NC.,Duke Clinical Research Institute Durham NC
| | - Kara Wegermann
- Division of Gastroenterology Duke University Medical Center Durham NC
| | - Ian J Neeland
- Harrington Heart and Vascular Institute University Hospitals Cleveland Medical CenterCase Western Reserve University School of Medicine Cleveland OH
| | - Ethan A Halm
- Division of Cardiology University of Texas Southwestern Medical Center Dallas TX
| | - Sandeep R Das
- Department of Internal Medicine Cardiology Division University of Texas Southwestern Medical Center Dallas TX
| | - Ambarish Pandey
- Department of Internal Medicine Cardiology Division University of Texas Southwestern Medical Center Dallas TX
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27
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Alhinai A, Patel K, Fonseca VA, Sebastiani G. Non-invasive diagnosis of nonalcoholic fatty liver disease in patients with type 2 diabetes. J Diabetes Complications 2021; 35:107978. [PMID: 34183247 DOI: 10.1016/j.jdiacomp.2021.107978] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 05/19/2021] [Accepted: 06/12/2021] [Indexed: 02/07/2023]
Abstract
Liver disease has emerged as a significant cause of death in people with type 2 diabetes (T2D). Due to a common underlying pathogenic mechanism, namely insulin resistance, T2D represents the main risk factor for nonalcoholic fatty liver disease (NAFLD), characterized by a buildup of fat in the liver. Globally, NAFLD is the most common liver disease, affecting a quarter of the general adult population. The development of nonalcoholic steatohepatitis (NASH) signifies an increased risk of liver fibrosis progression that can result in cirrhosis, hepatocellular carcinoma (HCC), and death. Liver fibrosis progression and development of cirrhosis is mostly asymptomatic until complications from decompensated end-stage liver disease arise. Traditionally, liver biopsy is used to diagnose NASH and stage fibrosis, however, it is invasive and costly. Non-invasive diagnostic alternatives include serum biomarkers and imaging techniques. Early identification of advanced liver fibrosis is pivotal to prompt initiation of targeted surveillance, including screening for HCC, as well as providing options for current and investigational therapeutic interventions to reduce fibrosis progression. This review gives an update on non-invasive diagnostic tools for NAFLD and liver fibrosis in the specific context of T2D, providing clinicians a pragmatic diagnostic approach to this frequent comorbidity in diabetes medicine.
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Affiliation(s)
- Alshaima Alhinai
- Division of Experimental Medicine, McGill University, Montreal, QC, Canada
| | - Keyur Patel
- Division of Gastroenterology and Hepatology, University Health Network Toronto, Toronto General Hospital, Toronto, ON, Canada
| | - Vivian A Fonseca
- Department of Medicine, Division of Endocrinology and Metabolism, School of Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA
| | - Giada Sebastiani
- Division of Experimental Medicine, McGill University, Montreal, QC, Canada; Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada.
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28
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Møller S, Kimer N, Kronborg T, Grandt J, Hove JD, Barløse M, Gluud LL. Nonalcoholic Fatty Liver Disease and Cardiovascular Disease: Overlapping Mechanisms. Semin Liver Dis 2021; 41:235-247. [PMID: 33992031 DOI: 10.1055/s-0041-1725022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) denotes a condition with excess fat in the liver. The prevalence of NAFLD is increasing, averaging > 25% of the Western population. In 25% of the patients, NAFLD progresses to its more severe form: nonalcoholic steatohepatitis and >25% of these progress to cirrhosis following activation of inflammatory and fibrotic processes. NAFLD is associated with obesity, type 2 diabetes, and the metabolic syndrome and represents a considerable and increasing health burden. In the near future, NAFLD cirrhosis is expected to be the most common cause for liver transplantation. NAFLD patients have an increased risk of developing cardiovascular disease as well as liver-related morbidity. In addition, hepatic steatosis itself appears to represent an independent cardiovascular risk factor. In the present review, we provide an overview of the overlapping mechanisms and prevalence of NAFLD and cardiovascular disease.
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Affiliation(s)
- Søren Møller
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Clinical Medicine, University of Copenhagen, Denmark
| | - Nina Kimer
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Denmark.,Bridge Translational Excellence Program, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark
| | - Thit Kronborg
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Denmark
| | - Josephine Grandt
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Denmark
| | - Jens Dahlgaard Hove
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Cardiology, Copenhagen University Hospital, Hvidovre, Denmark
| | - Mads Barløse
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark
| | - Lise Lotte Gluud
- Department of Clinical Medicine, University of Copenhagen, Denmark.,Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Denmark
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29
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Sumida Y, Yoneda M, Tokushige K, Kawanaka M, Fujii H, Yoneda M, Imajo K, Takahashi H, Eguchi Y, Ono M, Nozaki Y, Hyogo H, Koseki M, Yoshida Y, Kawaguchi T, Kamada Y, Okanoue T, Nakajima A, Japan Study Group of NAFLD (JSG-NAFLD). FIB-4 First in the Diagnostic Algorithm of Metabolic-Dysfunction-Associated Fatty Liver Disease in the Era of the Global Metabodemic. Life (Basel) 2021; 11:143. [PMID: 33672864 PMCID: PMC7917687 DOI: 10.3390/life11020143] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 01/22/2021] [Accepted: 01/25/2021] [Indexed: 12/16/2022] Open
Abstract
The prevalence of obesity or metabolic syndrome is increasing worldwide (globally metabodemic). Approximately 25% of the adult general population is suffering from nonalcoholic fatty liver disease (NAFLD), which has become a serious health problem. In 2020, global experts suggested that the nomenclature of NAFLD should be updated to metabolic-dysfunction-associated fatty liver disease (MAFLD). Hepatic fibrosis is the most significant determinant of all cause- and liver -related mortality in MAFLD. The non-invasive test (NIT) is urgently required to evaluate hepatic fibrosis in MAFLD. The fibrosis-4 (FIB-4) index is the first triaging tool for excluding advanced fibrosis because of its accuracy, simplicity, and cheapness, especially for general physicians or endocrinologists, although the FIB-4 index has several drawbacks. Accumulating evidence has suggested that vibration-controlled transient elastography (VCTE) and the enhanced liver fibrosis (ELF) test may become useful as the second step after triaging by the FIB-4 index. The leading cause of mortality in MAFLD is cardiovascular disease (CVD), extrahepatic malignancy, and liver-related diseases. MAFLD often complicates chronic kidney disease (CKD), resulting in increased simultaneous liver kidney transplantation. The FIB-4 index could be a predictor of not only liver-related mortality and incident hepatocellular carcinoma, but also prevalent and incident CKD, CVD, and extrahepatic malignancy. Although NITs as milestones for evaluating treatment efficacy have never been established, the FIB-4 index is expected to reflect histological hepatic fibrosis after treatment in several longitudinal studies. We here review the role of the FIB-4 index in the management of MAFLD.
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Affiliation(s)
- Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan;
| | - Masashi Yoneda
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan;
| | - Katsutoshi Tokushige
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo 162-8666, Japan;
| | - Miwa Kawanaka
- Department of General Internal Medicine2, Kawasaki Medical School, Okayama 700-8505, Japan;
| | - Hideki Fujii
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 558-8585, Japan;
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan; (M.Y.); (K.I.); (A.N.)
| | - Kento Imajo
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan; (M.Y.); (K.I.); (A.N.)
| | - Hirokazu Takahashi
- Department of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 840-8502, Japan;
| | | | - Masafumi Ono
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Women’s Medical University Medical Center East, Tokyo 116-8567, Japan;
| | - Yuichi Nozaki
- Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo 162-8655, Japan;
| | - Hideyuki Hyogo
- Department of Gastroenterology, JA Hiroshima General Hospital, Hiroshima 738-8503, Japan;
| | - Masahiro Koseki
- Division of Cardiovascular Medicine, Department of Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan;
| | - Yuichi Yoshida
- Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Osaka 564-8567, Japan;
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan;
| | - Yoshihiro Kamada
- Department of Advanced Gastroenterology & Hepatology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan;
| | - Takeshi Okanoue
- Hepatology Center, Saiseikai Suita Hospital, Osaka 564-0013, Japan;
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan; (M.Y.); (K.I.); (A.N.)
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30
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Fatty liver index and left ventricular mass: prospective associations from two independent cohorts. J Hypertens 2021; 39:961-969. [PMID: 33560053 DOI: 10.1097/hjh.0000000000002716] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVES Heart disease is the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Emerging data have shown that NAFLD may affect subclinical myocardial remodeling, mainly left ventricular hypertrophy; however, evidence from the prospective studies is still lacking. METHODS Prospective analyses were performed to investigate the association of fatty liver index (FLI) with left ventricular mass (LVM) among 1962 participants from the Bogalusa Heart Study (BHS, 1995-2010) and 1547 participants from the Cardiovascular Risk in Young Finns Study (YFS, 2001-2011) free of cardiovascular diseases (CVD) at baseline. LVM was assessed by two-dimensional guided M-mode echocardiography and indexed (LVMI) to body height (m2.7). Multivariable regression models were applied after adjustment for traditional CVD risk factors. RESULTS In both cohorts, we observed significant and positive associations between FLI and LVM (BHS: β=0.59, P < 0.001; YFS: β=0.41, P < 0.001) and LVMI (BHS: β=0.14, P < 0.001; YFS: β=0.09, P < 0.001). In addition, we found that the relationship between FLI and LVMI was stronger in women than men (BHS: P-interaction = 0.01; YFS: P-interaction < 0.01); and the relationship between FLI and LVM/LVMI was stronger in black than white individuals (LVM: P-interaction = 0.02; LVMI: P-interaction = 0.04). Moreover, we found that the associations of FLI with LVM and LVMI were attenuated by high physical activity, especially in BHS (P-interaction = 0.02). CONCLUSION Our findings from two independent prospective cohorts indicate that FLI is positively associated with LVM/LVMI, independent of traditional cardiovascular risk factors. Such relationships are more pronounced among women and black individuals and are attenuated by high physical activity.
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31
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Fudim M, Sobotka PA, Dunlap ME. Extracardiac Abnormalities of Preload Reserve: Mechanisms Underlying Exercise Limitation in Heart Failure with Preserved Ejection Fraction, Autonomic Dysfunction, and Liver Disease. Circ Heart Fail 2021; 14:e007308. [PMID: 33464948 DOI: 10.1161/circheartfailure.120.007308] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
While many of the cardiac limitations to exercise performance are now well-characterized, extracardiac limitations to exercise performance have been less well recognized but are nevertheless important. We propose that abnormalities of cardiac preload reserve represents an under-recognized but common cause of exercise limitations. We further propose that mechanistic links exist between conditions as seemingly disparate as heart failure with preserved ejection fraction, nonalcoholic fatty liver disease, and pelvic venous compression/obstruction syndromes (eg, May-Thurner). We conclude that extracardiac abnormalities of preload reserve serve as a major pathophysiologic mechanism underlying these and other disease states.
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Affiliation(s)
- Marat Fudim
- Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC (M.F.). Duke Clinical Research Institute, Durham, NC (M.F.)
| | - Paul A Sobotka
- Affiliated Faculty, Department of Medicine, Division of Cardiology, The Ohio State University, Columbus (P.A.S.)
| | - Mark E Dunlap
- Heart and Vascular Center, MetroHealth Campus of Case Western Reserve University, Cleveland, OH (M.E.D.)
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32
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Chiu LS, Pedley A, Massaro J, Benjamin EJ, Mitchell GF, McManus DD, Aragam J, Vasan RS, Cheng S, Long MT. The association of non-alcoholic fatty liver disease and cardiac structure and function-Framingham Heart Study. Liver Int 2020; 40:2445-2454. [PMID: 32654390 PMCID: PMC7669676 DOI: 10.1111/liv.14600] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 06/29/2020] [Accepted: 07/01/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease confers increased risk for cardiovascular disease, including heart failure (HF), for reasons that remain unclear. Possible pathways could involve an association of liver fat with cardiac structural or functional abnormalities even after accounting for body size. METHODS We analysed N = 2356 Framingham Heart Study participants (age 52 ± 12 years, 52% women) who underwent echocardiography and standardized computed tomography measures of liver fat. RESULTS In cross-sectional multivariable regression models adjusted for age, gender, cohort and cardiovascular risk factors, liver fat was positively associated with left ventricular (LV) mass (β = 1.45; 95% confidence interval (CI): 0.01, 2.88), LV wall thickness (β = 0.01; 95% CI: 0.00, 0.02), mass volume ratio (β = 0.02; 95% CI 0.01, 0.03), mitral peak velocity (E) (β = 0.83; 95% CI 0.31, 1.36) and LV filling pressure (E/e' ratio) (β = 0.16; 95% CI 0.09, 0.23); and inversely associated with global systolic longitudinal strain (β = 0.20, 95% CI 0.07, 0.33), diastolic annular velocity (e') (β = -0.12; 95% CI - 0.22, -0.03), and E/A ratio (β = -0.01; 95% CI - 0.02, -0.00). After additional adjustment for body mass index (BMI), statistical significance was attenuated for all associations except for that of greater liver fat with increased LV filling pressure, a possible precursor to HF (β = 0.11; 95% CI 0.03, 0.18). CONCLUSION Increased liver fat was associated with multiple subclinical cardiac dysfunction measures, with most of associations mediated by obesity. Interestingly, the association of liver fat and LV filling pressure was only partially mediated by BMI, suggesting a possible direct effect of liver fat on LV filling pressure. Further confirmatory studies are needed.
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Affiliation(s)
- Laura S. Chiu
- Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA
| | | | - Joseph Massaro
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA.,Department of Mathematics and Statistics, Boston University, Boston, MA, United States
| | - Emelia J. Benjamin
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA.,Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA,Department of Epidemiology, Boston University School of Public Health, Boston, MA
| | | | - David D. McManus
- Cardiology Division, Department of Medicine and the Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worchester, MA
| | - Jayashri Aragam
- Cardiovascular Division, VA Boston Healthcare System, West Roxbury, MA,Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, MA,Harvard Medical School, Boston, MA
| | - Ramachandran S. Vasan
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA.,Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA,Department of Epidemiology, Boston University School of Public Health, Boston, MA,Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston Medical Center, Boston, MA
| | - Susan Cheng
- Barbra Streisand Women’s Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Michelle T. Long
- Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA
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33
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Khan MS, Fonarow GC, McGuire DK, Hernandez AF, Vaduganathan M, Rosenstock J, Handelsman Y, Verma S, Anker SD, McMurray JJ, Kosiborod MN, Butler J. Glucagon-Like Peptide 1 Receptor Agonists and Heart Failure. Circulation 2020; 142:1205-1218. [PMID: 32955939 DOI: 10.1161/circulationaha.120.045888] [Citation(s) in RCA: 87] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
With worsening epidemiological trends for both the incidence and prevalence of type 2 diabetes mellitus (T2DM) and heart failure (HF) worldwide, it is critical to implement optimal prevention and treatment strategies for patients with these comorbidities, either alone or concomitantly. Several guidelines and consensus statements have recommended glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter type 2 inhibitors as add-ons to lifestyle interventions with or without metformin in those at high atherosclerotic cardiovascular disease risk. However, these recommendations are either silent about HF or fail to differentiate between the prevention of HF in those at risk versus the treatment of individuals with manifest HF. Furthermore, these documents do not differentiate among those with different HF phenotypes. This distinction, even though important, may not be critical for sodium-glucose cotransporter type 2 inhibitors in view of the consistent data for benefit for both atherosclerotic cardiovascular disease– and HF-related outcomes that have emerged from the regulatory-mandated cardiovascular outcome trials for all sodium-glucose cotransporter type 2 inhibitors and the recent DAPA-HF trial (Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction)demonstrating the benefit of dapagliflozin on HF-related outcomes in patients with HF with reduced ejection fraction with or without T2DM. However, the distinction may be crucial for glucagon-like peptide-1 receptor agonists and other antihyperglycemic agents. Indeed, in several of the new statements, glucagon-like peptide-1 receptor agonists are suggested treatment not only for patients with T2DM and atherosclerotic cardiovascular disease, but also in those with manifest HF, despite a lack of evidence for the latter recommendation. Although glucagon-like peptide-1 receptor agonists may be appropriate to use in patients at risk for HF, mechanistic insights and observations from randomized trials suggest no clear benefit on HF-related outcomes and even uncertainty regarding the safety in those with HF with reduced ejection fraction. Conversely, theoretical rationales suggest that these agents may benefit patients with HF with preserved ejection fraction. Considering that millions of patients with T2DM have HF, these concerns have public health implications that necessitate the thoughtful use of these therapies. Achieving this aim will require dedicated trials with these drugs in both patients who have HF with reduced ejection fraction and HF with preserved ejection fraction with T2DM to assess their efficacy, safety, and risk-benefit profile.
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Affiliation(s)
| | - Gregg C. Fonarow
- Division of Cardiology, Ronald Reagan-UCLA Medical Center, Los Angeles, CA (G.C.F.)
| | - Darren K. McGuire
- Division of Cardiology, University of Texas Southwestern Medical Center, Dallas (D.K.M.)
| | | | | | | | | | - Subodh Verma
- Department of Surgery, University of Toronto, Canada (S.V.)
| | - Stefan D. Anker
- Department of Cardiology (CVK); and Berlin Institute of Health Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) partner site Berlin; Charité Universitätsmedizin (S.D.A.)
| | - John J.V. McMurray
- British Heart Foundation Cardiovascular Research Center, University of Glasgow, United Kingdom (J.J.V.M.)
| | - Mikhail N. Kosiborod
- Saint Luke’s Mid America Heart Institute, Kansas City, MO (M.N.K.)
- University of Missouri–Kansas City (M.N.K.)
- The George Institute for Global Health, Sydney, Australia (M.N.K.)
- University of New South Wales, Sydney, Australia (M.N.K.)
| | - Javed Butler
- Department of Medicine, University of Mississippi, Jackson (J.B.)
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34
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Li C, Yang J, Wang Y, Qi Y, Yang W, Li Y. Farnesoid X Receptor Agonists as Therapeutic Target for Cardiometabolic Diseases. Front Pharmacol 2020; 11:1247. [PMID: 32982723 PMCID: PMC7479173 DOI: 10.3389/fphar.2020.01247] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 07/29/2020] [Indexed: 12/12/2022] Open
Abstract
Cardiometabolic diseases are characterized as a combination of multiple risk factors for cardiovascular disease (CVD) and metabolic diseases including diabetes mellitus and dyslipidemia. Cardiometabolic diseases are closely associated with cell glucose and lipid metabolism, inflammatory response and mitochondrial function. Farnesoid X Receptor (FXR), a metabolic nuclear receptor, are found to be activated by primary BAs such as chenodeoxycholic acid (CDCA), cholic acid (CA) and synthetic agonists such as obeticholic acid (OCA). FXR plays crucial roles in regulating cholesterol homeostasis, lipid metabolism, glucose metabolism, and intestinal microorganism. Recently, emerging evidence suggests that FXR agonists are functional for metabolic syndrome and cardiovascular diseases and are considered as a potential therapeutic agent. This review will discuss the pathological mechanism of cardiometabolic disease and reviews the potential mechanisms of FXR agonists in the treatment of cardiometabolic disease.
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Affiliation(s)
- Chao Li
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jie Yang
- Cardiovascular Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yu Wang
- Cardiovascular Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yingzi Qi
- School of Health, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Wenqing Yang
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yunlun Li
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China.,Cardiovascular Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
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35
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Benmassaoud A, Deschenes M, Chen T, Ghali P, Sebastiani G. Optimizing patients with non-alcoholic fatty liver disease pre-transplant. CANADIAN LIVER JOURNAL 2020; 3:237-250. [PMID: 35992526 PMCID: PMC9202706 DOI: 10.3138/canlivj-2019-0025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 11/17/2019] [Indexed: 06/01/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. Non-alcoholic steatohepatitis (NASH), which is the progressive counterpart of the disease, is becoming the leading indication for liver transplantation in North America. Owing to the lack of symptoms, NASH is often an incidental diagnosis, resulting in a significant proportion of patients being diagnosed when advanced liver disease has already developed. NAFLD has recently been characterized as the hepatic manifestation of metabolic syndrome. Consequently, it is a multisystem disease that often co-exists with several other conditions, such as obesity, diabetes, cardiovascular diseases, and extra-hepatic malignancy, which have an impact on selection of transplant recipients. The complexity of diagnostic approach, need for multidisciplinary clinical management, and lack of a specific treatment further complicate the picture of this extremely prevalent liver condition. NAFLD patients with advanced liver disease should be considered for early referral to liver transplant clinics for careful metabolic and cardiovascular risk stratification because they have worse survival rates after liver transplantation than other patients with chronic liver disease. Early referral will also facilitate optimization of metabolic comorbidities before proceeding with transplantation. This review provides an overview of strategies to identify patients with advanced NAFLD, with an emphasis on the management of associated comorbidities and optimal timing of pre-transplant evaluation. Other topics that have been shown to affect recipient optimization, such as the role of lifestyle changes and bariatric surgery in the management of obesity, as well as sarcopenia in decompensated NASH-related cirrhosis, are addressed.
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Affiliation(s)
- Amine Benmassaoud
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Marc Deschenes
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Tianyan Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Peter Ghali
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
- Division of Gastroenterology, Department of Medicine, University of Florida, Jacksonville, Florida, USA
| | - Giada Sebastiani
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
- Chronic Viral Illness Service, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
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36
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Mantovani A, Targher G, Zoppini G. Nonalcoholic Fatty Liver Disease and Implications for Older Adults with Diabetes. Clin Geriatr Med 2020; 36:527-547. [DOI: 10.1016/j.cger.2020.04.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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37
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Prevalence and staging of non-alcoholic fatty liver disease among patients with heart failure with preserved ejection fraction. Sci Rep 2020; 10:12440. [PMID: 32709942 PMCID: PMC7381602 DOI: 10.1038/s41598-020-69013-y] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 07/06/2020] [Indexed: 12/11/2022] Open
Abstract
Insulin resistance and altered energy metabolism is common in non-alcoholic fatty liver disease (NAFLD) and appears to also be associated with myocardial dysfunction. We aimed to evaluate prevalence, staging and clinical features correlated with NAFLD among patients with heart failure with preserved ejection fraction (HFpEF). Adults with HFpEF were prospectively enrolled. Demographic and clinical data were collected. NAFLD was defined based on liver biopsy, abdominal imaging or ICD-coding and the absence of other liver diseases. Descriptive, bivariate and multivariable analyses were performed. 181 patients were analyzed. The median age was 70 with 89% white, 59% female, median BMI 35.1, and 48% with diabetes. NAFLD was present in 27% of the full cohort and 50% of those with imaging. In patients with imaging, multivariable analysis identified diabetes (OR 3.38, 95% CI 1.29–8.88) and BMI (OR 1.11, 95% CI 1.04–1.19) as independent correlates of NAFLD. 54% of NAFLD patients had a NAFLD fibrosis score consistent with advanced fibrosis. Cirrhosis was present in 6.6% of patients overall and 11.5% with imaging. NAFLD patients had a higher frequency of advanced heart failure (75% vs 55%, p 0.01). NAFLD has a two-fold higher prevalence in HFpEF compared to the general population and is independently associated with BMI and diabetes. Patients with HFpEF and NAFLD also appeared to have more advanced fibrosis including cirrhosis suggesting a potential synergistic effect of cardiac dysfunction on fibrosis risk in NAFLD. This data supports consideration for evaluation of underlying liver disease in HFpEF patients.
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Sumida Y, Shima T, Mitsumoto Y, Katayama T, Umemura A, Yamaguchi K, Itoh Y, Yoneda M, Okanoue T. Epidemiology: Pathogenesis, and Diagnostic Strategy of Diabetic Liver Disease in Japan. Int J Mol Sci 2020; 21:E4337. [PMID: 32570776 PMCID: PMC7352222 DOI: 10.3390/ijms21124337] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 06/08/2020] [Accepted: 06/16/2020] [Indexed: 12/14/2022] Open
Abstract
Type 2 diabetes (T2D) is closely associated with nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to cirrhosis, hepatocellular carcinoma (HCC), and hepatic decompensation. Patients with T2D have twice the risk of HCC incidence compared with those without T2D. Because the hepatic fibrosis grade is the main determinant of mortality in patients with NAFLD, identifying patients with advanced fibrosis using non-invasive tests (NITs) or imaging modalities is crucial. Globally, the fibrosis-4 index (FIB-4 index), NAFLD fibrosis score, and enhanced liver fibrosis test have been established to evaluate hepatic fibrosis. Two-step algorithms using FIB-4 index as first triaging tool are globally accepted. It remains unknown which kinds of NITs or elastography are best as the second step tool. In Japan, type IV collagen 7s or the CA-fibrosis index (comprising type IV collagen 7s and aspartate aminotransferase (AST)) is believed to precisely predict advanced fibrosis in NAFLD. Patients with NAFLD who have high non-invasive test results should be screened for HCC or esophageal varices. Risk factors of rapid fibrosis progression in NAFLD includes age, severe obesity, presence of T2D, menopause in women, and a patatin-like phospholipase domain containing the 3 GG genotype. Patients with NAFLD who have these risk factors should be intensively treated with lifestyle modification or pharmacotherapies for preventing liver-related mortality.
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Affiliation(s)
- Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan;
| | - Toshihide Shima
- Center of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka 564-0013, Japan; (T.S.); (Y.M.); (T.K.); (T.O.)
| | - Yasuhide Mitsumoto
- Center of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka 564-0013, Japan; (T.S.); (Y.M.); (T.K.); (T.O.)
| | - Takafumi Katayama
- Center of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka 564-0013, Japan; (T.S.); (Y.M.); (T.K.); (T.O.)
| | - Atsushi Umemura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (A.U.); (K.Y.); (Y.I.)
| | - Kanji Yamaguchi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (A.U.); (K.Y.); (Y.I.)
| | - Yoshito Itoh
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (A.U.); (K.Y.); (Y.I.)
| | - Masashi Yoneda
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan;
| | - Takeshi Okanoue
- Center of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka 564-0013, Japan; (T.S.); (Y.M.); (T.K.); (T.O.)
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Jha AK, Lata S. Liver transplantation and cardiac illness: Current evidences and future directions. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2020; 27:225-241. [PMID: 31975575 DOI: 10.1002/jhbp.715] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Contraindications to liver transplantation are gradually narrowing. Cardiac illness and chronic liver disease may manifest independently or may be superimposed on each other due to shared pathophysiology. Cardiac surgery involving the cardiopulmonary bypass in patients with Child-Pugh Class C liver disease is associated with a high risk of perioperative morbidity and mortality. Liver transplantation involves hemodynamic perturbations, volume shifts, coagulation abnormalities, electrolyte disturbances, and hypothermia, which may prove fatal in patients with cardiac illness depending upon the severity. Additionally, cardiovascular complications are the major cause of adverse postoperative outcomes after liver transplantation even in the absence of cardiac pathologies. Clinical decision-making has remained an unsettled issue in these clinical scenarios. The absence of randomized clinical studies has further crippled our endeavours for a consensus on the management of patients with end-stage liver disease with cardiac illness. This review seeks to address this complex clinical setting by gathering information from published literature. The management algorithm in this review may facilitate clinical decision making and augur future research.
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Affiliation(s)
- Ajay Kumar Jha
- Department of Anesthesiology and Critical Care, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Suman Lata
- Department of Anesthesiology and Critical Care, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
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40
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Sayiner M, Arshad T, Golabi P, Paik J, Farhat F, Younossi ZM. Extrahepatic manifestations and healthcare expenditures of non-alcoholic fatty liver disease in the Medicare population. Hepatol Int 2020; 14:556-566. [DOI: 10.1007/s12072-020-10038-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 03/21/2020] [Indexed: 02/07/2023]
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41
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Diagnosis of Non-Alcoholic Fatty Liver Disease (NAFLD) Is Independently Associated with Cardiovascular Risk in a Large Austrian Screening Cohort. J Clin Med 2020; 9:jcm9041065. [PMID: 32283679 PMCID: PMC7230765 DOI: 10.3390/jcm9041065] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 04/03/2020] [Accepted: 04/06/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Many patients with non-alcoholic fatty liver disease (NAFLD) simultaneously suffer from cardiovascular (CV) disease and often carry multiple CV risk factors. Several CV risk factors are known to drive the progression of fibrosis in patients with NAFLD. OBJECTIVES To investigate whether an established CV risk score, the Framingham risk score (FRS), is associated with the diagnosis of NAFLD and the degree of fibrosis in an Austrian screening cohort for colorectal cancer. MATERIAL AND METHODS In total, 1965 asymptomatic subjects (59 ± 10 years, 52% females, BMI 27.2 ± 4.9 kg/m2) were included in this study. The diagnosis of NAFLD was present if (1) significantly increased echogenicity in relation to the renal parenchyma was present in ultrasound and (2) viral, autoimmune or hereditary liver disease and excess alcohol consumption were excluded. The FRS (ten-year risk of coronary heart disease) and NAFLD Fibrosis Score (NFS) were calculated for all patients. High CV risk was defined as the highest FRS quartile (>10%). Both univariable and multivariable logistic regression models were used to calculate associations of FRS with NAFLD and NFS. RESULTS Compared to patients without NAFLD (n = 990), patients with NAFLD (n = 975) were older (60 ± 9 vs. 58 ± 10 years; p < 0.001), had higher BMI (29.6 ± 4.9 vs. 24.9 ± 3.6 kg/m2; p < 0.001) and suffered from metabolic syndrome more frequently (33% vs. 7%; p < 0.001). Cardiovascular risk as assessed by FRS was higher in the NAFLD-group (8.7 ± 6.4 vs. 5.4 ± 5.2%; p < 0.001). A one-percentage-point increase of FRS was independently associated with NAFLD (OR 1.04, 95%CI 1.02-1.07; p < 0.001) after correction for relevant confounders in multivariable logistic regression. In patients with NAFLD, NFS correlated with FRS (r = 0.29; p < 0.001), and FRS was highest in patients with significant fibrosis (F3-4; 11.7 ± 5.4) compared to patients with intermediate results (10.9 ± 6.3) and those in which advanced fibrosis could be ruled-out (F0-2, 7.8 ± 5.9, p < 0.001). A one-point-increase of NFS was an independent predictor of high-risk FRS after correction for sex, age, and concomitant diagnosis of metabolic syndrome (OR 1.30, 95%CI 1.09-1.54; p = 0.003). CONCLUSION The presence of NAFLD might independently improve prediction of long-term risk for CV disease and the diagnosis of NAFLD might be a clinically relevant piece in the puzzle of predicting long-term CV outcomes. Due to the significant overlap of advanced NAFLD and high CV risk, aggressive treatment of established CV risk factors could improve prognosis in these patients.
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42
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Zhao R, Zhang Y, Wang X, Colgan TJ, Rehm JL, Reeder SB, Johnson KM, Hernando D. Motion-robust, high-SNR liver fat quantification using a 2D sequential acquisition with a variable flip angle approach. Magn Reson Med 2020; 84:2004-2017. [PMID: 32243665 DOI: 10.1002/mrm.28263] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 02/24/2020] [Accepted: 03/02/2020] [Indexed: 01/18/2023]
Abstract
PURPOSE Chemical shift encoded (CSE)-MRI enables quantification of proton-density fat fraction (PDFF) as a biomarker of liver fat content. However, conventional 3D Cartesian CSE-MRI methods require breath-holding. A motion-robust 2D Cartesian sequential method addresses this limitation but suffers from low SNR. In this work, a novel free breathing 2D Cartesian sequential CSE-MRI method using a variable flip angle approach with centric phase encoding (VFA-centric) is developed to achieve fat quantification with low T 1 bias, high SNR, and minimal blurring. METHODS Numerical simulation was performed for variable flip angle schedule design and preliminary evaluation of VFA-centric method, along with several alternative flip angle designs. Phantom, adults (n = 8), and children (n = 27) were imaged at 3T. Multi-echo images were acquired and PDFF maps were estimated. PDFF standard deviation was used as a surrogate for SNR. RESULTS In both simulation and phantom experiments, the VFA-centric method enabled higher SNR imaging with minimal T 1 bias and blurring artifacts. High correlation (slope = 1.00, intercept = 0.04, R 2 = 0.998) was observed in vivo between the proposed VFA-centric method obtained PDFF and reference PDFF (free breathing low-flip angle 2D sequential acquisition). Further, the proposed VFA-centric method (PDFF standard deviation = 1.5%) had a better SNR performance than the reference acquisition (PDFF standard deviation = 3.3%) with P < .001. CONCLUSIONS The proposed free breathing 2D Cartesian sequential CSE-MRI method with variable flip angle approach and centric-ordered phase encoding achieved motion robustness, low T 1 bias, high SNR compared to previous 2D sequential methods, and low blurring in liver fat quantification.
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Affiliation(s)
- Ruiyang Zhao
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA
| | - Yuxin Zhang
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA
| | - Xiaoke Wang
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.,Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA
| | - Timothy J Colgan
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA
| | - Jennifer L Rehm
- Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA
| | - Scott B Reeder
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA.,Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.,Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.,Department of Emergency Medicine, University of Wisconsin-Madison, Madison, WI, USA
| | - Kevin M Johnson
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA
| | - Diego Hernando
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA
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43
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Lee H, Kim G, Choi YJ, Huh BW, Lee BW, Kang ES, Cha BS, Lee EJ, Lee YH, Huh KB. Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus. Diabetes Metab J 2020; 44:267-276. [PMID: 30877708 PMCID: PMC7188976 DOI: 10.4093/dmj.2019.0001] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 01/16/2019] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Impaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM. METHODS We analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography. RESULTS LV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%, P=0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively; P for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34; P=0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51; P=0.002). CONCLUSIONS Liver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.
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Affiliation(s)
- Hokyou Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Gyuri Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young Ju Choi
- Huh's Diabetes Center and the 21st Century Diabetes and Vascular Research Institute, Seoul, Korea
| | - Byung Wook Huh
- Huh's Diabetes Center and the 21st Century Diabetes and Vascular Research Institute, Seoul, Korea
| | - Byung Wan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Seok Kang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Bong Soo Cha
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Jig Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Yong Ho Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
- Department of Systems Biology, Glycosylation Network Research Center, Yonsei University, Seoul, Korea.
| | - Kap Bum Huh
- Huh's Diabetes Center and the 21st Century Diabetes and Vascular Research Institute, Seoul, Korea
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44
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The clinical application of the ratio of transmitral early filling velocity to early diastolic strain rate: a systematic review and meta-analysis. J Echocardiogr 2020; 18:94-104. [DOI: 10.1007/s12574-020-00466-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Revised: 02/06/2020] [Accepted: 03/03/2020] [Indexed: 12/19/2022]
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45
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Packer M. Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction in Patients With Nonalcoholic Fatty Liver Disease. Am J Med 2020; 133:170-177. [PMID: 31622581 DOI: 10.1016/j.amjmed.2019.09.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 09/24/2019] [Accepted: 09/24/2019] [Indexed: 02/07/2023]
Abstract
The most common causes of chronic liver disease in the developed world-nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)-are the hepatic manifestations of an insulin-resistant state that is linked to visceral adiposity and systemic inflammation. NAFLD and NASH lead to an expansion of epicardial adipose tissue and the release of proinflammatory adipocytokines that cause microcirculatory dysfunction and fibrosis of the adjoining myocardium, resulting in atrial fibrillation as well as heart failure with a preserved ejection fraction (HFpEF). Inflammatory changes in the left atrium lead to electroanatomical remodeling; thus, NAFLD and NASH markedly increase the risk of atrial fibrillation. Simultaneously, patients with NAFLD or NASH commonly show diastolic dysfunction or latent HFpEF. Interventions include 1) weight loss by caloric restriction, bariatric surgery, or intensive exercise, and 2) drugs that ameliorate fat-mediated inflammation in both the liver and heart (eg, statins, metformin, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and pioglitazone). Patients with NAFLD or NASH commonly have an inflammation-related atrial and ventricular myopathy, which may contribute to symptoms and long-term outcomes.
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Affiliation(s)
- Milton Packer
- Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Tex; Imperial College, London, UK.
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46
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Assessment of left ventricular function in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease using three-dimensional speckle-tracking echocardiography. Anatol J Cardiol 2020; 23:41-48. [PMID: 31911565 PMCID: PMC7141431 DOI: 10.14744/anatoljcardiol.2019.66805] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objective: Using three-dimensional speckle-tracking echocardiography (3D-STE), we aimed to evaluate left ventricular (LV) function in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). Methods: In total, 97 T2: DM patients were categorized into three groups based on hepatic ultrasonography group A (those without NAFLD, n=30), group B (those with mild NAFLD, n=32), and group C (those with moderate-to-severe NAFLD, n=35). Our conventional echocardiographic parameters included transmitral peak early and late diastolic velocity (E and A), septal and lateral early (e’) mitral annular diastolic tissue velocities, and left atrial maximum volume index (LAVImax). LV end-diastolic and -systolic volume, LV mass index (LVMI), and LV ejection fraction were measured using real-time three-dimensional echocardiography. The 3D-STE parameters included LV global radial strain (GRS), global longitudinal strain (GLS), global area strain (GAS), and global circumferential strain (GCS). Results: Our results showed that in group C, GCS, GRS, GLS, GAS, and septal and lateral e’ velocity decreased, whereas average E/e’ and LAVImax increased compared to groups B and A (p<0.05). Multiple linear regression analysis showed that NAFLD is independently associated with 3D-STE parameters, and glycosylated hemoglobin also has negative impacts on all LV 3D strains. Conclusion: When combined with conventional echocardiography, 3D-STE can assess LV function effectively in T2DM patients with NAFLD. Additionally, the severity of LV dysfunction in the moderate-to-severe NAFLD group (group C) was worse than the mild and absent NAFLD groups (groups A and B).
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Ballestri S, Tana C, Di Girolamo M, Fontana MC, Capitelli M, Lonardo A, Cioni G. Semi-Quantitative Ultrasonographic Evaluation of NAFLD. Curr Pharm Des 2020; 26:3915-3927. [PMID: 32303161 DOI: 10.2174/1381612826666200417142444] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 03/20/2020] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) embraces histopathological entities ranging from the relatively benign simple steatosis to the progressive form nonalcoholic steatohepatitis (NASH), which is associated with fibrosis and an increased risk of progression to cirrhosis and hepatocellular carcinoma. NAFLD is the most common liver disease and is associated with extrahepatic comorbidities including a major cardiovascular disease burden. The non-invasive diagnosis of NAFLD and the identification of subjects at risk of progressive liver disease and cardio-metabolic complications are key in implementing personalized treatment schedules and follow-up strategies. In this review, we highlight the potential role of ultrasound semiquantitative scores for detecting and assessing steatosis severity, progression of NAFLD, and cardio-metabolic risk. Ultrasonographic scores of fatty liver severity act as sensors of cardio-metabolic health and may assist in selecting patients to submit to second-line non-invasive imaging techniques and/or liver biopsy.
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Affiliation(s)
- Stefano Ballestri
- Internal Medicine Unit, Pavullo Hospital, Azienda USL, Modena, Italy
| | - Claudio Tana
- Internal Medicine Unit, Pavullo Hospital, Azienda USL, Modena, Italy
| | - Maria Di Girolamo
- Internal Medicine Unit, Pavullo Hospital, Azienda USL, Modena, Italy
| | | | - Mariano Capitelli
- Internal Medicine Unit, Pavullo Hospital, Azienda USL, Modena, Italy
| | - Amedeo Lonardo
- Internal Medicine Unit, Pavullo Hospital, Azienda USL, Modena, Italy
| | - Giorgio Cioni
- Internal Medicine Unit, Pavullo Hospital, Azienda USL, Modena, Italy
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Serum levels of gamma-glutamyltransferase predict outcome in heart failure with preserved ejection fraction. Sci Rep 2019; 9:18541. [PMID: 31811258 PMCID: PMC6898583 DOI: 10.1038/s41598-019-55116-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 09/27/2019] [Indexed: 12/22/2022] Open
Abstract
Previous studies suggested an association between heart failure (HF) and hepatic disorders. Liver function parameters have been shown to predict outcome in HF with reduced ejection fraction, but their impact in HF with preserved ejection fraction (HFpEF) has not yet been investigated. Between January 2011 and February 2017, 274 patients with confirmed HFpEF were enrolled (age 71.3 ± 8.4 years, 69.3% female) in a prospective registry. During a median follow-up of 21.5 ± 18.6 months, 97 patients (35.4%) reached the combined endpoint defined as hospitalization due to HF and/ or death from any cause. By multivariable cox regression, serum gamma-glutamyltransferase (GT) was independently associated with outcome (Hazard Ratio (HR) 1.002, p = 0.004) along with N-terminal pro brain natriuretic peptide (HR 2.213, p = 0.001) and hemoglobin (HR 0.840, p = 0.006). Kaplan-Meier analysis showed that patients with serum gamma-GT levels above a median of 36 U/L had significantly more events as compared to the remainder of the group (log-rank p = 0.012). By multivariable logistic regression, higher early mitral inflow velocity/ mitral peak velocity of late filling (Odds Ratio (OR) 2.173, p = 0.024), higher right atrial (RA) pressure (OR 1.139, p < 0.001) and larger RA diameter (OR 1.070, p = 0.001) were independently associated with serum gamma-GT > 36 U/L. Serum levels of gamma-GT are associated with both left and right-sided cardiac alterations and may serve as a simple tool for risk prediction in HFpEF, especially when further diagnostic modalities are not available.
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Borges-Canha M, Neves JS, Libânio D, Von-Hafe M, Vale C, Araújo-Martins M, Leite AR, Pimentel-Nunes P, Carvalho D, Leite-Moreira A. Association between nonalcoholic fatty liver disease and cardiac function and structure-a meta-analysis. Endocrine 2019; 66:467-476. [PMID: 31482382 DOI: 10.1007/s12020-019-02070-0] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 08/21/2019] [Indexed: 12/13/2022]
Abstract
PURPOSE Nonalcoholic fatty liver disease is increasingly recognized as the hepatic counterpart of metabolic syndrome. It is hypothesized that structural and functional cardiac changes may be associated with this metabolic disease. We aimed to gather the existing information on the association of nonalcoholic fatty liver disease with cardiac alterations, and to evaluate a possible correlation between them. METHODS Systematic review of Medline searching results for original articles studying NAFLD and cardiac parameters until August 2018. A meta-analysis was conducted to each parameter of cardiac structure and function selected, using Review Manager 5.3 software. This study was conducted according to preferred reporting items for systematic reviews and meta-analysis (PRISMA). RESULTS A total of 16 studies met the eligibility criteria and were included in the meta-analysis. There was a significant association between nonalcoholic fatty liver disease and (1) higher left ventricle mass and ratios between left ventricle mass and both height and body surface area; (2) higher LVEDD; (3) higher left atrium diameter and ratio between left atrial volume and body surface area; (4) higher posterior wall and septum thickness; (5) lower E/A wave ratio; (6) higher E/E' ratio; (7) longer deceleration time and (8) longer relaxation time. CONCLUSION NAFLD associates with adverse structural alterations and cardiac dysfunction. Our results highlight the importance of identifying NAFLD in patients with metabolic dysfunction as this may represent an additional contributor to cardiovascular risk.
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Affiliation(s)
- Marta Borges-Canha
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
- Serviço de Endocrinologia, Diabetes e Metabolismo, Centro Hospitalar Universitário de São João, E.P.E, Porto, Portugal.
| | - João Sérgio Neves
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
- Serviço de Endocrinologia, Diabetes e Metabolismo, Centro Hospitalar Universitário de São João, E.P.E, Porto, Portugal
| | - Diogo Libânio
- Serviço de Gastroenterologia, Instituto Português de Oncologia do Porto, Porto, Portugal
| | - Madalena Von-Hafe
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - Catarina Vale
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - Miguel Araújo-Martins
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - Ana Rita Leite
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - Pedro Pimentel-Nunes
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
- Serviço de Gastroenterologia, Instituto Português de Oncologia do Porto, Porto, Portugal
| | - Davide Carvalho
- Serviço de Endocrinologia, Diabetes e Metabolismo, Centro Hospitalar Universitário de São João, E.P.E, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde (i3s), Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - Adelino Leite-Moreira
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
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Ferrara D, Montecucco F, Dallegri F, Carbone F. Impact of different ectopic fat depots on cardiovascular and metabolic diseases. J Cell Physiol 2019; 234:21630-21641. [PMID: 31106419 DOI: 10.1002/jcp.28821] [Citation(s) in RCA: 129] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 04/17/2019] [Accepted: 04/29/2019] [Indexed: 12/11/2022]
Abstract
A growing body of evidence is pointing out the pathophysiological role of fat accumulation in different organs. Ectopic fat depots within heart, liver, skeletal muscle, kidney, and pancreas as well as around blood vessels might be more associated to cardiometabolic risk than classical variables, such as body mass index. Among different mechanisms, lipid metabolism appears to be particularly influenced by ectopic fat depots. Indeed, intracellular accumulation of nonesterified fatty acids, and triglycerides promotes endoplasmic reticulum stress, mitochondrial uncoupling, oxidative stress, and altered membrane composition/function, finally promoting inflammatory response and cell death. The dysfunctional adipose tissue was shown to induce both local and systemic effects, with relevant clinical consequences. Epicardial fat and myocardial steatosis have been associated with the development of atrial fibrillation and ventricular dysfunction. Similarly perivascular adipose tissue appears to trigger atherosclerosis and hypertension. Nonalcoholic fatty liver disease has been recognized both as the hepatic manifestation of metabolic syndrome and as a cardiovascular (CV) risk factor. Importantly, the renal sinus fat emerged as a potential player in kidney dysfunction. Finally, both skeletal muscle and pancreatic fat depots have been indicated as potential endocrine modulators of insulin resistance. Considering the global rise in the prevalence of obesity, the understanding of mechanisms underlying ectopic fat accumulation represents an urgent need, with potential clinical implications for CV risk stratification. Here, we attempt to update the current knowledge of the different ectopic fat depots, focusing on underlying mechanisms and potential clinical implications.
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Affiliation(s)
- Daniele Ferrara
- Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, Genoa, Italy
| | - Fabrizio Montecucco
- Centre of Excellence for Biomedical Research (CEBR), Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, Genoa, Italy
| | - Franco Dallegri
- Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, Genoa, Italy
| | - Federico Carbone
- Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, Genoa, Italy
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