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Orfanidou M, Polyzos SA. Retinopathy in Metabolic Dysfunction-Associated Steatotic Liver Disease. MEDICINA (KAUNAS, LITHUANIA) 2024; 61:38. [PMID: 39859020 PMCID: PMC11766779 DOI: 10.3390/medicina61010038] [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: 11/28/2024] [Revised: 12/20/2024] [Accepted: 12/24/2024] [Indexed: 01/27/2025]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multisystemic disease, i.e., influencing various organ systems beyond the liver and, thus, contributing to comorbidities. Characterized by excessive fat accumulation in the hepatocytes, MASLD is frequently linked to metabolic syndrome components, such as obesity, insulin resistance, dyslipidemia, and hypertension. Therefore, exploring the intricate connection between MASLD and other organ systems, including the eyes, seems to be essential. In this context, retinopathy has been investigated for its potential association with MASLD, since both conditions share common pathogenetic pathways. Chronic low-grade inflammation, oxidative stress, insulin resistance, and endothelial dysfunction are only some of those mechanisms contributing to disease progression and, possibly, determining the bidirectional interplay between the liver and retinal pathology. This narrative review aims to summarize data concerning the multisystemicity of MASLD, primarily focusing on its potential association with the eyes and, particularly, retinopathy. Identifying this possible association may emphasize the need for early screening and integrated management approaches that address the liver and eyes as interconnected components within the framework of a systemic disease. Further research is necessary to delineate the precise mechanisms and develop targeted interventions to mitigate the bidirectional impact between the liver and eyes, aiming to reduce the overall burden of disease and improve patient outcomes.
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Affiliation(s)
- Myrsini Orfanidou
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
- First Department of Ophthalmology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Stergios A. Polyzos
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
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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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Argano C. Editorial: Interactions between NAFLD and cardiac conduction, structure and function: recent advances and treatments. Front Endocrinol (Lausanne) 2023; 14:1334227. [PMID: 38075054 PMCID: PMC10703450 DOI: 10.3389/fendo.2023.1334227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 11/14/2023] [Indexed: 12/18/2023] Open
Affiliation(s)
- Christiano Argano
- Department of Internal Medicine, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy
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En Li Cho E, Ang CZ, Quek J, Fu CE, Lim LKE, Heng ZEQ, Tan DJH, Lim WH, Yong JN, Zeng R, Chee D, Nah B, Lesmana CRA, Bwa AH, Win KM, Faulkner C, Aboona MB, Lim MC, Syn N, Kulkarni AV, Suzuki H, Takahashi H, Tamaki N, Wijarnpreecha K, Huang DQ, Muthiah M, Ng CH, Loomba R. Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis. Gut 2023; 72:2138-2148. [PMID: 37491159 DOI: 10.1136/gutjnl-2023-330110] [Citation(s) in RCA: 74] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/20/2023] [Indexed: 07/27/2023]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with type 2 diabetes mellitus (T2DM) as a major predictor. Insulin resistance and chronic inflammation are key pathways in the pathogenesis of T2DM leading to NAFLD and vice versa, with the synergistic effect of NAFLD and T2DM increasing morbidity and mortality risks. This meta-analysis aims to quantify the prevalence of NAFLD and the prevalence of clinically significant and advanced fibrosis in people with T2DM. METHODS MEDLINE and Embase databases were searched from inception until 13 February 2023. The primary outcomes were the prevalence of NAFLD, non-alcoholic steatohepatitis (NASH) and fibrosis in people with T2DM. A generalised linear mixed model with Clopper-Pearson intervals was used for the analysis of proportions with sensitivity analysis conducted to explore heterogeneity between studies. RESULTS 156 studies met the inclusion criteria, and a pooled analysis of 1 832 125 patients determined that the prevalence rates of NAFLD and NASH in T2DM were 65.04% (95% CI 61.79% to 68.15%, I2=99.90%) and 31.55% (95% CI 17.12% to 50.70%, I2=97.70%), respectively. 35.54% (95% CI 19.56% to 55.56%, I2=100.00%) of individuals with T2DM with NAFLD had clinically significant fibrosis (F2-F4), while 14.95% (95% CI 11.03% to 19.95%, I2=99.00%) had advanced fibrosis (F3-F4). CONCLUSION This study determined a high prevalence of NAFLD, NASH and fibrosis in people with T2DM. Increased efforts are required to prevent T2DM to combat the rising burden of NAFLD. PROSPERO REGISTRATION NUMBER CRD42022360251.
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Affiliation(s)
- Elina En Li Cho
- Department of Medicine, National University Hospital, Singapore
| | - Chong Zhe Ang
- Department of Medicine, National University Hospital, Singapore
| | - Jingxuan Quek
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Clarissa Elysia Fu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Lincoln Kai En Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Zane En Qi Heng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Rebecca Zeng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Douglas Chee
- Department of Medicine, National University Hospital, Singapore
| | - Benjamin Nah
- Department of Medicine, National University Hospital, Singapore
| | | | - Aung Hlaing Bwa
- Department of Medical Research, Union of Myanmar, Naypyidaw, Myanmar
| | - Khin Maung Win
- Department of Medical Research, Union of Myanmar, Naypyidaw, Myanmar
| | - Claire Faulkner
- Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Majd B Aboona
- Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Mei Chin Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Diagnostic Imaging, National University Health System, Singapore
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Anand V Kulkarni
- Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Hiroyuki Suzuki
- Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | | | - Nobuharu Tamaki
- Department of Medicine, University of California San Diego, La Jolla, California, USA
- Department of Medicine, Musashino Red Cross Hospital, Musashino, Japan
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, University of Michigan, Michigan, Michigan, USA
| | - Daniel Q Huang
- Department of Medicine, National University Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, National University Health System, Singapore
| | - Mark Muthiah
- Department of Medicine, National University Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, National University Health System, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Rohit Loomba
- Department of Medicine, University of California San Diego, La Jolla, California, USA
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Orfanidou M, Ntenti C, Evripidou K, Mataftsi A, Goulas A, Polyzos SA. Retinal Vascular Lesions in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. J Pers Med 2023; 13:1148. [PMID: 37511760 PMCID: PMC10381395 DOI: 10.3390/jpm13071148] [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: 05/24/2023] [Revised: 06/30/2023] [Accepted: 07/14/2023] [Indexed: 07/30/2023] Open
Abstract
Background: This systematic review and meta-analysis aimed to summarize and compare data on retinal vascular lesions between patients with nonalcoholic fatty liver disease (NAFLD) and individuals without the disease. Methods: Search was performed in PubMed, Scopus and Cochrane Library, complemented by handsearching (PROSPERO ID: CRD42022345558). Thirty-six studies comprising 24,985 individuals (12,387 NAFLD patients and 12,598 controls) were selected for the meta-analysis. Results: Apart from retinopathy, no study with a different type of retinal vascular lesion was retrieved. Overall, there was no significant difference in the presence of retinopathy in NAFLD patients compared to controls (Odds Ratio (OR) = 1.20; 95% Confidence Interval (CI): 0.91-1.59). Heterogeneity among studies was high (I2 = 93%; p < 0.00001), while Egger's test revealed no publication bias (p = 0.60). However, subgroup analysis showed positive association between retinopathy and NAFLD in type 1 diabetes mellitus (T1DM) (OR = 2.35; 95% CI: 1.53-3.60), but not in type 2 diabetes mellitus patients. Meta-regression analysis exploring potential confounders revealed no significant association. Conclusions: The presence of retinopathy was not overall different between individuals with and without NAFLD; however, T1DM patients with NAFLD had higher rates of retinopathy compared to T1DM patients without NAFLD, a finding warranting further research to show whether NAFLD may predict retinopathy in T1DM patients.
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Affiliation(s)
- Myrsini Orfanidou
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Charikleia Ntenti
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Kleo Evripidou
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Asimina Mataftsi
- Second Department of Ophthalmology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Antonis Goulas
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Stergios A Polyzos
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
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Riccio A, Mazzanti C, Vero L, Vanessa Fiorentino T, Succurro E, Miceli S, Perticone M, Sciacqua A, Andreozzi F, Cefalo CMA, Sesti G. Association between liver fibrosis and decreased myocardial mechano-energetic efficiency in individuals with different degree of glucose tolerance. Diabetes Res Clin Pract 2023; 199:110639. [PMID: 36963509 DOI: 10.1016/j.diabres.2023.110639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 03/16/2023] [Accepted: 03/20/2023] [Indexed: 03/26/2023]
Abstract
AIM Decreased myocardial mechano-energetic efficiency (MEEi) is associated with NAFLD and poorer prognosis in liver cirrhosis. We aim to investigate the association between liver fibrosis severity and MEEi in individuals participating in the CATAnzaro MEtabolic RIsk factors (CATAMERI) study. METHODS Myocardial MEEi, assessed by an echocardiography-derived measure, and fibrosis severity, estimated by the fibrosis-4 index (FIB-4), were evaluated in 2383 subjects with different degree of glucose tolerance. Participants were divided into four groups according to FIB-4 index values: lowest risk of fibrosis (<1.3); low risk of fibrosis (≥1.3 to < 1.67); moderate risk of fibrosis (≥1.67 to < 2.67); high risk of fibrosis (≥2.67). RESULTS Subjects with higher risk of liver fibrosis displayed a graded decrease in myocardial MEEi compare to those with the lowest risk of liver fibrosis. In a multivariable regression analysis, FIB-4 index was independently associated with MEEi (β = -0.080, P < 0.001), along with total cholesterol (β = -0.067, P = 0.01), hsCRP (β = -0.081, P < 0.001), sex (β = -0.099, P < 0.001), glucose tolerance status (β = -0.109, <0.001) and HOMA-IR index (β = -0.143, P < 0.001). CONCLUSION Compromised myocardial MEEi is already reported in individuals with high risk of hepatic fibrosis suggesting that its assessment may help to identify among subjects with NAFLD those with worst prognosis.
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Affiliation(s)
- Alessia Riccio
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, 00189 Rome, Italy
| | - Camilla Mazzanti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, 00189 Rome, Italy
| | - Laura Vero
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, 00189 Rome, Italy
| | - Teresa Vanessa Fiorentino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
| | - Elena Succurro
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
| | - Sofia Miceli
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
| | - Maria Perticone
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
| | - Francesco Andreozzi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
| | - Chiara M A Cefalo
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, 00189 Rome, Italy.
| | - Giorgio Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, 00189 Rome, Italy
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Hung WC, Yu TH, Wu CC, Lee TL, Tang WH, Chen CC, Lu IC, Chung FM, Lee YJ, Hsu CC. Nonalcoholic Fatty Liver Disease Is Related to Abnormal Corrected QT Interval and Left Ventricular Hypertrophy in Chinese Male Steelworkers. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:14555. [PMID: 36361436 PMCID: PMC9657484 DOI: 10.3390/ijerph192114555] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 11/03/2022] [Accepted: 11/04/2022] [Indexed: 06/16/2023]
Abstract
OBJECTIVES Nonalcoholic fatty liver disease (NAFLD) has been associated with an increased risks of corrected QT (QTc) prolongation and left ventricular hypertrophy (LVH), both of which are associated with the development of cardiovascular disease. Rotating night shift work and a higher risk of incident NAFLD have been reported in male steelworkers. This study aimed to investigate the association of the severity of NAFLD with a prolonged QTc interval and LVH in a large cohort of Chinese male steelworkers. METHODS We examined baseline data of 2998 male steel workers aged 26 to 71 years at two plants. All workers at both plants received regular health assessments, including 12-lead ECG and echocardiography. Abdominal ultrasonography was performed to evaluate the severity of NAFLD. QTc prolongation was defined as follows: normal ≤ 430 ms, borderline 431-450 ms, and abnormal ≥ 451 ms. LVH was defined as a left ventricular mass index (LVMI) >131 g/m2. Associations of NAFLD with an abnormal QTc interval and LVH were examined using univariate and multivariate analyses. RESULTS The QTc interval and the LVMI were significantly correlated with the NAFLD fibrosis score, and the severity of NAFLD was correlated with an abnormal QTc interval and LVH (p for trend < 0.05). Multivariate analysis showed that in comparison to the workers without NAFLD, the odds ratios of having an abnormal QTc interval and LVH were 2.54 (95% CI: 1.22-5.39, p = 0.013) times and 2.23 (95% CI: 1.02-5.01, p = 0.044) times higher in the workers with moderate/severe NAFLD. CONCLUSIONS NAFLD may be closely associated with the risks of an abnormal QTc interval and LVH, suggesting that regular electrocardiogram and echocardiogram monitoring could be used to evaluate the risk of arrhythmia and LVH in male steelworkers with NAFLD.
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Affiliation(s)
- Wei-Chin Hung
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
| | - Teng-Hung Yu
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
| | - Cheng-Ching Wu
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
- Division of Cardiology, Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung 82445, Taiwan
| | - Thung-Lip Lee
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
| | - Wei-Hua Tang
- Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Yuli Branch, Hualien 98142, Taiwan
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
| | - Chia-Chi Chen
- Department of Pathology, E-Da Hospital, Kaohsiung 82445, Taiwan
- College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
| | - I-Cheng Lu
- Department of Occupational Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
| | - Fu-Mei Chung
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
| | | | - Chia-Chang Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
- Health Examination Center, E-Da Dachang Hospital, Kaohsiung 80794, Taiwan
- The School of Chinese Medicine for Post Baccalaureate, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
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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: 6] [Impact Index Per Article: 2.0] [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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Catena C, Brosolo G, Da Porto A, Donnini D, Bulfone L, Vacca A, Soardo G, Sechi LA. Association of non-alcoholic fatty liver disease with left ventricular changes in treatment-naive patients with uncomplicated hypertension. Front Cardiovasc Med 2022; 9:1030968. [PMID: 36312275 PMCID: PMC9606246 DOI: 10.3389/fcvm.2022.1030968] [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: 08/29/2022] [Accepted: 09/27/2022] [Indexed: 11/13/2022] Open
Abstract
Background and aims Cardiac structural and functional changes have been demonstrated in patients with non-alcoholic fatty liver disease (NAFLD). Because of the frequent association of NAFLD with hypertension, we aimed to examine the relationship of liver steatosis with left ventricular (LV) changes in patients with hypertension. Materials and methods In a cross-sectional study, we included 360 untreated, essential hypertensive patients who were free of major cardiovascular and renal complications. Liver steatosis was assessed by three different biochemical scores (NAFLD Liver Fat Score, LFS; Fatty Liver Index, FLI; Hepatic Steatosis Index, HSI). Echocardiography was performed with standard B-mode and tissue-Doppler imaging. Results LV hypertrophy was present in 19.4% and LV diastolic dysfunction in 49.2% of patients who had significantly higher body mass index (BMI), blood pressure (BP), and homeostatic model assessment (HOMA) index and higher frequency of the metabolic syndrome and liver steatosis that was defined by presence of 2 or more positive scores. LV mass index increased progressively across patients who had none, 1, or 2 or more liver steatosis scores, with associated progressive worsening of LV diastolic function. LV mass index was significantly and positively correlated with age, BMI, BP, HOMA-index, LFS, and HSI. Logistic regression analysis showed that age, BP, and liver steatosis scores independently predicted LV hypertrophy and diastolic dysfunction. Liver steatosis independently predicted LV dysfunction but not LV hypertrophy even after inclusion in analysis of the HOMA-index. Conclusion NAFLD is associated with LV hypertrophy and diastolic dysfunction in untreated patients with hypertension. In hypertension, NAFLD could contribute to LV diastolic dysfunction with mechanisms unrelated to insulin resistance.
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Affiliation(s)
- Cristiana Catena
- Internal Medicine and European Hypertension Excellence Center, Department of Medicine, University of Udine, Udine, Italy
| | - Gabriele Brosolo
- Internal Medicine and European Hypertension Excellence Center, Department of Medicine, University of Udine, Udine, Italy
| | - Andrea Da Porto
- Diabetes and Metabolism Unit, Department of Medicine, University of Udine, Udine, Italy
| | - Debora Donnini
- Liver Unit, Department of Medicine, University of Udine, Udine, Italy
| | - Luca Bulfone
- Internal Medicine and European Hypertension Excellence Center, Department of Medicine, University of Udine, Udine, Italy
| | - Antonio Vacca
- Internal Medicine and European Hypertension Excellence Center, Department of Medicine, University of Udine, Udine, Italy
| | - Giorgio Soardo
- Liver Unit, Department of Medicine, University of Udine, Udine, Italy
| | - Leonardo A. Sechi
- Internal Medicine and European Hypertension Excellence Center, Department of Medicine, University of Udine, Udine, Italy,Diabetes and Metabolism Unit, Department of Medicine, University of Udine, Udine, Italy,Liver Unit, Department of Medicine, University of Udine, Udine, Italy,*Correspondence: Leonardo A. Sechi,
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10
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Hagström H, Kechagias S, Ekstedt M. Risk for hepatic and extra-hepatic outcomes in nonalcoholic fatty liver disease. J Intern Med 2022; 292:177-189. [PMID: 34118091 DOI: 10.1111/joim.13343] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is defined by presence of steatosis in more than 5% of liver cells. The gold standard for diagnosis is liver biopsy, but this is seldom achieved due to costs and risk for side effects, and that is why the diagnosis is mostly made based on a combination of radiology and exclusion of other liver diseases. Disease severity staging can be noninvasively achieved with radiological exams such as elastography or blood-based markers that usually have lower sensitivity and specificity. NAFLD is today the most common chronic liver disease globally with a prevalence estimated to be 25%. Fortunately, for many persons NAFLD is an incidental finding with a good prognosis. Whilst a major focus has been on liver-related outcomes in NAFLD, there has recently been an increased interest in extrahepatic consequences of NAFLD. The most commonly studied outcomes include cardiovascular disease and cancer. The risk of adverse outcomes generally differs according to the baseline fibrosis stage. There is a five-time higher risk of liver-related events in NAFLD patients with fibrosis stage 3 as compared to those with no or little fibrosis. Meanwhile, the presence of nonalcoholic steatohepatitis (NASH) does not seem to influence prognosis in addition to fibrosis stage. Patients with NAFLD clearly have a higher risk for cardiovascular outcomes compared to the general population, with a recent meta-analysis indicating a 37% increased hazard for cardiovascular events as opposed to individuals without NAFLD. The risk of liver cancer is increased, which is mostly driven by presence of cirrhosis, but the increased risk is present also in patients without cirrhosis, and to a greater extent than for other chronic liver disease. Around one-third of patients with NAFLD and liver cancer do not have cirrhosis. Additionally, the risk of extrahepatic malignancies is thought to be moderately increased, with most evidence for a link between NAFLD and colorectal cancer where the risk is approximately 50% higher compared to patients without NAFLD. A particularly salient point is if NAFLD can be considered an independent risk factor for outcomes. Many studies have not been able to adjust for key confounders, or suffer from different forms of bias. The clinical problem is nevertheless to identify persons with an increased risk for adverse hepatic and extrahepatic outcomes. We here discuss the evidence linking NAFLD to severe hepatic and extrahepatic outcomes.
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Affiliation(s)
- Hannes Hagström
- Division of Hepatology, Department of Upper GI diseases, Karolinska University Hospital, Stockholm, Sweden.,Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.,Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden
| | - Stergios Kechagias
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Mattias Ekstedt
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
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11
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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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12
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Minhas AMK, Bhopalwala HM, Dewaswala N, Salah HM, Khan MS, Shahid I, Biegus J, Lopes RD, Pandey A, Fudim M. Association of Non-Alcoholic Fatty Liver Disease with In-Hospital Outcomes in Primary Heart Failure Hospitalizations with Reduced or Preserved Ejection Fraction. Curr Probl Cardiol 2022:101199. [DOI: 10.1016/j.cpcardiol.2022.101199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 04/02/2022] [Indexed: 11/03/2022]
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13
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Fatty liver index and hypertension-mediated organ damage in never-treated hypertensive patients without diabetes mellitus. J Hypertens 2021; 39:2470-2477. [PMID: 34738990 DOI: 10.1097/hjh.0000000000002954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND We investigated whether fatty liver index (FLI), a surrogate marker of nonalcoholic fatty liver disease (NAFLD), is associated with hypertension-mediated organ damage (HMOD) in never-treated hypertensive patients without diabetes mellitus. METHODS We performed both clinic and ambulatory blood pressure (BP) measurements, and calculated the FLI for all participants. A FLI of no less than 60 indicates a high-risk of underlying NAFLD, whereas a FLI of less than 60 indicates lower risk. We evaluated left ventricular mass (LVM) by echocardiography, arterial stiffness by carotid--femoral pulse wave velocity (PWV), capillary rarefaction by nailfold capillaroscopy, as well as urinary albumin-to-creatinine ratio (ACR). HMOD was defined according to the categorical thresholds for each domain, except for capillary rarefaction in which case the categorization of patients was made by the median. RESULTS We included 146 hypertensive patients (men, 43.8%; mean age, 56.6 ± 10.8 years; BMI, 30.3 ± 4.9 kg/m2; FLI, 57.2 ± 27.7; office, systolic/diastolic, and 24-h BP, 153.5 ± 15.8/94.7 ± 9.8 mmHg, and 140.5 ± 9.9/83.8 ± 9 mmHg, respectively). Patients with FLI at least 60 (n = 76) were younger, with higher BMI and 24-h SBP, compared with patients with FLI less than 60 (n = 70). FLI was associated with HMOD after adjustment (LVM indexed to height, P = 0.004; PWV, P = 0.047; reduced capillary density, P = 0.001; and logACR, P = 0.003). High-risk FLI phenotype and FLI z scores increased the likelihood of any HMOD by 3.8 (95% confidence interval, 1.6-7.1) and 5.4 (95% confidence interval, 2.3-15.0) times, respectively. However, the increased number of HMOD domains has progressively stopped being determined by the FLI z scores (P = 0.65). CONCLUSION High-risk FLI pattern was associated with various HMOD, and may re-classify never-treated hypertensive patients without diabetes mellitus into a higher cardiovascular risk level.
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14
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Yoon H. The Relationship between the Serum Aspartate Aminotransferase/Alanine Aminotransferase Ratio and Pulse Pressure in Korean Adults with Hypertension. KOREAN JOURNAL OF CLINICAL LABORATORY SCIENCE 2021. [DOI: 10.15324/kjcls.2021.53.3.241] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Affiliation(s)
- Hyun Yoon
- Department of Clinical Laboratory Science, Wonkwang Health Science University, Iksan, Korea
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15
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Vidal-González D, López-Sánchez GN, Concha-Rebollar LA, Rodríguez-Herrera A, Morales-Ramirez F, Chávez-Tapia N, Uribe M, Nader-Kawachi JA, Nuño-Lámbarri N. Cerebral hemodynamics in the non-alcoholic fatty liver. Ann Hepatol 2021; 19:668-673. [PMID: 32683094 DOI: 10.1016/j.aohep.2020.06.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 06/08/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES The association between non-alcoholic fatty liver disease and cerebral hemodynamics arises from cardiovascular damage mechanisms such as endothelial dysfunction, arterial wall increased stiffness, high thickness of the intimate index of the internal carotid artery, left ventricular hypertrophy, left diastolic dysfunction, calcification coronary arteries and increased epicardial fat. The multidirectional relationship between systemic inflammation and lipid metabolism constitutes a common and simultaneous mechanism that causes vascular damage. This study aims to provide insight into the relationship between non-alcoholic fatty liver disease and the function of systemic circulation and cerebral circulation using Doppler ultrasound. PATIENTS AND METHODS Is an observational, cross-sectional, prospective, comparative study conducted at Medica Sur Hospital. Thirty-five patients were selected consecutively. The patients consulted neurological service for various symptoms without severity criteria, such as vertigo, primary headache and balance disturbances. RESULTS There is a difference in the variables mean of the right MCA PI (p = 0.023), left MCA PI" (p = 0.004), and left VA PI (p = 0.036) between the control and NAFLD groups. The correlation analysis between these variables and the CAP showed a positive correlation of the three variables with the CAP, "right MCA PI" (r = 0.384), left MCA PI "(r = 0.509) and" left VA PI " (r = 0.551). CONCLUSIONS This study demonstrates a subclinical process of the middle cerebral artery in subjects with NAFLD, which suggests it may be involved in the disease development and points the need to make decisions for this liver manifestation prevention and treatment.
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Affiliation(s)
| | | | | | | | | | - Norberto Chávez-Tapia
- Traslational Research Unit, Medica Sur Clinic & Foundation, Mexico; Obesity and Digestive Diseases Unit, Medica Sur Clinic & Foundation, Mexico.
| | - Misael Uribe
- Obesity and Digestive Diseases Unit, Medica Sur Clinic & Foundation, Mexico.
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16
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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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17
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Zou W, Zhang C, Gu X, Li X, Zhu H. Metformin in Combination with Malvidin Prevents Progression of Non-Alcoholic Fatty Liver Disease via Improving Lipid and Glucose Metabolisms, and Inhibiting Inflammation in Type 2 Diabetes Rats. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:2565-2576. [PMID: 34168429 PMCID: PMC8218939 DOI: 10.2147/dddt.s307257] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 04/22/2021] [Indexed: 12/30/2022]
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is one of the primary causes of chronic liver disease and is closely linked to insulin resistance, type 2 diabetes mellitus (T2DM), and dyslipidemia. However, no effective drug therapies have been approved to treat this disease. The present research aimed to evaluate the therapeutic effects of the combination of oral hypoglycemic drug metformin (MET) and a natural product malvidin (MAL) on hepatic damage in HFD/STZ-induced diabetic rats. Methods Sprague-Dawley rats were divided into five groups: normal control group (NC), diabetic control group (DC), DC+MET group, DC+MAL group, and DC+MET+MAL group and treated for eight weeks. Blood and liver tissue samples were collected for metabolic parameters, histological, and RT-qPCR analysis. Results Our findings indicated that hyperglycemia, insulin resistance, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD) in diabetic rats were alleviated after oral treatment with MET and MAL, particularly their combination therapy. Besides, the expression of SREBP-1c, ACC, FAS, IL-6, IL-8, and NF-κB mRNA was down-regulated by MET+MAL, and the expression of PPARα, CPT1, and LPL was up-regulated by MET+MAL. Conclusion The evidence of this research indicated that the combination therapy may represent an efficient strategy against NAFLD in T2DM rats via improving lipid and glucose metabolisms, and inhibiting inflammation.
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Affiliation(s)
- Wenlan Zou
- Department of Endocrinology, Fifth People's Hospital of Suzhou, Suzhou, Jiangsu, 215100, People's Republic of China
| | - Chen Zhang
- Department of Endocrinology, Fifth People's Hospital of Suzhou, Suzhou, Jiangsu, 215100, People's Republic of China
| | - Xuefang Gu
- Department of Endocrinology, Xiangcheng District Second People's Hospital of Suzhou, Suzhou, Jiangsu, 215100, People's Republic of China
| | - Xiaohong Li
- Department of Liver Disease, Fifth People's Hospital of Suzhou, Suzhou, Jiangsu, 215100, People's Republic of China
| | - Huiming Zhu
- Department of Gastroenterology, Fifth People's Hospital of Suzhou, Suzhou, Jiangsu, 215100, People's Republic of China
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18
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Oikonomidou AC, Doundoulakis I, Antza C, Kalopitas G, Dardavessis T, Chourdakis M. Evaluation of subclinical cardiac damage in biopsy-proven nonalcoholic fatty liver disease: a systematic review and meta-analysis. Ann Gastroenterol 2021; 34:424-430. [PMID: 33948069 PMCID: PMC8079885 DOI: 10.20524/aog.2021.0594] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 10/20/2020] [Indexed: 12/11/2022] Open
Abstract
Background Data on the association of nonalcoholic fatty liver disease (NAFLD) with subclinical cardiac damage are scanty. We performed a systematic review to provide comprehensive information on subclinical cardiac alterations among NAFLD subjects. Methods PubMed and the Cochrane Library were searched to identify studies comparing subclinical cardiac damage between NAFLD and healthy adults. We also searched PROSPERO to check for any similar meta-analysis in progress in order to avoid duplication with our study. Conference abstracts and the reference lists of relevant studies and systematic reviews were perused. The Newcastle-Ottawa quality assessment scale for case-control and cohort studies were used to assess study quality. Results Seven studies were finally included in the meta-analysis (1 cross sectional and 6 case-control), with a total of 602 individuals (362 patients with NAFLD). Epicardial fat thickness were statistically significantly higher in patients with NAFLD than in controls (mean difference [MD] 1.17, 95% confidence interval [CI] 0.45-1.89, I2=89%). Global longitudinal strain was lower in NAFLD, to a statistically significant degree (MD -3.17, 95%CI -5.09 to -1.24, I2=89%). However, significant heterogeneity of the findings was observed. Conclusions Our findings indicate that NAFLD is related to subclinical cardiac damage. Further studies with a larger number of biopsy-proven NAFLD patients are needed to confirm this finding. Preventive and therapeutic interventions early in the course of the disease might decrease morbidity in this high-risk patient group.
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Affiliation(s)
- Artemis Christina Oikonomidou
- Department of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki (Artemis Christina Oikonomidou, Ioannis Doundoulakis, Theodoros Dardavessis, Michail Chourdakis)
| | - Ioannis Doundoulakis
- Department of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki (Artemis Christina Oikonomidou, Ioannis Doundoulakis, Theodoros Dardavessis, Michail Chourdakis).,Department of Cardiology, 424 General Military Training Hospital, Thessaloniki (Ioannis Doundoulakis)
| | - Christina Antza
- 3 Department of Internal Medicine, G.H. "Papageorgiou", School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki (Christina Antza)
| | - Georgios Kalopitas
- Division of Gastroenterology and Hepatology, 1 Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki (Georgios Kalopitas), Greece
| | - Theodoros Dardavessis
- Department of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki (Artemis Christina Oikonomidou, Ioannis Doundoulakis, Theodoros Dardavessis, Michail Chourdakis)
| | - Michail Chourdakis
- Department of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki (Artemis Christina Oikonomidou, Ioannis Doundoulakis, Theodoros Dardavessis, Michail Chourdakis)
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19
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Fiorentino TV, Miceli S, Succurro E, Sciacqua A, Andreozzi F, Sesti G. Nonalcoholic fatty liver disease is associated with a decreased myocardial mechano-energetic efficiency. J Intern Med 2021; 289:221-231. [PMID: 32633873 DOI: 10.1111/joim.13155] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 06/26/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is linked to a raised risk of cardiovascular diseases (CVD), although the underlying mechanisms are not completely known. A reduced myocardial mechano-energetic efficiency (MEE) has been found to be an independent predictor of CVD. OBJECTIVE To evaluate the association between NAFLD and a compromised MEE. METHODS Myocardial MEE was assessed by a validated echocardiography-derived measure in 699 nondiabetic individuals subdivided into two groups according to ultrasonography defined presence of NAFLD. RESULTS Subjects with NAFLD displayed higher levels of systolic (SBP) and diastolic blood pressure (DBP), triglycerides, fasting and postload glucose, high-sensitivity C-reactive protein (hsCRP), insulin resistance (IR) estimated by HOMA-IR and liver IR index, and lower values of high-density lipoprotein (HDL) in comparison with those without NAFLD. Presence of NAFLD was associated with increased levels of myocardial oxygen demand and reduced values of MEE. MEE was negatively correlated with male sex, age, BMI, waist circumference, SBP, DBP, total cholesterol, triglycerides, fasting and postload glucose, HOMA-IR and liver IR index, hsCRP and positively with HDL levels. In a multivariable regression analysis, presence of NAFLD was associated with MEE regardless of several cardio-metabolic risk factors such as age, gender, waist circumference, SBP, DBP, total and HDL cholesterol, triglycerides, glucose tolerance and hsCRP (β = -0.09, P = 0.04), but not independently of IR estimates. CONCLUSION Ultrasound-defined presence of NAFLD is associated with a decreased MEE, a predictor of adverse cardiovascular events. The relationship between NAFLD and a compromised MEE is dependent of IR.
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Affiliation(s)
- T V Fiorentino
- From the, Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - S Miceli
- From the, Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - E Succurro
- From the, Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - A Sciacqua
- From the, Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - F Andreozzi
- From the, Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - G Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome, Italy
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20
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Fiorentino TV, Succurro E, Sciacqua A, Andreozzi F, Perticone F, Sesti G. Non-alcoholic fatty liver disease is associated with cardiovascular disease in subjects with different glucose tolerance. Diabetes Metab Res Rev 2020; 36:e3333. [PMID: 32356922 DOI: 10.1002/dmrr.3333] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 04/23/2020] [Accepted: 04/24/2020] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) in patients with type 2 diabetes; nonetheless, it is unknown whether the relationship between NAFLD and CVD occurs also in subjects with prediabetes. Herein, we evaluated whether NAFLD is associated with prevalent CVD in subjects with different glucose tolerance states independently of cardiovascular risk factors. MATERIALS AND METHODS Presence of NALFD, defined by liver ultrasound, and its association with prevalent composite and individual CVD, including coronary artery disease (CAD) and cerebrovascular disease, was assessed in a cohort of 1254 Caucasian subjects classified as having normal glucose tolerance (NGT, n = 517), prediabetes (n = 397) or type 2 diabetes (n = 340). RESULTS Prevalence of NAFLD in the study population was 47.9%. Presence of NAFLD was linked to an augmented prevalence of composite CVD and individual CAD in all the three glucose tolerance groups. In a logistic regression model adjusted for several cardio-metabolic risk factors, subjects with NGT and NAFLD exhibited a 3.2- and 3.4-fold increased risk of having CVD or CAD, respectively, as compared with those without NAFLD. Similarly, subjects with prediabetes and NAFLD showed an increased risk of having CVD or CAD by 2.3- and 2.0-fold, respectively, in comparison to their counterpart without NAFLD. Within the group with type 2 diabetes, subjects having NAFLD displayed a 2.3- and 2.0-fold higher risk of having CVD or CAD, respectively, in comparison to those without NAFLD. CONCLUSION Ultrasonography-defined NAFLD is independently associated with an increased risk of having CVD in individuals with different glucose tolerance.
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Affiliation(s)
- Teresa Vanessa Fiorentino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Elena Succurro
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Francesco Andreozzi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Francesco Perticone
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Giorgio Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome, Italy
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21
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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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22
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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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Xu X, Wang W, Lin L, Chen P. Liraglutide in combination with human umbilical cord mesenchymal stem cell could improve liver lesions by modulating TLR4/NF-kB inflammatory pathway and oxidative stress in T2DM/NAFLD rats. Tissue Cell 2020; 66:101382. [PMID: 32933722 DOI: 10.1016/j.tice.2020.101382] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 05/08/2020] [Accepted: 05/08/2020] [Indexed: 12/27/2022]
Abstract
Studies have shown that liraglutide, or human umbilical cord mesenchymal stem cell (hUC-MSCs) can improve non-alcoholic fatty liver disease (NAFLD). However there have been no studies on the combination of the two used to treat NAFLD. This study aimed to explore the therapeutic effects of combination of liraglutide and hUC-MSCs on liver injury in rats with type 2 diabetes mellitus (T2DM) and NAFLD, and further investigate their mechanisms. Sprague Dawley rats fed by a high fat and high sucrose diet were randomly divided into 5 groups, including NC group, T2DM/NAFLD group, liraglutide group (treated with liraglutide, 200 μg/kg, twice daily for 8 weeks), hUC-MSCs group (treated with hUC-MSCs at the first and fifth weeks), liraglutid＋hUC-MSCs group (treated with liraglutide and hUC-MSCs). Liver tissue was procured for histological examination, real-time qRT-PCR and Western blot analysis. After treatment, liraglutide and hUC-MSCs reduced serum ALT and AST levels, alleviate liver inflammation and improved liver histopathology. The expressions of inflammatory cytokines, TLR4 and NF-κB in serum and liver were significantly inhibited, particularly in the combination treatment group. Eight weeks after liraglutide or hUC-MSCs administration, FBG, HbA1c, HOMA-IR, ALT, AST, Liver wet eight and hepatic TLR4, NF-κB, IL-6, TNF-α, 8-OHdG mRNA and proteins were significantly decreased, and the levels of SOD expression were significantly increased in three treatment groups compared with T2DM/NAFLD group. This study suggests that liraglutide in combination with hUC-MSCs could significantly improve glycolipid metabolism, insulin resistance and liver injury in T2DM/NAFLD rats. Its mechanism may be related to the down-regulation of the TLR4/NF-κB inflammatory pathway and improvement in oxidative stress.
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Affiliation(s)
- Xiangjin Xu
- 900 Hospital of the Joint Logistics Team, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou 365000, Fujian, China
| | - Wenqing Wang
- The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China
| | - Lu Lin
- 900 Hospital of the Joint Logistics Team, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou 365000, Fujian, China
| | - Pin Chen
- 900 Hospital of the Joint Logistics Team, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou 365000, Fujian, China.
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El Hadi H, Di Vincenzo A, Vettor R, Rossato M. Relationship between Heart Disease and Liver Disease: A Two-Way Street. Cells 2020; 9:cells9030567. [PMID: 32121065 PMCID: PMC7140474 DOI: 10.3390/cells9030567] [Citation(s) in RCA: 89] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 02/23/2020] [Accepted: 02/25/2020] [Indexed: 12/18/2022] Open
Abstract
In clinical practice, combined heart and liver dysfunctions coexist in the setting of the main heart and liver diseases because of complex cardiohepatic interactions. It is becoming increasingly crucial to identify these interactions between heart and liver in order to ensure an effective management of patients with heart or liver disease to provide an improvement in overall prognosis and therapy. In this review, we aim to summarize the cross-talk between heart and liver in the setting of the main pathologic conditions affecting these organs. Accordingly, we present the clinical manifestation, biochemical profiles, and histological findings of cardiogenic ischemic hepatitis and congestive hepatopathy due to acute and chronic heart failure, respectively. In addition, we discuss the main features of cardiac dysfunction in the setting of liver cirrhosis, nonalcoholic fatty liver disease, and those following liver transplantation.
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Affiliation(s)
- Hamza El Hadi
- Internal Medicine 3, Department of Medicine—DIMED, University of Padova, Via Giustiniani 2, 35100 Padova, Italy; (H.E.H.); (A.D.V.); (R.V.)
- Department of Medicine, Klinikum Rheine, 48431 Rheine, Germany
| | - Angelo Di Vincenzo
- Internal Medicine 3, Department of Medicine—DIMED, University of Padova, Via Giustiniani 2, 35100 Padova, Italy; (H.E.H.); (A.D.V.); (R.V.)
| | - Roberto Vettor
- Internal Medicine 3, Department of Medicine—DIMED, University of Padova, Via Giustiniani 2, 35100 Padova, Italy; (H.E.H.); (A.D.V.); (R.V.)
| | - Marco Rossato
- Internal Medicine 3, Department of Medicine—DIMED, University of Padova, Via Giustiniani 2, 35100 Padova, Italy; (H.E.H.); (A.D.V.); (R.V.)
- Correspondence: ; Tel.: +39-049-8218747; Fax: +39049-8213332
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Lee Y, Lai HTM, de Oliveira Otto MC, Lemaitre RN, McKnight B, King IB, Song X, Huggins GS, Vest AR, Siscovick DS, Mozaffarian D. Serial Biomarkers of De Novo Lipogenesis Fatty Acids and Incident Heart Failure in Older Adults: The Cardiovascular Health Study. J Am Heart Assoc 2020; 9:e014119. [PMID: 32020839 PMCID: PMC7070205 DOI: 10.1161/jaha.119.014119] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 12/06/2019] [Indexed: 12/14/2022]
Abstract
Background De novo lipogenesis (DNL) is an endogenous pathway that converts excess dietary starch, sugar, protein, and alcohol into specific fatty acids (FAs). Although elevated DNL is linked to several metabolic abnormalities, little is known about how long-term habitual levels and changes in levels of FAs in the DNL pathway relate to incident heart failure (HF). Methods and Results We investigated whether habitual levels and changes in serial measures of FAs in the DNL pathway were associated with incident HF among 4249 participants free of HF at baseline. Plasma phospholipid FAs were measured at baseline, 6 years, and 13 years using gas chromatography, and risk factors for HF were measured using standardized methods. Incident HF was centrally adjudicated using medical records. We prospectively evaluated associations with HF risk of (1) habitual FA levels, using cumulative updating to assess long-term exposure, and (2) changes in FA levels over time. During 22.1 years of follow-up, 1304 HF cases occurred. After multivariable adjustment, habitual levels and changes in levels of palmitic acid (16:0) were positively associated with incident HF (interquintile hazard ratio [95% CI]=1.17 [1.00-1.36] and 1.26 [1.03-1.55], respectively). Changes in levels of 7-hexadecenoic acid (16:1n-9) and vaccenic acid (18:1n-7) were each positively associated with risk of HF (1.36 [1.13-1.62], and 1.43 [1.18-1.72], respectively). Habitual levels and changes in levels of myristic acid (14:0), palmitoleic acid (16:1n-7), stearic acid (18:0), and oleic acid (18:1n-9) were not associated with incident HF. Conclusions Both habitual levels and changes in levels of 16:0 were positively associated with incident HF in older adults. Changes in 16:1n-9 and 18:1n-7 were also positively associated with incident HF. These findings support a potential role of DNL or these DNL-related FAs in the development of HF.
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Affiliation(s)
- Yujin Lee
- Friedman School of Nutrition Science and PolicyTufts UniversityBostonMA
| | - Heidi T. M. Lai
- Friedman School of Nutrition Science and PolicyTufts UniversityBostonMA
| | - Marcia C. de Oliveira Otto
- Division of EpidemiologyHuman Genetics and Environmental SciencesThe University of Texas Health Science Center at Houston (UTHealth) School of Public HealthHoustonTX
| | - Rozenn N. Lemaitre
- Cardivascular Health Research UnitDepartment of MedicineUniversity of WashingtonSeattleWA
| | | | - Irena B. King
- Department of Internal MedicineUniversity of New MexicoAlbuquerqueNM
| | | | - Gordon S. Huggins
- Molecular Cardiology Research Institute Center for Translational GenomicsTufts Medical CenterBostonMA
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Metabolic disturbances and cardiovascular risk factors in obese children with vitamin D deficiency. Arch Pediatr 2020; 27:140-145. [PMID: 31955958 DOI: 10.1016/j.arcped.2019.12.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 11/07/2019] [Accepted: 12/30/2019] [Indexed: 11/21/2022]
Abstract
OBJECTIVES The prevalence of obesity among children and adolescents has been rapidly increasing in recent years. Obese individuals are at risk of vitamin D deficiency. The aim of this study was to investigate the relationship between vitamin D deficiency and anthropometric measurements, cardiovascular risk factors, and glucose homeostasis in obese children. METHODS Between June 2011 and January 2012, 40 obese and 30 non-obese children (between 7 and 14 years of age) were evaluated at Tepecik Training and Research Hospital. The following characteristics were recorded: height; weight; body mass index (BMI); total body fat content; fasting glucose, insulin, and lipid levels; basic biochemical parameters; complete blood count; bilateral carotid intima media thickness; liver ultrasound results; and left ventricular wall thickness were recorded. 25-hydroxy (OH) vitamin D levels were measured from serum. RESULTS The serum 25(OH) vitamin D level was low in 45 children (64.3%). The 24-h ambulatory blood pressure measurements, carotid intima-media thickness, and the prevalence of 25(OH) vitamin D deficiency were different between obese and non-obese children (P<0.05). The incidence of dyslipidemia was not statistically different between obese and non-obese children (P>0.05). Plasma 25(OH) vitamin D concentrations were negatively correlated with age, BMI, total body fat content, 24-h ambulatory blood pressure, and carotid intima-media thickness (P<0.05). Plasma 25(OH) vitamin D levels were not correlated with fasting plasma glucose, HOMA-IR, triglycerides, total cholesterol, low-density cholesterol, and high-density cholesterol (P>0.05). CONCLUSION Vitamin D deficiency is more prevalent in obese children. Serum 25(OH)vitamin D was significantly associated with several cardiometabolic risk factors. There was no relationship between abnormal glucose homeostasis and dyslipidemia with vitamin D deficiency in obese children.
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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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Dong Y, Li G. Cardiac abnormalities in patients with nonalcoholic fatty liver disease : Insights from auxiliary examinations. Herz 2019; 46:158-163. [PMID: 31538216 DOI: 10.1007/s00059-019-04855-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 08/19/2019] [Accepted: 08/26/2019] [Indexed: 12/16/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease in developed countries and is associated with type 2 diabetes mellitus, obesity, hypertension, dyslipidemia, and metabolic syndrome. It is defined as steatosis in over 5% of hepatocytes. The disease spectrum of NAFLD ranges from simple fatty liver to nonalcoholic steatohepatitis, liver fibrosis, even hepatic cirrhosis. The disease affects various extra-hepatic systems such as the cardiovascular system and urinary system. Heart-related disease is identified as the leading cause of mortality in NAFLD patients rather than liver-related disease. In this review, we summarize the cardiac abnormalities (structural, functional, arrhythmic cardiac complications etc.) seen in NAFLD patients with the assistance of auxiliary examinations, such as electrocardiography, echocardiography, computed tomography, magnetic resonance imaging etc. In addition, the epidemiology of NAFLD and how NAFLD affects the myocardium are also discussed.
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Affiliation(s)
- Yu Dong
- Department of Ultrasound, the Second Affiliated Hospital, Dalian Medical University, 116027, Dalian, China
| | - Guangsen Li
- Department of Ultrasound, the Second Affiliated Hospital, Dalian Medical University, 116027, Dalian, China.
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Cardiovascular Risk in Non-Alcoholic Fatty Liver Disease: Mechanisms and Therapeutic Implications. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16173104. [PMID: 31455011 PMCID: PMC6747357 DOI: 10.3390/ijerph16173104] [Citation(s) in RCA: 126] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2019] [Revised: 08/18/2019] [Accepted: 08/21/2019] [Indexed: 02/06/2023]
Abstract
New evidence suggests that non-alcoholic fatty liver disease (NAFLD) has a strong multifaceted relationship with diabetes and metabolic syndrome, and is associated with increased risk of cardiovascular events, regardless of traditional risk factors, such as hypertension, diabetes, dyslipidemia, and obesity. Given the pandemic-level rise of NAFLD—in parallel with the increasing prevalence of obesity and other components of the metabolic syndrome—and its association with poor cardiovascular outcomes, the question of how to manage NAFLD properly, in order to reduce the burden of associated incident cardiovascular events, is both timely and highly relevant. This review aims to summarize the current knowledge of the association between NAFLD and cardiovascular disease, and also to discuss possible clinical strategies for cardiovascular risk assessment, as well as the spectrum of available therapeutic strategies for the prevention and treatment of NAFLD and its downstream events.
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Chang W, Wang Y, Sun L, Yu D, Li Y, Li G. Evaluation of left atrial function in type 2 diabetes mellitus patients with nonalcoholic fatty liver disease by two-dimensional speckle tracking echocardiography. Echocardiography 2019; 36:1290-1297. [PMID: 31206765 DOI: 10.1111/echo.14400] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Revised: 05/11/2019] [Accepted: 05/14/2019] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVE To assess left atrial function in type 2 diabetes mellitus (T2DM) patients with nonalcoholic fatty liver disease (NAFLD) by two-dimensional speckle tracking echocardiography (2D-STE). METHODS We classified 97 patients with T2DM into three groups according to the results of liver ultrasonography: group A (without NAFLD), group B (mild fatty liver), and group C (moderate to severe fatty liver). Conventional echocardiography parameters included left atrial end-systolic diameter (LAD), left ventricular end-systolic and end-diastolic diameter (LVDs, LVDd), end-diastolic thickness of ventricular septumi and LV posterior wall (IVSTd, LVPWTd), peak E and A of mitralis (E, A), septal and lateral early (e') mitral annular diastolic tissue velocities, then calculated E/A and E/mean e'. We measured LV ejection fraction (LVEF) and left atrial (LA) volumes (max, min, and preatrial contraction volume) by Simpson's rule, then calculated LA passive and active ejection fraction (LAPEF, LAAEF), left atrial maximum volume index (LAVImax). The global peak longitudinal systolic strain (LASRs), early diastolic strain (LASRe), and late diastolic strain (LASRa) rates of the LA were obtained by 2D-STE. RESULTS No differences were found between groups A and B (all P > 0.05). In group C, LAAEF and LASRa were obviously higher, while LAPEF, LASRe, and LASRs were obviously decreased compared with those values in groups A and B (all P < 0.05). The association between the severity of NAFLD and the differences in LA strain values remained significant after adjustment for confounders. CONCLUSION Two-dimensional speckle tracking echocardiography can evaluate the left atrial function in T2DM patients with NAFLD.
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Affiliation(s)
- Wenxing Chang
- Department of Ultrasound, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ying Wang
- Department of Ultrasound, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Lihua Sun
- Department of Ultrasound, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Dong Yu
- Department of Ultrasound, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ying Li
- Department of Ultrasound, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Guangsen Li
- Department of Ultrasound, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
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Abstract
The first clinical application of magnetic resonance elastography (MRE) was in the evaluation of chronic liver disease (CLD) for detection and staging of liver fibrosis. In the past 10 years, MRE has been incorporated seamlessly into a standard magnetic resonance imaging (MRI) liver protocol worldwide. Liver MRE is a robust technique for evaluation of liver stiffness and is currently the most accurate noninvasive imaging technology for evaluation of liver fibrosis. Newer MRE sequences including spin-echo MRE and 3 dimensional MRE have helped in reducing the technical limitations of clinical liver MRE that is performed with 2D gradient recalled echo (GRE) MRE. Advances in MRE technology have led to understanding of newer mechanical parameters such as dispersion, attenuation, and viscoelasticity that may be useful in evaluating pathological processes in CLD and may prove useful in their management.This review article will describe the changes in CLD that cause an increase in stiffness followed by principle and technique of liver MRE. In the later part of the review, we will briefly discuss the advances in liver MRE.
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Jelenik T, Flögel U, Álvarez-Hernández E, Scheiber D, Zweck E, Ding Z, Rothe M, Mastrototaro L, Kohlhaas V, Kotzka J, Knebel B, Müller-Wieland D, Moellendorf S, Gödecke A, Kelm M, Westenfeld R, Roden M, Szendroedi J. Insulin Resistance and Vulnerability to Cardiac Ischemia. Diabetes 2018; 67:2695-2702. [PMID: 30257974 PMCID: PMC6245221 DOI: 10.2337/db18-0449] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Accepted: 09/05/2018] [Indexed: 12/20/2022]
Abstract
Hepatic and myocardial ectopic lipid deposition has been associated with insulin resistance (IR) and cardiovascular risk. Lipid overload promotes increased hepatic oxidative capacity, oxidative stress, and impaired mitochondrial efficiency, driving the progression of nonalcoholic fatty liver disease (NAFLD). We hypothesized that higher lipid availability promotes ischemia-induced cardiac dysfunction and decreases myocardial mitochondrial efficiency. Mice with adipose tissue-specific overexpression of sterol element-binding protein 1c as model of lipid overload with combined NAFLD-IR and controls underwent reperfused acute myocardial infarcts (AMIs). Whereas indexes of left ventricle (LV) contraction were similar in both groups at baseline, NAFLD-IR showed severe myocardial dysfunction post-AMI, with prominent LV reshaping and increased end-diastolic and end-systolic volumes. Hearts of NAFLD-IR displayed hypertrophy, steatosis, and IR due to 18:1/18:1-diacylglycerol-mediated protein kinase Cε (PKCε) activation. Myocardial fatty acid-linked respiration and oxidative stress were increased, whereas mitochondrial efficiency was decreased. In humans, decreased myocardial mitochondrial efficiency of ventricle biopsies related to IR and troponin levels, a marker of impaired myocardial integrity. Taken together, increased lipid availability and IR favor susceptibility to ischemia-induced cardiac dysfunction. The diacylglycerol-PKCε pathway and reduced mitochondrial efficiency both caused by myocardial lipotoxicity may contribute to the impaired LV compensation of the noninfarcted region of the myocardium.
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Affiliation(s)
- Tomas Jelenik
- Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany
- German Center for Diabetes Research, München-Neuherberg, Germany
| | - Ulrich Flögel
- Department of Molecular Cardiology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Elisa Álvarez-Hernández
- Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany
- German Center for Diabetes Research, München-Neuherberg, Germany
| | - Daniel Scheiber
- Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Elric Zweck
- Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Zhaoping Ding
- Department of Molecular Cardiology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Maik Rothe
- Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany
- German Center for Diabetes Research, München-Neuherberg, Germany
| | - Lucia Mastrototaro
- Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany
- German Center for Diabetes Research, München-Neuherberg, Germany
| | - Vivien Kohlhaas
- Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany
- German Center for Diabetes Research, München-Neuherberg, Germany
| | - Jörg Kotzka
- German Center for Diabetes Research, München-Neuherberg, Germany
- Institute for Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany
| | - Birgit Knebel
- German Center for Diabetes Research, München-Neuherberg, Germany
- Institute for Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany
| | | | - Sarah Moellendorf
- Department of Cardiovascular Physiology, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Axel Gödecke
- Department of Cardiovascular Physiology, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Malte Kelm
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Ralf Westenfeld
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany
- German Center for Diabetes Research, München-Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Julia Szendroedi
- Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany
- German Center for Diabetes Research, München-Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
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Wang Q, Ma W, Xia J. Nonalcoholic Fatty Liver Is Associated With Further Left Ventricular Abnormalities in Patients With Type 2 Diabetes Mellitus: A 3-Dimensional Speckle-Tracking Study. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2018; 37:1899-1911. [PMID: 29363154 DOI: 10.1002/jum.14536] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Revised: 10/17/2017] [Accepted: 10/20/2017] [Indexed: 06/07/2023]
Abstract
OBJECTIVES The aim of this study was to detect left ventricular (LV) structure and function abnormalities in patients with type 2 diabetes mellitus with or without nonalcoholic fatty liver (NAFL) using 3-dimensional speckle-tracking echocardiography. METHODS Eighty patients with type 2 diabetes and a normal LV ejection fraction (≥55%), including 40 with coexistent NAFL, and 40 age- and sex-matched control participants were recruited. Conventional echocardiography and 3-dimensional speckle-tracking echocardiography were performed, and global longitudinal strain, global circumferential strain, global area strain, and global radial strain values were measured. RESULTS Significant differences in 2-dimensional LV functional patterns were found among the 3 groups (P = .031), and LV hypertrophy was the most prevalent in patients with diabetes and NAFL. The patients with diabetes only had significantly lower global longitudinal strain, global circumferential strain, and global radial strain than the controls (all P < .05). The patients with diabetes and NAFL had severely lower global longitudinal strain, global circumferential strain, global area strain, and global radial strain than the controls (all P < .001), and they also had severely lower global longitudinal strain, global area strain, and global radial strain than the patients with diabetes only (all P < 0.001). The hemoglobin A1c level and NAFL were independently associated with strain values in all patients with diabetes. The strain values in multiple directions (≥2 of global longitudinal, global circumferential, global area, and global radial strain) decreased significantly in the patients with diabetes and moderate and severe NAFL compared to those with mild NAFL (all P < .05). CONCLUSIONS Nonalcoholic fatty liver could aggravate LV hypertrophy and dysfunction in patients with type 2 diabetes. The combined application of conventional and 3-dimensional speckle-tracking echocardiography could detect these asymptomatic preclinical abnormalities.
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Affiliation(s)
- Qingqing Wang
- Department of Ultrasound, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Wenyan Ma
- Department of Ultrasound, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jizhu Xia
- Department of Ultrasound, Affiliated Hospital of Southwest Medical University, Luzhou, China
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is an important cause of chronic hepatic disease and liver transplant in Western societies. The increasing prevalence is related to dietary changes and sedentarism and follows the increasing frequency of obesity and type 2 diabetes mellitus. Growing evidence of association of NAFLD with cardiovascular diseases (CVD), independent of cardiovascular risk factors, has prompted the clarification of whether the liver is mainly a key-effector or a target-organ of the metabolic disarrangements in the metabolic syndrome. The therapeutic strategies able to alter liver disease progression and, through this, reduce the cardiovascular risk have also been tested in the last 2 decades. This review focus on the possible interactions between hepatic disease, metabolic syndrome, and CVD, and on their implications for clinical practice.
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Affiliation(s)
- Elisabete Martins
- Department of Medicine, Faculty of Medicine.,Instituto de Investigação e Inovação em Saúde (i3s), University of Porto.,Department of Cardiology
| | - Ana Oliveira
- Department of Nuclear Medicine, São João Hospital Center, Porto, Portugal
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Risk of cardiomyopathy and cardiac arrhythmias in patients with nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2018; 15:425-439. [PMID: 29713021 DOI: 10.1038/s41575-018-0010-0] [Citation(s) in RCA: 174] [Impact Index Per Article: 24.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common, progressive liver disease that affects up to one-quarter of the adult population worldwide. The clinical and economic burden of NAFLD is mainly due to liver-related morbidity and mortality (nonalcoholic steatohepatitis, cirrhosis or hepatocellular carcinoma) and an increased risk of developing fatal and nonfatal cardiovascular disease, chronic kidney disease and certain types of extrahepatic cancers (for example, colorectal cancer and breast cancer). Additionally, there is now accumulating evidence that NAFLD adversely affects not only the coronary arteries (promoting accelerated coronary atherosclerosis) but also all other anatomical structures of the heart, conferring an increased risk of cardiomyopathy (mainly left ventricular diastolic dysfunction and hypertrophy, leading to the development of congestive heart failure), cardiac valvular calcification (mainly aortic-valve sclerosis), cardiac arrhythmias (mainly atrial fibrillation) and some cardiac conduction defects. This Review focuses on the association between NAFLD and non-ischaemia-related cardiac disease, discusses the putative pathophysiological mechanisms and briefly summarizes current treatment options for NAFLD that might also beneficially affect cardiac disease.
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Targher G, Lonardo A, Byrne CD. Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus. Nat Rev Endocrinol 2018; 14:99-114. [PMID: 29286050 DOI: 10.1038/nrendo.2017.173] [Citation(s) in RCA: 285] [Impact Index Per Article: 40.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus are common diseases that often coexist and might act synergistically to increase the risk of hepatic and extra-hepatic clinical outcomes. NAFLD affects up to 70-80% of patients with type 2 diabetes mellitus and up to 30-40% of adults with type 1 diabetes mellitus. The coexistence of NAFLD and diabetes mellitus increases the risk of developing not only the more severe forms of NAFLD but also chronic vascular complications of diabetes mellitus. Indeed, substantial evidence links NAFLD with an increased risk of developing cardiovascular disease and other cardiac and arrhythmic complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus. NAFLD is also associated with an increased risk of developing microvascular diabetic complications, especially chronic kidney disease. This Review focuses on the strong association between NAFLD and the risk of chronic vascular complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus, thereby promoting an increased awareness of the extra-hepatic implications of this increasingly prevalent and burdensome liver disease. We also discuss the putative underlying mechanisms by which NAFLD contributes to vascular diseases, as well as the emerging role of changes in the gut microbiota (dysbiosis) in the pathogenesis of NAFLD and associated vascular diseases.
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Affiliation(s)
- Giovanni Targher
- Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Stefani 1, 37126 Verona, Italy
| | - Amedeo Lonardo
- Azienda Ospedaliera Universitaria di Modena, Ospedale Civile Sant'Agostino Estense, Via Giardini 1355, 41126 Baggiovara, Modena, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, Institute of Developmental Sciences (IDS), MP887, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
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Piontek K, Schmidt CO, Baumeister SE, Lerch MM, Mayerle J, Dörr M, Felix SB, Völzke H. Is hepatic steatosis associated with left ventricular mass index increase in the general population? World J Hepatol 2017; 9:857-866. [PMID: 28740597 PMCID: PMC5504361 DOI: 10.4254/wjh.v9.i19.857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 12/31/2016] [Accepted: 04/20/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the association between hepatic steatosis and change in left ventricular mass index (LVMI) over five years, and examine whether systolic and diastolic blood pressures are mediators of the association between hepatic steatosis and LVMI using a general population sample.
METHODS We analyzed data from the Study of Health in Pomerania. The study population comprised 1298 individuals aged 45 to 81 years. Hepatic steatosis was defined as the presence of a hyperechogenic pattern of the liver together with elevated serum alanine transferase levels. Left ventricular mass was determined echocardiographically and indexed to height2.7. Path analyses were conducted to differentiate direct and indirect paths from hepatic steatosis to LVMI encompassing systolic and diastolic blood pressure as potential mediating variables.
RESULTS Hepatic steatosis was a significant predictor for all measured echocardiographic characteristics at baseline. Path analyses revealed that the association of hepatic steatosis with LVMI change after five years was negligibly small (β = -0.12, s.e. = 0.21, P = 0.55). Systolic blood pressure at baseline was inversely associated with LVMI change (β = -0.09, s.e. = 0.03, P < 0.01), while no association between diastolic blood pressure at baseline and LVMI change was evident (β = 0.03, s.e. = 0.05, P = 0.56). The effect of the indirect path from hepatic steatosis to LVMI via systolic baseline blood pressure was small (β = -0.20, s.e. = 0.10, P = 0.07). No indirect effect was observed for the path via diastolic baseline blood pressure (β = 0.03, s.e. = 0.06, P = 0.60). Similar associations were observed in the subgroup of individuals not receiving beta-blockers, calcium channel blockers, or drugs acting on the renin-angiotensin system.
CONCLUSION Baseline associations between hepatic steatosis and LVMI do not extend to associations with LVMI change after five years. More studies are needed to study the longitudinal effects of hepatic steatosis on LVMI.
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Mangi MA, Rehman H, Minhas AM, Rafique M, Bansal V, Constantin J. Non-Alcoholic Fatty Liver Disease Association with Cardiac Arrhythmias. Cureus 2017; 9:e1165. [PMID: 28507837 PMCID: PMC5429146 DOI: 10.7759/cureus.1165] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become a public health burden all over the world. A significant percentage of the patients with NAFLD have a co-existing metabolic syndrome that is a risk factor for cardiovascular disease. Clinical as well as epidemiological research shows that NAFLD is not simply related to liver-related morbidity and mortality but is also associated with an elevated risk of coronary heart disease (CHD), irregularities of cardiac function as well as cardiac structure, valvular heart disease, and arrhythmias. Animal studies suggest that NAFLD by itself exacerbates systemic/hepatic insulin resistance, leads to atherogenic dyslipidemia and generates a number of pro-inflammatory, pro-coagulant and profibrogenic mediators which play an essential role in the pathophysiology of cardiac abnormalities including arrhythmias. Hence, it is suggested that the patients with NAFLD may derive benefit from intensive monitoring and treatment methods to reduce the risk of CHD along with other cardiac/arrhythmic complications. The intent of this clinical review is to sum up the quickly increasing body of evidence that provides support for a robust relationship between NAFLD and cardiac arrhythmias and to present the putative biological mechanisms underlying this correlation.
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Affiliation(s)
| | - Hiba Rehman
- GME Internal Medicine, Orange Park Medical Center
| | | | | | - Vikas Bansal
- Critical Care Medicine , Mayo Clinic Jacksonville, Fl
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Käräjämäki AJ, Bloigu R, Kauma H, Kesäniemi YA, Koivurova OP, Perkiömäki J, Huikuri H, Ukkola O. Non-alcoholic fatty liver disease with and without metabolic syndrome: Different long-term outcomes. Metabolism 2017; 66:55-63. [PMID: 27423871 DOI: 10.1016/j.metabol.2016.06.009] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Revised: 06/20/2016] [Accepted: 06/21/2016] [Indexed: 12/21/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are both shown to increase the risk of cardiovascular diseases and type 2 diabetes. However, there is a great overlap between these two diseases. The present study was aimed to examine the cardiovascular and metabolic prognosis of non-alcoholic fatty liver disease with and without metabolic syndrome. METHODS Middle-aged subjects (n=958) were divided into four subgroups, those with NAFLD and MetS, those with NAFLD or MetS, and healthy controls. The baseline characteristics of the subgroups were analyzed. The follow-up time for cardiovascular events was about 16years. After approximately 21years the cardiac ultrasound and laboratory parameters were re-analyzed and new type 2 diabetes cases were recorded. RESULTS Those with both diseases were at the greatest risk for cardiovascular events (p<0.001). Compared to healthy controls, only those with MetS, with or without NAFLD, were at increased risk for the development of type 2 diabetes (p<0.001) and for an increase in left ventricular mass index (p=0.001 and p=0.005, respectively). The cardiovascular and metabolic risk in subjects with NAFLD only was quite similar to that in healthy controls. The I148M variant of the patatin-like phospholipase domain-containing 3 gene (PNPLA3 polymorphism) was most present in those with NAFLD only (p=0.008). CONCLUSIONS NAFLD with MetS implies a considerable risk for cardiovascular diseases, type 2 diabetes and the increase of left ventricular mass index whereas NAFLD without MetS does not.
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Affiliation(s)
- Aki Juhani Käräjämäki
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland
| | - Risto Bloigu
- Medical Informatics and Statistics Research Group, University of Oulu, Oulu, Finland
| | - Heikki Kauma
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland
| | - Y Antero Kesäniemi
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland
| | - Olli-Pekka Koivurova
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland
| | - Juha Perkiömäki
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland
| | - Heikki Huikuri
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland
| | - Olavi Ukkola
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland.
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Polyzos SA, Bugianesi E, Kountouras J, Mantzoros CS. Nonalcoholic fatty liver disease: Updates on associations with the metabolic syndrome and lipid profile and effects of treatment with PPAR-γ agonists. Metabolism 2017; 66:64-68. [PMID: 27594084 DOI: 10.1016/j.metabol.2016.08.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 08/03/2016] [Indexed: 02/08/2023]
Affiliation(s)
- Stergios A Polyzos
- Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Greece.
| | - Elisabetta Bugianesi
- Division of Gastroenterology, Department of Medical Sciences, University of Torino, Italy
| | - Jannis Kountouras
- Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Greece
| | - Christos S Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA
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Cardiovascular Disease and Myocardial Abnormalities in Nonalcoholic Fatty Liver Disease. Dig Dis Sci 2016; 61:1246-67. [PMID: 26809873 DOI: 10.1007/s10620-016-4040-6] [Citation(s) in RCA: 85] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2015] [Accepted: 01/11/2016] [Indexed: 02/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in many developed countries, affecting an estimated 30 % of the adult population. In this updated clinical review, we summarize the current knowledge regarding the strong association between NAFLD and the risk of coronary heart disease (CHD) and other functional, structural, and arrhythmic cardiac complications (e.g., left ventricular dysfunction, heart valve diseases and atrial fibrillation). We also briefly discuss the putative biological mechanisms linking NAFLD with these important extra-hepatic complications. To date, a large body of evidence has suggested that NAFLD is not simply a marker of CHD and other functional, structural, and arrhythmic cardiac complications, but also may play a part in the development and progression of these cardiac complications. The clinical implication of these findings is that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions aimed at decreasing the risk of CHD and other cardiac and arrhythmic complications.
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Blood pressure is associated with the presence and severity of nonalcoholic fatty liver disease across the spectrum of cardiometabolic risk. J Hypertens 2016; 33:1207-14. [PMID: 25693058 DOI: 10.1097/hjh.0000000000000532] [Citation(s) in RCA: 95] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
OBJECTIVES To determine the relationship between clinically relevant blood pressure (BP) groups and nonalcoholic fatty liver disease (NAFLD) presence and severity especially in the milieu of other metabolic risk factors. PATIENTS AND METHODS From a Brazilian cohort of 5362 healthy middle-aged men and women who presented for yearly physical examination and testing, the cross-sectional relationship between BP categories and NAFLD was assessed. BP groups were categorized as normal, prehypertension (PHT), and hypertension (HTN) according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classification. NAFLD was ultrasound diagnosed, excluding persons with alcohol consumption more than 20 g/day. NAFLD severity was estimated using the Fibrosis-4 (FIB-4) risk score. RESULTS The prevalence of NAFLD was 36.2%. Participants with NAFLD were older (mean 46 vs. 42 years, P < 0.001) and had elevated BMI (mean 29.0 vs. 24.7 kg/m, P < 0.001). The prevalence of NAFLD among persons with normal BP, PHT, and HTN was 16.5, 37.5, and 59.3%, respectively. In multivariate analyses, PHT and HTN were associated with elevated odds of NAFLD (PHT-adjusted odds ratio 1.3, 95% confidence interval 1.1, 1.6; HTN-adjusted odds ratio 1.8, 95% confidence interval 1.4-2.3) compared with normal BP. Among nonobese hypertensive patients, BP control (BP < 140/90 mmHg) was independently associated with 40% lower odds of prevalent NAFLD. Compared with hypertensive patients, both normotensive individuals and prehypertensive patients were more likely to have a low fibrosis risk (FIB-4 ≥ 1.3). CONCLUSION Prevalent NAFLD may be seen early in the development of hypertension, even in the absence of other metabolic risk factors. Controlling BP among nonobese hypertensive patients may be beneficial in preventing or limiting NAFLD.
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Association of Nonalcoholic Fatty Liver Disease with Subclinical Cardiovascular Changes: A Systematic Review and Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2015; 2015:213737. [PMID: 26273598 PMCID: PMC4529899 DOI: 10.1155/2015/213737] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Revised: 02/13/2015] [Accepted: 02/18/2015] [Indexed: 02/06/2023]
Abstract
In the last 20 years, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide, primarily as a result of the epidemic of obesity. NAFLD is strongly associated with insulin resistance, glucose intolerance, and dyslipidemia and is currently regarded as the liver manifestation of the metabolic syndrome, a highly atherogenic condition even at a very early age. Patients with NAFLD including pediatric subjects have a higher prevalence of subclinical atherosclerosis, as shown by impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, which are independent of obesity and other established risk factors. More recent work has identified NAFLD as a risk factor not only for premature coronary heart disease and cardiovascular events, but also for early subclinical abnormalities in myocardial structure and function. Thus, we conducted a systematic review and meta-analysis to test the hypothesis that NAFLD is associated with evidence of subclinical cardiac structural and functional abnormalities.
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Serum alanine aminotransferase predicts interventricular septum thickness and left ventricular mass in patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2014; 26:654-60. [PMID: 24667349 DOI: 10.1097/meg.0000000000000086] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Alanine aminotransferase (ALT) is a marker of nonalcoholic fatty liver disease (NAFLD) and predicts type 2 diabetes mellitus (DM2) as well as coronary events independently of traditional risk factors and the features of the metabolic syndrome. The extent to which interventricular septum thickness (IVS) and left ventricular mass (LVM) are associated with ALT levels in cohorts of individuals with body weights ranging from overweight to morbid obesity and NAFLD remains still unknown. MATERIALS AND METHODS This was a cross-sectional pilot study involving 151 young White participants with liver ultrasound-proven NAFLD. Standard echocardiograms were used to define LVM, IVS, and left ventricle diastolic function [mitral inflow velocity pattern (E/A ratio) and mitral annulus velocity by tissue Doppler imaging (Em/Am ratio)]. Participants were classified according to ALT quartiles: p25, p50, p75, and p100. RESULTS The study included 36 men and 115 women with an age of 38.4 ± 0.7 years and BMI of 43.9 ± 0.6 kg/m2. p100 participants disclosed significantly higher homeostasis model assessment (P=0.003), DM2 (P=0.002), and hypertension (P=0.01) prevalence, whereas LVM, IVS, E/A, and Em/Am ratios were significantly higher in this group when compared with their p25 peers (P<0.01). IVS's and LVM's variance were significantly predicted by the statistical models including ALT independently of BMI, hypertension, and DM2. CONCLUSION ALT levels predict both IVS and LVM in NAFLD individuals irrespective of their BMI, DM2, hypertension, age, and sex. ALT levels behave as a surrogate marker of left ventricular hypertrophy in overweight and/or obese NAFLD patients. Hence, it seems worth obtaining cardiac ultrasounds in NAFLD patients with elevated ALT levels.
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Kim NH, Park J, Kim SH, Kim YH, Kim DH, Cho GY, Baik I, Lim HE, Kim EJ, Na JO, Lee JB, Lee SK, Shin C. Non-alcoholic fatty liver disease, metabolic syndrome and subclinical cardiovascular changes in the general population. Heart 2014; 100:938-43. [PMID: 24721975 DOI: 10.1136/heartjnl-2013-305099] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE The effect of non-alcoholic fatty liver disease (NAFLD) on cardiovascular system remains controversial. We investigated the independent contribution of NAFLD to cardiovascular structure and function in the general population. METHODS A total of 1886 participants without known cardiovascular disease were enrolled from the Korean Genome Epidemiology Study. The participants were divided into four groups, based on the presence of NAFLD, metabolic syndrome (MetS), neither or both. NAFLD was diagnosed by CT. Changes in cardiovascular structure and function were assessed by tissue Doppler imaging (TDI) echocardiography, carotid ultrasound and brachial-ankle pulse wave velocity (baPWV). RESULTS In multivariate analyses, subjects with both NAFLD and MetS had a higher E/Ea ratio and baPWV, as well as a lower TDI Ea velocity (all p<0.001) than those with neither NAFLD nor MetS. Subjects with either NAFLD or MetS also showed significant differences in TDI Ea velocity and baPWV (all p<0.05). However, no significant differences of carotid intima-media thickness (CIMT) values were seen among the four groups. Multivariate linear regression revealed that both NAFLD and MetS were independent predictors of TDI Ea velocity and baPWV (all p<0.001). Both MetS and NAFLD were not a determinant of CIMT. CONCLUSIONS NAFLD was associated with early alterations of cardiovascular system, independent of established cardiovascular risk factors and MetS.
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Affiliation(s)
- Nan Hee Kim
- Division of Endocrinology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Juri Park
- Division of Endocrinology, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea
| | - Seong Hwan Kim
- Division of Cardiology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Yong Hyun Kim
- Division of Cardiology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Dong Hyuk Kim
- Division of Cardiology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Goo-Yeong Cho
- Division of Cardiology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Inkyung Baik
- Department of Foods and Nutrition, College of Natural Sciences, Kookmin University, Seoul, Korea
| | - Hong Euy Lim
- Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
| | - Eung Ju Kim
- Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
| | - Jin Oh Na
- Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
| | - Jung Bok Lee
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, Seoul, Korea
| | - Seung Ku Lee
- Institute of Human Genomic Study, Korea University Ansan Hospital, Ansan, Korea
| | - Chol Shin
- Institute of Human Genomic Study, Korea University Ansan Hospital, Ansan, Korea
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Lai YC, Cheng BC, Hwang JC, Lee YT, Chiu CH, Kuo LC, Chen JB. Association of fatty liver disease with nonfatal cardiovascular events in patients undergoing maintenance hemodialysis. Nephron Clin Pract 2014; 124:218-23. [PMID: 24503573 DOI: 10.1159/000357952] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2013] [Accepted: 11/29/2013] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND/AIMS The prevalence of cardiovascular (CV) disease in patients undergoing maintenance hemodialysis (HD) is reportedly higher than that in healthy individuals. In the present study, we aimed to investigate whether ultrasonographically documented fatty liver disease (FLD) is an independent risk factor for nonfatal CV events in patients undergoing HD. METHODS A retrospective cohort study was conducted in a medical center in southern Taiwan. The medical records of 490 patients undergoing HD who were enrolled between July 1998 and October 2012 were screened. Finally, 278 patients who had undergone hepatic ultrasonography and had available data were recruited in the present study. The patients included 130 men and 148 women; their mean age was 59.9 years. The primary endpoint was nonfatal CV events in the observation period. The comparable data included epidemiological, hematological, and biochemical profiles. A time-dependent statistical method was used to analyze the associated factors. RESULTS The prevalence of nonfatal CV events was significantly increased in the patients with FLD compared with those without FLD (CV events: 32 vs. 18%, respectively; p = 0.008). After adjusting for associated risk factors (sex, age, body mass index, smoking, diabetes, hypertension, dyslipidemia, and Kt/V), multivariate analyses identified FLD (CV events: hazard ratio 2.84, 95% confidence interval 1.52-5.28, p = 0.001), advanced age, and diabetes to be independently associated with nonfatal CV events. CONCLUSION The study suggests that FLD was an independent risk factor for nonfatal CV events in patients undergoing maintenance HD.
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Affiliation(s)
- Yu-Cheng Lai
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC
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Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in western countries and is closely related to the metabolic syndrome. When NAFLD is associated with hepatocellular damage and inflammation (non-alcoholic steatohepatitis [NASH]) it can lead to severe liver disease. However, it has become clear that NAFLD is also associated with an increased risk of cardiovascular disease (CVD), independently of classical known risk factors for the latter. In the current review we briefly summarise the current clinical evidence on the role of NAFLD in CVD and discuss the potential mechanisms by which NAFLD can be linked to the pathophysiology of CVD.
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Affiliation(s)
- Sven M Francque
- Department of Gastroenterology Hepatology, University Hospital Antwerp & Laboratory of Experimental Medicine and Paediatrics, Division of Gastroenterology Hepatology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
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