1
|
Mai X, Li M, Jin X, Huang S, Xu M, Yan B, Wei Y, Long X, Wu Y, Mo Z. Identification of a Risk-Prediction Model for Hypertension Patients Concomitant with Nonalcoholic Fatty Liver Disease. Healthcare (Basel) 2025; 13:969. [PMID: 40361747 PMCID: PMC12071756 DOI: 10.3390/healthcare13090969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 04/07/2025] [Accepted: 04/18/2025] [Indexed: 05/15/2025] Open
Abstract
Objective: Our study aims to develop a personalized nomogram model for predicting the risk of nonalcoholic fatty liver disease (NAFLD) in hypertension (HTN) patients and further validate its effectiveness. Methods: A total of 1250 hypertensive (HTN) patients from Guangxi, China, were divided into a training group (875 patients, 70%) and a validation set (375 patients, 30%). LASSO regression, in combination with univariate and multivariate logistic regression analyses, was used to identify predictive factors associated with nonalcoholic fatty liver disease (NAFLD) in HTN patients within the training set. Subsequently, the performance of an NAFLD nomogram prediction model was evaluated in the separate validation group, including assessments of differentiation ability, calibration performance, and clinical applicability. This was carried out using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: The risk-prediction model for the HTN patients concomitant with NAFLD included oral antidiabetic drugs (OADs) (OR = 2.553, 95% CI: 1.368-4.763), antihypertensives (AHs) (OR = 7.303, 95% CI: 4.168-12.794), body mass index (BMI) (OR = 1.145, 95% CI: 1.084-1.209), blood urea nitrogen (BUN) (OR = 0.924, 95% CI: 0.860-0.992), triglycerides (TGs) (OR = 1.474, 95% CI: 1.201-1.809), aspartate aminotransferase (AST) (OR = 1.061, 95% CI: 1.018-1.105), and AST/ALT ratio (AAR) (OR = 0.249, 95% CI: 0.121-0.514) as significant predictors. The AUC of the NAFLD risk-prediction model in the training set and the validation set were 0.816 (95% CI: 0.785-0.847) and 0.794 (95% CI: 0.746-0.842), respectively. The Hosmer-Lemeshow test showed that the model has a good goodness-of-fit (p-values were 0.612 and 0.221). DCA suggested the net benefit of using a nomogram to predict the risk of HTN patients concomitant with NAFLD is higher. These results suggested that the model showed moderate predictive ability and good calibration. Conclusions: BMI, OADs, AHs, BUN, TGs, AST, and AAR were independent influencing factors of HTN combined with NAFLD, and the risk prediction model constructed based on this could help to identify the high-risk group of HTN combined with NAFLD at an early stage and guide the development of interventions. Larger cohorts with multiethnic populations are essential to verify our findings.
Collapse
Affiliation(s)
- Xiaoyou Mai
- School of Public Health, Guangxi Medical University, Nanning 530021, China; (X.M.); (Y.W.); (X.L.)
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
| | - Mingli Li
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
| | - Xihui Jin
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
- Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530021, China
| | - Shengzhu Huang
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
| | - Mingjie Xu
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
- Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530021, China
| | - Boteng Yan
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
- Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530021, China
| | - Yushuang Wei
- School of Public Health, Guangxi Medical University, Nanning 530021, China; (X.M.); (Y.W.); (X.L.)
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
| | - Xinyang Long
- School of Public Health, Guangxi Medical University, Nanning 530021, China; (X.M.); (Y.W.); (X.L.)
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
| | - Yongxian Wu
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
- Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530021, China
| | - Zengnan Mo
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
- Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530021, China
| |
Collapse
|
2
|
Bansal B, Lajeunesse-Trempe F, Keshvani N, Lavie CJ, Pandey A. Impact of Metabolic Dysfunction-associated Steatotic Liver Disease on Cardiovascular Structure, Function, and the Risk of Heart Failure. Can J Cardiol 2025:S0828-282X(25)00315-0. [PMID: 40258400 DOI: 10.1016/j.cjca.2025.04.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Revised: 04/01/2025] [Accepted: 04/10/2025] [Indexed: 04/23/2025] Open
Abstract
Mounting evidence has established metabolic dysfunction-associated steatotic liver disease (MASLD) as an independent risk factor for heart failure (HF), particularly HF with preserved ejection fraction (HFpEF). In this narrative review we explore the impact of MASLD on cardiovascular structure and function. We summarize findings from multiple cohort studies demonstrating that MASLD is associated with distinct patterns of adverse cardiac remodeling, including increased left ventricular concentricity and impaired diastolic function. These subclinical changes in cardiac structure and function often precede overt HF development and appear to occur in the context of multiple interconnected pathways involving metabolic dysfunction, systemic inflammation, adipose tissue dysregulation, vascular dysfunction, and altered hepatic hemodynamics. Early identification of cardiac structural and functional abnormalities through systematic screening may enable timely intervention in this high-risk population. Lifestyle modifications remain foundational, but achieving and maintaining significant weight loss is challenging. Recent clinical trials have shown promising results with cardiometabolic agents, particularly glucagon-like protein 1 receptor agonists, which demonstrate significant weight loss and hepatic and cardiovascular benefits. Despite these advances, key knowledge gaps remain regarding optimal screening strategies, mechanisms linking MASLD to HF, and targeted therapeutic approaches. Addressing these gaps will be essential for developing effective prevention and treatment strategies in this high-risk population.
Collapse
Affiliation(s)
- Bhavik Bansal
- All India Institute of Medical Sciences, New Delhi, India; Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Fannie Lajeunesse-Trempe
- Department of Internal Medicine, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec City, Québec, Canada
| | - Neil Keshvani
- Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Baylor Scott and White Research Institute, Dallas, Texas, USA; Baylor Scott & White The Heart Hospital, Plano, Texas, USA
| | - Carl J Lavie
- Department of Cardiovascular Diseases and Internal Medicine, Ochsner Clinic Foundation, New Orleans, Louisiana, USA
| | - Ambarish Pandey
- Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
| |
Collapse
|
3
|
Pecani M, Andreozzi P, Cangemi R, Corica B, Miglionico M, Romiti GF, Stefanini L, Raparelli V, Basili S. Metabolic Syndrome and Liver Disease: Re-Appraisal of Screening, Diagnosis, and Treatment Through the Paradigm Shift from NAFLD to MASLD. J Clin Med 2025; 14:2750. [PMID: 40283580 PMCID: PMC12028215 DOI: 10.3390/jcm14082750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 04/11/2025] [Accepted: 04/12/2025] [Indexed: 04/29/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), encompasses a spectrum of liver diseases characterized by hepatic steatosis, the presence of at least one cardiometabolic risk factor, and no other apparent cause. Metabolic syndrome (MetS) is a cluster of clinical conditions associated with increased risk of cardiovascular disease, type 2 diabetes, and overall morbidity and mortality. This narrative review summarizes the changes in the management of people with MetS and NAFLD/MASLD from screening to therapeutic strategies that have occurred in the last decades. Specifically, we underline the clinical importance of considering the different impacts of simple steatosis and advanced fibrosis and provide an up-to-date overview on non-invasive diagnostic tests (i.e., imaging and serum biomarkers), which now offer acceptable accuracy and are globally more accessible. Early detection of MetS and MASLD is a top priority as it allows for timely interventions, primarily through lifestyle modification. The liver and cardiovascular benefits of a global and multidimensional approach are not negligible. Therefore, a holistic approach to both conditions, MetS and related chronic liver disease, should be applied to improve overall health and longevity.
Collapse
Affiliation(s)
- Marin Pecani
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
| | - Paola Andreozzi
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Roberto Cangemi
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Bernadette Corica
- Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Polyclinic of Modena, 41121 Modena, Italy
| | - Marzia Miglionico
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
| | - Giulio Francesco Romiti
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Lucia Stefanini
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Valeria Raparelli
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Stefania Basili
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| |
Collapse
|
4
|
Zisis M, Chondrogianni ME, Androutsakos T, Rantos I, Oikonomou E, Chatzigeorgiou A, Kassi E. Linking Cardiovascular Disease and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): The Role of Cardiometabolic Drugs in MASLD Treatment. Biomolecules 2025; 15:324. [PMID: 40149860 PMCID: PMC11940321 DOI: 10.3390/biom15030324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 02/14/2025] [Accepted: 02/19/2025] [Indexed: 03/29/2025] Open
Abstract
The link between cardiovascular disease (CVD) and metabolic dysfunction-associated steatotic liver disease (MASLD) is well-established at both the epidemiological and pathophysiological levels. Among the common pathophysiological mechanisms involved in the development and progression of both diseases, oxidative stress and inflammation, insulin resistance, lipid metabolism deterioration, hepatokines, and gut dysbiosis along with genetic factors have been recognized to play a pivotal role. Pharmacologic interventions with drugs targeting common modifiable cardiometabolic risk factors, such as T2DM, dyslipidemia, and hypertension, are a reasonable strategy to prevent CVD development and progression of MASLD. Recently, a novel drug for metabolic dysfunction-associated steatohepatitis (MASH), resmetirom, has shown positive effects regarding CVD risk, opening new opportunities for the therapeutic approach of MASLD and CVD. This review provides current knowledge on the epidemiologic association of MASLD to CVD morbidity and mortality and enlightens the possible underlying pathophysiologic mechanisms linking MASLD with CVD. The role of cardiometabolic drugs such as anti-hypertensive drugs, hypolipidemic agents, glucose-lowering medications, acetylsalicylic acid, and the thyroid hormone receptor-beta agonist in the progression of MASLD is also discussed. Metformin failed to prove beneficial effects in MASLD progression. Studies on the administration of thiazolinediones in MASLD suggest effectiveness in improving steatosis, steatohepatitis, and fibrosis, while newer categories of glucose-lowering agents such as GLP-1Ra and SGLT-2i are currently being tested for their efficacy across the whole spectrum of MASLD. Statins alone or in combination with ezetimibe have yielded promising results. The conduction of long-duration, large, high-quality, randomized-controlled trials aiming to assess by biopsy the efficacy of cardiometabolic drugs to reverse MASLD progression is of great importance.
Collapse
Affiliation(s)
- Marios Zisis
- Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, 11527 Athens, Greece; (M.Z.); (I.R.)
| | - Maria Eleni Chondrogianni
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
- Endocrine Unit, 1st Department of Propaedeutic and Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Theodoros Androutsakos
- Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str., 11527 Athens, Greece;
| | - Ilias Rantos
- Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, 11527 Athens, Greece; (M.Z.); (I.R.)
| | - Evangelos Oikonomou
- 3rd Department of Cardiology, “Sotiria” Thoracic Diseases Hospital of Athens, University of Athens Medical School, 11527 Athens, Greece;
| | - Antonios Chatzigeorgiou
- Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str., 11527 Athens, Greece;
| | - Eva Kassi
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
- Endocrine Unit, 1st Department of Propaedeutic and Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
| |
Collapse
|
5
|
Kipp ZA, Badmus OO, Stec DE, Hall B, Hinds TD. Bilirubin bioconversion to urobilin in the gut-liver-kidney axis: A biomarker for insulin resistance in the Cardiovascular-Kidney-Metabolic (CKM) Syndrome. Metabolism 2025; 163:156081. [PMID: 39580049 DOI: 10.1016/j.metabol.2024.156081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 10/17/2024] [Accepted: 11/16/2024] [Indexed: 11/25/2024]
Abstract
The rising rates of obesity worldwide have increased the incidence of cardiovascular disease (CVD), making it the number one cause of death. Higher plasma bilirubin levels have been shown to prevent metabolic dysfunction and CVD. However, reducing levels leads to deleterious outcomes, possibly due to reduced bilirubin half-life that escalates the production of its catabolized product, urobilinogen, produced by gut bacteria and naturally oxidized to urobilin. Recent findings suggest that the involvement of the microbiome catabolism of bilirubin to urobilin and its absorption via the hepatic portal vein contributes to CVD, suggesting a liver-gut axis involvement. We discuss the studies that demonstrate that urobilin is frequently raised in the urine of persons with CVD and its probable role in acquiring the disease. Urobilin is excreted from the kidneys into the urine and may serve as a biomarker for Cardiovascular-Kidney-Metabolic (CKM) Syndrome. We deliberate on the newly discovered bilirubin reductase (BilR) bacterial enzyme that produces urobilin. We discuss the bacterial species expressing BilR, how they impact CVD, and whether suppressing urobilin production and increasing bilirubin may provide new therapeutic strategies for CKM. Possible therapeutic mechanisms for achieving this goal are discussed.
Collapse
Affiliation(s)
- Zachary A Kipp
- Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Olufunto O Badmus
- Department of Physiology and Biophysics, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS, USA
| | - David E Stec
- Department of Physiology and Biophysics, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS, USA
| | - Brantley Hall
- Center for Bioinformatics and Computational Biology, Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA
| | - Terry D Hinds
- Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA.
| |
Collapse
|
6
|
Gao Z, Deng H, Qin B, Bai L, Li J, Zhang J. Impact of hypertension on liver fibrosis in patients with metabolic dysfunction-associated fatty liver disease. Front Med (Lausanne) 2025; 12:1539283. [PMID: 39911867 PMCID: PMC11794791 DOI: 10.3389/fmed.2025.1539283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 01/07/2025] [Indexed: 02/07/2025] Open
Abstract
Background This study aims to evaluate the association between hypertension and the risk of fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD) patients, as well as to investigate the impact of hypertension on the progression of liver fibrosis within this population. Methods We utilized data from the NHANES 2017 to March 2020. Multivariate logistic regression models were employed to control for sociodemographic and metabolic factors to determine the associations between hypertension, MASLD, and fibrosis. Results Of the total cohort (N = 5,967) 57.92% had hypertension, 38.8% had MASLD, 25.88% had both MASLD and hypertension. Patients with MASLD were more likely to have hypertension (64.24% vs. 44.80%). There was a significant association between stage I (OR1.70, 95% CI: 1.15-2.53) and stage II hypertension (OR1.98, 95% CI: 1.38-2.85) and an increased risk of SF. After adjusting for multiple confounding factors, stage I (OR1.59, 95% CI: 1.09-2.24) and stage II hypertension (OR1.48, 95% CI: 1.06-2.06) remained significantly associated with the risk of SF. Patients with both MASLD and hypertension had higher rates of SF at 14.83% and AF at 7.47%. After adjusting for sociodemographic factors, those patients still had an 8.02-fold increased risk of SF (OR8.02, 95% CI: 4.47-14.39) and a 15.13-fold increased risk of AF (OR15.13, 95% CI: 7.09-32.3). Further adjustment for metabolic factors, those patients still had a significantly higher risk of SF (OR3.07, 95% CI: 1.83-5.14) and AF (OR4.01, 95% CI: 1.48-10.89). Conclusion MASLD and hypertension are at risk for fibrosis, and the coexistence of the two has a more significant impact on the risk of fibrosis.
Collapse
Affiliation(s)
- Zhifeng Gao
- Department of General Surgery Unit-4, The Second Affiliated Hospital of Xi’an, Jiaotong University Xi’an, Xi'an, Shaanxi, China
| | - Huan Deng
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China
| | - Bowen Qin
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China
| | - Liang Bai
- Department of General Surgery Unit-4, The Second Affiliated Hospital of Xi’an, Jiaotong University Xi’an, Xi'an, Shaanxi, China
| | - Jiangwei Li
- Department of General Surgery Unit-4, The Second Affiliated Hospital of Xi’an, Jiaotong University Xi’an, Xi'an, Shaanxi, China
| | - Jian Zhang
- Department of General Surgery Unit-4, The Second Affiliated Hospital of Xi’an, Jiaotong University Xi’an, Xi'an, Shaanxi, China
| |
Collapse
|
7
|
Doustmohammadian A, Zamani F, Hébert JR, Moradi-Lakeh M, Esfandyiari S, Amirkalali B, Motamed N, Maadi M, Price S, Gholizadeh E, Ajdarkosh H. Exploring the link between dietary inflammatory index and NAFLD through a structural equation modeling approach. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2024; 43:224. [PMID: 39719637 DOI: 10.1186/s41043-024-00721-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Accepted: 12/14/2024] [Indexed: 12/26/2024]
Abstract
Nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global public health dilemma with wide-ranging social and economic implications. Diet and lifestyle modifications remain essential components of NAFLD management. The current study investigated the association between diet-related inflammation and NAFLD among 3110 Iranian adults participating in the Amol Cohort Study (AmolCS), employing the Structural Equation Modeling (SEM) approach.The inflammatory potential of the diet was quantified using an energy-adjusted dietary index (E-DII) score. Findings showed that in the total sample and separately in males, the E-DII score had a significant effect on NAFLD, with mediation through hypertension (βstandardized = 0.16, and 0.13, p < 0.001, respectively) and c-reactive protein (CRP) (βstandardized = 0.07, and 0.07, p < 0.001, respectively). In the total sample and separately in females, the E-DII score significantly affected NAFLD, with mediation through diabetes (βstandardized = 0.06, p < 0.001, and 0.07, p = 0.006, respectively). In full and both gender-specific models, dyslipidemia was a risk factor for NAFLD and partially mediated the effect of hypertension on NAFLD.The current study concluded a mediated association between dietary inflammation and NAFLD through hypertension, CRP, diabetes, and dyslipidemia, suggesting further longitudinal studies, especially in high-risk populations. These findings underscore the complex interplay between diet, inflammation, and NAFLD in Iranian adults.
Collapse
Affiliation(s)
- Azam Doustmohammadian
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Farhad Zamani
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - James R Hébert
- Cancer Prevention & Control Program, University of South Carolina, Columbia, SC, 29208, USA
- Department of Epidemiology & Biostatistics, University of South Carolina, Columbia, SC, 29208, USA
| | - Maziar Moradi-Lakeh
- Preventive Medicine and Public Health Research Center, Psychosocial Health Research Institute, University of Medical Sciences, Tehran, Iran
| | - Sepideh Esfandyiari
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahareh Amirkalali
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Nima Motamed
- Department of Social Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mansooreh Maadi
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Sherry Price
- Cancer Prevention & Control Program, University of South Carolina, Columbia, SC, 29208, USA
- Department of Epidemiology & Biostatistics, University of South Carolina, Columbia, SC, 29208, USA
| | - Esmaeel Gholizadeh
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Ajdarkosh
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
8
|
Minetti ET, Hamburg NM, Matsui R. Drivers of cardiovascular disease in metabolic dysfunction-associated steatotic liver disease: the threats of oxidative stress. Front Cardiovasc Med 2024; 11:1469492. [PMID: 39411175 PMCID: PMC11473390 DOI: 10.3389/fcvm.2024.1469492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 08/30/2024] [Indexed: 10/19/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), now known as metabolic-associated steatotic liver disease (MASLD), is the most common liver disease worldwide, with a prevalence of 38%. In these patients, cardiovascular disease (CVD) is the number one cause of mortality rather than liver disease. Liver abnormalities per se due to MASLD contribute to risk factors such as dyslipidemia and obesity and increase CVD incidents. In this review we discuss hepatic pathophysiological changes the liver of MASLD leading to cardiovascular risks, including liver sinusoidal endothelial cells, insulin resistance, and oxidative stress with a focus on glutathione metabolism and function. In an era where there is an increasingly robust recognition of what causes CVD, such as the factors included by the American Heart Association in the recently developed PREVENT equation, the inclusion of liver disease may open doors to how we approach treatment for MASLD patients who are at risk of CVD.
Collapse
Affiliation(s)
| | | | - Reiko Matsui
- Whitaker Cardiovascular Institute, Section of Vascular Biology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United States
| |
Collapse
|
9
|
Zheng H, Sechi LA, Navarese EP, Casu G, Vidili G. Metabolic dysfunction-associated steatotic liver disease and cardiovascular risk: a comprehensive review. Cardiovasc Diabetol 2024; 23:346. [PMID: 39342178 PMCID: PMC11439309 DOI: 10.1186/s12933-024-02434-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 09/09/2024] [Indexed: 10/01/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), poses a significant global health challenge due to its increasing prevalence and strong association with cardiovascular disease (CVD). This comprehensive review summarizes the current knowledge on the MASLD-CVD relationship, compares analysis of how different terminologies for fatty liver disease affect cardiovascular (CV) risk assessment using different diagnostic criteria, explores the pathophysiological mechanisms connecting MASLD to CVD, the influence of MASLD on traditional CV risk factors, the role of noninvasive imaging techniques and biomarkers in the assessment of CV risk in patients with MASLD, and the implications for clinical management and prevention strategies. By incorporating current research and clinical guidelines, this review provides a comprehensive overview of the complex interplay between MASLD and cardiovascular health.
Collapse
Affiliation(s)
- Haixiang Zheng
- Department of Biomedical Sciences, University of Sassari, 07100, Sassari, Italy
- Department of Cardiology, The Second Affiliated Hospital of Shantou University Medical College, 515041, Shantou, China
| | - Leonardo Antonio Sechi
- Department of Biomedical Sciences, University of Sassari, 07100, Sassari, Italy
- Complex Structure of Microbiology and Virology, AOU Sassari, 07100, Sassari, Italy
| | - Eliano Pio Navarese
- Clinical and Experimental Cardiology, Clinical and Interventional Cardiology, University of Sassari, Sassari, Italy
| | - Gavino Casu
- Clinical and Experimental Cardiology, Clinical and Interventional Cardiology, University of Sassari, Sassari, Italy
| | - Gianpaolo Vidili
- Department of Medicine, Surgery, and Pharmacy, University of Sassari, Azienda Ospedaliero, 07100, Sassari, Italy.
| |
Collapse
|
10
|
Suwała S, Junik R. Assessment of the Liver Steatosis and Fibrosis Risk in Metabolic Syndrome and Its Individual Components, Considering the Varying Definitions Used in Clinical Practice throughout Time: A Retrospective Cross-Sectional Study. Biomedicines 2024; 12:1739. [PMID: 39200204 PMCID: PMC11351204 DOI: 10.3390/biomedicines12081739] [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: 07/06/2024] [Revised: 07/25/2024] [Accepted: 07/31/2024] [Indexed: 09/02/2024] Open
Abstract
Multiple modifications of metabolic syndrome diagnostic criteria have been made-NCEP: ATP III (from 2001, modified in 2004), IDF (2005), IDF Consortium (2009), or Polish Scientific Society Consortium standards (2022) are now frequently in use. Hepatosteatosis and hepatofibrosis are commonly mentioned aspects of metabolic syndrome that greatly increase the likelihood of developing complications. The objective of the study was to assess different diagnostic criteria for metabolic syndrome based on the prevalence of liver steatosis and fibrosis. A retrospective analysis was conducted on the medical data of 2102 patients. Out of all the single criteria, meeting the obesity criterion based on waist circumference showed the highest increase in the risk of hepatosteatosis (by 64-69%, depending on the definition used)-hypertriglyceridemia increased the risk of hepatofibrosis by 71%. Regardless of the specific criteria used, patients with metabolic syndrome had a 34-36% increased likelihood of developing hepatosteatosis-the probability of hepatofibrosis varied between 42% and 47% for the criteria established in 2004, 2005, and 2009, while the Polish 2022 criteria were not statistically significant (p = 0.818). It seems appropriate to establish consistent metabolic syndrome diagnostic criteria-the 2009 IDF guidelines are the most effective in assessing hepatosteatosis and fibrosis risk.
Collapse
Affiliation(s)
- Szymon Suwała
- Department of Endocrinology and Diabetology, Nicolaus Copernicus University, Collegium Medicum, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland;
| | | |
Collapse
|
11
|
Najafi F, Pasdar Y, Nazar MM, Darbandi M. Association between obesity phenotypes and non-alcoholic fatty liver: a large population- based study. BMC Endocr Disord 2024; 24:96. [PMID: 38918729 PMCID: PMC11197192 DOI: 10.1186/s12902-024-01630-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 06/20/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND The aim of this study was to examine the association between different metabolic obesity phenotypes and the non-alcoholic fatty liver disease (NAFLD). METHODS This cross-sectional analysis utilized data from the baseline phase of the Ravansar non-communicable diseases (RaNCD) cohort study, which involved 8,360 adults. Participants with a Fatty Liver Index (FLI) score of ≥ 60 was classified as having NAFLD. The FLI score was calculated using liver non-invasive markers and anthropometric measurements. Participants were categorized into four phenotypes based on the presence or absence of metabolic syndrome and obesity. Logistic regression analysis was used to evaluate the association of NAFLD and obesity phenotypes. RESULTS According to the FLI index, the prevalence of NAFLD was 39.56%. Participants with FLI scores of ≥ 60 had higher energy intake compared to those in the FLI < 60 group (P = 0.033). In subjects with metabolically unhealthy phenotypes, the level of physical activity was lower compared to those with metabolically healthy phenotypes. The risk of NAFLD in males with the metabolically healthy-obese phenotype increased by 8.92 times (95% CI: 2.20, 15.30), those with the metabolically unhealthy-non-obese phenotype increased by 7.23 times (95% CI: 5.82, 8.99), and those with the metabolically unhealthy-obese phenotype increased by 32.97 times (95% CI: 15.70, 69.22) compared to the metabolically healthy-non-obese phenotype. Similarly, these results were observed in females. CONCLUSION This study demonstrated that the risk of NAFLD is higher in individuals with metabolically healthy/obese, metabolically unhealthy/non-obese, and metabolically unhealthy/obese phenotypes compared to those with non-obese/metabolically healthy phenotypes.
Collapse
Affiliation(s)
- Farid Najafi
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Yahya Pasdar
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mehdi Moradi Nazar
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mitra Darbandi
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| |
Collapse
|
12
|
Somi MH, Faramarzi E, Jahangiry S, Sanaie S, Molani-Gol R. The relationship between liver enzymes, prehypertension and hypertension in the Azar cohort population. BMC Cardiovasc Disord 2024; 24:294. [PMID: 38849721 PMCID: PMC11157708 DOI: 10.1186/s12872-024-03969-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Accepted: 06/03/2024] [Indexed: 06/09/2024] Open
Abstract
BACKGROUND The incidence of hypertension (HTN) as a worldwide health problem is rising rapidly. Early identification and management of pre-HTN before HTN development can help reduce its related complications. We evaluated the relationship between liver enzymes levels and pre-HTN/HTN in the Azar cohort population. METHOD This cross-sectional study was based on data from the large Azar cohort study and a total of 14,184 participants were included. Pre-HTN and HTN were defined based on the American Heart Association guideline. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) levels were measured by Pars Azmoon kits. The relationship between pre-HTN/HTN and liver enzyme levels was evaluated by logistic regression. RESULTS Of 14,184 participants, 5.7% and 39.6% had pre-HTN and HTN, respectively. In the adjusted model, AST levels of 19-23 IU/l were associated with an elevated risk of pre-HTN (OR [95% CI]: 1.24 [1.04-1.48]). A dose-response increase was seen in pre-HTN in relation to ALT, with the highest OR in the third tertile (1.34 [1.09-1.63]). The odds of pre-HTN also increased with GGT in the third tertile (1.25[1.03-1.52]). In addition, the odds of HTN increased with increased levels of AST, ALT, ALP, and GGT, such that the highest ORs were recorded in the third tertile (OR 1.22 [1.09-1.37], 1.51 [1.35-1.70], 1.19 [1.07-1.34], and 1.68 [1.49-1.89], respectively). Among these enzymes, GGT had the highest OR regarding HTN. CONCLUSION This study indicates that AST, ALT, ALP and GGT levels were associated with pre-HTN (except for ALP) and HTN, independent of known risk factors. Hence, it may be possible to use liver enzymes to predict the incidence of pre-HTN and HTN, empowering primary care providers to make the necessary interventions promptly.
Collapse
Affiliation(s)
- Mohammd Hossein Somi
- Liver and Gastrointestinal Diseases Research Center of Tabriz university of medical sciences, Tabriz, Iran
| | - Elnaz Faramarzi
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sima Jahangiry
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sarvin Sanaie
- Research center for integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Roghayeh Molani-Gol
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
| |
Collapse
|
13
|
Badmus OO, da Silva AA, Li X, Taylor LC, Greer JR, Wasson AR, McGowan KE, Patel PR, Stec DE. Cardiac lipotoxicity and fibrosis underlie impaired contractility in a mouse model of metabolic dysfunction-associated steatotic liver disease. FASEB Bioadv 2024; 6:131-142. [PMID: 38706754 PMCID: PMC11069051 DOI: 10.1096/fba.2023-00139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 02/20/2024] [Accepted: 02/23/2024] [Indexed: 05/07/2024] Open
Abstract
The leading cause of death among patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is cardiovascular disease. A significant percentage of MASLD patients develop heart failure driven by functional and structural alterations in the heart. Previously, we observed cardiac dysfunction in hepatocyte-specific peroxisome proliferator-activated receptor alpha knockout (Ppara HepKO), a mouse model that exhibits hepatic steatosis independent of obesity and insulin resistance. The goal of the present study was to determine mechanisms that underlie hepatic steatosis-induced cardiac dysfunction in Ppara HepKO mice. Experiments were performed in 30-week-old Ppara HepKO and littermate control mice fed regular chow. We observed decreased cardiomyocyte contractility (0.17 ± 0.02 vs. 0.24 ± 0.02 μm, p < 0.05), increased cardiac triglyceride content (0.96 ± 0.13 vs. 0.68 ± 0.06 mM, p < 0.05), collagen type 1 (4.65 ± 0.25 vs. 0.31 ± 0.01 AU, p < 0.001), and collagen type 3 deposition (1.32 ± 0.46 vs. 0.05 ± 0.03 AU, p < 0.05). These changes were associated with increased apoptosis as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining (30.9 ± 4.7 vs. 13.1 ± 0.8%, p < 0.006) and western blots showing increased cleaved caspase-3 (0.27 ± 0.006 vs. 0.08 ± 0.01 AU, p < 0.003) and pro-caspase-3 (5.4 ± 1.5 vs. 0.5 ± 0.3 AU, p < 0.02), B-cell lymphoma protein 2-associated X (0.68 ± 0.07 vs. 0.04 ± 0.04 AU, p < 0.001), and reduced B-cell lymphoma protein 2 (0.29 ± 0.01 vs. 1.47 ± 0.54 AU, p < 0.05). We further observed elevated circulating natriuretic peptides and exercise intolerance in Ppara HepKO mice when compared to controls. Our data demonstrated that lipotoxicity, and fibrosis underlie cardiac dysfunction in MASLD.
Collapse
Affiliation(s)
- Olufunto O. Badmus
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Alexandre A. da Silva
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Xuan Li
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Lucy C. Taylor
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Jennifer R. Greer
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Andrew R. Wasson
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Karis E. McGowan
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Parth R. Patel
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - David E. Stec
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| |
Collapse
|
14
|
Hu C, Yu Z, Wei C, Sheng G, Chen J, Zou Y. Evaluating the relative importance of different blood pressure indices in screening for NAFLD: a survey report based on a health examination population. Front Cardiovasc Med 2024; 11:1338156. [PMID: 38742174 PMCID: PMC11089114 DOI: 10.3389/fcvm.2024.1338156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 04/18/2024] [Indexed: 05/16/2024] Open
Abstract
Objective While hypertension is a well-recognized risk factor for non-alcoholic fatty liver disease (NAFLD), the specific roles of various common blood pressure measurements [diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), mean arterial pressure (MAP)] in detecting NAFLD and evaluating the associated risk in adults remain unclear. Methods A retrospective analysis was conducted on 14,251 adult participants undergoing health screenings in the NAfld in the Gifu Area, Longitudinal Analysis project (NAGALA). Following the Z-transformation of the independent variables, we evaluated the relationships between the four blood pressure indices and NAFLD through multivariable logistic regression models. This analysis documented the odds ratio (OR) and 95% confidence interval (CI) for each standard deviation (SD) increase. Additionally, the effectiveness of these indices in identifying NAFLD was comparatively analyzed using receiver operating characteristic (ROC) curves. Results After adequately adjusting for confounders, all blood pressure indices except PP showed a positive correlation with NAFLD. For each SD increment, MAP had the strongest association with NAFLD compared to SBP and DBP. This finding was confirmed in populations without exercise habits, under 60 years of age, with normal blood pressure, and in non-obese groups. Furthermore, based on ROC analysis, MAP was found to have the highest accuracy in identifying NAFLD compared to the other three blood pressure indices. Conclusion Among the four blood pressure indices evaluated, MAP demonstrates the greatest efficacy in identifying NAFLD and assessing its associated risk. These findings underscore the potential of MAP as the most promising blood pressure index for screening NAFLD.
Collapse
Affiliation(s)
- Chong Hu
- Department of Gastroenterology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China
| | - Ziqi Yu
- Munich Medical Research School, LMU Munich, Munich, Germany
| | - Changli Wei
- Department of Gastroenterology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China
| | - Guotai Sheng
- Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China
| | - Jianyong Chen
- Department of Gastroenterology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China
| | - Yang Zou
- Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China
| |
Collapse
|
15
|
Su X, Xu Q, Li Z, Ren Y, Jiao Q, Wang L, Wang Y. Role of the angiopoietin-like protein family in the progression of NAFLD. Heliyon 2024; 10:e27739. [PMID: 38560164 PMCID: PMC10980950 DOI: 10.1016/j.heliyon.2024.e27739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 03/05/2024] [Accepted: 03/06/2024] [Indexed: 04/04/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver disease, with a range of conditions including non-alcoholic fatty liver, non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Currently recognized as the liver component of the metabolic syndrome, NAFLD is intimately linked to metabolic diseases. Angiopoietin-like proteins (ANGPTLs) comprise a class of proteins that resemble angiopoietins structurally. It is closely related to obesity, insulin resistance and lipid metabolism, and may be the critical factor of metabolic syndrome. In recent years, many studies have found that there is a certain correlation between ANGPTLs and the occurrence and progression of NAFLD disease spectrum. This article reviews the possible mechanisms and roles of ANGPTL protein in the pathogenesis and progression of NAFLD.
Collapse
Affiliation(s)
- Xin Su
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, China
| | - Qinchen Xu
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, China
| | - Zigan Li
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, China
| | - Yidan Ren
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong Province, China
| | - Qinlian Jiao
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong Province, China
| | - Lina Wang
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, China
| | - Yunshan Wang
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong Province, China
| |
Collapse
|
16
|
Yuan M, He J, Hu X, Yao L, Chen P, Wang Z, Liu P, Xiong Z, Jiang Y, Li L. Hypertension and NAFLD risk: Insights from the NHANES 2017-2018 and Mendelian randomization analyses. Chin Med J (Engl) 2024; 137:457-464. [PMID: 37455323 PMCID: PMC10876227 DOI: 10.1097/cm9.0000000000002753] [Citation(s) in RCA: 20] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Indexed: 07/18/2023] Open
Abstract
BACKGROUND Hypertension and non-alcoholic fatty liver disease (NAFLD) share several pathophysiologic risk factors, and the exact relationship between the two remains unclear. Our study aims to provide evidence concerning the relationship between hypertension and NAFLD by analyzing data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 and Mendelian randomization (MR) analyses. METHODS Weighted multivariable-adjusted logistic regression was applied to assess the relationship between hypertension and NAFLD risk by using data from the NHANES 2017-2018. Subsequently, a two-sample MR study was performed using the genome-wide association study (GWAS) summary statistics to identify the causal association between hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and NAFLD. The primary inverse variance weighted (IVW) and other supplementary MR approaches were conducted to verify the causal association between hypertension and NAFLD. Sensitivity analyses were adopted to confirm the robustness of the results. RESULTS A total of 3144 participants were enrolled for our observational study in NHANES. Weighted multivariable-adjusted logistic regression analysis suggested that hypertension was positively related to NAFLD risk (odds ratio [OR] = 1.677; 95% confidence interval [CI], 1.159-2.423). SBP ≥130 mmHg and DBP ≥80 mmHg were also significantly positively correlated with NAFLD. Moreover, hypertension was independently connected with liver steatosis ( β = 7.836 [95% CI, 2.334-13.338]). The results of MR analysis also supported a causal association between hypertension (OR = 7.203 [95% CI, 2.297-22.587]) and NAFLD. Similar results were observed for the causal exploration between SBP (OR = 1.024 [95% CI, 1.003-1.046]), DBP (OR = 1.047 [95% CI, 1.005-1.090]), and NAFLD. The sensitive analysis further confirmed the robustness and reliability of these findings (all P >0.05). CONCLUSION Hypertension was associated with an increased risk of NAFLD.
Collapse
Affiliation(s)
- Mengqin Yuan
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, China
| | - Jian He
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510010, China
| | - Xue Hu
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, China
| | - Lichao Yao
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, China
| | - Ping Chen
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, China
| | - Zheng Wang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, China
| | - Pingji Liu
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, China
| | - Zhiyu Xiong
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, China
| | - Yingan Jiang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, China
| | - Lanjuan Li
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, China
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, China
| |
Collapse
|
17
|
Branković M, Dukić M, Gmizić T, Popadić V, Nikolić N, Sekulić A, Brajković M, Đokić J, Mahmutović E, Lasica R, Vojnović M, Milovanović T. New Therapeutic Approaches for the Treatment of Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Increased Cardiovascular Risk. Diagnostics (Basel) 2024; 14:229. [PMID: 38275476 PMCID: PMC10814440 DOI: 10.3390/diagnostics14020229] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/16/2024] [Accepted: 01/16/2024] [Indexed: 01/27/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) was previously known as nonalcoholic fatty liver disease (NAFLD). The main characteristic of the disease is the process of long-term liver inflammation, which leads to hepatocyte damage followed by liver fibrosis and eventually cirrhosis. Additionally, these patients are at a greater risk for developing cardiovascular diseases (CVD). They have several pathophysiological mechanisms in common, primarily lipid metabolism disorders and lipotoxicity. Lipotoxicity is a factor that leads to the occurrence of heart disease and the occurrence and progression of atherosclerosis. Atherosclerosis, as a multifactorial disease, is one of the predominant risk factors for the development of ischemic heart disease. Therefore, CVD are one of the most significant carriers of mortality in patients with metabolic syndrome. So far, no pharmacotherapy has been established for the treatment of MASLD, but patients are advised to reduce their body weight and change their lifestyle. In recent years, several trials of different drugs, whose basic therapeutic indications include other diseases, have been conducted. Because it has been concluded that they can have beneficial effects in the treatment of these conditions as well, in this paper, the most significant results of these studies will be presented.
Collapse
Affiliation(s)
- Marija Branković
- University Hospital Medical Center Bežanijska Kosa, 11000 Belgrade, Serbia; (M.D.); (T.G.); (V.P.); (N.N.); (A.S.); (M.B.); (J.Đ.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (R.L.); (T.M.)
| | - Marija Dukić
- University Hospital Medical Center Bežanijska Kosa, 11000 Belgrade, Serbia; (M.D.); (T.G.); (V.P.); (N.N.); (A.S.); (M.B.); (J.Đ.)
| | - Tijana Gmizić
- University Hospital Medical Center Bežanijska Kosa, 11000 Belgrade, Serbia; (M.D.); (T.G.); (V.P.); (N.N.); (A.S.); (M.B.); (J.Đ.)
| | - Višeslav Popadić
- University Hospital Medical Center Bežanijska Kosa, 11000 Belgrade, Serbia; (M.D.); (T.G.); (V.P.); (N.N.); (A.S.); (M.B.); (J.Đ.)
| | - Novica Nikolić
- University Hospital Medical Center Bežanijska Kosa, 11000 Belgrade, Serbia; (M.D.); (T.G.); (V.P.); (N.N.); (A.S.); (M.B.); (J.Đ.)
| | - Ana Sekulić
- University Hospital Medical Center Bežanijska Kosa, 11000 Belgrade, Serbia; (M.D.); (T.G.); (V.P.); (N.N.); (A.S.); (M.B.); (J.Đ.)
| | - Milica Brajković
- University Hospital Medical Center Bežanijska Kosa, 11000 Belgrade, Serbia; (M.D.); (T.G.); (V.P.); (N.N.); (A.S.); (M.B.); (J.Đ.)
| | - Jelena Đokić
- University Hospital Medical Center Bežanijska Kosa, 11000 Belgrade, Serbia; (M.D.); (T.G.); (V.P.); (N.N.); (A.S.); (M.B.); (J.Đ.)
| | - Edvin Mahmutović
- Department of Internal Medicine, General Hospital Novi Pazar, 36300 Novi Pazar, Serbia;
| | - Ratko Lasica
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (R.L.); (T.M.)
- Department of Cardiology, Emergency Center, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Marko Vojnović
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Serbia, 11000 Belgrade, Serbia;
| | - Tamara Milovanović
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (R.L.); (T.M.)
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Serbia, 11000 Belgrade, Serbia;
| |
Collapse
|
18
|
Wang T, Xi Y, Raji A, Crutchlow M, Fernandes G, Engel SS, Zhang X. Overall and subgroup prevalence of non-alcoholic fatty liver disease and prevalence of advanced fibrosis in the United States: An updated national estimate in National Health and Nutrition Examination Survey (NHANES) 2011-2018. Ann Hepatol 2024; 29:101154. [PMID: 37742743 DOI: 10.1016/j.aohep.2023.101154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 08/07/2023] [Accepted: 09/09/2023] [Indexed: 09/26/2023]
Abstract
INTRODUCTION AND OBJECTIVES Data on the prevalence of non-alcoholic fatty liver disease (NAFLD) in subgroups of the United States (US) population are limited. This study was conducted to estimate NAFLD prevalence overall and by subgroups, and prevalence of NAFLD with advanced fibrosis. MATERIALS AND METHODS Using the National Health and Nutrition Examination Survey (NHANES) 2011-2018 data, a cross-sectional study was conducted. NAFLD was defined as having a US Fatty Liver Index (USFLI) ≥ 30 in the absence of other causes of liver disease, including excessive alcohol intake, chronic hepatitis B, and chronic hepatitis C. Likelihood for having advanced fibrosis was determined by the calculated NAFLD fibrosis score (NFS; high ≥ 0.676; low < -1.445) and fibrosis-4 index (FIB-4; high ≥ 2.67; low < 1.30). RESULTS The weighted national prevalence of NAFLD in US adults was 26.7% (95% confidence interval: 25.3%-28.1%). Prevalence was higher among those aged ≥ 65 years, males, Mexican Americans, with BMI ≥ 35 kg/m2 (class 2 and 3 obesity) and with type 2 diabetes (T2D). Of those meeting the USFLI criterion for NAFLD, 18.1% and 3.7% were determined as having a high probability of advanced fibrosis based on NFS ≥ 0.676 and FIB-4 ≥ 2.67 cut-off values, respectively. CONCLUSIONS This study supports an increased prevalence of NAFLD in specific subpopulations (aged ≥ 65 years, males, Mexican Americans, obese population, and patients with T2D). The observed difference in the prevalence of advanced fibrosis as estimated by NFS and FIB-4 highlights the challenge of choosing optimal cut-off values.
Collapse
Affiliation(s)
| | - Yuzhi Xi
- University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Annaswamy Raji
- Global Clinical Development, Merck & Co., Inc., Rahway, NJ, USA
| | | | - Gail Fernandes
- Center for Observational and Real-World Evidence, Merck & Co., Inc., Rahway, NJ, USA
| | - Samuel S Engel
- Global Clinical Development, Merck & Co., Inc., Rahway, NJ, USA
| | - Xiao Zhang
- Epidemiology, Merck & Co., Inc., Rahway, NJ, USA.
| |
Collapse
|
19
|
Huang X, Zhang Z, Wang J, Yang Y, Hao T, Zhang S, Liu L, Wang G. Extracellular volume fraction of liver and pancreas using spectral CT in hypertensive patients: A comparative study. JOURNAL OF X-RAY SCIENCE AND TECHNOLOGY 2024; 32:1351-1362. [PMID: 39240616 PMCID: PMC11787814 DOI: 10.3233/xst-240130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/07/2024]
Abstract
BACKGROUND Besides the direct impact on the cardiovascular system, hypertension is closely associated with organ damage in the kidneys, liver, and pancreas. Chronic liver and pancreatic damage in hypertensive patients may be detectable via imaging. OBJECTIVE To explore the correlation between hypertension-related indicators and extracellular volume fraction (ECV) of liver and pancreas measured by iodine maps, and to evaluate corresponding clinical value in chronic damage of liver and pancreas in hypertensive patients. METHODS A prospective study from June to September 2023 included abdominal patients who underwent contrast-enhanced spectral CT. Normal and various grades of hypertensive blood pressure groups were compared. Upper abdominal iodine maps were constructed, and liver and pancreatic ECVs calculated. Kruskal-Wallis and Spearman analyses evaluated ECV differences and correlations with hypertension indicators. RESULTS In 300 patients, hypertensive groups showed significantly higher liver and pancreatic ECV than the normotensive group, with ECV rising alongside hypertension severity. ECVliver displayed a stronger correlation with hypertension stages compared to ECVpancreas. Regression analysis identified hypertension severity as an independent predictor for increased ECV. CONCLUSIONS ECVliver and ECVpancreas positively correlates with hypertension indicators and serves as a potential clinical marker for chronic organ damage due to hypertension, with ECVliver being more strongly associated than ECVpancreas.
Collapse
Affiliation(s)
- Xiaoming Huang
- Department of Radiology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Zhen Zhang
- Department of Radiology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Jiansheng Wang
- Department of Radiology, Laixi People's Hospital, Laixi, China
| | - Yaqing Yang
- Department of Radiology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
- Graduate School, Dalian Medical University, Dalian, China
| | - Tianqi Hao
- Department of Radiology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
- Graduate School, Dalian Medical University, Dalian, China
| | - Shuai Zhang
- CT Imaging Research Center, GE Healthcare China, Shanghai, China
| | - Ling Liu
- CT Imaging Research Center, GE Healthcare China, Shanghai, China
| | - Guohua Wang
- Department of Radiology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| |
Collapse
|
20
|
Chen C, Zhang W, Yan G, Tang C. Identifying metabolic dysfunction-associated steatotic liver disease in patients with hypertension and pre-hypertension: An interpretable machine learning approach. Digit Health 2024; 10:20552076241233135. [PMID: 38389508 PMCID: PMC10883118 DOI: 10.1177/20552076241233135] [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: 09/23/2023] [Accepted: 01/30/2024] [Indexed: 02/24/2024] Open
Abstract
Objective Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most prevalent liver diseases and is associated with pre-hypertension and hypertension. Our research aims to develop interpretable machine learning (ML) models to accurately identify MASLD in hypertensive and pre-hypertensive populations. Methods The dataset for 4722 hypertensive and pre-hypertensive patients is from subjects in the NAGALA study. Six ML models, including the decision tree, K-nearest neighbor, gradient boosting, naive Bayes, support vector machine, and random forest (RF) models, were used in this study. The optimal model was constructed according to the performances of models evaluated by K-fold cross-validation (k = 5), the area under the receiver operating characteristic curve (AUC), average precision (AP), accuracy, sensitivity, specificity, and F1. Shapley additive explanation (SHAP) values were employed for both global and local interpretation of the model results. Results The prevalence of MASLD in hypertensive and pre-hypertensive patients was 44.3% (362 cases) and 28.3% (1107 cases), respectively. The RF model outperformed the other five models with an AUC of 0.889, AP of 0.800, accuracy of 0.819, sensitivity of 0.816, specificity of 0.821, and F1 of 0.729. According to the SHAP analysis, the top five important features were alanine aminotransferase, body mass index, waist circumference, high-density lipoprotein cholesterol, and total cholesterol. Further analysis of the feature selection in the RF model revealed that incorporating all features leads to optimal model performance. Conclusions ML algorithms, especially RF algorithm, improve the accuracy of MASLD identification, and the global and local interpretation of the RF model results enables us to intuitively understand how various features affect the chances of MASLD in patients with hypertension and pre-hypertension.
Collapse
Affiliation(s)
- Chen Chen
- School of Cyber Science and Engineering, Southeast University, Nanjing, Jiangsu, China
- School of Telecommunications and Information Engineering, Nanjing University of Posts and Telecommunications, Nanjing, Jiangsu, China
| | - Wenkang Zhang
- Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China
- School of Medicine, Southeast University, Nanjing, Jiangsu, China
| | - Gaoliang Yan
- Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China
| | - Chengchun Tang
- Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China
- School of Medicine, Southeast University, Nanjing, Jiangsu, China
| |
Collapse
|
21
|
Kakouri NS, Thomopoulos CG, Siafi EP, Valatsou AE, Dimitriadis KS, Mani IP, Patsilinakos SP, Tousoulis DM, Tsioufis KP. Overview of the Association between Non-Alcoholic Fatty Liver Disease and Hypertension. CARDIOLOGY DISCOVERY 2023. [DOI: 10.1097/cd9.0000000000000113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and its prevalence is rising. NAFLD is closely associated with metabolic syndrome, with both conditions sharing common clinical characteristics such as obesity, insulin resistance, type 2 diabetes mellitus, hypertension, and hypertriglyceridemia. Several observational studies have evaluated the relationship between NAFLD and hypertension, with the overall evidence suggesting a bidirectional relationship. It is hypothesized that activation of the sympathetic nervous and renin-angiotensin systems, observed in NAFLD with or without insulin resistance promotes the development of hypertension. In patients with hypertension, activation of these systems can lead to hepatic fibrosis and progressive inflammation through increased oxidative stress and activation of hepatic stellate cells and Kupffer cells. The present review examines the pathophysiologic and clinical evidence supporting the bidirectional association between NAFLD and hypertension.
Collapse
Affiliation(s)
- Niki S. Kakouri
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens 11527, Greece
| | | | - Eirini P. Siafi
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens 11527, Greece
| | - Angeliki E. Valatsou
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens 11527, Greece
| | - Kyriakos S. Dimitriadis
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens 11527, Greece
| | - Iliana P. Mani
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens 11527, Greece
| | | | - Dimitrios M. Tousoulis
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens 11527, Greece
| | - Konstantinos P. Tsioufis
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens 11527, Greece
| |
Collapse
|
22
|
Pirola CJ, Sookoian S. Non-alcoholic fatty liver disease mediates the effect of obesity on arterial hypertension. Liver Int 2023; 43:2167-2176. [PMID: 37312639 DOI: 10.1111/liv.15643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 05/30/2023] [Accepted: 05/31/2023] [Indexed: 06/15/2023]
Abstract
BACKGROUND It has been consistently shown that obesity contributes directly to arterial hypertension and cardiovascular disease (CVD), independently of other risk factors. Likewise, non-alcoholic fatty liver disease (NAFLD) is acknowledged as a contributor and a risk enhancer for CVD. OBJECTIVES We tested the hypothesis of a causal role of NAFLD in the effect of obesity on arterial hypertension. METHODS Using causal mediation analysis, we quantified the magnitude of the body mass index (BMI) effect on arterial hypertension and CV-traits mediated by NAFLD. First, we analysed data from 1348 young adults in the Bogalusa Heart Study (BHS), a cohort aimed at assessing the natural history of CVD. Then, we used data from 3359 participants of the National Health and Nutrition Examination Survey (2017-2018 cycle, NHANES) to replicate the findings. RESULTS We found that roughly 92% of the effects of BMI on arterial hypertension in the BHS and 51% in the NHANES population are mediated by NAFLD. In addition, indirect effects of BMI on systolic (SBP) and diastolic (DBP) blood pressure, and heart rate (HR) through NAFLD explained up to 91%, 93%, and 100% of the total effect, respectively, in the BHS. In the NHANES survey, indirect effects of BMI through NAFLD on CV traits explain a significant proportion of the total effects (SBP = 60.4%, HR = 100%, and pulse pressure = 88%). CONCLUSION NAFLD mediates a substantial proportion of the effect of obesity on the presence of hypertension and CV-parameters independently of relevant covariates. This conclusion has implications for clinical management.
Collapse
Affiliation(s)
- Carlos J Pirola
- Systems Biology of Complex Diseases, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
| | - Silvia Sookoian
- Clinical and Molecular Hepatology, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
- Universidad Maimónides, Buenos Aires, Argentina
| |
Collapse
|
23
|
Attaran F, Emami S, Sohrabi M, Malek M, Ajdarkosh H, Khoonsari M, Ismail-Beigi F, Khamseh ME. Effect of Empagliflozin and Pioglitazone on left ventricular function in patients with type two diabetes and nonalcoholic fatty liver disease without established cardiovascular disease: a randomized single-blind clinical trial. BMC Gastroenterol 2023; 23:327. [PMID: 37742004 PMCID: PMC10517489 DOI: 10.1186/s12876-023-02948-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 09/06/2023] [Indexed: 09/25/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic disorder that increases the risk for cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Global longitudinal strain (GLS) is an indicator of left ventricular (LV) mechanics and can detect subclinical myocardial dysfunction. We compared the effects of pioglitazone and empagliflozin on GLS in patients with T2DM and NAFLD without established atherosclerotic cardiovascular disease. METHODS This study was a 24-week randomized, single-blind, and parallel-group (1: 1 ratio) clinical trial. Seventy-three participants with T2DM (being treated with metformin) and NAFLD but without established atherosclerotic cardiovascular disease (ASCVD) were randomized to empagliflozin or pioglitazone. Liver steatosis and fibrosis were measured using transient elastography, and GLS was measured by echocardiography. The primary endpoint was the change in GLS from baseline to week 24. Secondary end points include changes in controlled attenuation parameter (CAP) and Liver stiffness measure (LSM). RESULTS In this study, GLS improved by 1.56 ± 2.34% (P < 0.01) in the pioglitazone group and 1.06 ± 1.83% (P < 0.01) in the empagliflozin group without a significant difference between the two groups (P = 0.31). At baseline, GLS was inversely associated with the severity of liver fibrosis: r = - 0.311, P = 0.007. LSM in the pioglitazone and empagliflozin group [(-0.73 ± 1.59) and (-1.11 ± 1.33)] kpa (P < 0.01) decreased significantly. It was without substantial difference between the two groups (P = 0.26). Empagliflozin and pioglitazone both improved controlled attenuation parameter. The improvement was more critical in the empagliflozin group: -48.22 + 35.02 dB/m vs. -25.67 + 41.50 dB/m, P = 0.01. CONCLUSION Subclinical cardiac dysfunction is highly important in patients with T2DM and with NAFLD. Empagliflozin and Pioglitazone improve LV mechanics and fibrosis in patients without established ASCVD. This has a prognostic importance on cardiovascular outcomes in high-risk patients with T2DM. Moreover, empagliflozin ameliorates liver steatosis more effectively them pioglitazone. This study can serve as a start point hypothesis for the future. Further studies are needed to explore the concept in larger populations. TRIAL REGISTRATION This trial was registered in the Iranian Registry of Clinical Trials (IRCT): "A Comparison between the Effect of Empagliflozin and Pioglitazone on Echocardiographic Indices in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease" IRCT20190122042450N5, 29 November 2020. https://www.irct.ir/search/result?query=IRCT20190122042450N5 .
Collapse
Affiliation(s)
- Fereshte Attaran
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Iran University of Medical Science, No. 10, Firoozeh St., Vali-asr Ave., Vali-asr Sq, Tehran, Iran
| | - Sepideh Emami
- Department of Cardiology, Firoozgar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Masoudreza Sohrabi
- Gastrointestinal and liver diseases research center, Iran University of Medical Sciences, Tehran, Iran
| | - Mojtaba Malek
- Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Ajdarkosh
- Gastrointestinal and liver diseases research center, Iran University of Medical Sciences, Tehran, Iran
| | - Mahmoodreza Khoonsari
- Gastrointestinal and liver diseases research center, Iran University of Medical Sciences, Tehran, Iran
| | | | - Mohammad E Khamseh
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Science, Tehran, Iran.
| |
Collapse
|
24
|
Golubeva JA, Sheptulina AF, Elkina AY, Liusina EO, Kiselev AR, Drapkina OM. Which Comes First, Nonalcoholic Fatty Liver Disease or Arterial Hypertension? Biomedicines 2023; 11:2465. [PMID: 37760906 PMCID: PMC10525922 DOI: 10.3390/biomedicines11092465] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/28/2023] [Accepted: 09/02/2023] [Indexed: 09/29/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and arterial hypertension (AH) are widespread noncommunicable diseases in the global population. Since hypertension and NAFLD are diseases associated with metabolic syndrome, they are often comorbid. In fact, many contemporary published studies confirm the association of these diseases with each other, regardless of whether other metabolic factors, such as obesity, dyslipidemia, and type 2 diabetes mellites, are present. This narrative review considers the features of the association between NAFLD and AH, as well as possible pathophysiological mechanisms.
Collapse
Affiliation(s)
- Julia A. Golubeva
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
| | - Anna F. Sheptulina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
- Department of Therapy and Preventive Medicine, A.I. Evdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
| | - Anastasia Yu. Elkina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
- Department of Intermediate Level Therapy, Saratov State Medical University, 410012 Saratov, Russia
| | - Ekaterina O. Liusina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
| | - Anton R. Kiselev
- Coordinating Center for Fundamental Research, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
| | - Oxana M. Drapkina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
- Department of Therapy and Preventive Medicine, A.I. Evdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
| |
Collapse
|
25
|
Testino G, Pellicano R. Corrected and republished from: Metabolic associated liver disease. Panminerva Med 2023; 65:391-399. [PMID: 37750860 DOI: 10.23736/s0031-0808.23.04850-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/27/2023]
Abstract
Alcohol consumption (AC) and metabolic syndrome (MS) represent the first cause of liver disease, hepatocellular carcinoma and liver transplantation. The habit of consuming alcoholic beverages and the presence of MS and non-alcoholic fatty liver disease (NAFLD) often coexist in the same patient. The histoclinical boundaries between alcohol related liver disease (ALD) and NAFLD are often not well defined. The co-presence of AC and MS increases the risk of hepatic and extra-hepatic disease. The terminological evolution from NAFLD to metabolic associated fatty liver disease (MAFLD) is certainly a useful advance. However, it is known that the appearance of liver fibrosis increases oncologic and cardiovascular disease risk, which in the case of cirrhosis can be present even in the absence of steatosis and that the mechanisms of fibrogenesis can act independently of the presence of steatosis/steatohepatitis. For this reason, as already stated recently, a further terminological evolution can be hypothesized. This article was originally published with mistakes in the text. The new corrected citable version appears below.
Collapse
Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology/Alcohological Regional Centre, ASL3 c/o Polyclinic San Martino Hospital, Genoa, Italy -
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette-SGAS Hospital, Turin, Italy, Corrected and republished from: Panminerva Medica 2022 December
| |
Collapse
|
26
|
Jaiswal V, Ang SP, Huang H, Momi NK, Hameed M, Naz S, Batra N, Ishak A, Doshi N, Gera A, Sharath M, Waleed MS, Raj N, Aguilera Alvarez VH. Association between nonalcoholic fatty liver disease and atrial fibrillation and other clinical outcomes: a meta-analysis. J Investig Med 2023; 71:591-602. [PMID: 37002665 DOI: 10.1177/10815589231164777] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/20/2023]
Abstract
The association between nonalcoholic fatty liver disease (NAFLD) with cardiovascular and cerebrovascular outcomes, as well as their clinical impact, has yet to be established in the literature. This meta-analysis aims to evaluate the association between the NAFLD patients and the risk of atrial fibrillation (AF), heart failure (HF), stroke, cardiovascular mortality (CVM), and revascularization incidence. We performed a systematic literature search using PubMed, Embase, Scopus, and Cochrane libraries for relevant articles from inception until August 2022. A total of 12 cohort studies with 18,055,072 patients (2,938,753 NAFLD vs 15,116,319 non-NAFLD) were included in our analysis. The mean age of the NAFLD patients group and the non-NAFLD group was comparable (55.68 vs 55.87). The most common comorbidities among the NAFLD patients group included hypertension (38% vs 24%) and diabetes mellitus (14% vs 8%). The mean follow-up duration was 6.26 years. The likelihood of AF (risk ratio (RR), 1.42 (95% CI 1.19, 1.68), p < 0.001), HF (RR, 1.43(95% CI 1.03, 2.00), p < 0.001), stroke (RR, 1.26(95% CI 1.16, 1.36), p < 0.001), revascularization (RR, 4.06(95% CI 1.44, 11.46), p = 0.01), and CVM (RR, 3.10(95% CI 1.43, 6.73), p < 0.001) was significantly higher in the NAFLD patients group compared to that of the non-NAFLD group. However, all-cause mortality was comparable between both the groups of patients (RR, 1.30 (95% CI 0.63, 2.67), p = 0.48). In conclusion, the patients with NAFLD are at increased risk of AF, HF, and CVM.
Collapse
Affiliation(s)
- Vikash Jaiswal
- JCCR Cardiology, Varanasi, Uttar Pradesh, India
- Department of Research and Academic Affairs, Larkin Community Hospital, South Miami, Florida, USA
| | - Song Peng Ang
- Division of Internal Medicine, Rutgers Health/Community Medical Center, Toms River, NJ, USA
| | - Helen Huang
- Royal College of Surgeons in Ireland, Dublin, Ireland
| | | | - Maha Hameed
- Department of Research and Academic Affairs, Larkin Community Hospital, South Miami, Florida, USA
| | - Sidra Naz
- The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - Nitya Batra
- Department of Internal Medicine, Beaumont Hospital, Royal Oak, MI, USA
| | - Angela Ishak
- Department of Research and Academic Affairs, Larkin Community Hospital, South Miami, Florida, USA
| | - Neel Doshi
- Department of Medicine, Pravara Institute of Medical Science, Ahmednagar, Maharashtra, India
| | - Asmita Gera
- Department of Research and Academic Affairs, Larkin Community Hospital, South Miami, Florida, USA
| | - Medha Sharath
- Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India
| | | | - Nishchita Raj
- JCCR Cardiology, Varanasi, Uttar Pradesh, India
- B.P Koirala Institute of Health Science, Dharan, Nepal
| | | |
Collapse
|
27
|
Li M, Zhang W, Li X, Liang S, Zhang Y, Mo Y, Rao S, Zhang H, Huang Y, Zhu Y, Zhang Z, Yang W. Metabolic and Risk Profiles of Lean and Non-Lean Hepatic Steatosis among US Adults. Nutrients 2023; 15:2856. [PMID: 37447183 DOI: 10.3390/nu15132856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 06/19/2023] [Accepted: 06/21/2023] [Indexed: 07/15/2023] Open
Abstract
Hepatic steatosis can occur in lean individuals, while its metabolic and risk profiles remain unclear. We aimed to characterize the clinical and risk profiles of lean and non-lean steatosis. This cross-sectional study included 1610 patients with transient elastography-assessed steatosis. The metabolic and risk profiles were compared. Compared to their non-lean counterparts, lean subjects with steatosis had a lower degree of fibrosis (F0-F1: 91.9% vs. 80.9%), had a lower prevalence of diabetes (27.9% vs. 32.8%), dyslipidemia (54.7% vs. 60.2%) and hypertension (50.0% vs. 51.3%), and had higher levels of high-density lipoprotein cholesterol while lower fasting insulin and homeostatic model assessment for insulin resistance (all p < 0.05). Of the 16 potential risk factors, being Hispanic was associated with higher odds of non-lean steatosis but not with lean steatosis (odds ratio (OR): 2.07 vs. 0.93), while excessive alcohol consumption had a different trend in the ratio (OR: 1.47 vs.6.65). Higher waist-to-hip ratio (OR: 7.48 vs. 2.45), and higher waist circumference (OR: 1.14 vs. 1.07) showed a stronger positive association with lean steatosis than with non-lean steatosis (all Pheterogeneity < 0.05). Although lean individuals with steatosis presented a healthier metabolic profile, both lean and non-lean steatosis had a significant proportion of metabolic derangements. In addition, the etiological heterogeneity between lean and non-lean steatosis may exist.
Collapse
Affiliation(s)
- Meiling Li
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
- Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei 230032, China
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei 230032, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics/Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei 230032, China
| | - Weiping Zhang
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Xiude Li
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Shaoxian Liang
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Yaozong Zhang
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Yufeng Mo
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Songxian Rao
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Honghua Zhang
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Yong Huang
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Yu Zhu
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Zhuang Zhang
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Wanshui Yang
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
- Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei 230032, China
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei 230032, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics/Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei 230032, China
| |
Collapse
|
28
|
Yip TCF, Wong GLH, Wong VWS, Goh GBB, Chan WK. Nonalcoholic Fatty Liver Disease: A Unique Entity or Part of the Metabolic Syndrome or Both. Med Clin North Am 2023; 107:449-463. [PMID: 37001947 DOI: 10.1016/j.mcna.2022.12.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a global public health problem. NAFLD is bidirectionally correlated with metabolic syndrome, which includes obesity, type 2 diabetes, hypertension, and dyslipidemia as major components. The presence of metabolic syndrome is associated with a higher prevalence of NAFLD, and vice versa. Also, the presence of metabolic syndrome in patients with NAFLD has been linked to a higher risk of cardiovascular diseases, liver-related complications, extrahepatic malignancies, and mortality, and possibly vice versa. Multidisciplinary care pathways including lifestyle modifications, control of metabolic risk, and potentially beneficial treatments are important to improve the clinical outcomes of patients with NAFLD.
Collapse
Affiliation(s)
- Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong; Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong; Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong; Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong; Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong; Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong; Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - George Boon-Bee Goh
- Department of Gastroenterology and Hepatology, Singapore General Hospital, 20 College Road, Academia, Singapore 169856; Duke-NUS Medical School, Singapore.
| | - Wah-Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
| |
Collapse
|
29
|
Chin Y, Lim J, Kong G, Ng CH, Goh R, Muthiah M, Mehta A, Chong B, Lin C, Chan KE, Kong W, Poh KK, Foo R, Chai P, Yeo TC, Low AF, Lee CH, Tan HC, Chan MYY, Richards AM, Loh PH, Chew NWS. Hepatic steatosis and advanced hepatic fibrosis are independent predictors of long-term mortality in acute myocardial infarction. Diabetes Obes Metab 2023; 25:1032-1044. [PMID: 36546614 DOI: 10.1111/dom.14950] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 12/07/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022]
Abstract
AIM To examine the prevalence and prognosis of hepatic steatosis and fibrosis in post-acute myocardial infarction (AMI) patients. METHODS Patients presenting with AMI to a tertiary hospital were examined from 2014 to 2021. Hepatic steatosis and advanced hepatic fibrosis were determined using the Hepatic Steatosis Index and fibrosis-4 index, respectively. The primary outcome was all-cause mortality. Cox regression models identified determinants of mortality after adjustments and Kaplan-Meier curves were constructed for all-cause mortality, stratified by hepatic steatosis and advanced fibrosis. RESULTS Of 5765 patients included, 24.8% had hepatic steatosis, of whom 41.7% were diagnosed with advanced fibrosis. The median follow-up duration was 2.7 years. Patients with hepatic steatosis tended to be younger, female, with elevated body mass index and an increased metabolic burden of diabetes, hypertension and hyperlipidaemia. Patients with hepatic steatosis (24.6% vs. 20.9% mortality, P < .001) and advanced fibrosis (45.6% vs. 32.9% mortality, P < .001) had higher all-cause mortality rates compared with their respective counterparts. Hepatic steatosis (adjusted hazard ratio 1.364, 95% CI 1.145-1.625, P = .001) was associated with all-cause mortality after adjustment for confounders. Survival curves showed excess mortality in patients with hepatic steatosis compared with those without (P = .002). CONCLUSIONS Hepatic steatosis and advanced fibrosis have a substantial prevalence among patients with AMI. Both are associated with mortality, with an incrementally higher risk when advanced fibrosis ensues. Hepatic steatosis and fibrosis could help risk stratification of AMI patients beyond conventional risk factors.
Collapse
Affiliation(s)
- YipHan Chin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jieyu Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Gwyneth Kong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Rachel Goh
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Mark Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Anurag Mehta
- Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, VCU Health Pauley Heart Center, Richmond, Virginia, Richmond, USA
| | - Bryan Chong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Chaoxing Lin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Kai En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - William Kong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
| | - Kian Keong Poh
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
| | - Roger Foo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
| | - Ping Chai
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
| | - Tiong-Cheng Yeo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
| | - Adrian F Low
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
| | - Chi Hang Lee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
| | - Huay Cheem Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
| | - Mark Yan-Yee Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
| | - A Mark Richards
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
- Christchurch Heart Institute, University of Otago, Dunedin, New Zealand
| | - Poay-Huan Loh
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
- Division of Cardiology, Department of Medicine, Ng Teng Fong General Hospital, Singapore, Singapore
| | - Nicholas W S Chew
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
| |
Collapse
|
30
|
Huang Q, Yu H, Zhong X, Tian Y, Cui Z, Quan Z. Association between hypertension and nonalcoholic fatty liver disease: a cross-sectional and meta-analysis study. J Hum Hypertens 2023; 37:313-320. [PMID: 35411023 DOI: 10.1038/s41371-022-00686-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 03/11/2022] [Accepted: 03/30/2022] [Indexed: 11/08/2022]
Abstract
The association between hypertension and nonalcoholic fatty liver disease (NAFLD) is not completely understood. This study aimed to investigate the association between hypertension and hepatic ultrasound examination-diagnosed positive NAFLD in healthy people; to conduct a comprehensive meta-analysis combining the results of previous studies; to explore whether hypertension was a risk factor for NAFLD. This study included 2049 adults (male: 870 and female: 1179), aged ≥20 years, whose anthropometric parameters were measured to analyze the risk of hypertension on NAFLD. We also collected data from 11 cross-sectional studies relevant to this topic using PubMed, Embase, Web of Science, CNKI, Wanfang, and CQVIP from beginning till 31 August 2020 and combined it with our data for a meta-analysis to explore whether hypertension was a risk factor for NAFLD. After adjusting for confounding factors, the odds of NAFLD in hypertensive subjects was 1.473 (95%CI: 1.119-1.938). After combining with 10 selected studies, 42711 participants were enrolled in meta-analysis. Hypertension was a risk factor for NAFLD (Z = 13.46, P < 0.001); the odds of NAFLD in hypertensive subjects was 1.43 (95%CI: 1.36-1.51). The results were consistent with the results of the meta-analysis. Further studies are required to confirm these results.
Collapse
Affiliation(s)
- Qingzhi Huang
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China
| | - Hana Yu
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China
| | - Xin Zhong
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China
| | - Ying Tian
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China
| | - Zhenhua Cui
- Department of Nephrology, Yanbian University Hospital, 119 Juzi Street, Yanji, 133000, Jilin, China
| | - Zhenyu Quan
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China.
| |
Collapse
|
31
|
Kong L, Yang Y, Li H, Shan Y, Wang X, Shan X. Prevalence of nonalcoholic fatty liver disease and the related risk factors among healthy adults: A cross-sectional study in Chongqing, China. Front Public Health 2023; 11:1127489. [PMID: 37077190 PMCID: PMC10108879 DOI: 10.3389/fpubh.2023.1127489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 02/27/2023] [Indexed: 04/03/2023] Open
Abstract
Background Epidemiological characteristics of nonalcoholic fatty liver disease (NAFLD) in Chongqing, a west-central city of China, remain unclear. The objective of this study was to investigate the prevalence of NAFLD and the related risk factors among healthy adults for physical examination in Chongqing. Methods A total of 110,626 subjects were enrolled in the present study. Each of the participants underwent physical examination, laboratory measurements, and abdominal ultrasonography. The chi-square test was employed to compare differences in the NAFLD prevalence, and logistic regression analysis was used to estimate the odds ratio for risk factors of NAFLD. Results The prevalence of NAFLD in individuals in the population of Chongqing was 28.5%, and the prevalence in men (38.1%) was significantly higher than that in women (13.6%) (OR = 2.44; 95% CI: 2.31-2.58). NAFLD was more common in men aged 51-60 years and women over 60 years. Approximately 79.1% of the people with obesity and 52.1% of the people with central obesity had NAFLD. The prevalence of NAFLD in people with hypertension and cholelithiasis was 48.9 and 38.4%, respectively. Logistic regression showed that gender, age, body max index (BMI), central obesity, hypertension, impaired fasting glucose/diabetes mellitus (DM), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hyperuricemia (HUA), alanine transaminase (ALT), and cholelithiasis were independently associated with the presence of NAFLD. Conclusion The prevalence of NAFLD among healthy adults in Chongqing was high. To improve the prevention and management of NAFLD, special attention should be paid to the factors associated with the presence of NAFLD, including higher BMI, higher waist circumference, higher blood glucose, hypertension, hypertriglyceridemia, hyperuricemia, cholelithiasis, and elevated ALT.
Collapse
Affiliation(s)
- Lingxi Kong
- Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yang Yang
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Haidong Li
- Foreign Affairs Department of Scientific Research, Stomatological Hospital of Chongqing Medical University, Chongqing, China
| | - Youlan Shan
- Department of Infectious Disease, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xin Wang
- West China School of Public Health, Sichuan University, Chengdu, China
| | - Xuefeng Shan
- Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| |
Collapse
|
32
|
Song Q, Ling Q, Fan L, Deng Y, Gao Q, Yang R, Chen S, Wu S, Cai J. Severity of non-alcoholic fatty liver disease is a risk factor for developing hypertension from prehypertension. Chin Med J (Engl) 2023:00029330-990000000-00475. [PMID: 37027402 DOI: 10.1097/cm9.0000000000002111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Indexed: 04/08/2023] Open
Abstract
BACKGROUND There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension. METHODS The study cohort comprised 25, 433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD. RESULTS During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10-1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10-1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07-1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03-1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association. CONCLUSIONS NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.
Collapse
Affiliation(s)
- Qirui Song
- Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Qianhui Ling
- State Key Laboratory of Cardiovascular Disease of China, Fuwai Hospital, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Luyun Fan
- Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Yue Deng
- Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Qiannan Gao
- Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Ruixue Yang
- Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Shuohua Chen
- Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei 063000, China
| | - Shouling Wu
- Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei 063000, China
| | - Jun Cai
- Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| |
Collapse
|
33
|
Gheorghe L, Nemteanu R, Clim A, Botnariu GE, Costache II, Plesa A. Risk Scores for Prediction of Major Cardiovascular Events in Non-Alcoholic Fatty Liver Disease: A No Man's Land? Life (Basel) 2023; 13:life13040857. [PMID: 37109386 PMCID: PMC10146692 DOI: 10.3390/life13040857] [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: 02/16/2023] [Revised: 03/18/2023] [Accepted: 03/21/2023] [Indexed: 04/29/2023] Open
Abstract
Over the past 100 years, cardiovascular disease (CVD) has become a leading cause of mortality and morbidity in developed countries, and similar trends have occurred for chronic liver disease. Subsequent research also indicated that people with non-alcoholic fatty liver disease (NAFLD) had a twofold increased risk of CV events and that this risk was doubled in those with liver fibrosis. However, no validated CVD risk score specific for NAFLD patients has yet been validated, as traditional risk scores tend to underestimate the CV risk in NAFLD patients. From a practical perspective, identifying NAFLD patients and assessing severity of liver fibrosis when concurrent atherosclerotic risk factors are already established may serve as an important criterion in new CV risk scores. The current review aims to assess current risk scores and their utility for the prediction of CV events among patients with NAFLD.
Collapse
Affiliation(s)
- Liliana Gheorghe
- Department of Radiology, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
- Radiology Clinic, "St. Spiridon" County Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Roxana Nemteanu
- Medical I Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, Saint Spiridon Hospital, 700111 Iasi, Romania
| | - Andreea Clim
- Medical I Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Gina Eosefina Botnariu
- Diabetes, Nutrition and Metabolic Diseases Department, University of Medicine and Pharmacy "Gr. T. Popa", 700115 Iasi, Romania
| | - Irina Iuliana Costache
- Medical I Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
- Cardiology Clinic, "St. Spiridon" County Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Alina Plesa
- Medical I Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, Saint Spiridon Hospital, 700111 Iasi, Romania
| |
Collapse
|
34
|
Shim SY, Jung SJ, Kim SU, Kim HC. Ideal cardiovascular health metrics and the risk of nonalcoholic fatty liver disease in Korean adults. Clin Hypertens 2023; 29:3. [PMID: 36641485 PMCID: PMC9840828 DOI: 10.1186/s40885-022-00227-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 09/26/2022] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND The association between cardiovascular risk factors and nonalcoholic fatty liver disease (NAFLD) is well established, but whether cardiovascular health (CVH) metrics is associated with NAFLD had not been fully studied. Thus, we examined the association between CVH metrics and NAFLD in the middle-aged Korean population. METHODS We used data of 2,928 (851 men and 2,077 women) participants aged 30-64 years from the Cardiovascular and Metabolic Disease Etiology Research Center study. CVH metrics were measured using a modified version of Life's Simple 7 by the American Heart Association. NAFLD diagnosis was based on the fatty liver index or liver-to-spleen ratio on computed tomography. A multiple logistic regression model was used to investigate the cross-sectional and longitudinal associations between CVH metrics and NAFLD. RESULTS In the cross-sectional analysis, the odds ratio for NAFLD was lower in participants with ideal CVH (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.08-0.18), while it was higher in individuals with poor CVH (OR, 2.87; 95% CI, 2.13-3.86). Similarly, the risk of new-onset NAFLD was lower in participants with ideal CVH (OR, 0.28; 95% CI, 0.11-0.74), and higher in individuals with poor CVH (OR, 2.20; 95% CI, 0.50-9.72) in the longitudinal analysis of a subgroup. CONCLUSIONS Ideal CVH was associated with a lower risk of NAFLD while poor CVH was associated with a higher risk of NAFLD. These findings suggest that making efforts to encourage people to manage their CVH to the ideal level may prevent and manage NAFLD.
Collapse
Affiliation(s)
- Sun Young Shim
- College of Nursing, Yonsei University, Seoul, Republic of Korea
| | - Sun Jae Jung
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyeon Chang Kim
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Institute for Innovation in Digital Healthcare, Yonsei University Health System, Seoul, Republic of Korea.
| |
Collapse
|
35
|
Yang D, Lan J, Cen J, Han Y, Hu H. Association Between Hypertension and New-Onset Non-Alcoholic Fatty Liver Disease in Chinese Non-Obese People: A Longitudinal Cohort Study. Diabetes Metab Syndr Obes 2023; 16:345-363. [PMID: 36788988 PMCID: PMC9922508 DOI: 10.2147/dmso.s396011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 01/18/2023] [Indexed: 02/10/2023] Open
Abstract
BACKGROUND Quantification of the relationship between hypertension and non-alcoholic fatty liver disease (NAFLD) risk is limited and controversial. This study aimed to investigate the relationship between hypertension and NAFLD in non-obese Chinese and to use different methods to demonstrate that hypertension is an independent risk factor for NAFLD. METHODS On 16,153 nonobese individuals, a retrospective cohort study was conducted in China to examine the impact of hypertension on incident NAFLD. We compared five methods: multivariable Cox proportional-hazards regression, propensity score-matched (PSM) analysis, propensity score adjustment method (considering the propensity score as a covariate in a multivariable Cox proportional-hazard regression), and two propensity score-based weighted methods-The first one estimated the hypertension effect in the overall study population-inverse probability of treatment weights (IPTW), the other in the hypertensive population-standardized mortality ratio (SMR) weights. We also used a genetic matching (GenMatch) algorithm to match the participants for sensitive analysis. RESULTS Between 2010 and 2014, 16,153 participants met our inclusion criteria, including 2427 (15.03%) with hypertension. A total of 2321 (14.37%) participants developed NAFLD during the median follow-up of 2.98 years. The crude hazard ratio (HR) between hypertension and incident NAFLD was 2.05 (95% confidence interval (CI): 1.87, 2.25). The adjusted HR depended on the different methods, ranging from 1.09 (95% CI: 0.77, 1.23) for the PSM method to 2.24 (95% CI: 2.05, 2.44) for the SMR weighted analysis. Hypertensive participants with high propensity scores had a higher risk of developing NAFLD in the future. Excluding participants with propensity scores <8% yielded comparable hazard ratios with a narrower range, from 1.04 to 1.80. After adjusting for the confounding variables, the relationship also existed in the GenMatch cohort as a sensitivity analysis (HR=1.06, 95% CI 1.01-1.13). CONCLUSION Hypertension is a significant cause of NAFLD in Chinese adults in non-obese Chinese adults, with the hazard ratio ranging from 1.09 to 2.24.
Collapse
Affiliation(s)
- Dezhi Yang
- Department of Cardiology Second Ward, Hechi People’s Hospital, Hechi, People’s Republic of China
| | - Jing Lan
- Department of Gastroenterology, Hechi People’s Hospital, Hechi, People’s Republic of China
| | - Ji Cen
- Department of Nephrology, Hechi People’s Hospital, Hechi, People’s Republic of China
| | - Yong Han
- Department of Emergency, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China
- Department of Emergency, The First Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China
- Shenzhen University Health Science Center, Shenzhen University, Shenzhen, People’s Republic of China
- Correspondence: Yong Han, Department of Emergency, Shenzhen Second People’s Hospital, No. 3002 Sungang Road, Futian District, Shenzhen, Guangdong Province, People’s Republic of China, Tel +86-755-83366388, Email
| | - Haofei Hu
- Shenzhen University Health Science Center, Shenzhen University, Shenzhen, People’s Republic of China
- Department of Nephrology, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China
- Haofei Hu, Department of Nephrology, Shenzhen Second People’s Hospital, No. 3002 Sungang Road, Futian District, Shenzhen, Guangdong Province, People’s Republic of China, Tel +86-755-83366388, Email
| |
Collapse
|
36
|
Fan H, Xu C, Li W, Huang Y, Hua R, Xiong Y, Yang Y, Feng X, Wang Z, Yuan Z, Zhou J. Ideal Cardiovascular Health Metrics Are Associated with Reduced Severity of Hepatic Steatosis and Liver Fibrosis Detected by Transient Elastography. Nutrients 2022; 14:nu14245344. [PMID: 36558503 PMCID: PMC9780817 DOI: 10.3390/nu14245344] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/07/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
Life's Simple 7 (LS7) is the American Heart Association's (AHA) proposal for a healthy lifestyle, also known as cardiovascular health (CVH) metrics. However, the association between CVH metrics and the severity of hepatic steatosis and liver fibrosis detected by transient elastography is unknown. We performed a cross-sectional study using the data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) cycle. The controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were used to evaluate the severity of hepatic steatosis and liver fibrosis and to define NAFLD, advanced liver fibrosis, and cirrhosis. A total of 2679 participants were included. Multivariate linear regression analysis revealed that per 1-unit increase in the CVH metric, CAP and LSM decreased by 8.565 units and 0.274 units, respectively. In the multivariate logistic regression analysis, the risk of NAFLD, advanced liver fibrosis, and cirrhosis were 7, 10, and 6 times higher in the poor CVH group than in the ideal CVH group. Subgroup analysis indicated that CVD patients and non-Hispanic whites could benefit more from ideal CVH. In conclusion, adherence to ideal CVH metrics, as proposed by the AHA, can significantly reduce the risk of hepatic steatosis and liver fibrosis.
Collapse
Affiliation(s)
- Heze Fan
- Cardiovascular Department, First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, China
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an 710061, China
| | - Chenbo Xu
- Cardiovascular Department, First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, China
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an 710061, China
| | - Wenyuan Li
- Cardiovascular Department, First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, China
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an 710061, China
| | - Yuzhi Huang
- Cardiovascular Department, First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, China
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an 710061, China
| | - Rui Hua
- Cardiovascular Department, First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, China
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an 710061, China
| | - Ying Xiong
- Cardiovascular Department, First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, China
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an 710061, China
| | - Yuxuan Yang
- Cardiovascular Department, First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, China
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an 710061, China
| | - Xueying Feng
- Cardiovascular Department, First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, China
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an 710061, China
| | - Zihao Wang
- Cardiovascular Department, First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, China
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an 710061, China
| | - Zuyi Yuan
- Cardiovascular Department, First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, China
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an 710061, China
- Correspondence:
| | - Juan Zhou
- Cardiovascular Department, First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an 710061, China
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an 710061, China
| |
Collapse
|
37
|
Testino G, Pellicano R. Metabolic associated liver disease. Panminerva Med 2022; 64:555-563. [PMID: 36533665 DOI: 10.23736/s0031-0808.22.04730-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/28/2023]
Abstract
In real practice the patient with liver disease is often the carrier of multiple etiological factors such as metabolic syndrome (MS) and alcohol consumption (AC). Their copresence is often underestimated and AC is not adequately studied. Traditionally to diagnose non-alcoholic fatty liver disease (NAFLD), AC must not exceed 30 gr for men and 20 gr for women per day. This limit should still be reduced, especially in relation to the AC and fibrogenesis ratio and also frequent misestimation of AC or unrecognized MS may underestimate multi caused liver injury. AC is a contributing cause of MS and alcoholic and non-alcoholic liver disease have a substantially overlapping histopathological picture. Moreover, AC and MS are cause and contributing cause of extra-hepatic morbidity and mortality. It can be concluded that the possible simplification of terminology at metabolic associated liver disease (MALD) makes clinical activity more usable and immediate, facilitates better communication and cooperation between scientific societies and specialists who apparently deal with different medical sectors, facilitates early identification of related hepatic and extra-hepatic pathology, allows to "see the person in a unitary way," to create more streamlined care pathways, to reduce the hospitalization rate with relative cost-benefit advantage and to create unitary prevention and health promotion policies.
Collapse
Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology/Alcohological Regional Centre, ASL3 c/o Polyclinic San Martino Hospital, Genoa, Italy -
| | | |
Collapse
|
38
|
Le MH, Yeo YH, Li X, Li J, Zou B, Wu Y, Ye Q, Huang DQ, Zhao C, Zhang J, Liu C, Chang N, Xing F, Yan S, Wan ZH, Tang NSY, Mayumi M, Liu X, Liu C, Rui F, Yang H, Yang Y, Jin R, Le RHX, Xu Y, Le DM, Barnett S, Stave CD, Cheung R, Zhu Q, Nguyen MH. 2019 Global NAFLD Prevalence: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2022; 20:2809-2817.e28. [PMID: 34890795 DOI: 10.1016/j.cgh.2021.12.002] [Citation(s) in RCA: 367] [Impact Index Per Article: 122.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 11/25/2021] [Accepted: 12/02/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The increasing rates of obesity and type 2 diabetes mellitus may lead to increased prevalence of nonalcoholic fatty liver disease (NAFLD). We aimed to determine the current and recent trends on the global and regional prevalence of NAFLD. METHODS Systematic search from inception to March 26, 2020 was performed without language restrictions. Two authors independently performed screening and data extraction. We performed meta-regression to determine trends in NAFLD prevalence. RESULTS We identified 17,244 articles from literature search and included 245 eligible studies involving 5,399,254 individuals. The pooled global prevalence of NAFLD was 29.8% (95% confidence interval [CI], 28.6%-31.1%); of these, 82.5% of included articles used ultrasound to diagnose NAFLD, with prevalence of 30.6% (95% CI, 29.2%-32.0%). South America (3 studies, 5716 individuals) and North America (4 studies, 18,236 individuals) had the highest NAFLD prevalence at 35.7% (95% CI, 34.0%-37.5%) and 35.3% (95% CI, 25.4%-45.9%), respectively. From 1991 to 2019, trend analysis showed NAFLD increased from 21.9% to 37.3% (yearly increase of 0.7%, P < .0001), with South America showing the most rapid change of 2.7% per year, followed by Europe at 1.1%. CONCLUSIONS Despite regional variation, the global prevalence of NAFLD is increasing overall. Policy makers must work toward reversing the current trends by increasing awareness of NAFLD and promoting healthy lifestyle environments.
Collapse
Affiliation(s)
- Michael H Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Division of General Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, California
| | - Xiaohe Li
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Division of Infectious Disease, The Third People's Hospital of Shenzhen, Shenzhen, China
| | - Jie Li
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Biyao Zou
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California
| | - Yuankai Wu
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Infectious Diseases, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qing Ye
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; The Third Central Clinical College of Tianjin Medical University, Tianjin; Department of Hepatology of The Third Central Hospital of Tianjin; Tianjin Key Laboratory of Artificial Cells, Tianjin, China
| | - Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine and Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
| | - Changqing Zhao
- Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of T.C.M., Shanghai, China
| | - Jie Zhang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Chenxi Liu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Na Chang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Feng Xing
- Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of T.C.M., Shanghai, China
| | - Shiping Yan
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Zi Hui Wan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Natasha Sook Yee Tang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Maeda Mayumi
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Xinting Liu
- Medical School of Chinese People's Liberation Army, Beijing, and Department of Pediatrics, the First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Chuanli Liu
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Fajuan Rui
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Hongli Yang
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Yao Yang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Ruichun Jin
- Jining Medical University, Jining, Shandong, China
| | - Richard H X Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Yayun Xu
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - David M Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Scott Barnett
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | | | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
| | - Qiang Zhu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California.
| |
Collapse
|
39
|
Cattazzo F, Lombardi R, Mantovani A, Bevilacqua M, Zoncapè M, Iogna Prat L, Roccarina D, Fortuna L, Cespiati A, Sacerdoti D, Fracanzani AL, Tsochatzis E, Fava C, Dalbeni A. Subclinical and clinical atherosclerosis in non-alcoholic fatty liver disease is associated with the presence of hypertension. Nutr Metab Cardiovasc Dis 2022; 32:2839-2847. [PMID: 36404479 DOI: 10.1016/j.numecd.2022.08.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 07/31/2022] [Accepted: 08/03/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND AIMS Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular (CV) risk. However, it is unclear whether NAFLD contributes independently to the development of CV disease. Our study aimed at assessing the differences in several indices of atherosclerosis, arterial stiffness and cardiac morphology among patients with isolated NAFLD, isolated hypertension (HT) or a combination of the two conditions. METHODS AND RESULTS A total of 169 participants (mean age = 50.4 ± 10.2 yrs; males = 73.6%) were divided according to the presence of NAFLD and HT into three groups: only NAFLD (55 patients), only HT (49 patients), and NAFLD + HT (65 patients). Exclusion criteria were a BMI≥35 kg/m2 and a diagnosis of diabetes mellitus. Carotid ultrasonography was performed to measure markers of atherosclerosis and arterial stiffness. Cardiac remodeling was analyzed using echocardiography. The prevalence of subclinical and overt atherosclerosis was significantly higher in the NAFLD + HT patients as compared to the other two groups (atherosclerotic plaques: 43.1%, 10.9%, and 22.4% (p < 0.001) in NAFLD + HT, NAFLD, and HT groups, respectively). No differences were found among indices of arterial stiffening and cardiac remodeling across the three groups. In multivariate regression analysis, the coexistence of NAFLD and HT was an independent risk factor for overt atherosclerosis (OR = 4.88, CI 95% 1.14-20.93), while no association was found when either NAFLD or HT was considered alone. CONCLUSION Overt atherosclerosis was significantly present only in NAFLD + HT patients, but not in patients with isolated NAFLD. This implies that the impact of NAFLD on vascular structure and function could depend on the coexistence of other major CV risk factors, such as HT.
Collapse
Affiliation(s)
- Filippo Cattazzo
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
| | - Rosa Lombardi
- Unit of Internal Medicine and Metabolic Disease, Ca' Granda IRCCS Foundation, Policlinico Hospital, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Anna Mantovani
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy; UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
| | - Michele Bevilacqua
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Mirko Zoncapè
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Laura Iogna Prat
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
| | - Davide Roccarina
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
| | - Leonardo Fortuna
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Annalisa Cespiati
- Unit of Internal Medicine and Metabolic Disease, Ca' Granda IRCCS Foundation, Policlinico Hospital, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - David Sacerdoti
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Anna L Fracanzani
- Unit of Internal Medicine and Metabolic Disease, Ca' Granda IRCCS Foundation, Policlinico Hospital, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Emmanouil Tsochatzis
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
| | - Cristiano Fava
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Andrea Dalbeni
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| |
Collapse
|
40
|
Association between arterial hypertension and liver outcomes using polygenic risk scores: a population-based study. Sci Rep 2022; 12:15581. [PMID: 36114231 PMCID: PMC9481629 DOI: 10.1038/s41598-022-20084-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 09/08/2022] [Indexed: 12/03/2022] Open
Abstract
Arterial hypertension (HTA) is associated with liver disease, but causality remains unclear. We investigated whether genetic predisposition to HTA is associated with liver disease in the population, and if antihypertensive medication modifies this association. Participants of the Finnish health-examination surveys, FINRISK 1992–2012 and Health 2000 (n = 33,770), were linked with national electronic healthcare registers for liver-related outcomes (K70-K77, C22.0) and with the drug reimbursement registry for new initiation of antihypertensive medication during follow-up. Genetic predisposition to HTA was defined by polygenic risk scores (PRSs). During a median 12.9-year follow-up (409,268.9 person-years), 441 liver-related outcomes occurred. In the fully-adjusted Cox-regression models, both measured systolic blood pressure and clinically defined HTA were associated with liver-related outcomes. PRSs for systolic and diastolic blood pressure were significantly associated with liver-related outcomes (HR/SD 1.19, 95% CI 1.01–1.24, and 1.12, 95% CI 1.01–1.25, respectively). In the highest quintile of the systolic blood pressure PRS, new initiation of antihypertensive medication was associated with reduced rates of liver-related outcomes (HR 0.55, 95% CI 0.31–0.97). HTA and a genetic predisposition for HTA are associated with liver-related outcomes in the population. New initiation of antihypertensive medication attenuates this association in persons with high genetic risk for HTA.
Collapse
|
41
|
Roeb E, Canbay A, Bantel H, Bojunga J, de Laffolie J, Demir M, Denzer UW, Geier A, Hofmann WP, Hudert C, Karlas T, Krawczyk M, Longerich T, Luedde T, Roden M, Schattenberg J, Sterneck M, Tannapfel A, Lorenz P, Tacke F. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:1346-1421. [PMID: 36100202 DOI: 10.1055/a-1880-2283] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- E Roeb
- Gastroenterologie, Medizinische Klinik II, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - A Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - H Bantel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - J Bojunga
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin., Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - J de Laffolie
- Allgemeinpädiatrie und Neonatologie, Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - M Demir
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
| | - U W Denzer
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Marburg, Deutschland
| | - A Geier
- Medizinische Klinik und Poliklinik II, Schwerpunkt Hepatologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - W P Hofmann
- Gastroenterologie am Bayerischen Platz - Medizinisches Versorgungszentrum, Berlin, Deutschland
| | - C Hudert
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - T Karlas
- Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - M Krawczyk
- Klinik für Innere Medizin II, Gastroent., Hepat., Endokrin., Diabet., Ern.med., Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - T Longerich
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - T Luedde
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - M Roden
- Klinik für Endokrinologie und Diabetologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - J Schattenberg
- I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
| | - M Sterneck
- Klinik für Hepatobiliäre Chirurgie und Transplantationschirurgie, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - A Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - P Lorenz
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - F Tacke
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
| |
Collapse
|
42
|
Authors, Collaborators:. Updated S2k Clinical Practice Guideline on Non-alcoholic Fatty Liver Disease (NAFLD) issued by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) - April 2022 - AWMF Registration No.: 021-025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e733-e801. [PMID: 36100201 DOI: 10.1055/a-1880-2388] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
|
43
|
Kountouras J, Papaefthymiou A, Polyzos SA, Kazakos E, Vardaka E, Touloumtzi M, Tzitiridou-Chatzopoulou M, Liatsos C, Sgantzou IK, Knuchel J, Doulberis M. Impacto da Síndrome Metabólica Relacionada à Infecção por Helicobacter pylori Ativa na Hipertensão Arterial Sistêmica. Arq Bras Cardiol 2022; 119:502-504. [PMID: 36074383 PMCID: PMC9438526 DOI: 10.36660/abc.20210931] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
|
44
|
Muzurović E, Peng CCH, Belanger MJ, Sanoudou D, Mikhailidis DP, Mantzoros CS. Nonalcoholic Fatty Liver Disease and Cardiovascular Disease: a Review of Shared Cardiometabolic Risk Factors. Hypertension 2022; 79:1319-1326. [PMID: 35465684 DOI: 10.1161/hypertensionaha.122.17982] [Citation(s) in RCA: 78] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) is rising. NAFLD/nonalcoholic steatohepatitis (NASH) is associated not only with hepatic morbidity and mortality but also with an increased cardiovascular risk. NAFLD and cardiovascular disease (CVD) share several risk factors, such as obesity, metabolic syndrome, hypertension, dyslipidemia, type 2 diabetes, and chronic kidney disease. This review summarizes the evidence linking cardiometabolic risk factors and NAFLD in the context of risk for CVD. The cause of NAFLD/NASH is complex, involving a range of factors from genetics to lifestyle and energy balance. Genetically driven high liver fat content does not appear to be causally associated with increased CVD risk. In contrast, metabolic dysfunction not only predisposes to liver pathology but also leads to a significantly higher CVD risk. Given that NAFLD pathophysiology is influenced by multiple factors, each patient is unique as to their risk of developing CVD and liver pathology. At the same time, the rising burden of NAFLD/NASH is closely linked with the global increase in metabolic disorders, including obesity and type 2 diabetes. Therefore, both personalized therapeutic approaches that recognize individual pathophysiology, as well as public health policies that address the root causes of cardiometabolic risk factors for NAFLD may be needed to effectively address the NAFLD/NASH epidemic.
Collapse
Affiliation(s)
- Emir Muzurović
- Department of Internal Medicine, Endocrinology Section, Clinical Centre of Montenegro, Podgorica (E.M.).,Faculty of Medicine, University of Montenegro, Podgorica, Montenegro (E.M.)
| | - Carol Chiung-Hui Peng
- Section of Endocrinology, Diabetes, Nutrition & Weight Management, Boston University School of Medicine, Boston, MA (C.C.-H.P.)
| | | | - Despina Sanoudou
- Clinical Genomics and Pharmacogenomics Unit, 4 Department of Internal Medicine, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Greece (D.S.).,Biomedical Research Foundation of the Academy of Athens, Greece (D.S.)
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London, Medical School, University College London (UCL), United Kingdom (D.P.M.).,Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai (D.P.M.)
| | - Christos S Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.M.)
| |
Collapse
|
45
|
Koralegedara IS, Warnasekara JN, Rathnayake A, Dayaratne KG, Agampodi SB. Fatty Liver Index is a valid predictor of non-alcoholic fatty liver disease (NAFLD) in pregnancy. BMJ Open Gastroenterol 2022; 9:e000913. [PMID: 35728866 PMCID: PMC9214354 DOI: 10.1136/bmjgast-2022-000913] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 05/31/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Despite the evidence for adverse pregnancy outcomes, non-alcoholic fatty liver disease (NAFLD) is not routinely addressed in early pregnancy. The Fatty Liver Index (FLI) has been proposed as a screening tool for NAFLD in the general population. We aim to develop mathematical models for predicting NAFLD in pregnancy and validate the FLI for first-trimester pregnant women. METHODS Biochemical and biophysical parameters were analysed in pregnant women with period of gestation <12 weeks was done among Rajarata Pregnancy Cohort, Sri Lanka. Fatty liver was graded as (FLG) 0, I or II by ultrasound scan. Binary logistic regression models were employed to identify the factors predicting FLG-II. Six FLIs were developed to predict FLG-II. Validity of the FLIs was compared using the receiver operating characteristic curves. RESULTS The study sample consisted of 632 pregnant women with a mean age of 28.8 years (SD: 5.8 years). Age (OR: 1.6, 95% CI 1.1 to 2.3), body mass index (OR: 1.7, 95% CI 1.1 to 2.5) and gamma-glutamyl transferase levels (OR: 2.1, 95% CI 1.5 to 3.0) were the independent predictors of FLG-II. While the model with liver enzymes provided the best prediction of NAFLD (both FLG I and II) (area under the curve [(AUC]): -0.734), the highest AUC (0.84) for predicting FLG-II was observed with the full model (model with all parameters). The proposed budget model (AUC >0.81) is the best model for screening fatty liver in community health setup. CONCLUSION FLIs could be used as screening tools for NAFLD based on resource availability in different settings. External validation of the FLI and further investigation of the proposed FLI as a predictor of adverse pregnancy outcomes are recommended.
Collapse
Affiliation(s)
| | - Janith Niwanthaka Warnasekara
- Department of Community Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka
| | - Ashani Rathnayake
- Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka
| | | | - Suneth Buddhika Agampodi
- Department of Community Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka
| |
Collapse
|
46
|
Hassen G, Singh A, Belete G, Jain N, De la Hoz I, Camacho-Leon GP, Dargie NK, Carrera KG, Alemu T, Jhaveri S, Solomon N. Nonalcoholic Fatty Liver Disease: An Emerging Modern-Day Risk Factor for Cardiovascular Disease. Cureus 2022; 14:e25495. [PMID: 35783879 PMCID: PMC9242599 DOI: 10.7759/cureus.25495] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 05/30/2022] [Indexed: 11/05/2022] Open
|
47
|
Liu YH, Chen SC, Lee WH, Chen YC, Huang JC, Wu PY, Hung CH, Kuo CH, Su HM. Liver-function parameters are associated with incident hypertension in a large Taiwanese population follow-up study. J Hum Hypertens 2022:10.1038/s41371-022-00694-w. [PMID: 35618874 DOI: 10.1038/s41371-022-00694-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 03/27/2022] [Accepted: 04/07/2022] [Indexed: 11/09/2022]
Abstract
Previous studies demonstrated inconsistent results regarding the association between liver function and hypertension. In addition, large cohort follow-up studies are lacking. Therefore, this longitudinal study aimed to investigate the association between liver function and incident hypertension using data from the Taiwan Biobank (TWB). We evaluated liver biomarkers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, alpha-fetoprotein (AFP), total bilirubin, and gamma-glutamyl transferase (GGT) in this study. A total of 21,293 participants without hypertension at baseline were analyzed. During the mean 3.9-year follow-up, 3002 participants developed hypertension (defined as incident hypertension). Multivariable analysis revealed that high AST (odds ratio [OR], 1.004; 95% confidence interval [CI], 1.001-1.007; p = 0.014), high ALT (OR, 1.004; 95% CI, 1.002-1.006; p < 0.001), high albumin (OR, 1.897; 95% CI, 1.573-2.286; p < 0.001), and high GGT (OR, 1.004; 95% CI, 1.003-1.005; p < 0.001) were significantly associated with incident hypertension in all study participants. In subgroup analysis of the participants with an ALT level ≤2 times the normal limit (80 u/l) (n = 20,983), multivariable analysis demonstrated that high ALT (OR, 1.009; 95% CI, 1.005-1.012; p < 0.001) and high GGT (OR, 1.005; 95% CI, 1.003-1.006; p < 0.001) were significantly associated with incident hypertension. In conclusion, we found that elevated AST, ALT, albumin, and GGT were associated with incident hypertension in a large Taiwanese cohort. A greater understanding of potential risk factors for hypertension may help to reduce the burden of hypertension in this Taiwanese population.
Collapse
Affiliation(s)
- Yi-Hsueh Liu
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan.,Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Szu-Chia Chen
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan.,Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wen-Hsien Lee
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan.,Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ying-Chih Chen
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan.,Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Jiun-Chi Huang
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan.,Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pei-Yu Wu
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan
| | - Chih-Hsing Hung
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chao-Hung Kuo
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan.,Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ho-Ming Su
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan. .,Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. .,Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| |
Collapse
|
48
|
Branković M, Jovanović I, Dukić M, Radonjić T, Oprić S, Klašnja S, Zdravković M. Lipotoxicity as the Leading Cause of Non-Alcoholic Steatohepatitis. Int J Mol Sci 2022; 23:ijms23095146. [PMID: 35563534 PMCID: PMC9105530 DOI: 10.3390/ijms23095146] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 04/30/2022] [Accepted: 04/30/2022] [Indexed: 12/11/2022] Open
Abstract
The emerging issues nowadays are non-alcoholic fatty liver disease (NAFLD) and its advanced stage non-alcoholic steatohepatitis (NASH), which further can be a predisposing factor for chronic liver complications, such as cirrhosis and/or development of hepatocellular carcinoma (HCC). Liver lipotoxicity can influence the accumulation of reactive oxygen species (ROS), so oxidative stress is also crucial for the progression of NASH. Moreover, NASH is in strong connection with metabolic disorders, and supporting evidence shows that insulin resistance (IR) is in a close relation to NAFLD, as it is involved in the progression to NASH and further progression to hepatic fibrosis. The major issue is that, at the moment, NASH treatment is based on lifestyle changes only due to the fact that no approved therapeutic options are available. The development of new therapeutic strategies should be conducted towards the potential NAFLD and NASH treatment by the modulation of IR but also by dietary antioxidants. As it seems, NASH is going to be the leading indication for liver transplantation as a consequence of increased disease prevalence and the lack of approved treatment; thus, an effective solution is needed as soon as possible.
Collapse
Affiliation(s)
- Marija Branković
- University Hospital Medical Center Bežanijska kosa, Dr Žorža Matea bb, 11000 Belgrade, Serbia; (I.J.); (M.D.); (T.R.); (S.O.); (S.K.); (M.Z.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
- Correspondence:
| | - Igor Jovanović
- University Hospital Medical Center Bežanijska kosa, Dr Žorža Matea bb, 11000 Belgrade, Serbia; (I.J.); (M.D.); (T.R.); (S.O.); (S.K.); (M.Z.)
| | - Marija Dukić
- University Hospital Medical Center Bežanijska kosa, Dr Žorža Matea bb, 11000 Belgrade, Serbia; (I.J.); (M.D.); (T.R.); (S.O.); (S.K.); (M.Z.)
| | - Tijana Radonjić
- University Hospital Medical Center Bežanijska kosa, Dr Žorža Matea bb, 11000 Belgrade, Serbia; (I.J.); (M.D.); (T.R.); (S.O.); (S.K.); (M.Z.)
| | - Svetlana Oprić
- University Hospital Medical Center Bežanijska kosa, Dr Žorža Matea bb, 11000 Belgrade, Serbia; (I.J.); (M.D.); (T.R.); (S.O.); (S.K.); (M.Z.)
| | - Slobodan Klašnja
- University Hospital Medical Center Bežanijska kosa, Dr Žorža Matea bb, 11000 Belgrade, Serbia; (I.J.); (M.D.); (T.R.); (S.O.); (S.K.); (M.Z.)
| | - Marija Zdravković
- University Hospital Medical Center Bežanijska kosa, Dr Žorža Matea bb, 11000 Belgrade, Serbia; (I.J.); (M.D.); (T.R.); (S.O.); (S.K.); (M.Z.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
| |
Collapse
|
49
|
Comprehensive Review and Updates on Holistic Approach Towards Non-Alcoholic Fatty Liver Disease Management with Cardiovascular Disease. Curr Atheroscler Rep 2022; 24:515-532. [PMID: 35507280 DOI: 10.1007/s11883-022-01027-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/01/2022] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW The global prevalence of non-alcoholic fatty liver disease (NAFLD) presents an unmet need in treating these, often asymptomatic, individuals. In this review, we summarised NAFLD management and described recent developments in non-alcoholic steatohepatitis (NASH) therapeutics that can shape the future of NAFLD. RECENT FINDINGS A multi-disciplinary effort in promoting sustainable lifestyle measures is paramount, with the goal of either limiting energy surplus alone or in combination with targeting downstream pathways of inflammation and fibrosis. Several antidiabetic medications like PPAR-γ agonist and glucagon-like peptide receptor agonists have beneficial effects on the metabolic profile as well as NASH histology. Vitamin E has shown promise in specific groups of patients with the haptoglobin2 allele protein. Newer drugs have demonstrated promising results in NASH resolution and fibrosis improvement such as obeticholic acid, resmetirom, aramchol, efruxifermin, aldafermin and lanifibranor. Apart from discussing the results of late stage clinical trials and the possible challenges in managing these patients with limited approved therapies, we also discussed the specific management of comorbidities (diabetes, hypertension, hyperlipidaemia, cardiovascular diseases) in NAFLD patients. Treatment strategy needs to target improvements in liver-related outcomes and cardiometabolic profile.
Collapse
|
50
|
Song Q, Liu S, Ling QH, Gao QN, Yang RX, Chen SH, Wu S, Chen ML, Cai J. Severity of Nonalcoholic Fatty Liver Disease is Associated With Cardiovascular Outcomes in Patients With Prehypertension or Hypertension: A Community-Based Cohort Study. Front Endocrinol (Lausanne) 2022; 13:942647. [PMID: 36093080 PMCID: PMC9453754 DOI: 10.3389/fendo.2022.942647] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 06/15/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND It is unclear whether more severe non-alcoholic fatty liver disease (NAFLD) combined with prehypertension or hypertension is associated with a higher risk of cardiovascular events (CVEs). To evaluate the relationship between the severity of NAFLD and CVEs among patients with prehypertension or hypertension. METHODS In this prospective community-based Kailuan cohort, participants without cardiovascular disease and alcohol abuse, or other liver diseases were enrolled. NAFLD was diagnosed by abdominal ultrasonography. Prehypertension was defined as systolic blood pressure (BP) of 120-139 mmHg or diastolic BP of 80-89 mmHg. Participants with NAFLD were divided into mild, moderate, and severe subgroups. Follow-up for CVEs including myocardial infarction, hemorrhagic stroke, and ischemic stroke. The Cox proportional hazards model was used to estimate hazard ratios and 95% CIs of CVEs according to the severity of NAFLD and hypertensive statutes. The C-statistic was used to evaluate the efficiency of models. RESULTS A total of 71926 participants (mean [SD] age, 51.83 [12.72] years, 53794 [74.79%] men, and 18132 [25.21%] women) were enrolled in this study, 6,045 CVEs occurred during a median of 13.02 (0.65) years of follow-up. Compared with participants without NAFLD, the hazard ratios of CVEs for patients with mild, moderate, and severe NAFLD were 1.143 (95% CI 1.071-1.221, P < 0.001), 1.218 (95% CI 1.071-1.221, P < 0.001), and 1.367 (95% CI 1.172-1.595, P < 0.001), respectively. Moreover, participants with prehypertension plus moderate/severe NAFLD and those with hypertension plus moderate/severe NAFLD had 1.558-fold (95% CI 1.293-1.877, P < 0.001) and 2.357-fold (95% CI 2.063-2.691, P < 0.001) higher risks of CVEs, respectively, compared with those with normal BP and no NAFLD. Adding a combination of NAFLD and BP status to the crude Cox model increased the C-statistic by 0.0130 (0.0115-0.0158, P < 0.001). CONCLUSIONS Our findings indicated that the increased cardiovascular risk with elevated BP is largely driven by the coexistence of moderate/severe NAFLD, suggesting that the severity of NAFLD may help further stratify patients with prehypertension and hypertension.
Collapse
Affiliation(s)
- Qi–Rui Song
- State Key Laboratory of Cardiovascular Disease of China, Hypertension Center, Fuwai Hospital, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuo–Lin Liu
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China
| | - Qian-Hui Ling
- State Key Laboratory of Cardiovascular Disease of China, Hypertension Center, Fuwai Hospital, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qian-Nan Gao
- State Key Laboratory of Cardiovascular Disease of China, Hypertension Center, Fuwai Hospital, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Rui-Xue Yang
- State Key Laboratory of Cardiovascular Disease of China, Hypertension Center, Fuwai Hospital, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuo-Hua Chen
- Department of Cardiology, Kailuan General Hospital, Tangshan, China
| | - Shou–Ling Wu
- Department of Cardiology, Kailuan General Hospital, Tangshan, China
- *Correspondence: Shou–Ling Wu, ; Mu-Lei Chen, ; Jun Cai,
| | - Mu-Lei Chen
- Heart Center and Beijing Key Laboratory of Hypertension, Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
- *Correspondence: Shou–Ling Wu, ; Mu-Lei Chen, ; Jun Cai,
| | - Jun Cai
- State Key Laboratory of Cardiovascular Disease of China, Hypertension Center, Fuwai Hospital, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Shou–Ling Wu, ; Mu-Lei Chen, ; Jun Cai,
| |
Collapse
|