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Giangregorio F, Mosconi E, Debellis MG, Provini S, Esposito C, Garolfi M, Oraka S, Kaloudi O, Mustafazade G, Marín-Baselga R, Tung-Chen Y. A Systematic Review of Metabolic Syndrome: Key Correlated Pathologies and Non-Invasive Diagnostic Approaches. J Clin Med 2024; 13:5880. [PMID: 39407941 PMCID: PMC11478146 DOI: 10.3390/jcm13195880] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 09/26/2024] [Accepted: 09/27/2024] [Indexed: 10/20/2024] Open
Abstract
Background and Objectives: Metabolic syndrome (MetS) is a condition marked by a complex array of physiological, biochemical, and metabolic abnormalities, including central obesity, insulin resistance, high blood pressure, and dyslipidemia (characterized by elevated triglycerides and reduced levels of high-density lipoproteins). The pathogenesis develops from the accumulation of lipid droplets in the hepatocyte (steatosis). This accumulation, in genetically predisposed subjects and with other external stimuli (intestinal dysbiosis, high caloric diet, physical inactivity, stress), activates the production of pro-inflammatory molecules, alter autophagy, and turn on the activity of hepatic stellate cells (HSCs), provoking the low grade chronic inflammation and the fibrosis. This syndrome is associated with a significantly increased risk of developing type 2 diabetes mellitus (T2D), cardiovascular diseases (CVD), vascular, renal, pneumologic, rheumatological, sexual, cutaneous syndromes and overall mortality, with the risk rising five- to seven-fold for T2DM, three-fold for CVD, and one and a half-fold for all-cause mortality. The purpose of this narrative review is to examine metabolic syndrome as a "systemic disease" and its interaction with major internal medicine conditions such as CVD, diabetes, renal failure, and respiratory failure. It is essential for internal medicine practitioners to approach this widespread condition in a "holistic" rather than a fragmented manner, particularly in Western countries. Additionally, it is important to be aware of the non-invasive tools available for assessing this condition. Materials and Methods: We conducted an exhaustive search on PubMed up to July 2024, focusing on terms related to metabolic syndrome and other pathologies (heart, Lung (COPD, asthma, pulmonary hypertension, OSAS) and kidney failure, vascular, rheumatological (osteoarthritis, rheumatoid arthritis), endocrinological, sexual pathologies and neoplastic risks. The review was managed in accordance with the PRISMA statement. Finally, we selected 300 studies (233 papers for the first search strategy and 67 for the second one). Our review included studies that provided insights into metabolic syndrome and non-invasive techniques for evaluating liver fibrosis and steatosis. Studies that were not conducted on humans, were published in languages other than English, or did not assess changes related to heart failure were excluded. Results: The findings revealed a clear correlation between metabolic syndrome and all the pathologies above described, indicating that non-invasive assessments of hepatic fibrosis and steatosis could potentially serve as markers for the severity and progression of the diseases. Conclusions: Metabolic syndrome is a multisystem disorder that impacts organs beyond the liver and disrupts the functioning of various organs. Notably, it is linked to a higher incidence of cardiovascular diseases, independent of traditional cardiovascular risk factors. Non-invasive assessments of hepatic fibrosis and fibrosis allow clinicians to evaluate cardiovascular risk. Additionally, the ability to assess liver steatosis may open new diagnostic, therapeutic, and prognostic avenues for managing metabolic syndrome and its complications, particularly cardiovascular disease, which is the leading cause of death in these patients.
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Affiliation(s)
- Francesco Giangregorio
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Emilio Mosconi
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Maria Grazia Debellis
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Stella Provini
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Ciro Esposito
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Matteo Garolfi
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Simona Oraka
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Olga Kaloudi
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Gunel Mustafazade
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Raquel Marín-Baselga
- Department of Internal Medicine, Hospital Universitario La Paz, Paseo Castellana 241, 28046 Madrid, Spain;
| | - Yale Tung-Chen
- Department of Internal Medicine, Hospital Universitario La Paz, Paseo Castellana 241, 28046 Madrid, Spain;
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Khoshbaten M, Maleki SH, Hadad S, Baral A, Rocha AV, Poudel L, Abdshah A. Association of nonalcoholic fatty liver disease and carotid media-intima thickness: A systematic review and a meta-analysis. Health Sci Rep 2023; 6:e1554. [PMID: 37701352 PMCID: PMC10493365 DOI: 10.1002/hsr2.1554] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 07/04/2023] [Accepted: 08/29/2023] [Indexed: 09/14/2023] Open
Abstract
Introduction The relationship between cardiovascular disorders and nonalcoholic fatty liver disease (NAFLD) has been extensively studied. To better pool this data and make a more definite conclusion, we performed a meta-analysis to evaluate the association between NAFLD and the thickness of media and intima of carotid artery (CIMT) and cardiovascular disorders. Methods We searched PubMed, Ovid, Scopus, ProQuest, Web of Science, and the Cochrane Library, and analyzed the pooled data using R studio and the "metafor" package. Results The final analysis included a total of 59 studies with 16,179 cases and 26,120 control individuals. NAFLD was shown to be associated with an increase of 0.1231 mm (20.6%) in carotid artery intima-media thickness (CIMT) (p = 0.002, 95% confidence interval [CI]: 0.0462-0.2000) in individuals with NAFLD. The prevalence of atherosclerotic plaques in the carotid arteries and the occurrence of NAFLD are significantly correlated, according to a meta-analysis based on 17 distinct studies (p = 0.001, 1.28-1.43, 95% CI, odds ratio = 1.356). Conclusion Patients with increased CIMT are considerably more likely to have NAFLD. Large prospective investigations are required to corroborate these findings and their prognostic significance, along with the effectiveness of the available interventions.
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Affiliation(s)
- Manouchehr Khoshbaten
- Liver and Gastrointestinal Diseases Research CenterTabriz University of Medical SciencesTabrizIran
| | - Sepideh H. Maleki
- Department of PathologyImam Reza Hospital, Tabriz University of Medical SciencesTabrizIran
| | - Sara Hadad
- Liver and Gastrointestinal Diseases Research CenterTabriz University of Medical SciencesTabrizIran
| | - Amrit Baral
- Department of Public Health SciencesMiller School of Medicine, University of MiamiMiamiFloridaUSA
| | - Ana V. Rocha
- Department of Public Health SciencesMiller School of Medicine, University of MiamiMiamiFloridaUSA
| | | | - Alireza Abdshah
- Department of Public Health SciencesMiller School of Medicine, University of MiamiMiamiFloridaUSA
- School of MedicineTehran University of Medical SciencesTehranIran
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Wong MYZ, Yap JJL, Sultana R, Cheah M, Goh GBB, Yeo KK. Association between non-alcoholic fatty liver disease and subclinical atherosclerosis in Western and Asian cohorts: an updated meta-analysis. Open Heart 2021; 8:openhrt-2021-001850. [PMID: 34933963 PMCID: PMC8693165 DOI: 10.1136/openhrt-2021-001850] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 10/25/2021] [Indexed: 11/16/2022] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is a well-established risk factor for cardiovascular disease, with ethnic and regional differences noted. With the recent surge of research within this field, we re-examine the evidence associating NAFLD with subclinical atherosclerosis, and investigate potential regional differences. Methods This is a systematic review and meta-analysis. PubMed and EMBASE were systematically searched for publications from January 1967 to July 2020 using standardised criteria. Original, observational studies investigating the association between NAFLD and either carotid intima-media thickness (CIMT) and/or coronary artery calcification (CAC) were included. Key outcomes included differences in mean CIMT, the presence of increased CIMT, the presence of CAC and the development/progression of CAC. Pooled ORs and pooled standard differences in means were calculated using random-effects models. Between-study heterogeneity was quantified using the Q statistic and I². Subgroup analyses stratified by region of study (Asian vs Western) were also conducted. Results 64 studies involving a total of 172 385 participants (67 404 with NAFLD) were included. 44 studies assessed the effect of NAFLD on CIMT, with the presence of NAFLD associated with increased CIMT (OR 2.00, 95% CI 1.56 to 2.56). 22 studies assessed the effects of NAFLD on CAC score, with the presence of NAFLD associated with the presence of any coronary calcification (OR 1.21, 95% CI 1.12 to 1.32), and the development/progression of CAC (OR 1.26, 95% CI 1.04 to 1.52). When stratified by region, these associations remained consistent across both Asian and Western populations (p>0.05). The majority (n=39) of studies were classified as ‘high quality’, with the remaining 25 of ‘moderate quality’. Conclusions There is a significant positive association between various measures of subclinical atherosclerosis and NAFLD, seen across both Western and Asian populations. These results re-emphasise the importance of early risk evaluation and prophylactic intervention measures to preclude progression to clinical cardiovascular disease in patients with NAFLD.
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Affiliation(s)
| | - Jonathan Jiunn Liang Yap
- Department of Cardiology, National Heart Center Singapore, Singapore.,Duke-NUS Medical School, Singapore
| | | | - Mark Cheah
- Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore
| | - George Boon Bee Goh
- Duke-NUS Medical School, Singapore.,Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore
| | - Khung Keong Yeo
- Department of Cardiology, National Heart Center Singapore, Singapore .,Duke-NUS Medical School, Singapore
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Muzurović E, Mikhailidis DP, Mantzoros C. Non-alcoholic fatty liver disease, insulin resistance, metabolic syndrome and their association with vascular risk. Metabolism 2021; 119:154770. [PMID: 33864798 DOI: 10.1016/j.metabol.2021.154770] [Citation(s) in RCA: 164] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/25/2021] [Accepted: 03/27/2021] [Indexed: 02/07/2023]
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases, is rising. About 25% of adults worldwide are probably affected by NAFLD. Insulin resistance (IR) and fat accumulation in the liver are strongly related. The association between NAFLD, metabolic syndrome (MetS) and IR is established, but an independent impact of NAFLD on vascular risk and progression of cardiovascular (CV) disease (CVD) still needs to be confirmed. This narrative review considers the evidence regarding the link between NAFLD, IR and CVD risk. There is strong evidence for a "concomitantly rising incidence" of NAFLD, IR, MetS and CVD but there is no definitive evidence regarding whether NAFLD is, or is not, an independent and significant risk factor the development of CVD. There are also considerations that type 2 diabetes mellitus (T2DM) may be a common link between NAFLD/non-alcoholic steatohepatitis (NASH) and CVD. NAFLD may be associated with widespread abnormal peri-organ or intra-organ fat (APIFat) deposition (e.g. epicardial adipose tissue) which may further contribute to CV risk. It is clear that NAFLD patients have a greater CV risk (independent or not) which needs to be addressed in clinical practice.
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Affiliation(s)
- Emir Muzurović
- Department of Internal Medicine, Endocrinology Section, Clinical Centre of Montenegro, Ljubljanska bb, 81000 Podgorica, Montenegro; Faculty of Medicine, University of Montenegro, Kruševac bb, 81000 Podgorica, Montenegro.
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), Pond Street, London NW3 2QG, UK; Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Christos Mantzoros
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA 02115, USA
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Translational insight into prothrombotic state and hypercoagulation in nonalcoholic fatty liver disease. Thromb Res 2020; 198:139-150. [PMID: 33340925 DOI: 10.1016/j.thromres.2020.12.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 11/17/2020] [Accepted: 12/07/2020] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an emerging and threatening pathological condition, ranging from fatty liver (FL) to chronic steatohepatitis (NASH), liver cirrhosis, and eventually to hepatocellular carcinoma (HCC). Recent findings suggest that patients with NAFLD have a higher risk of cardiovascular events and thromboembolism and that this risk is independent of metabolic diseases that are frequently associated with NAFLD, such as diabetes, hyperlipidaemia, and obesity. The vascular involvement of NAFLD might be considered its systemic burden, conditioning higher mortality in patients affected by the disease. These clinical findings suggested the existence of a prothrombotic state in NAFLD, which is partially unexplored and whose underlying mechanisms are to date not completely understood. Here, we review the mechanisms involved in the pathogenesis of the prothrombotic state in NAFLD across the progression from the healthy liver through the different stages of the disease. We focused on the possible role of several metabolic features of NAFLD possibly leading to hypercoagulation other than endothelial and platelet activation, such as insulin-resistance, nitric oxide production regulation, and gut microbiota homeostasis. Also, we analysed the involvement of plasminogen activator inhibitor-1 (PAI-1) and thromboinflammation taking place in NAFLD. Finally, we described factors striking a prothrombotic imbalance in NASH cirrhosis, with a particular focus on the pathogenesis of portal vein thrombosis.
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Lonardo A, Leoni S, Alswat KA, Fouad Y. History of Nonalcoholic Fatty Liver Disease. Int J Mol Sci 2020; 21:5888. [PMID: 32824337 PMCID: PMC7460697 DOI: 10.3390/ijms21165888] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 08/10/2020] [Accepted: 08/12/2020] [Indexed: 12/15/2022] Open
Abstract
Based on the assumption that characterizing the history of a disease will help in improving practice while offering a clue to research, this article aims at reviewing the history of nonalcoholic fatty liver disease (NAFLD) in adults and children. To this end, we address the history of NAFLD histopathology, which begins in 1980 with Ludwig's seminal studies, although previous studies date back to the 19th century. Moreover, the principal milestones in the definition of genetic NAFLD are summarized. Next, a specific account is given of the evolution, over time, of our understanding of the association of NAFLD with metabolic syndrome, spanning from the outdated concept of "NAFLD as a manifestation of the Metabolic Syndrome", to the more appropriate consideration that NAFLD has, with metabolic syndrome, a mutual and bi-directional relationship. In addition, we also report on the evolution from first intuitions to more recent studies, supporting NAFLD as an independent risk factor for cardiovascular disease. This association probably has deep roots, going back to ancient Middle Eastern cultures, wherein the liver had a significance similar to that which the heart holds in contemporary society. Conversely, the notions that NAFLD is a forerunner of hepatocellular carcinoma and extra-hepatic cancers is definitely more modern. Interestingly, guidelines issued by hepatological societies have lagged behind the identification of NAFLD by decades. A comparative analysis of these documents defines both shared attitudes (e.g., ultrasonography and lifestyle changes as the first approaches) and diverging key points (e.g., the threshold of alcohol consumption, screening methods, optimal non-invasive assessment of liver fibrosis and drug treatment options). Finally, the principal historical steps in the general, cellular and molecular pathogenesis of NAFLD are reviewed. We conclude that an in-depth understanding of the history of the disease permits us to better comprehend the disease itself, as well as to anticipate the lines of development of future NAFLD research.
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Affiliation(s)
- Amedeo Lonardo
- Ospedale Civile di Baggiovara, UOC Medicina Metabolica, Dipartimento di Medicina Interna Generale, d’Urgenza e post Acuzie, Azienda Ospedaliero-Universitaria di Modena, Via Giardini 1135, 41125 Modena, Italy
| | - Simona Leoni
- Internal Medicine Unit, Department of Digestive Diseases, S.Orsola-Malpighi Hospital, Via Massarenti 9, 40136 Bologna, Italy;
| | - Khalid A. Alswat
- Liver Research Center, Department of Medicine, College of Medicine, King Saud University, Riyadh 11322, Saudi Arabia;
| | - Yasser Fouad
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University, Minya 19111, Egypt;
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Chi ZC. Relationship between non-alcoholic fatty liver disease and cardiovascular disease. Shijie Huaren Xiaohua Zazhi 2020; 28:313-329. [DOI: 10.11569/wcjd.v28.i9.313] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
With the in-depth study of non-alcoholic fatty liver disease (NAFLD), it has been found in recent years that NAFLD is closely related to cardiovascular disease (CVD). It has been proved that NAFLD is not only an important risk factor for CVD, but it is also an important mechanism of atherosclerosis, coronary heart disease, and hypertension in young people. This article reviews the recent progress in the understanding of the relationship between NAFLD and CVD, with an aim to improve the knowledge of CVD physicians on liver disease and provide reference for prevention and treatment of these conditions.
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Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
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Sanghera DK, Bejar C, Sharma S, Gupta R, Blackett PR. Obesity genetics and cardiometabolic health: Potential for risk prediction. Diabetes Obes Metab 2019; 21:1088-1100. [PMID: 30667137 PMCID: PMC6530772 DOI: 10.1111/dom.13641] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 01/17/2019] [Accepted: 01/19/2019] [Indexed: 02/06/2023]
Abstract
The increasing burden of obesity worldwide and its effect on cardiovascular disease (CVD) risk is an opportunity for evaluation of preventive approaches. Both obesity and CVD have a genetic background and polymorphisms within genes which enhance expression of variant proteins that influence CVD in obesity. Genome-based prediction may therefore be a feasible strategy, but the identification of genetically driven risk factors for CVD manifesting as clinically recognized phenotypes is a major challenge. Clusters of such risk factors include hyperglycaemia, hypertension, ectopic liver fat, and inflammation. All involve multiple genetic pathways having complex interactions with variable environmental influences. The factors that make significant contributions to CVD risk include altered carbohydrate homeostasis, ectopic deposition of fat in muscle and liver, and inflammation, with contributions from the gut microbiome. A futuristic model depends on harnessing the predictive power of plausible genetic variants, phenotype reversibility, and effective therapeutic choices based on genotype-phenotype interactions. Inverting disease phenotypes into ideal cardiovascular health metrics could improve genetic and epigenetic assessment, and form the basis of a future model for risk detection and early intervention.
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Affiliation(s)
- Dharambir K. Sanghera
- Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Cynthia Bejar
- Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Sonali Sharma
- Department of Biochemistry, College of Medical Sciences, Rajasthan University of Health Sciences, Kumbha Marg, Pratap Nagar, Jaipur 302033, India
| | - Rajeev Gupta
- Academic Research Development Unit, College of Medical Sciences, Rajasthan University of Health Sciences, Kumbha Marg, Pratap Nagar, Jaipur 302033, India
| | - Piers R. Blackett
- Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
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Sao R, Aronow WS. Association of non-alcoholic fatty liver disease with cardiovascular disease and subclinical atherosclerosis. Arch Med Sci 2018; 14:1233-1244. [PMID: 30393477 PMCID: PMC6209727 DOI: 10.5114/aoms.2017.68821] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Accepted: 05/19/2016] [Indexed: 02/08/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) refers to fatty infiltration of liver in the absence of significant alcohol intake, use of steatogenic medication, or hereditary disorders. It is a common cause of chronic liver disease with a worldwide estimated prevalence ranging from 6.3% to 33%. The NAFLD is considered a hepatic manifestation of the metabolic syndrome. Insulin resistance and increased oxidative stress are central to pathogenesis of NAFLD, and risk factors include metabolic syndrome, diabetes mellitus, obesity, lack of physical activity, smoking, and high fat diet. NAFLD is associated with higher mortality as compared to the general population with cardiovascular disease being the most common cause of death. The NAFLD is associated with a higher prevalence of subclinical atherosclerosis as evidenced by odds of higher coronary artery calcification, higher average and maximum carotid intima-media thickness. It is also associated with stiff arteries as evidenced by higher cardio-ankle vascular index and higher brachial-ankle pulse wave velocity. Increasing evidence has linked NAFLD with atherosclerotic cardiovascular diseases. The NAFLD is associated with a higher prevalence of coronary artery disease (CAD), more severe CAD, poor coronary collateral development, and higher incidence of coronary events. The NAFLD is also associated with ischemic stroke. Studies have shown that the association between NAFLD and atherosclerotic cardiovascular diseases is independent of shared risk factors.
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Affiliation(s)
- Rahul Sao
- Cardiology Division, Department of Medicine, Westchester Medical Center/New York Medical College, Valhalla, NY, USA
| | - Wilbert S Aronow
- Cardiology Division, Department of Medicine, Westchester Medical Center/New York Medical College, Valhalla, NY, USA
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Correlation between nonalcoholic fatty liver and cardiovascular disease in elderly hemodialysis patients. Int Urol Nephrol 2016; 48:883-9. [PMID: 26905407 DOI: 10.1007/s11255-016-1237-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Accepted: 02/02/2016] [Indexed: 02/08/2023]
Abstract
PURPOSE The number of elderly patients with end-stage kidney disease is on the rise. Nonalcoholic fatty liver disease (NAFLD) is characterized by parenchymal fat accumulation in patients without information about alcohol abuse. The aim of our study was to determine correlation between NAFLD and cardiovascular diseases in elderly hemodialysis patients. METHODS The examination was organized as observational and cross-sectional study in elderly patients on hemodialysis. An abdominal ultrasound examination was made in order to define NAFLD. Intima-media thickness of the carotid arteries was quantified by Doppler ultrasound. Biochemical parameters, gender, anthropometric characteristics, duration, adequacy of hemodialysis, blood pressure, smoking and cardiovascular disease were determined. Respondents were divided into a group with NAFLD (37/72 patients, 51 %) and group without NAFLD (35/72 patients, 49 %). RESULTS Patients with NAFLD have significantly more cardiovascular disease (p = 0.017) as well as significantly higher values of intima-media thickness of the carotid arteries (p = 0.03) in correlation with patients without NAFLD. Patients without NAFLD have a statistically lower triglyceride (p = 0.04), aspartate aminotransferase (p = 0.006), alanine aminotransferase (p = 0.013) and gamma-glutamyl transpeptidase (p = 0.029) compared to patients with NAFLD. Patients with cardiovascular disease have a higher risk of NAFLD; likewise, patients with NAFLD have a three times higher chance for developing cardiovascular diseases (OR 3.01). CONCLUSION Elderly patients on hemodialysis with cardiovascular disease have a higher risk of NAFLD; likewise, patients with NAFLD have a three times higher chance for developing cardiovascular diseases.
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Madan SA, John F, Pyrsopoulos N, Pitchumoni CS. Nonalcoholic fatty liver disease and carotid artery atherosclerosis in children and adults: a meta-analysis. Eur J Gastroenterol Hepatol 2015; 27:1237-1248. [PMID: 26193052 DOI: 10.1097/meg.0000000000000429] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Observational studies suggest that nonalcoholic fatty liver disease (NAFLD) is associated with increased carotid intimal medial thickness (C-IMT) and carotid plaques in both children and adults. We carried out a meta-analysis to evaluate the relationship between NAFLD and carotid atherosclerosis measured as C-IMT and carotid plaque prevalence. Medline (Ovid), PubMed, Web of Science, and CINAHL databases were searched from 1946 to September 2014, complemented with a manual review of references of the published articles for studies that compared C-IMT or carotid plaque prevalence in adults and children. Results were pooled using both fixed and random effects models. Of the studies identified, 20 were suitable for testing the effect of NAFLD on C-IMT in adults, 13 for testing the effect of NAFLD on carotid plaque prevalence in adults, and five for testing the effect of NAFLD on C-IMT in the pediatric population. The pooled data from 20 studies (19,274 adult participants: NAFLD=8652, controls=10,622) showed significantly increased C-IMT in patients with NAFLD, compared with controls without NAFLD, according to both fixed [standardized mean difference (SMD)=0.251, 95% confidence interval (CI): 0.220-0.282, P<0.001] and random effects models (SMD=0.944, 95% CI: 0.728-1.160, P<0.001). NAFLD was also found to be associated with a higher carotid artery plaque prevalence when compared with controls, according to both fixed (OR=1.273, 95% CI=1.162-1.394, P<0.001) and random effects models (OR=1.769, 95% CI: 1.213-2.581, P=0.003), on pooling of 13 studies (14,445 adult participants: NAFLD=5399 and controls=9046). Analysis of pooled data from five studies in the pediatric population (1121 pediatric participants: NAFLD=312 and controls=809) also found NAFLD to be associated with significantly increased C-IMT according to fixed (SMD=0.995, 95% CI: 0.840-1.150, P<0.001) and random effects models (1.083, 95% CI: 0.457-1.709, P=0.001). NAFLD is associated with increased C-IMT in both children and adults, and with increased carotid plaque prevalence in adults. Individuals identified with carotid disease should be evaluated for NAFLD and vice versa.
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Affiliation(s)
- Shivank A Madan
- aDepartment of Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, New York City, New York bDepartment of Medicine, Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School/Saint Peters University Hospital, New Brunswick cDepartment of Medicine, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School/University Hospital, Newark, New Jersey, USA
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Hoffmann A, Ebert T, Klöting N, Dokas J, Jeromin F, Jessnitzer B, Burkhardt R, Fasshauer M, Kralisch S. Leptin dose-dependently decreases atherosclerosis by attenuation of hypercholesterolemia and induction of adiponectin. Biochim Biophys Acta Mol Basis Dis 2015; 1862:113-20. [PMID: 26521149 DOI: 10.1016/j.bbadis.2015.10.022] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Revised: 10/08/2015] [Accepted: 10/17/2015] [Indexed: 12/20/2022]
Abstract
OBJECTIVES Conflicting evidence concerning leptin in atherosclerosis has been published. Furthermore, dose-dependent effects of leptin on atherogenesis have not been studied. METHODS Leptin-deficient low-density lipoprotein receptor (LDLR) knockout (LDLR(-/-);ob/ob) mice were treated with saline, 0.1, 0.5, or 3.0mg/kg body weight (BW)/d recombinant leptin over 12weeks starting at 8weeks of age. Aortic root and brachiocephalic artery (BCA) atherosclerotic lesions were analyzed by oil red O staining. Furthermore, glucose homeostasis, lipid metabolism, and liver function including tissue studies were assessed in all animals. RESULTS Leptin treatment dose-dependently decreased BW in LDLR(-/-);ob/ob mice as compared to saline. Mice in the 0.1 and 0.5mg/kgBW/d groups remained heavier (i.e. subphysiological leptin dose) and in the 3.0mg/kgBW/d group had similar weight (i.e. physiological leptin dose) as compared to non-leptin-deficient LDLR(-/-) animals. Recombinant leptin dose-dependently reduced plaque area in the aortic root and the BCA by 36% and 58%, respectively. Leptin-mediated reductions of plasma total and LDL-cholesterol (Chol) remained independent predictors for aortic root plaque area. Chol content in liver, as well as hepatic expression of key lipid and proinflammatory genes, were dose-dependently regulated by leptin. Furthermore, leptin treatment increased circulating levels and adipose tissue mRNA expression of the adipokine adiponectin. CONCLUSIONS Leptin administration within the subphysiological to physiological range diminishes atherosclerotic lesions. Leptin appears to mediate its antiatherogenic effects indirectly through reduction of hypercholesterolemia and liver steatosis, as well as upregulation of insulin-sensitizing and atheroprotective adiponectin.
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Affiliation(s)
- Annett Hoffmann
- University of Leipzig, Department of Endocrinology and Nephrology, 04103 Leipzig, Germany
| | - Thomas Ebert
- University of Leipzig, Department of Endocrinology and Nephrology, 04103 Leipzig, Germany; Leipzig University Medical Center, IFB AdiposityDiseases, 04103 Leipzig, Germany
| | - Nora Klöting
- Leipzig University Medical Center, IFB AdiposityDiseases, 04103 Leipzig, Germany
| | - Janine Dokas
- University of Leipzig, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, 04103 Leipzig, Germany
| | - Franziska Jeromin
- University of Leipzig, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, 04103 Leipzig, Germany
| | - Beate Jessnitzer
- University of Leipzig, Department of Endocrinology and Nephrology, 04103 Leipzig, Germany
| | - Ralph Burkhardt
- University of Leipzig, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, 04103 Leipzig, Germany
| | - Mathias Fasshauer
- University of Leipzig, Department of Endocrinology and Nephrology, 04103 Leipzig, Germany; Leipzig University Medical Center, IFB AdiposityDiseases, 04103 Leipzig, Germany
| | - Susan Kralisch
- University of Leipzig, Department of Endocrinology and Nephrology, 04103 Leipzig, Germany; Leipzig University Medical Center, IFB AdiposityDiseases, 04103 Leipzig, Germany.
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Liccardo D, Mosca A, Petroni S, Valente P, Giordano U, Mico' AGA, Pescosolido S, Buzzonetti L, Nobili V. The association between retinal microvascular changes, metabolic risk factors, and liver histology in pediatric patients with non-alcoholic fatty liver disease (NAFLD). J Gastroenterol 2015; 50:903-12. [PMID: 25516385 DOI: 10.1007/s00535-014-1024-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Accepted: 11/26/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND The prevalence of childhood obesity is increasing worldwide. Studies in adult populations show that retinal microvascular changes are associated with obesity and components of the metabolic syndrome. In our study we have assessed the effect of body mass index (BMI), metabolic parameters, and adiposity on the retinal microvasculature in children. METHODS Fifty-four consecutive children with biopsy-proven NAFLD were enrolled in this study. Anthropometric and laboratory parameters were obtained using standardized protocols. Retinal caliber was quantified from digital retinal images using well-known computer-based programs. Twenty-four-hour ambulatory blood pressure monitoring was measured using a standard protocol. RESULTS In our population, the prevalence of retinopathy was of 53 % (13 males). The 29 patients with retinopathy (mean age 10.91 ± 3.10) showed significantly higher values of triglycerides (mg/day) (105.57 vs. 90.20, p = 0.04), basal insulin (mUI/ml) (17.20 vs. 12.97, p = 0.02), and HOMA-IR (3.37 vs. 2.76, p = 0.04). The patients with a HOMA-IR >2.5 (OR = 3.34, p = 0.02; 95 % IC, 1.07-10.39), and systolic non-dipping (OR 4.16, p = 0.028, 95 % IC, 1.11-13.67), have an increased risk of retinopathy. Moreover, the study of correlation between all stages of liver biopsy (CRN criteria) and the grade of retinopathy showed a positive correlation with fibrosis (r = 0.31) and an NAS score (r = 0.28). CONCLUSIONS We found an association between metabolic parameters and nocturnal blood pressure on the retinal microvasculature among the obese children with NAFLD. Furthermore, for the first time, we report the positive relationship between hepatic fibrosis in pediatric NAFLD patients and the degree of retinopathy signs.
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Affiliation(s)
- D Liccardo
- Hepato-Metabolic Disease Unit, "Bambino Gesù" Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy
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Kasumov T, Li L, Li M, Gulshan K, Kirwan JP, Liu X, Previs S, Willard B, Smith JD, McCullough A. Ceramide as a mediator of non-alcoholic Fatty liver disease and associated atherosclerosis. PLoS One 2015; 10:e0126910. [PMID: 25993337 PMCID: PMC4439060 DOI: 10.1371/journal.pone.0126910] [Citation(s) in RCA: 167] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2014] [Accepted: 04/09/2015] [Indexed: 12/12/2022] Open
Abstract
Cardiovascular disease (CVD) is a serious comorbidity in nonalcoholic fatty liver disease (NAFLD). Since plasma ceramides are increased in NAFLD and sphingomyelin, a ceramide metabolite, is an independent risk factor for CVD, the role of ceramides in dyslipidemia was assessed using LDLR-/- mice, a diet-induced model of NAFLD and atherosclerosis. Mice were fed a standard or Western diet (WD), with or without myriocin, an inhibitor of ceramide synthesis. Hepatic and plasma ceramides were profiled and lipid and lipoprotein kinetics were quantified. Hepatic and intestinal expression of genes and proteins involved in insulin, lipid and lipoprotein metabolism were also determined. WD caused hepatic oxidative stress, inflammation, apoptosis, increased hepatic long-chain ceramides associated with apoptosis (C16 and C18) and decreased very-long-chain ceramide C24 involved in insulin signaling. The plasma ratio of ApoB/ApoA1 (proteins of VLDL/LDL and HDL) was increased 2-fold due to increased ApoB production. Myriocin reduced hepatic and plasma ceramides and sphingomyelin, and decreased atherosclerosis, hepatic steatosis, fibrosis, and apoptosis without any effect on oxidative stress. These changes were associated with decreased lipogenesis, ApoB production and increased HDL turnover. Thus, modulation of ceramide synthesis may lead to the development of novel strategies for the treatment of both NAFLD and its associated atherosclerosis.
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Affiliation(s)
- Takhar Kasumov
- Department of Gastroenterology& Hepatology, Cleveland Clinic, Cleveland, OH, United States of America
- * E-mail: (TK); (AM)
| | - Ling Li
- Department of Research Core Services, Cleveland Clinic, Cleveland, OH, United States of America
| | - Min Li
- Department of Pathobiology, Cleveland Clinic, Cleveland, OH, United States of America
| | - Kailash Gulshan
- Department of Cellular & Molecular Medicine, Cleveland Clinic, Cleveland, OH, United States of America
| | - John P. Kirwan
- Department of Pathobiology, Cleveland Clinic, Cleveland, OH, United States of America
| | - Xiuli Liu
- Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, United States of America
| | - Stephen Previs
- Department of Nutrition & Medicine, Case Western Reserve University School of Medicine Cleveland Clinic, Cleveland, OH, United States of America
| | - Belinda Willard
- Department of Research Core Services, Cleveland Clinic, Cleveland, OH, United States of America
| | - Jonathan D. Smith
- Department of Cellular & Molecular Medicine, Cleveland Clinic, Cleveland, OH, United States of America
| | - Arthur McCullough
- Department of Gastroenterology& Hepatology, Cleveland Clinic, Cleveland, OH, United States of America
- Department of Pathobiology, Cleveland Clinic, Cleveland, OH, United States of America
- * E-mail: (TK); (AM)
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15
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Yang W, Xu H, Yu X, Wang Y. Association between retinal artery lesions and nonalcoholic fatty liver disease. Hepatol Int 2015; 9:278-82. [PMID: 25788195 PMCID: PMC4387273 DOI: 10.1007/s12072-015-9607-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Accepted: 01/07/2015] [Indexed: 12/21/2022]
Abstract
Objective Retinal artery lesions have been reported to be a risk marker of morbidity and mortality for cardiovascular and cerebrovascular diseases in various study populations. Nonalcoholic fatty liver disease (NAFLD) is also a risk factor for cardiovascular disease. However, the relationship between retinal artery lesions and NAFLD is less certain. Methods Data were obtained from 2,454 patients who attended their annual health examination (2,143 males and 311 females, aged 62.34 ± 10.03 years). NAFLD was diagnosed by hepatic ultrasonography. Retinal artery lesions were diagnosed according to the criteria. Total plasma cholesterol, plasma triglyceride and fasting glucose levels were determined by using a multichannel analyzer; the body mass index, systolic blood pressure, diastolic blood pressure, incidence of hypertension and coronary artery disease were measured or analyzed by statistical analysis. Results Patients with NAFLD had older age and higher values of BMI, systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol and triglycerides and had a higher incidence of hypertension, coronary artery disease and retinal artery lesions (p < 0.01). Retinal artery lesions were taken as a dependent variable, and age, gender, BMI, systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol and triglyceride levels, and NAFLD were taken as covariates. We found that age ≥65 years (p < 0.01, OR 1.968), being male (p < 0.01, OR 1.668), BMI ≥ 25 (p < 0.01, OR 0.743), SBP ≥ 140 mmHg (p < 0.01, OR 1.368) and NAFLD (p < 0.01, OR 2.378) were significantly associated with a risk of retinal artery lesions by binary logistic regression analysis. Conclusions Patients with NAFLD were older and had higher values for BMI, systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol and triglycerides, and higher incidence of hypertension, coronary artery disease and retinal artery lesions. NAFLD is a risk factor for retinal artery lesions.
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Affiliation(s)
- Wen Yang
- Geriatric Digestive System Department, Navy General Hospital, No. 6 Fuchenglu Road, Beijing, 100048, China,
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16
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Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in western countries and is closely related to the metabolic syndrome. When NAFLD is associated with hepatocellular damage and inflammation (non-alcoholic steatohepatitis [NASH]) it can lead to severe liver disease. However, it has become clear that NAFLD is also associated with an increased risk of cardiovascular disease (CVD), independently of classical known risk factors for the latter. In the current review we briefly summarise the current clinical evidence on the role of NAFLD in CVD and discuss the potential mechanisms by which NAFLD can be linked to the pathophysiology of CVD.
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Affiliation(s)
- Sven M Francque
- Department of Gastroenterology Hepatology, University Hospital Antwerp & Laboratory of Experimental Medicine and Paediatrics, Division of Gastroenterology Hepatology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
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Athyros VG, Katsiki N, Karagiannis A. Nonalcoholic Fatty Liver Disease and Severity of Cardiovascular Disease Manifestations. Angiology 2013; 64:572-5. [DOI: 10.1177/0003319713481101] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Affiliation(s)
- Vasilios G. Athyros
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
| | - Niki Katsiki
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
| | - Asterios Karagiannis
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
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Sciacqua A, Perticone M, Miceli S, Laino I, Tassone EJ, Grembiale RD, Andreozzi F, Sesti G, Perticone F. Endothelial dysfunction and non-alcoholic liver steatosis in hypertensive patients. Nutr Metab Cardiovasc Dis 2011; 21:485-491. [PMID: 20227260 DOI: 10.1016/j.numecd.2009.11.015] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2009] [Revised: 10/21/2009] [Accepted: 11/19/2009] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Non-alcoholic fatty liver disease, characterized by insulin resistance, has been correlated with several clinical and pathological manifestations, such as intima-media thickness. At present, no data are available regarding endothelial dysfunction, the first step in atherosclerosis, and non-alcoholic fatty liver disease. The aim of this study was to test a possible association between non-alcoholic fatty liver disease and endothelium-dependent vasodilation in a group of hypertensive patients. METHODS AND RESULTS A total of 40 never-treated uncomplicated hypertensive outpatients were enrolled. Patients underwent a complete clinical and biochemical work-up including ultrasonographic scanning to detect liver steatosis. Insulin sensitivity was estimated by using the homeostasis model assessment (HOMA) index. Endothelial function was assessed by strain-gauge plethysmography during intra-arterial infusion of increasing doses of acetylcholine and sodium nitroprusside. Endothelium-dependent vasodilation was significantly reduced in hypertensive patients with liver steatosis in comparison with those without. Statistical analysis demonstrated that the HOMA index was the strongest predictor of both endothelium-dependent vasodilation and liver steatosis. In particular, one point of HOMA accounts for 37.9% of forearm blood flow variation, and increases the risk of liver steatosis by 86.4%. CONCLUSION Our data demonstrate that hypertensive patients with liver steatosis have a reduced endothelium-dependent vasodilation and highest insulin resistance. In keeping with this, it is possible to hypothesize that liver steatosis may be considered a marker of vascular damage in essential hypertension.
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Affiliation(s)
- A Sciacqua
- Department of Experimental and Clinical Medicine, G. Salvatore, University Magna Græcia of Catanzaro, Italy
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19
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Caserta CA, Pendino GM, Amante A, Vacalebre C, Fiorillo MT, Surace P, Messineo A, Surace M, Alicante S, Cotichini R, Zuin M, Rosmini F, Mele A, Marcucci F. Cardiovascular risk factors, nonalcoholic fatty liver disease, and carotid artery intima-media thickness in an adolescent population in southern Italy. Am J Epidemiol 2010; 171:1195-202. [PMID: 20457571 DOI: 10.1093/aje/kwq073] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The objective of this study was to determine, in an adolescent population, the prevalence of nonalcoholic fatty liver disease (NAFLD) and the association of NAFLD and cardiovascular risk factors with carotid artery intima-media thickness (IMT), a marker of subclinical atherosclerosis. The authors conducted a population-based study among 642 randomly selected adolescents aged 11-13 years in Reggio Calabria, southern Italy, between November 2007 and October 2008. Prevalences of overweight and obesity were 30.5% and 13.5%, respectively. The overall prevalence of NAFLD was 12.5%, increasing to 23.0% in overweight/obese adolescents. In univariate analysis, increased IMT was positively associated with the presence of NAFLD, body mass index (BMI), waist circumference, systolic blood pressure (all P's < 0.001), diastolic blood pressure (P = 0.006), gamma-glutamyl transpeptidase (P = 0.006), alanine aminotransferase (P = 0.007), and C-reactive protein (P = 0.008) and was inversely associated with high density lipoprotein cholesterol (P < 0.001). In multivariate analysis, NAFLD (P = 0.002), BMI (P = 0.004), waist circumference (P = 0.003), and systolic blood pressure (P = 0.005) retained significant associations. The authors conclude that NAFLD, BMI, waist circumference, and systolic blood pressure are independent markers of increased IMT in a random sample of adolescents.
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20
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Yilmaz Y, Kurt R, Yonal O, Polat N, Celikel CA, Gurdal A, Oflaz H, Ozdogan O, Imeryuz N, Kalayci C, Avsar E. Coronary flow reserve is impaired in patients with nonalcoholic fatty liver disease: association with liver fibrosis. Atherosclerosis 2010; 211:182-6. [PMID: 20181335 DOI: 10.1016/j.atherosclerosis.2010.01.049] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2010] [Revised: 01/27/2010] [Accepted: 01/28/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. Coronary flow reserve (CFR) is widely used to examine the integrity of coronary microvascular circulation. We evaluated the prevalence of impaired CFR in patients with biopsy-proven NAFLD. We also investigated the independent clinical, biochemical, and liver histology predictors of CFR in the setting of NAFLD. METHODS Fifty-nine consecutive patients with NAFLD and 77 age- and gender-matched controls were evaluated. CFR recordings were performed by transthoracic Doppler harmonic echocardiography. CFR>or=2.0 was considered normal. RESULTS CFR was significantly lower in patients with NAFLD than in controls (2.11+/-0.45 vs. 2.52+/-0.62, P<0.001). An impaired CFR (i.e. <2) was found in 25 NAFLD patients (42.4%) whereas all controls had normal CFR values (P<0.001). A stepwise linear regression analysis in NAFLD patients identified liver fibrosis scores as the only independent predictor of CFR values (beta=-0.60; t=-2.44, P=0.021). CONCLUSION Our findings indicate that in patients with biopsy-proven NAFLD: (a) an abnormal CFR is found in approximately 42.4% of cases, and (b) liver fibrosis scores are an independent predictor of depressed CFR.
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Affiliation(s)
- Yusuf Yilmaz
- Department of Gastroenterology, Marmara University School of Medicine, Tophanelioglu Cad. No: 13/15 Altunizade, 34662 Istanbul, Turkey.
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Pillai AA, Rinella ME. Non-alcoholic fatty liver disease: is bariatric surgery the answer? Clin Liver Dis 2009; 13:689-710. [PMID: 19818313 DOI: 10.1016/j.cld.2009.07.012] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
As the worldwide obesity epidemic continues to increase, the prevalence of non-alcoholic fatty liver disease (NAFLD) and specifically non-alcoholic steatohepatitis (NASH) will become increasingly prominent. NASH will surpass chronic hepatitis C infection as the primary indication for orthotopic liver transplantation in the near future. With the evolution of surgical techniques, bariatric surgery is currently recognized as the most effective method for achieving sustained weight loss and reversing numerous comorbidities in severely obese individuals. This review focuses on the potential risks and benefits of bariatric surgery in subjects with NAFLD and explores its role in the management of NASH in the obese patient.
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Affiliation(s)
- Anjana A Pillai
- Department of Transplant Surgery, Northwestern University, Feinberg School of Medicine, 675 N. St. Clair Avenue, Galter 17-200, Chicago, IL 60611, USA
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Abstract
Non-alcoholic fatty liver disease (NAFLD) affects a substantial proportion of the general population and is frequently associated with many features of the metabolic syndrome (MetS). Currently, the importance of NAFLD and its relationship with the MetS is being increasingly recognized, and this has stimulated an interest in the possible role of NAFLD in the development of atherosclerosis. Recent studies have reported the association of NAFLD with multiple classical and non-classical risk factors for cardiovascular disease (CVD). Moreover, there is a strong association between the severity of liver histopathology in NAFLD patients and greater carotid artery intima-media thickness and plaque, and lower endothelial flow-mediated vasodilation (as markers of subclinical atherosclerosis) independent of obesity and other MetS components. Finally, it has recently been demonstrated that NAFLD is associated with an increased risk of all-cause death and predicts future CVD events independently of other prognostic factors, including MetS components. Overall, therefore, the evidence from these recent studies strongly emphasizes the importance of assessing the global CVD risk in patients with NAFLD. Moreover, these novel findings suggest a more complex picture and raise the possibility that NAFLD, as a component of the MetS, might not only be a marker but also an early mediator of CVD.
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Affiliation(s)
- G Targher
- Division of Internal Medicine and Diabetes Unit, 'Sacro Cuore' Hospital of Negrar, Italy.
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Targher G, Bertolini L, Padovani R, Zenari L, Scala L, Cigolini M, Arcaro G. Serum 25-hydroxyvitamin D3 concentrations and carotid artery intima-media thickness among type 2 diabetic patients. Clin Endocrinol (Oxf) 2006; 65:593-7. [PMID: 17054459 DOI: 10.1111/j.1365-2265.2006.02633.x] [Citation(s) in RCA: 164] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To estimate the prevalence of hypovitaminosis D among type 2 diabetic adults and to assess the relationship between hypovitaminosis D and intimal medial thickening (IMT) of the common carotid artery, a marker of preclinical atherosclerosis. DESIGN, PATIENTS AND MEASUREMENTS We compared winter serum 25-hydroxyvitamin D3 [25(OH)D] concentrations in 390 consecutive type 2 diabetic patients and 390 nondiabetic controls who were comparable for age and sex. Common carotid IMT was measured with ultrasonography only in diabetic patients by a single trained operator blinded to subjects' details. RESULTS The prevalence of hypovitaminosis D (i.e. 25(OH)D <or= 37.5 nmol/l) was higher in diabetic patients (34.0 vs 16.4%, P < 0.001) than in controls. Among diabetic patients, those with hypovitaminosis D (n = 130) had a marked increase in common carotid IMT (1.10 +/- 0.15 vs 0.87 +/- 0.14 mm, P < 0.001) when compared with their vitamin d-sufficient counterparts (n = 260). These patients also had significantly higher haemoglobin A1c, fibrinogen and C-reactive protein (hs-CRP) concentrations. In multivariate regression analysis, low 25(OH)D concentrations independently predicted carotid IMT (P < 0.001) in people with type 2 diabetes after adjustment for classical risk factors, diabetes duration, HbA1c, calcium, renal function tests, inflammatory markers, use of medications, and presence of the metabolic syndrome (as defined by the Adult Treatment Panel III criteria). CONCLUSIONS Hypovitaminosis D is highly prevalent in type 2 diabetic adults and is strongly and independently associated with increased carotid IMT. Further investigation into whether vitamin D may play a role in the prevention of atherosclerosis appears to be warranted.
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Affiliation(s)
- Giovanni Targher
- Division of Internal Medicine, Sacro Cuore Hospital, Negrar (VR), Italy.
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Lonardo A, Lombardini S, Scaglioni F, Ballestri S, Verrone AM, Bertolotti M, Carulli L, Ganazzi D, Carulli N, Loria P. Fatty liver, carotid disease and gallstones: a study of age-related associations. World J Gastroenterol 2006; 12:5826-5833. [PMID: 17007049 PMCID: PMC4100664 DOI: 10.3748/wjg.v12.i36.5826] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2006] [Revised: 08/02/2006] [Accepted: 08/10/2006] [Indexed: 02/07/2023] Open
Abstract
AIM To evaluate carotid intima-media thickening (IMT) and plaques, gallstone disease (GD) and fatty liver (FL) as a function of age. METHODS In 449 subjects, FL and carotid disease were assessed ultrasonographically. In a subgroup of 65/449 patients with non-alcoholic fatty liver disease (NAFLD), carotid disease, GD and associated factors were determined. RESULTS FL of unspecified etiology was more common in younger and GD in older individuals. FL subjects had an increased prevalence of IMT and a decreased prevalence of plaques and manifested carotid disease earlier. Plaques were more common in subjects with GD. Age was an independent predictor of carotid disease outcome and FL was a protective factor for plaques. In NAFLD, there was an inverse correlation between body weight and age and the latter independently predicted carotid findings. CONCLUSION Cardiovascular risk in patients with FL and NAFLD needs to be assessed as a function of age and body weight.
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Affiliation(s)
- Amedeo Lonardo
- University of Modena and Reggio Emilia-Azienda USL, Department of Internal Medicine, Metabolism, Endocrinology and Geriatrics, Ospedale di Baggiovara, Via Giardini, 41100 Modena, Italy.
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Targher G. Non-alcoholic fatty liver disease as a determinant of cardiovascular disease. Atherosclerosis 2006; 190:18-9; author reply 20-1. [PMID: 16828776 DOI: 10.1016/j.atherosclerosis.2006.06.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2006] [Indexed: 01/14/2023]
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26
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Targher G, Bertolini L, Padovani R, Rodella S, Zoppini G, Zenari L, Cigolini M, Falezza G, Arcaro G. Relations between carotid artery wall thickness and liver histology in subjects with nonalcoholic fatty liver disease. Diabetes Care 2006; 29:1325-30. [PMID: 16732016 DOI: 10.2337/dc06-0135] [Citation(s) in RCA: 304] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is closely associated with several metabolic syndrome features. We assessed whether NAFLD is associated with carotid artery intima-media thickness (IMT) as a marker of subclinical atherosclerosis and whether such an association is independent of classical risk factors, insulin resistance, and metabolic syndrome features. RESEARCH DESIGN AND METHODS We compared carotid IMT, as assessed by ultrasonography, in 85 consecutive patients with biopsy-proven NAFLD and 160 age-, sex-, and BMI-matched healthy control subjects. RESULTS NAFLD patients had a markedly greater carotid IMT (1.14 +/- 0.20 vs. 0.82 +/- 0.12 mm; P < 0.001) than control subjects. The metabolic syndrome (according to Adult Treatment Panel III criteria) and its individual components were more frequent in those with NAFLD (P < 0.001). The marked differences in carotid IMT observed between the groups were only slightly weakened after adjustment for age, sex, BMI, smoking history, LDL cholesterol, insulin resistance (by homeostasis model assessment), and metabolic syndrome components. Notably, carotid IMT was strongly associated with degree of hepatic steatosis, necroinflammation, and fibrosis among NAFLD patients (P < 0.001 for all). Similarly, by logistic regression analysis, the severity of histological features of NAFLD independently predicted carotid IMT (P < 0.001) after adjustment for all potential confounders. CONCLUSIONS These results suggest that the severity of liver histopathology among NAFLD patients is strongly associated with early carotid atherosclerosis, independent of classical risk factors, insulin resistance, and the presence of metabolic syndrome.
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Affiliation(s)
- Giovanni Targher
- Division of Internal Medicine and Diabetes Unit, Ospedale Sacro Cuore-don Calabria, Via Sempreboni 5, 37024 Negrar (VR), Italy.
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