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Zhyzhneuskaya SV, Al‐Mrabeh AH, Peters C, Barnes AC, Hollingsworth KG, Welsh P, Sattar N, Lean MEJ, Taylor R. Clinical utility of liver function tests for resolution of metabolic dysfunction-associated steatotic liver disease after weight loss in the Diabetes Remission Clinical Trial. Diabet Med 2025; 42:e15462. [PMID: 39645664 PMCID: PMC11823348 DOI: 10.1111/dme.15462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Revised: 09/26/2024] [Accepted: 10/18/2024] [Indexed: 12/10/2024]
Abstract
AIMS Ectopic fat is reduced by effective weight management, but difficult to assess clinically. METHODS We evaluated paired data on 42 participants in the intervention group of the Diabetes Remission Clinical Trial (DiRECT) at baseline, 12 and 24 months after weight loss as indicators of liver fat content measured by 3-point Dixon MRI. RESULTS Baseline liver fat was elevated at 13.0 [7.8-23.3]% with fasting plasma glucose 7.9 [7.1-10.1] mmol/L. Prevalence of baseline MASLD was 86.4%. After weight loss of 11.9 ± 1.2 kg (0-37 kg) at 12 months, remission of MASLD occurred in 74% and liver fat normalised for many (1.8 [1.2-5.2]%; p < 0.0001) as did fasting glucose (5.9 [5.5-7.2] mmol/L; p < 0.0001). Alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) decreased at 12 months by 38 [19-60]% (p < 0·0001) and 38 [16-53]% (p < 0.0001) respectively. The positive predictive value for decrease in liver fat, with baseline values of >40 IU/L, was 100% for ALT and 87.5% for GGT. As expected, change in liver fat correlated with change in ALT (r = 0.64; p < 0.0001), GGT (r = 0.38; p = 0.013), AST (r = 0.36; p = 0.018), fatty liver index (r = 0.50; p < 0.0001) and hepatic steatosis index (r = 0.44; p < 0.0001). CONCLUSION Metabolic dysfunction-associated steatotic liver disease, an important marker of ill-health is improved by intentional weight loss. If enzyme levels are raised at baseline, following weight loss, changes in ALT and GGT usefully reflect change in liver fat content, with high positive predictive value. Monitoring liver enzymes can provide a simple way to assess change in liver fat following weight loss in day-to-day clinical practice.
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Affiliation(s)
- S. V. Zhyzhneuskaya
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle UniversityNewcastle upon TyneUK
- University Hospital of North Durham, County Durham and Darlington NHS Foundation TrustDurhamUK
| | - A. H. Al‐Mrabeh
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle UniversityNewcastle upon TyneUK
- Centre for Cardiovascular Science, Queen's Medical Research Institute, University of EdinburghEdinburghUK
| | - C. Peters
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle UniversityNewcastle upon TyneUK
| | - A. C. Barnes
- Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle UniversityNewcastle upon TyneUK
| | - K. G. Hollingsworth
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle UniversityNewcastle upon TyneUK
| | - P. Welsh
- School of Cardiovascular and Metabolic Health, College of Medical Veterinary and Life Sciences, University of GlasgowGlasgowUK
| | - N. Sattar
- School of Cardiovascular and Metabolic Health, College of Medical Veterinary and Life Sciences, University of GlasgowGlasgowUK
| | - M. E. J. Lean
- Human Nutrition, School of Medicine, Dentistry and Nursing, College of Medical Veterinary and Life Sciences, University of GlasgowGlasgowUK
| | - R. Taylor
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle UniversityNewcastle upon TyneUK
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Liang Q, Zou M, Peng Z. Associations between Life's Essential 8 and liver function: a cross-sectional study. Front Nutr 2025; 11:1515883. [PMID: 39834466 PMCID: PMC11743538 DOI: 10.3389/fnut.2024.1515883] [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: 10/23/2024] [Accepted: 12/17/2024] [Indexed: 01/22/2025] Open
Abstract
Background Life's Essential 8 (LE8) score, developed by the American Heart Association, assesses cardiovascular health using eight components: diet, physical activity, nicotine exposure, sleep health, body mass index, lipids, blood glucose, and blood pressure. Liver function is a critical indicator of overall health, with impairments linked to numerous chronic diseases. While the LE8 score has been extensively studied in relation to cardiovascular outcomes, its association with liver function remains underexplored. Understanding this relationship is crucial for integrating cardiovascular and hepatic health management, particularly given the shared metabolic pathways underlying these systems. This study aims to examine the relationship between LE8 scores and liver function indicators in a large cohort, addressing a critical gap in understanding the interplay between cardiovascular and liver health. Methods Data from the 2007-2018 National Health and Nutrition Examination Survey (NHANES) were used in this cross-sectional study. The study included 21,873 participants, stratified into low (0-49), moderate (50-79), and high (80-100) LE8 score categories. The relationship between LE8 scores and liver function markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and ALT/AST ratio, was evaluated using multivariable linear regression, smoothed curve fitting, threshold effect analysis, and weighted quantile sum (WQS) regression. Subgroup analyses were performed based on sex and age to assess potential interactions. Results Higher LE8 scores were significantly associated with improved liver function, particularly highlighted by two major findings. First, nonlinear associations were observed between LE8 scores and liver function parameters, including ALT and ALT/AST ratio, with stronger effects beyond specific thresholds (ALT: 50.625, ALT/AST: 61.875). Second, subgroup analyses revealed that these associations were more pronounced in younger participants (<60 years), suggesting age-specific differences in the relationship. These age-related differences might be attributed to variations in metabolic function or differences in the severity of cardiovascular and liver-related risk factors between younger and older individuals. WQS regression identified body mass index, blood pressure, blood glucose, and nicotine exposure as the strongest contributors to liver function markers. These findings underscore the potential of LE8 scores as a comprehensive indicator for liver health, particularly in younger populations. Conclusion This study suggests that LE8 scores is associated with improved liver function. Clinicians and public health practitioners could consider integrating LE8 scores into routine assessments to help identify individuals at risk for liver dysfunction, particularly among younger populations. Further research should explore whether interventions targeting cardiovascular health could also improve liver function outcomes.
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Affiliation(s)
- Qiaoli Liang
- Doumen Qiaoli Hospital of Traditional Chinese Medicine, Zhuhai, Guangdong, China
| | - Menglong Zou
- The First Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Ziming Peng
- Fangchenggang Hospital of Traditional Chinese Medicine, Fangchenggang, Guangxi, China
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Hasan A, Newaj A, Trisha AD, Hafsa JM, Mohanto NC, Ali N. Assessment of the Relationship Between Liver Enzymes and Cardiovascular Disease: A Study in Bangladeshi Adults. Endocrinol Diabetes Metab 2024; 7:e00481. [PMID: 38494432 PMCID: PMC10944799 DOI: 10.1002/edm2.481] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 02/27/2024] [Accepted: 03/03/2024] [Indexed: 03/19/2024] Open
Abstract
OBJECTIVES Elevated liver enzyme levels are suggested to be associated with an increased risk of cardiovascular disease (CVD). However, few studies have explored the relationship between liver enzymes and myocardial infarction (MI). This study aimed to evaluate the potential association of elevated liver enzymes with MI within a population group in Bangladesh. METHODS In this cross-sectional study, 348 participants were enrolled, 189 with MI in the CVD group and 159 in the control group. Serum levels of liver enzymes (AST, ALT and GGT) and other biochemical parameters were measured using standard methods. Multivariate logistic regression models were applied to determine the associations between elevated liver enzymes and CVD. RESULT In the CVD group, 51.6%, 30.9% and 67.7% of individuals had elevated serum AST, ALT and GGT levels, respectively. On the contrary, the control group had 17.0%, 15.1% and 35.2% of individuals with high serum AST, ALT and GGT levels, respectively. Overall, 71.8% of the subjects in the CVD group and 44.7% of the subjects in the control group had at least one or more elevated liver enzymes (p < 0.001). The mean level of all three liver enzymes was significantly higher in the CVD group than in the control group (p < 0.001). In both the CVD and control groups, males had higher levels of liver enzymes than females. In the regression models, the serum levels of AST, ALT and GGT showed a positive and independent association with the prevalence of CVD (p < 0.001). However, GGT showed the strongest association among the three enzymes. CONCLUSIONS This study shows a high prevalence of liver enzyme abnormalities in individuals with CVD. Serum levels of AST, ALT and GGT were independently associated with the prevalence of CVD. This suggests that measuring liver enzyme levels could be a useful marker in predicting CVD at an early stage.
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Affiliation(s)
- Akibul Hasan
- Department of Biochemistry and Molecular BiologyShahjalal University of Science and TechnologySylhetBangladesh
| | - Ali Newaj
- Department of Biochemistry and Molecular BiologyShahjalal University of Science and TechnologySylhetBangladesh
| | - Aporajita Das Trisha
- Department of Biochemistry and Molecular BiologyShahjalal University of Science and TechnologySylhetBangladesh
| | - Jaasia Momtahena Hafsa
- Department of Biochemistry and Molecular BiologyShahjalal University of Science and TechnologySylhetBangladesh
| | - Nayan Chandra Mohanto
- Department of Biochemistry and Molecular BiologyShahjalal University of Science and TechnologySylhetBangladesh
| | - Nurshad Ali
- Department of Biochemistry and Molecular BiologyShahjalal University of Science and TechnologySylhetBangladesh
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Kim K, Jung H, Di Giovanna E, Jun TJ, Kim YH. Increased risk of ischemic stroke associated with elevated gamma-glutamyl transferase level in adult cancer survivors: a population-based cohort study. Sci Rep 2023; 13:16837. [PMID: 37803039 PMCID: PMC10558526 DOI: 10.1038/s41598-023-43839-8] [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: 05/31/2023] [Accepted: 09/28/2023] [Indexed: 10/08/2023] Open
Abstract
Adult cancer survivors may have an increased risk of developing ischemic stroke, potentially influenced by cancer treatment-related factors and shared risk factors with stroke. However, the association between gamma-glutamyl transferase (GGT) levels and the risk of ischemic stroke in this population remains understudied. Therefore, our study aimed to examine the relationship between GGT levels and the risk of ischemic stroke using a population-based cohort of adult cancer survivors. A population-based cohort of adult cancer survivors was derived from the National Health Insurance Service-Health Screening Cohort between 2003 and 2005 who survived after diagnosis of primary cancer and participated in the biennial national health screening program between 2009 and 2010. Cox proportional hazards model adjusted for sociodemographic factors, health status and behavior, and clinical characteristics was used to investigate the association between GGT level and ischemic stroke in adult cancer survivors. Among 3095 adult cancer survivors, 80 (2.58%) incident cases of ischemic stroke occurred over a mean follow-up of 8.2 years. Compared to the lowest GGT quartile, the hazard ratios (HRs) for ischemic stroke were 1.56 (95% CI 0.75-3.26), 2.36 (95% CI 1.12-4.99), and 2.40 (95% CI 1.05-5.46) for the second, third, and fourth sex-specific quartiles, respectively (Ptrend = 0.013). No significant effect modification was observed by sex, insurance premium, and alcohol consumption. High GGT level is associated with an increased risk of ischemic stroke in adult cancer survivors independent of sex, insurance premium, and alcohol consumption.
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Affiliation(s)
- Kyuwoong Kim
- National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea
| | - Hyeyun Jung
- The Institute of Clinical Sciences, Imperial College London, London, UK
| | - Edvige Di Giovanna
- Department of Diagnostic and Interventional Radiology, Ammerland-Klinik, Westerstede, Lower Saxony, Germany
| | - Tae Joon Jun
- Big Data Research Center, Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
| | - Young-Hak Kim
- Division of Cardiology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Republic of Korea.
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Javid M, Mirdamadi A, Javid M, Amini-Salehi E, Vakilpour A, Keivanlou MH, Porteghali P, Hassanipour S. Gamma glutamyl transferase as a biomarker to predict contrast-induced nephropathy among patients with acute coronary syndrome undergoing coronary interventions: a meta-analysis. Ann Med Surg (Lond) 2023; 85:4033-4040. [PMID: 37554858 PMCID: PMC10406001 DOI: 10.1097/ms9.0000000000000967] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 06/11/2023] [Indexed: 08/10/2023] Open
Abstract
The third most frequent reason for hospitalized acute kidney injury is contrast-induced nephropathy (CIN). Percutaneous coronary intervention (PCI) and coronary angiography (CAG) are two interventions that can result in CIN. In this study, we sought to determine how well gamma-glutamyl transferase (GGT) can predict CIN following CAG and PCI. Method Two researchers searched through PubMed, Scopus, and Web of Science in November 2022 to find articles that examined GGT levels in CIN patients following PCI or CAG. To rate the quality of the studies, the Joanna Briggs Institute Critical Appraisal Checklist was employed. The Cochran test and I2 statistics were utilized to assess study heterogeneity. To calculate the number of participants required to reject the null hypothesis, power analysis was used. We evaluated the epidemiologic strength of the results using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The authors used Comprehensive Meta-analysis Version 3 to summarize the results. Results GGT was shown to be considerably greater in patients with CIN according to the meta-analysis's findings (odds ratio: 3.21, 95% CI: 1.26-8.15, P=0.014); nevertheless, the findings were accompanied by significant heterogeneity (I2=91.93%, P<0.001). Although the relationship between CIN and GGT was power full regarding power analysis (1- β =1, number of effect sizes=4, the average number per group=336), very low quality of evidence was observed regarding GRADE criteria. Conclusions These results suggest the GGT level may be a predictor of contrast-induced nephropathy in patients having cardiac catheterization; however, more research is required to prove the epidemiological validity.
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Affiliation(s)
- Mona Javid
- Student Research Committee, School of Medicine
| | | | | | | | | | | | | | - Soheil Hassanipour
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
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Byeon WJ, Lee SJ, Khil TG, Jeong AY, Han BD, Sohn MS, Choi JW, Kim YH. Association between a Marine Healing Program and Metabolic Syndrome Components and Mental Health Indicators. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1263. [PMID: 37512073 PMCID: PMC10384087 DOI: 10.3390/medicina59071263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 06/16/2023] [Accepted: 06/26/2023] [Indexed: 07/30/2023]
Abstract
Background and Objectives: Metabolic syndrome is a growing health concern globally, and its prevalence continues to increase. This study investigated whether a marine healing program could improve metabolic syndrome indicators and mental health in adults with a metabolic syndrome and those at risk of developing it. Materials and Methods: This study enrolled 30 participants who were assigned to either the experimental or control groups. The duration of the study was set at 4 weeks. Both groups received metabolic syndrome management education, and the experimental group additionally participated in two marine healing programs. Anthropometric indicators, biochemical indicators, and mental health indicators were collected before and after the intervention. Results: The findings indicate that the experimental group had significantly lower systolic blood pressure, triglycerides, and body weight, as well as higher levels of high-density lipoprotein (HDL-C) and uric acid. Mental health indicators (Hospital Anxiety and Depression Scale and quality of life measures) additionally showed improvement. Pre-post comparisons between the experimental group and the control group showed that the experimental group had significantly decreased by 1.05 kg in body weight, whereas the control group increased by 0.29 kg in body weight. In addition, HDL-C decreased by 0.91 mg/dL in the control group and increased by 3.7 mg/dL in the experimental group. Conclusions: Overall, these results suggest that marine healing programs could improve metabolic syndrome indicators such as body weight and HDL-C better than the control treatment.
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Affiliation(s)
- Woo-Jin Byeon
- Department of Public Health, Graduate School, Korea University, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Sung-Jae Lee
- Department of Integrative Medicine, College of Medicine, Korea University, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Tae-Gyu Khil
- Department of Integrative Medicine, College of Medicine, Korea University, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Ah-Young Jeong
- Department of Integrative Medicine, College of Medicine, Korea University, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Byoung-Duck Han
- Department of Family Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Min-Sung Sohn
- Department of Health and Medical Sciences, Cyber University of Korea, 161 Jeongneung-ro, Seongbuk-gu, Seoul 02708, Republic of Korea
| | - Jae-Wook Choi
- Department of Preventive Medicine, College of Medicine, Korea University, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Yang-Hyun Kim
- Department of Family Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
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Wang Y, Liang Y, Seth I, Wu G, Du Z, Huang Y, Shang X, Liu S, Hu Y, Fang Y, Zhu Z, Hu Y, Zhang X, Yang X, Yu H. Determinants of Incident Atherosclerotic Cardiovascular Disease Events and All-Cause Mortality in Patients With Age-Related Macular Degeneration: Prospective Cohort Study of UK Biobank. Asia Pac J Ophthalmol (Phila) 2023; 12:293-302. [PMID: 37249901 DOI: 10.1097/apo.0000000000000612] [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: 05/31/2023] Open
Abstract
PURPOSE Major risk factors of atherosclerotic cardiovascular disease (ASCVD) and mortality have been well-established in the general population. Our study is aimed at assessing longitudinal relationships between ASCVD risk factors and incident ASCVD events or all-cause mortality in patients with age-related macular degeneration (AMD). METHODS Multivariable-adjusted Cox proportional hazards models were used to study the association between cardiovascular risk factors with adjudicated incident ASCVD events and all-cause mortality outcomes followed until 2021. A restricted cubic spline approach was utilized to assess nonlinear associations between potential cardiovascular risk factors and ASCVD or mortality. RESULTS We identified 3508 eligible patients [mean (SD) age = 61.45 (6.43) years; 37.76% males] with AMD at baseline. During a median follow-up year of 12, there were 110 cases of ASCVD events and 186 cases of all-cause mortality. After multivariable adjustment, each 10 U/L increase of serum gamma-glutamyl transferase level was linearly associated with incident ASCVD [hazard ratio (HR) = 1.03, 95% CI = 1.00-1.07, Pnonlinear = 0.85)] in AMD. A history of chronic kidney disease (HR = 1.94, 95% CI = 1.09-3.46) and lower vitamin D [HR = 0.98, 95% CI = 0.97-0.99, per nanomoles per liter (nmol/L)] were significantly associated with all-cause mortality in patients with AMD, with the association between vitamin D and all-cause mortality presenting a U shape (Pnonlinear = 0.02). In contrast, risk factors significantly associated with ASCVD and all-cause mortality in healthy controls differed from patients with AMD. CONCLUSIONS Our findings demonstrate risk factors associated with ASCVD events and all-cause mortality among individuals with AMD differed from healthy controls and suggest the long-term management of risk factors in patients with AMD.
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Affiliation(s)
- Yaxin Wang
- Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Yingying Liang
- Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Ishith Seth
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
| | - Guanrong Wu
- Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Zijing Du
- Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Yu Huang
- Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Xianwen Shang
- Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Shunming Liu
- Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Yunyan Hu
- Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Ying Fang
- Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Zhuoting Zhu
- Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Yijun Hu
- Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Xiayin Zhang
- Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Xiaohong Yang
- Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Honghua Yu
- Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, China
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Bortz JH. Metabolic-Associated Fatty Liver Disease: Opportunistic Screening at CT Colonography. CT COLONOGRAPHY FOR RADIOGRAPHERS 2023:277-290. [DOI: 10.1007/978-3-031-30866-6_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Abdulali AA, Murad SK, Shahid RA. Clinical Study of Serum Gamma- Glutamyl Levels in Cigarette Smokers with Nonalcoholic Fatty Liver Disease, Governorate – Iraq. 2022 INTERNATIONAL SYMPOSIUM ON MULTIDISCIPLINARY STUDIES AND INNOVATIVE TECHNOLOGIES (ISMSIT) 2022:176-181. [DOI: 10.1109/ismsit56059.2022.9932771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Affiliation(s)
| | - Sarah Kadhim Murad
- College of Health and Medical Technology, Al-Ayen University,Thi-Qar,Iraq
| | - Rola Ali Shahid
- College of Health and Medical Technology, Al-Ayen University,Thi-Qar,Iraq
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Aimo A, Chiappino S, Paolicchi A, Della Latta D, Martini N, Clemente A, Musetti V, Masotti S, Panichella G, Piagneri V, Storti S, Monteleone A, Passino C, Chiappino D, Franzini M, Emdin M. Big gamma-glutamyltransferase is associated with epicardial fat volume and cardiovascular outcome in the general population. Eur J Prev Cardiol 2022; 29:1510-1518. [PMID: 34928344 DOI: 10.1093/eurjpc/zwab215] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 08/08/2021] [Accepted: 12/01/2021] [Indexed: 01/06/2023]
Abstract
AIMS Gamma-glutamyltransferase (GGT) has been recognized as a cardiovascular risk factor, and its highest molecular weight fraction [big GGT (b-GGT)] is found in vulnerable atherosclerotic plaques. We explored the relationship between b-GGT, computed tomography findings, and long-term outcomes in the general population. METHODS AND RESULTS Between May 2010 and October 2011, subjects aged 45-75 years living in a Tuscan city and without known cardiac disease were screened. The primary endpoint was a composite of cardiovascular death or acute coronary syndrome requiring urgent coronary revascularization. Gamma-glutamyltransferase fractions were available in 898 subjects [median age 65 years (25th-75th percentile 55-70), 46% men]. Median plasma GGT was 20 IU (15-29), and b-GGT was 2.28 (1.28-4.17). Coronary artery calcium (CAC) score values were 0 (0-60), and the volume of pro-atherogenic epicardial fat was 155 mL (114-204). In a model including age, sex, low-density lipoprotein (LDL) cholesterol, current or previous smoking status, hypertension, diabetes, obesity, b-GGT independently predicted epicardial fat volume (EFV) (r = 0.162, P < 0.001), but not CAC (P = 0.198). Over a 10.3-year follow-up (9.6-10.8), 27 subjects (3%) experienced the primary endpoint. We evaluated couples of variables including b-GGT and a cardiovascular risk factor, CAC or EFV. Big GGT yielded independent prognostic significance from age, LDL cholesterol, current or previous smoking status, hypertension, diabetes, obesity, but not CAC or EFV. Conversely, GGT predicted the primary endpoint even independently from CAC and EFV. CONCLUSION Big GGT seemed at least as predictive as the commonly available GGT assay; therefore, the need for b-GGT rather than GGT measurement should be carefully examined.
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Affiliation(s)
- Alberto Aimo
- Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124 Pisa, Italy
- Fondazione Toscana Gabriele Monasterio, Pisa and Massa, Italy
| | - Sara Chiappino
- Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124 Pisa, Italy
- Fondazione Toscana Gabriele Monasterio, Pisa and Massa, Italy
| | - Aldo Paolicchi
- Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | | | - Nicola Martini
- Fondazione Toscana Gabriele Monasterio, Pisa and Massa, Italy
| | | | - Veronica Musetti
- Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124 Pisa, Italy
| | - Silvia Masotti
- Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124 Pisa, Italy
| | - Giorgia Panichella
- Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124 Pisa, Italy
| | | | - Simona Storti
- Fondazione Toscana Gabriele Monasterio, Pisa and Massa, Italy
| | | | - Claudio Passino
- Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124 Pisa, Italy
- Fondazione Toscana Gabriele Monasterio, Pisa and Massa, Italy
| | - Dante Chiappino
- Fondazione Toscana Gabriele Monasterio, Pisa and Massa, Italy
| | - Maria Franzini
- Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Michele Emdin
- Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124 Pisa, Italy
- Fondazione Toscana Gabriele Monasterio, Pisa and Massa, Italy
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11
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Ho FK, Ferguson LD, Celis-Morales CA, Gray SR, Forrest E, Alazawi W, Gill JMR, Katikireddi SV, Cleland JGF, Welsh P, Pell JP, Sattar N. Association of gamma-glutamyltransferase levels with total mortality, liver-related and cardiovascular outcomes: A prospective cohort study in the UK Biobank. EClinicalMedicine 2022; 48:101435. [PMID: 35706481 PMCID: PMC9112033 DOI: 10.1016/j.eclinm.2022.101435] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 04/08/2022] [Accepted: 04/14/2022] [Indexed: 02/09/2023] Open
Abstract
BACKGROUND Gamma-glutamyltransferase (GGT) levels in the blood can be a sensitive marker of liver injury but the extent to which they give insight into risk across multiple outcomes in a clinically useful way remains uncertain. METHODS Using data from 293,667 UK Biobank participants, the relationship of GGT concentrations to self-reported alcohol intake and adiposity markers were investigated. We next investigated whether GGT predicted liver-related, cardiovascular (CV) or all-cause mortality, and potentially improved CV risk prediction. FINDINGS Higher alcohol intake and greater waist circumference (WC) were associated with higher GGT; the association was stronger for alcohol with evidence of a synergistic effect of WC. Higher GGT concentrations were associated with multiple outcomes. Compared to a GGT of 14.5 U/L (lowest decile), values of 48 U/L for women and 60 U/L for men (common upper limits of 'normal') had hazard ratios (HRs) for liver-related mortality of 1.83 (95% CI 1.60-2.11) and 3.25 (95% CI 2.38-4.42) respectively, for CV mortality of 1.21 (95% CI 1.14-1.28) and 1.43 (95% CI 1.27-1.60) and for all-cause mortality of 1.15 (95% CI 1.12-1.18) and 1.31 (95% CI 1.24-1.38). Adding GGT to a risk algorithm for CV mortality reclassified an additional 1.24% (95% CI 0.14-2.34) of participants across a binary 5% 10-year risk threshold. INTERPRETATION Our study suggests that a modest elevation in GGT levels should trigger a discussion with the individual to review diet and lifestyle including alcohol intake and consideration of formal liver disease and CV risk assessment if not previously done. FUNDING British Heart Foundation Centre of Research Excellence Grant (grant number RE/18/6/34217), NHS Research Scotland (grant number SCAF/15/02), the Medical Research Council (grant number MC_UU_00022/2); and the Scottish Government Chief Scientist Office (grant number SPHSU17).
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Affiliation(s)
- Frederick K Ho
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Lyn D Ferguson
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
| | - Carlos A Celis-Morales
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
| | - Stuart R Gray
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
| | - Ewan Forrest
- Gastroenterology Unit, Glasgow Royal Infirmary and University of Glasgow, Glasgow, UK
| | - William Alazawi
- Blizard Institute – Faculty of Medicine and Dentistry, Queen Mary University of London, UK
| | - Jason MR Gill
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
| | | | - John GF Cleland
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
- Robertson Centre for Biostatistics and Clinical Trials, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Paul Welsh
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
| | - Jill P Pell
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
- Corresponding author.
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12
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Obese Vegetarians and Omnivores Show Different Metabolic Changes: Analysis of 1340 Individuals. Nutrients 2022; 14:nu14112204. [PMID: 35684004 PMCID: PMC9182907 DOI: 10.3390/nu14112204] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 05/23/2022] [Accepted: 05/23/2022] [Indexed: 02/05/2023] Open
Abstract
Our study evaluated the association between the increase in body mass index (BMI) in men and women (menstruating and non-menstruating) (n = 1340) with different dietary groups (omnivores, semi-vegetarians, lacto-ovo-vegetarian, and vegans) and the measurement of the biochemical markers high-sensitive C-reactive protein (hs-CRP), ferritin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), glycated hemoglobin (HbA1C), and insulin resistance index (HOMA-IR). Increasing BMI values in all groups and dietary profiles were related to a significant increase in hs-CRP (p < 0.0001), ALT (p = 0.02), ferritin (p = 0.009), and HbA1C (p < 0.0001), with no difference between dietary groups (p < 0.05). The increase in BMI increases the levels of HOMA-IR (p < 0.0001) and GGT (p < 0.05), with higher values found in men when compared to women (p < 0.0001 for HOMA- IR and p = 0.0048 for GGT). The association between ALT and BMI was different between dietary groups, as it showed a decrease in vegan women who do not menstruate compared to other dietary groups (p = 0.0099). When including only obese individuals (BMI ≥ 30 kg/m2, n = 153) in the analysis, we observed lower concentrations of GGT and ferritin in vegetarians than in omnivores, regardless of gender and menstrual blood loss (p = 0.0395). Our data showed that for both vegetarians and omnivores, the higher the BMI, the worse the metabolic parameters. However, regarding obesity, vegetarians showed better antioxidant status (lower GGT elevation) and lower inflammatory status (lower ferritin elevation), which may provide them with potential protection in the development of morbidities associated with overweight.
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13
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Park MJ, Choi KM. Association between Variability of Metabolic Risk Factors and Cardiometabolic Outcomes. Diabetes Metab J 2022; 46:49-62. [PMID: 35135078 PMCID: PMC8831817 DOI: 10.4093/dmj.2021.0316] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 12/07/2021] [Indexed: 11/10/2022] Open
Abstract
Despite strenuous efforts to reduce cardiovascular disease (CVD) risk by improving cardiometabolic risk factors, such as glucose and cholesterol levels, and blood pressure, there is still residual risk even in patients reaching treatment targets. Recently, researchers have begun to focus on the variability of metabolic variables to remove residual risks. Several clinical trials and cohort studies have reported a relationship between the variability of metabolic parameters and CVDs. Herein, we review the literature regarding the effect of metabolic factor variability and CVD risk, and describe possible mechanisms and potential treatment perspectives for reducing cardiometabolic risk factor variability.
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Affiliation(s)
- Min Jeong Park
- Division of Endocrinology & Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Kyung Mook Choi
- Division of Endocrinology & Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
- Corresponding author: Kyung Mook Choi https://orcid.org/0000-0001-6175-0225 Division of Endocrinology & Metabolism, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-ro, Guro-gu, Seoul 08308, Korea E-mail:
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14
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Sivam S, Wang D, Wong KKH, Piper AJ, Zheng YZ, Gauthier G, Hockings C, McGuinness O, Menadue C, Melehan K, Cooper S, Hilmisson H, Phillips CL, Thomas RJ, Yee BJ, Grunstein RR. Cardiopulmonary coupling and serum cardiac biomarkers in obesity hypoventilation syndrome and obstructive sleep apnea with morbid obesity. J Clin Sleep Med 2021; 18:1063-1071. [PMID: 34879904 DOI: 10.5664/jcsm.9804] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
STUDY OBJECTIVES The main cause of death in patients with obesity hypoventilation syndrome (OHS) is cardiac rather than respiratory failure. Here, we investigated autonomic-respiratory coupling and serum cardiac biomarkers in patients with OHS and obstructive sleep apnea (OSA) with comparable body mass index (BMI) and apnea-hypopnea index (AHI). METHODS Cardiopulmonary coupling (CPC) and cyclic variation of heart rate (CVHR) analysis was performed on the electrocardiogram signal from the overnight polysomnogram. Cardiac serum biomarkers were obtained in patients with OHS and OSA with a BMI > 40kg/m2. Samples were obtained at baseline and after 3 months of positive airway pressure (PAP) therapy in both groups. RESULTS Patients with OHS (n=15) and OSA (n=36) were recruited. No group differences in CPC, CVHR and serum biomarkers were observed at baseline and after 3 months of PAP therapy. An improvement in several CPC metrics, including the sleep apnea index, unstable sleep (low frequency coupling and elevated low frequency coupling narrow band [e-LFCNB]) and CVHR were observed in both groups with PAP use. However, distinct differences in response characteristics were noted. e-LFCNB coupling correlated with highly sensitive troponin (hs-troponin-T, p<0.05) in the combined cohort. Baseline hs-troponin-T inversely correlated with awake oxygen saturation in the OHS group (p<0.05). CONCLUSIONS PAP therapy can significantly improve CPC stability in obese patients with OSA or OHS, with key differences. e-LFCNB may function as a surrogate biomarker for early subclinical cardiac disease. Low awake oxygen saturation could also increase this biomarker in OHS. CLINICAL TRIAL REGISTRATION Registry: Australian New Zealand Clinical Trials Registry; Name: Obesity Hypoventilation Syndrome and Neurocognitive Dysfunction; URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367492; Identifier: ACTRN12615000122550.
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Affiliation(s)
- Sheila Sivam
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, Australia.,Woolcock Institute of Medical Research, Sleep and Circadian Research Group, Sydney, Australia
| | - David Wang
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, Australia.,Woolcock Institute of Medical Research, Sleep and Circadian Research Group, Sydney, Australia
| | - Keith K H Wong
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, Australia.,Woolcock Institute of Medical Research, Sleep and Circadian Research Group, Sydney, Australia
| | - Amanda J Piper
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, Australia.,Woolcock Institute of Medical Research, Sleep and Circadian Research Group, Sydney, Australia
| | - Yi Zhong Zheng
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, Australia.,Woolcock Institute of Medical Research, Sleep and Circadian Research Group, Sydney, Australia
| | - Gislaine Gauthier
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - Christine Hockings
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - Olivia McGuinness
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - Collette Menadue
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - Kerri Melehan
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - Sara Cooper
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, Australia.,Woolcock Institute of Medical Research, Sleep and Circadian Research Group, Sydney, Australia
| | | | - Craig L Phillips
- Faculty of Medicine and Health, University of Sydney, Sydney, Australia.,Woolcock Institute of Medical Research, Sleep and Circadian Research Group, Sydney, Australia
| | - Robert J Thomas
- Department of Medicine, Division of Pulmonary, Critical Care & Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
| | - Brendon J Yee
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, Australia.,Woolcock Institute of Medical Research, Sleep and Circadian Research Group, Sydney, Australia
| | - Ronald R Grunstein
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, Australia.,Woolcock Institute of Medical Research, Sleep and Circadian Research Group, Sydney, Australia
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15
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Spoto B, D'Arrigo G, Tripepi G, Bolignano D, Zoccali C. Serum gamma-glutamyltransferase, oxidized LDL and mortality in the elderly. Aging Clin Exp Res 2021; 33:1393-1397. [PMID: 31677124 DOI: 10.1007/s40520-019-01391-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 10/15/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Serum gamma-glutamyltransferase (GGT) is a liver enzyme involved in the metabolism of glutathione (GSH), a major antioxidant in humans. GGT is a risk factor for mortality in young and middle-aged individuals but this association has been poorly investigated in the elderly. METHODS We studied the relationship between GGT and all-cause mortality and tested whether oxidized low-density lipoproteins (oxLDL) modify this association in a cohort of 1038 elderly individuals. RESULTS During the observation time (median 9 years), 401 individuals died. In a Cox regression model adjusting for potential confounders, GGT was an independent risk factor for all-cause mortality [HR (20U/L increase in serum GGT): 1.11, 95% CI 1.02-1.21, P = 0.02]. Furthermore, increasing levels of oxLDL amplified the risk excess for all-cause mortality associated with GGT (P for the effect modification = 0.003). CONCLUSIONS In the elderly, serum GGT is an independent risk factor for all-cause mortality and circulating oxLDL amplify the magnitude of this association.
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Affiliation(s)
- Belinda Spoto
- National Council of Research, Institute of Clinical Physiology (CNR-IFC), Ospedali Riuniti c/o EUROLINE di Barillà, Via Vallone Petrara 55-57, 89124, Reggio Calabria, Italy.
| | - Graziella D'Arrigo
- National Council of Research, Institute of Clinical Physiology (CNR-IFC), Ospedali Riuniti c/o EUROLINE di Barillà, Via Vallone Petrara 55-57, 89124, Reggio Calabria, Italy
| | - Giovanni Tripepi
- National Council of Research, Institute of Clinical Physiology (CNR-IFC), Ospedali Riuniti c/o EUROLINE di Barillà, Via Vallone Petrara 55-57, 89124, Reggio Calabria, Italy
| | - Davide Bolignano
- National Council of Research, Institute of Clinical Physiology (CNR-IFC), Ospedali Riuniti c/o EUROLINE di Barillà, Via Vallone Petrara 55-57, 89124, Reggio Calabria, Italy
| | - Carmine Zoccali
- National Council of Research, Institute of Clinical Physiology (CNR-IFC), Ospedali Riuniti c/o EUROLINE di Barillà, Via Vallone Petrara 55-57, 89124, Reggio Calabria, Italy
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16
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Han Y, Zhang Y, Liu S, Chen G, Cao L, Xin Y. Association of LDLR rs1433099 with the Risk of NAFLD and CVD in Chinese Han Population. J Clin Transl Hepatol 2021; 9:203-209. [PMID: 34007802 PMCID: PMC8111099 DOI: 10.14218/jcth.2020.00163] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 02/01/2021] [Accepted: 02/07/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND AND AIMS Recent genome-wide association studies have shown that low-density lipoprotein receptor (LDLR) rs1433099 polymorphism is associated with cardiovascular disease (CVD) risk in many countries. However, the association of LDLR rs1433099 with CVD in China has not been reported yet. There are no studies on LDLR rs1433099 and non-alcoholic fatty liver disease (NAFLD) as well. The purpose of this study was to investigate whether LDLR rs1433099 is related to CVD or NAFLD in the Chinese population. METHODS LDLR rs1433099 polymorphism was genotyped in 507 individuals, including 140 healthy controls, 79 NAFLD patients, 185 CVD patients, and 103 patients with NAFLD combined with CVD. The expression of LDLR was tested by the sequence detection system, and clinical parameters were assessed by biochemical tests and physical examination. RESULTS The genotype distribution of LDLR rs1433099 was not statistically different among the NAFLD group, the CVD group, the combined group, and the healthy control group (p>0.05). There was no significant correlation of LDLR rs1433099 genotypic distribution or allele frequency and the risk of NAFLD, CVD or NAFLD combined with CVD (p>0.05). In the CVD group, T allele carriers had higher alkaline phosphatase and gamma-glutamyl transpeptidase than non-carriers (p<0.05). CONCLUSIONS Our study demonstrated that the LDLR rs1433099 polymorphism is not a risk factor of NAFLD. The LDLR rs1433099 polymorphism may increase the risk of CVD through a mechanism involving alkaline phosphatase and gamma-glutamyl transpeptidase.
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Affiliation(s)
- Yi Han
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, Shandong, China
- Department of Gastroenterology, The First People’s Hospital of Xuzhou, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yongshuo Zhang
- Administrative Management Office, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Shousheng Liu
- Clinical Research Center, Qingdao Municipal Hospital, Qingdao, Shandong, China
| | - Guangxia Chen
- Department of Gastroenterology, The First People’s Hospital of Xuzhou, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Linlin Cao
- Department of Gastroenterology, The First People’s Hospital of Xuzhou, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yongning Xin
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, Shandong, China
- Correspondence to: Yongning Xin, Department of Infectious Disease, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong 266011, China. ORCID: http://orcid.org/0000-0002-3692-7655. Tel: +86-532-82789463, Fax: +86-532-85968434, E-mail:
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17
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Lee CH, Han K, Kim DH, Kwak MS. Repeatedly elevated γ-glutamyltransferase levels are associated with an increased incidence of digestive cancers: A population-based cohort study. World J Gastroenterol 2021; 27:176-188. [PMID: 33510558 PMCID: PMC7807301 DOI: 10.3748/wjg.v27.i2.176] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 12/05/2020] [Accepted: 12/16/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The association between elevated γ-glutamyltransferase (GGT) at a certain point and incident cancer has been suggested; however, no study has evaluated the association between repeatedly elevated GGT and cancer incidence.
AIM To investigate the effects of repeatedly elevated GGT on the incidence of digestive cancers.
METHODS Participants who had undergone health screening from 2009 to 2012 and 4 consecutive previous examinations were enrolled. GGT points were calculated as the number of times participants met the criteria of quartile 4 of GGT in four serial measurements (0-4 points). Multivariable Cox proportional hazard regression models were applied.
RESULTS In total, 3559109 participants were included; among them, 43574 digestive cancers developed during a median of 6.8 years of follow-up. The incidence of total digestive cancers increased in a dose-response manner in men [adjusted hazard ratio (aHR) compared with those with 0 GGT points = 1.28 and 95% confidence interval (CI) = 1.24-1.33 in those with 1 point; aHR = 1.40 and 95%CI = 1.35-1.46 in those with 2 points; aHR = 1.52 and 95%CI = 1.46-1.58 in those with 3 points; aHR = 1.88 and 95%CI = 1.83-1.94 in those with 4 points; P for trend < 0.001]. This trend was more prominent in men than in women and those with healthy habits (no smoking, no alcohol consumption, and a low body mass index) than in those with unhealthy habits.
CONCLUSION Repeatedly elevated GGT levels were associated with an increased risk of incident digestive cancer in a dose-responsive manner, particularly in men and those with healthy habits. Repeated GGT measurements may be a good biomarker of incident digestive cancer and could help physicians identify high-risk populations.
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Affiliation(s)
- Chang-Hoon Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul 06978, South Korea
| | - Da Hye Kim
- Department of Biostatistics, College of Medicine, Catholic University of Korea, Seoul 06591, South Korea
| | - Min-Sun Kwak
- Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 06236, South Korea
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18
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Lorzadeh E, Akhondi-Meybodi M, Mozaffari-Khosravi H, Mirzaei M, Salehi-Abargouei A. Association between empirically derived dietary patterns and liver function tests in adults: Shahedieh cohort study. Nutrition 2021; 81:110897. [PMID: 32738511 DOI: 10.1016/j.nut.2020.110897] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 05/03/2020] [Accepted: 06/06/2020] [Indexed: 12/27/2022]
Abstract
OBJECTIVES Limited data exist on the association between dietary patterns (DPs) and enzymes mainly produced by the liver. This study aimed to examine the relationship between empirically derived DPs and serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma glutamyl transferase (GGT) levels in addition to the alanine/aspartate aminotransferase ratio. METHODS This cross-sectional study was conducted on adults in the baseline phase of the Shahedieh cohort study in Yazd, Iran. Blood samples were taken from participants in a fasted state to provide data on dietary intake and other variables. Major DPs were derived using a principal component analysis. RESULTS In total, 4973 participants (age 46.33 ± 9.08 y) were included in the study. Three DPs were derived: Traditional diet (high in vegetables, fruits, tomatoes, dairy, dried fruits, fruit juice, yogurt, olive and olive oil, sweet desserts, and high-fat dairy products), western diet (high in pizza, refined grains, soft drinks, high-fat dairy products, processed meats, mayonnaise, and snack foods), and hydrogenated fat and sugar diet (high in hydrogenated fat, potatoes, sugars, and legumes). After adjustment for all confounders, the western DP had a significant linear association with serum GGT (P < 0.001). This diet was also associated with higher odds for developing abnormal levels of serum GGT (Ptrend < 0.001). Although the other DPs had some linear associations with enzymes levels, they were not associated with the likelihood for developing abnormally high liver enzymes levels. CONCLUSIONS A higher consumption of a western DP might adversely affect serum GGT levels. Prospective studies are recommended to confirm our results.
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Affiliation(s)
- Elnaz Lorzadeh
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohsen Akhondi-Meybodi
- Department of Internal Medicine, School of Medicine, Shahid Sadoughi General Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hassan Mozaffari-Khosravi
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Masoud Mirzaei
- Yazd Cardiovascular Research Center, Shahid Sadoughi General Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Amin Salehi-Abargouei
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Serum Gamma Glutamyltransferase Is Associated with 25-Hydroxyvitamin D Status in Elderly Patients with Stable Coronary Artery Disease. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17238980. [PMID: 33276664 PMCID: PMC7729888 DOI: 10.3390/ijerph17238980] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 11/20/2020] [Accepted: 12/01/2020] [Indexed: 11/16/2022]
Abstract
Background: No previous study has investigated the association between gamma glutamyltransferase (GGT) and vitamin D in patients with stable coronary artery disease (CAD). We investigated the cross-sectional associations between vitamin D status as assessed by serum 25(OH)D and GGT. Methods: 169 patients were enrolled. Study population was divided into three groups: 1: 25(OH)D < 10 ng/mL (n = 59); 2: 25(OH)D 10–20 ng/mL (n = 82), and 3: 25(OH)D > 20 ng/mL (n = 28). Based on a cut-off GGT value identified in ROC analysis, we also divided the study population to compare the following groups: GGT ≤19 (n = 66) and GGT >19 (n = 103). Results: GGT activity was the highest in vitamin D severely deficient patients and the lowest in vitamin D insufficient patients. GGT was inversely correlated with 25(OH)D concentrations (R = −0.23; p = 0.002). The receiver operating characteristics curve identified the discrimination threshold of GGT of >19 U/L in predicting vitamin D deficiency. Higher leukocyte and neutrophil counts and lower 25(OH)D concentration were found in patients with GGT > 19 U/L. Conclusions: We identified an interaction between declining 25(OH)D levels and rising GGT levels with increasing age, which resulted in an unfavorable 25(OH)D-to-GGT ratio in stable CAD patients. These results suggest that these changes might further contribute to a high cardiovascular risk in the elderly.
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20
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Kim YG, Park GM, Lee SB, Yang DH, Kang JW, Lim TH, Kim HK, Choe J, Lee SW, Kim YH. Association of gamma-glutamyl transferase with subclinical coronary atherosclerosis and cardiac outcomes in non-alcoholics. Sci Rep 2020; 10:17994. [PMID: 33093619 PMCID: PMC7581814 DOI: 10.1038/s41598-020-75078-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 10/12/2020] [Indexed: 12/12/2022] Open
Abstract
In an asymptomatic population, we determined the relationship between serum gamma-glutamyl transferase (GGT) and subclinical atherosclerosis, using coronary computed tomography angiography (CCTA). This was a retrospective observational cohort study which analyzed 5120 consecutive asymptomatic individuals with no prior history of coronary artery disease or significant alcohol intake who voluntarily underwent CCTA as part of a general health examination. All subjects were stratified into tertiles based on GGT levels. Degree and extent of subclinical coronary atherosclerosis were evaluated using CCTA. Cardiac events were a composite of all-cause death, myocardial infarction, unstable angina, and coronary revascularization. After adjustment for cardiovascular risk factors, there were no significant differences among GGT tertiles in terms of adjusted odds ratios for non-calcified and mixed plaques. The risk of any atherosclerotic and calcified plaques, significant stenosis, multi-vessel disease, and significant stenosis in the left main or proximal left anterior descending artery was higher in the third GGT tertile than in the first tertile (all p < 0.05). Over a median 5.4-year follow-up, the third GGT tertile had significant adjusted hazards ratios for cardiac events than did the first GGT tertile, even after stepwise adjustment for cardiovascular risk factors (all p < 0.01). In asymptomatic individuals, elevated GGT was independently associated with high-risk feature atherosclerosis and poorer cardiac outcomes.
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Affiliation(s)
- Yong-Giun Kim
- Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, 877, Bangeojinsunhwan-doro, Dong-gu, Ulsan, 44033, Republic of Korea
| | - Gyung-Min Park
- Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, 877, Bangeojinsunhwan-doro, Dong-gu, Ulsan, 44033, Republic of Korea.
| | - Seung Bum Lee
- Department of Gastroenterology and Hepatology, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwando-ro, Dong-gu, Ulsan, 44033, Republic of Korea.
| | - Dong Hyun Yang
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Joon-Won Kang
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Tae-Hwan Lim
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hong-Kyu Kim
- Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jaewon Choe
- Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seung-Whan Lee
- Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young-Hak Kim
- Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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21
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Oni ET, Figueredo V, Aneni E, Veladar E, McEvoy JW, Blaha MJ, Blumenthal RS, Conceicao RD, Carvalho JAM, Santos RD, Nasir K. Non-Alcoholic Fatty Liver Disease Modifies Serum Gamma-Glutamyl Transferase in Cigarette Smokers. J Clin Med Res 2020; 12:472-482. [PMID: 32849935 PMCID: PMC7430878 DOI: 10.14740/jocmr3932] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 01/22/2020] [Indexed: 11/11/2022] Open
Abstract
Background Serum gamma-glutamyl transferase (GGT) is a marker of oxidative stress, associated with increased cardiovascular (CV) risk. The impact of smoking on oxidative stress may be aggravated in individuals with non-alcoholic fatty liver disease (NAFLD). We aimed to ascertain the association of smoking on GGT levels in the presence or absence of NAFLD. Methods We evaluated 6,354 healthy subjects (43 ± 10 years, 79% males) without clinical cardiovascular disease (CVD) undergoing an employer-sponsored physical between December 2008 and December 2010. NAFLD was diagnosed by ultrasound and participants were categorized as current or non-smokers by self report. A multivariate linear regression of the cross-sectional association between smoking and GGT was conducted based on NAFLD status. Results The prevalence of NAFLD was 36% (n = 2,299) and 564 (9%) were current smokers. Smokers had significantly higher GGT levels in the presence of NAFLD (P < 0.001). After multivariable adjustment, current smoking was associated with 4.65 IU/L higher GGT level, P < 0.001, compared to non-smokers. When stratified by NAFLD, the magnitude of this association was higher in subjects with NAFLD (β-coefficient: 11.12; 95% confidence interval (CI): 5.76 - 16.48; P < 0.001); however, no such relationship was observed in those without NAFLD (β: -0.02; 95% CI: -3.59, 3.56; P = 0.992). Overall the interaction of NAFLD and smoking with GGT levels as markers of oxidative stress was statistically significant. Conclusions Smoking is independently associated with significantly increased oxidative stress as measured by GGT level. This association demonstrates effect modification by NAFLD status, suggesting that smoking may intensify CV risk in individuals with NAFLD.
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Affiliation(s)
- Ebenezer T Oni
- Cardiology Division, Heart and Vascular Institute, Einstein Medical Center, Philadelphia, PA, USA
| | - Vincent Figueredo
- St. Mary Medical Center, 1203 Langhorne-Newtown Road, Suite 320, Langhorne, PA 19047, USA
| | - Ehimen Aneni
- Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine
| | - Emir Veladar
- Center of Advanced Analytics, Baptist Health South Florida, 8900 North Kendall Drive, Miami, FL 33176, USA
| | - John W McEvoy
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA
| | - Michael J Blaha
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA.,Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Roger S Blumenthal
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA
| | - Raquel D Conceicao
- Preventive Medicine Center Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | - Jose A M Carvalho
- Preventive Medicine Center Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | - Raul D Santos
- Preventive Medicine Center Hospital Israelita Albert Einstein, Sao Paulo, Brazil.,Lipid Clinic-Heart Institute (InCor) University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil
| | - Khurram Nasir
- Houston Methodist, Debakey Heart and Vascualr Institute, Houston, TX, USA
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22
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Saki S, Saki N, Poustchi H, Malekzadeh R. Assessment of Genetic Aspects of Non-alcoholic Fatty Liver and Premature Cardiovascular Events. Middle East J Dig Dis 2020; 12:65-88. [PMID: 32626560 PMCID: PMC7320986 DOI: 10.34172/mejdd.2020.166] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 03/19/2019] [Indexed: 12/12/2022] Open
Abstract
Recent evidence has demonstrated a strong interplay and multifaceted relationship between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). CVD is the major cause of death in patients with NAFLD. NAFLD also has strong associations with diabetes and metabolic syndrome. In this comprehensive review, we aimed to overview the primary environmental and genetic risk factors of NAFLD, and CVD and also focus on the genetic aspects of these two disorders. NAFLD and CVD are both heterogeneous diseases with common genetic and molecular pathways. We have searched for the latest published articles regarding this matter and tried to provide an overview of recent insights into the genetic aspects of NAFLD and CVD. The common genetic and molecular pathways involved in NAFLD and CVD are insulin resistance (IR), subclinical inflammation, oxidative stress, and atherogenic dyslipidemia. According to an investigation, the exact associations between genomic characteristics of NAFLD and CVD and casual relationships are not fully determined. Different gene polymorphisms have been identified as the genetic components of the NAFLDCVD association. Some of the most documented ones of these gene polymorphisms are patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), adiponectin-encoding gene (ADIPOQ), apolipoprotein C3 (APOC3), peroxisome proliferator-activated receptors (PPAR), leptin receptor (LEPR), sterol regulatory element-binding proteins (SREBP), tumor necrosis factor-alpha (TNF-α), microsomal triglyceride transfer protein (MTTP), manganese superoxide dismutase (MnSOD), membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), and mutation in DYRK1B that substitutes cysteine for arginine at position 102 in kinase-like domain. Further cohort studies with a significant sample size using advanced genomic assessments and next-generation sequencing techniques are needed to shed more light on genetic associations between NAFLD and CVD.
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Affiliation(s)
- Sara Saki
- Tehran University of Medical Sciences, Tehran, Iran
| | - Nader Saki
- Hoveizeh Cohort Study, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hossein Poustchi
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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23
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Adeyemi WJ, Olayaki LA, Abdussalam TA, Toriola AP, Olowu AB, Yakub AJ, Raji AO. Investigation of the effects of dietary modification in experimental obesity: low dose of virgin coconut oil has a potent therapeutic value. Biomed Pharmacother 2020; 126:110110. [PMID: 32244146 DOI: 10.1016/j.biopha.2020.110110] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 03/13/2020] [Accepted: 03/17/2020] [Indexed: 12/28/2022] Open
Abstract
There is no report in literature on possible physiological changes that accompany dietary modification in obese condition. Moreover, there is no conclusive evidence on the optimal amount of virgin coconut oil (VCO) that could be of health benefit, although it is known to enhance lipid metabolism. Therefore, we investigated the antiobesitogenic action of graded doses of VCO (200, 400 and 600 mg/kg) in obese rats fed with normo/hyper-lipidaemic diet. Sixty rats (n = 10) were divided into 6 groups and treated as follows: the control and high fat diet (HFD) groups were administered normal saline (0.1 mL/day, p.o.) during the last four weeks of the study, and were fed with normal and HFD respectively throughout the twenty weeks duration of the experiment. Groups 3-6 were fed with HFD for 16 weeks, then normal diet during the next 4 weeks. While group - 3 received saline (0.1 mL/day, p.o.) during the last four weeks, groups 4-6 received graded doses of VCO. The results showed that HFD-induced obesity caused impaired glucose homeostasis, distorted hepatic histoarchitecture, selected deviations in hepatic function indices, pro-inflammatory, pro-oxidant, and dsylipidaemic effects. There were evidence of escalated and reversed pathological actions following the replacement of HFD with normal diet. VCO showed no effect on glucose, insulin, insulin resistance, total protein, uric acid and TAC; but equitable effects on CAT, IL-6, CRP, ALT, AST & GGT, irrespective of the dose. Compared to the effects of VCO at 400 and 600 mg/kg, at 200 mg/kg, VCO had more significant therapeutic effects on LDH, MDA, SOD, GPX, TC, TG, LDL-C, total bilirubin, atherogenic and lee indices and hepatic histoarchitecture. Conclusively, VCO, preferably at a low dose could be used to reverse hepatic structural alteration and some biochemical deviations following dietary modifications in obese condition.
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Affiliation(s)
| | | | - Tahir Ahmad Abdussalam
- Anatomy and Physiology Department, University of Ilorin Teaching Hospital, Ilorin, Nigeria
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24
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Younossi ZM, Ratziu V, Loomba R, Rinella M, Anstee QM, Goodman Z, Bedossa P, Geier A, Beckebaum S, Newsome PN, Sheridan D, Sheikh MY, Trotter J, Knapple W, Lawitz E, Abdelmalek MF, Kowdley KV, Montano-Loza AJ, Boursier J, Mathurin P, Bugianesi E, Mazzella G, Olveira A, Cortez-Pinto H, Graupera I, Orr D, Gluud LL, Dufour JF, Shapiro D, Campagna J, Zaru L, MacConell L, Shringarpure R, Harrison S, Sanyal AJ. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 2019; 394:2184-2196. [PMID: 31813633 DOI: 10.1016/s0140-6736(19)33041-7] [Citation(s) in RCA: 907] [Impact Index Per Article: 151.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 10/24/2019] [Accepted: 10/30/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. METHODS In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. FINDINGS Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). INTERPRETATION Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes. FUNDING Intercept Pharmaceuticals.
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Affiliation(s)
- Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Vlad Ratziu
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Institute for Cardiometabolism and Nutrition, Paris, France
| | - Rohit Loomba
- NAFLD Rsearch Center, University of California San Diego, San Diego, CA, USA
| | - Mary Rinella
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Quentin M Anstee
- The Newcastle Liver Research Group, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Zachary Goodman
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Pierre Bedossa
- Service d'Anatomie Pathologique, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Andreas Geier
- Department of Hepatology, University of Wuerzburg, Wuerzburg, Germany
| | | | - Philip N Newsome
- National Institute for Health Research Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - David Sheridan
- Institute of Translational & Stratified Medicine, University of Plymouth and University Hospitals Plymouth NHS Trust, Plymouth, UK
| | | | - James Trotter
- Baylor Health, Liver Consultants of Texas, Dallas, TX, USA
| | | | - Eric Lawitz
- Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX, USA
| | - Manal F Abdelmalek
- Division of Gastroenterology and Hepatology, Duke University Medical Center, Durham, NC, USA
| | | | - Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Canada
| | - Jerome Boursier
- HIFIH Laboratory, UPRES EA3859, SFR 4208, Angers University, Angers, France; Hepato-Gastroenterology Department, Angers University Hospital, Angers, France
| | | | | | - Giuseppe Mazzella
- Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna, Bologna, Italy
| | - Antonio Olveira
- Department of Gastroenterology, Hospital Universitario La Paz, Madrid, Spain
| | - Helena Cortez-Pinto
- Clínica Universitária de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Isabel Graupera
- Liver Unit, Hospital Clínic de Barcelona, Barcelona, Spain; Institut D'investigacions Biomèdiques August Pi I Sunyer, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
| | - David Orr
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | - Lise Lotte Gluud
- The Gastrounit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Jean-Francois Dufour
- University Clinic for Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, Switzerland
| | | | | | - Luna Zaru
- Intercept Pharmaceuticals, San Diego, CA, USA
| | | | | | | | - Arun J Sanyal
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, USA.
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25
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Chung HS, Lee JS, Kim JA, Roh E, Lee YB, Hong SH, Yoo HJ, Baik SH, Kim NH, Seo JA, Kim SG, Kim NH, Choi KM. γ-Glutamyltransferase Variability and the Risk of Mortality, Myocardial Infarction, and Stroke: A Nationwide Population-Based Cohort Study. J Clin Med 2019; 8:jcm8060832. [PMID: 31212805 PMCID: PMC6617005 DOI: 10.3390/jcm8060832] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Revised: 06/08/2019] [Accepted: 06/11/2019] [Indexed: 12/24/2022] Open
Abstract
Although it has been suggested that the γ-glutamyltransferase (GGT) level is an indicator of cardiometabolic disorders, there is no previous study to evaluate the implication of GGT variability on the development of myocardial infarction (MI), stroke, all-cause mortality, and cardiovascular disease (CVD)-related mortality. GGT variability was measured as the coefficient variance (GGT-CV), standard deviation (GGT-SD), and variability independent of the mean (GGT-VIM). Using the population-based Korean National Health Insurance Service-Health Screening Cohort, we followed 158,736 Korean adults over a median duration of 8.4 years. In multivariable Cox proportional hazard analysis, the risk of mortality, MI, and stroke showed a stepwise increase according to the quartiles of GGT-CV, GGT-SD or GGT-VIM. In the highest quartile of GGT-CV compared to the lowest quartile after adjusting for confounding variables including mean GGT, the hazard ratios (HRs) for incident MI, stroke, mortality, and CVD-related mortality were 1.19 (95% confidence interval (CI), 1.06–1.34; p < 0.001), 1.20 (95% CI, 1.10–1.32; p < 0.001), 1.41 (95% CI, 1.33–1.51; p < 0.001), and 1.52 (95% CI, 1.30–1.78; p < 0.001), respectively, which were similar or even higher compared with those associated with total cholesterol variability. This is the first study to demonstrate that high GGT variability is associated with increased risk of MI, stroke, all-cause mortality, and CVD-related mortality in the general population.
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Affiliation(s)
- Hye Soo Chung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, #1, Singil-ro, Yeongdeungpo-gu, Seoul 07441, Korea.
| | - Ji Sung Lee
- Clinical Research Center, Asan Medical Center, College of Medicine, Ulsan University, #88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.
| | - Jung A Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Guro Hospital, College of Medicine, Korea University, 80 Guro-Dong, Guro-Gu, Seoul 08308, Korea.
| | - Eun Roh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Guro Hospital, College of Medicine, Korea University, 80 Guro-Dong, Guro-Gu, Seoul 08308, Korea.
| | - You Bin Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Guro Hospital, College of Medicine, Korea University, 80 Guro-Dong, Guro-Gu, Seoul 08308, Korea.
| | - So Hyeon Hong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Guro Hospital, College of Medicine, Korea University, 80 Guro-Dong, Guro-Gu, Seoul 08308, Korea.
| | - Hye Jin Yoo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Guro Hospital, College of Medicine, Korea University, 80 Guro-Dong, Guro-Gu, Seoul 08308, Korea.
| | - Sei Hyun Baik
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Guro Hospital, College of Medicine, Korea University, 80 Guro-Dong, Guro-Gu, Seoul 08308, Korea.
| | - Nan Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Ansan Hospital, College of Medicine, Korea University, #123, Jeokgeum-ro, Danwon-gu, Ansan-si 15355, Korea.
| | - Ji A Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Ansan Hospital, College of Medicine, Korea University, #123, Jeokgeum-ro, Danwon-gu, Ansan-si 15355, Korea.
| | - Sin Gon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, College of Medicine, Korea University, #145, Anam-ro, Seongbuk-gu, Seoul 02841, Korea.
| | - Nam Hoon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, College of Medicine, Korea University, #145, Anam-ro, Seongbuk-gu, Seoul 02841, Korea.
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Guro Hospital, College of Medicine, Korea University, 80 Guro-Dong, Guro-Gu, Seoul 08308, Korea.
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26
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Yang P, Wu P, Liu X, Feng J, Zheng S, Wang Y, Fan Z. Association Between γ-Glutamyltransferase Level and Cardiovascular or All-Cause Mortality in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis. Angiology 2019; 70:844-852. [PMID: 31122026 DOI: 10.1177/0003319719850058] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
This meta-analysis assessed the prognostic value of serum γ-glutamyltransferase (GGT) level for cardiovascular (CV) and all-cause mortality in patients with coronary artery disease (CAD). We conducted a systematic literature search of PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang, and Weipu databases until December 2018. Observational studies investigating the prognostic role of serum GGT level for CV and all-cause mortality in patients with CAD were included. Pooled risk ratios (RR) with 95% confidence intervals (CI) for the highest versus the lowest GGT level were used to summarize the prognostic value. Twelve studies involving 12 531 patients with CAD were included. Meta-analysis showed that elevated GGT level was significantly associated with higher risk of CV mortality (RR: 2.04; 95% CI: 1.57-2.64) and all-cause mortality (RR: 1.49; 95% CI: 1.27-1.74) in patients with CAD. This meta-analysis suggests that elevated serum GGT levels are an independent predictor of CV and all-cause mortality in patients with CAD. Determination of GGT level may improve the prediction of CV and all-cause mortality in patients with CAD.
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Affiliation(s)
- Ping Yang
- 1 Department of Vasculocardiology, the Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China
| | - Peng Wu
- 2 Department of Cardiovascular Medicine, Ya'an People's Hospital, Ya'an, City, Sichuan Province, China
| | - Xing Liu
- 1 Department of Vasculocardiology, the Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China
| | - Jian Feng
- 1 Department of Vasculocardiology, the Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China
| | - Shuzhan Zheng
- 1 Department of Vasculocardiology, the Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China
| | - Yan Wang
- 1 Department of Vasculocardiology, the Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China
| | - Zhongcai Fan
- 1 Department of Vasculocardiology, the Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China
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Kreutzer F, Krause D, Klaassen-Mielke R, Trampisch HJ, Diehm C, Rudolf H. Gamma-glutamyl transferase as a risk factor for mortality and cardiovascular events in older adults - results from a prospective cohort study in a primary care setting (getABI). VASA 2019; 48:313-319. [PMID: 30994055 DOI: 10.1024/0301-1526/a000790] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Background: In primary care, the gamma-glutamyl transferase (GGT) activity is used for assessing hepatobiliary dysfunction, but is also known to be associated with the risk of cardiovascular events as well as overall mortality. As this knowledge is mainly based on cohorts with middle-aged participants, we aim to assess these associations in elderly patients in a primary care setting. Patients and methods: 6,880 unselected primary care patients, aged 65 years or older, were enrolled by 344 general practitioners all over Germany (getABI study). During seven years of follow-up, coronary heart disease (CHD) events (myocardial infarction or coronary revascularization), cerebrovascular events (stroke or carotid revascularization) and deaths were recorded. Event rates were calculated and Cox regression analysis with adjustment for age, gender, GGT, classical and other risk factors (e.g. education, homocysteine, C-reactive protein, vitamin D) was performed. Results: 1,243 patients died. 27.8 deaths per 1,000 patient years (0.95 confidence interval [0.95 CI]: 26.2-29.3) occurred in the whole cohort. 605 participants had a CHD event, i.e. 16.1 per 1,000 patient years (0.95 CI: 14.8-17.4). 296 cerebrovascular events were observed, i.e. 7.7 per 1,000 patient years (0.95 CI: 6.9-8.6). Cox regression analysis with adjustment for the above-mentioned risk factors showed a significant impact of baseline elevation of GGT above the 3rd quartile (women > 18 U/L, men > 26 U/L) compared to the rest on mortality (hazard ratio [HR] 1.38, 95% CI 1.22-1.56, p < 0.001) and cerebrovascular events (1.39, 95% CI: 1.08-1.79), p = 0.010), whereas the association with CHD events (HR: 1.16, 95% CI: 0.97-1.39, p = 0.103) showed no significance. Conclusions: In a primary care setting, GGT values have a significant association with overall mortality and cerebrovascular events, but not with CHD events in elderly patients.
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Affiliation(s)
- Florian Kreutzer
- 1 Department of Medical Informatics, Biometry and Epidemiology, Ruhr University Bochum, Bochum, Germany
| | - Dietmar Krause
- 1 Department of Medical Informatics, Biometry and Epidemiology, Ruhr University Bochum, Bochum, Germany
| | - Renate Klaassen-Mielke
- 1 Department of Medical Informatics, Biometry and Epidemiology, Ruhr University Bochum, Bochum, Germany
| | - Hans-Joachim Trampisch
- 1 Department of Medical Informatics, Biometry and Epidemiology, Ruhr University Bochum, Bochum, Germany
| | - Curt Diehm
- 2 Praxis Prof. Diehm, Dr. Lawall, Ettlingen, Germany
| | - Henrik Rudolf
- 1 Department of Medical Informatics, Biometry and Epidemiology, Ruhr University Bochum, Bochum, Germany
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Arasteh S, Moohebati M, Avan A, Esmaeili H, Ghazizadeh H, Mahdizadeh A, Rahmani F, Mohamamdazade E, Ferns GA, Parizadeh MR, Ghayour-Mobarhan M. Serum level of gamma-glutamyl transferase as a biomarker for predicting stenosis severity in patients with coronary artery disease. Indian Heart J 2018; 70:788-792. [PMID: 30580846 PMCID: PMC6306306 DOI: 10.1016/j.ihj.2017.11.017] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 10/24/2017] [Accepted: 11/20/2017] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Gamma glutamyl transferase (GGT) is associated with pathogenesis of various diseases such as coronary artery disease (CAD). GGT activity displays an essential role in the catabolism of glutathione which is reported as a major antioxidant. The aim of this study was to explore the association of GGT activity with obstruction severity of artery in 500 CAD patients. RESULTS Our finding showed a significant association between serum GGT activity and CAD patients. In particular, the level of GGT in patients who had ≥50% obstruction was higher, compared to healthy and patients with less than 50% obstruction in their coronary arteries (the level of GGT in patients with at least one (1 SVD), two (2VD), three (3VD) coronary artery obstruction were 55.6±9.7, 71.7±12.7 and 84.7±13.4, while these values in patients with negative angio or control group were 28±10 and 17±4.6). Furthermore, the activity of this marker was associated with increased the risk of CAD (Odd ratio of GGT in 3VD group: 2, 95%CI: 1.8-2.3), which was also related with HDL-C. Of note, the level of GGT was enhanced progressively with increasing the obstruction severity of arteries. CONCLUSION We demonstrate the prognostic value of serum level of GGT as a biomarker for predicting obstruction severity in patients with CAD.
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Affiliation(s)
- Siavash Arasteh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Moohebati
- Cardiovascular Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Habibollah Esmaeili
- Department of Biostatistics, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamideh Ghazizadeh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Adeleh Mahdizadeh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Farzad Rahmani
- Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elham Mohamamdazade
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH, UK
| | - Mohammad Reza Parizadeh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Majid Ghayour-Mobarhan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Demirtaş K, Yayla Ç, Sade LE, Yildirir A, Özin MB, Haberal A, Müderrisoğlu IH. Platelet Membrane Γ-Glutamyl Transferase-Specific Activity and the Clinical Course of Acute Coronary Syndrome. Angiology 2018; 70:166-173. [DOI: 10.1177/0003319718787367] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
γ-Glutamyl transferase (GGT) participates in oxidative and inflammatory reactions inside the atheroma plaque and platelets. We evaluated whether platelet membrane γ-glutamyl transferase (Plt-GGT) activity is a predictor of major adverse cardiac events (MACEs) during 3 months follow-up of patients with acute coronary syndrome (ACS; MACE-3M). We included 105 patients who were hospitalized consecutively with the diagnosis of ACS. Patients with an MACE-3M were older, more likely to have hypertension, hyperlipidemia, family history of coronary artery disease(CAD), thrombolysis in myocardial infarction (TIMI) risk score >4, higher Plt-GGT and serum GGT activities, serum C-reactive protein level, and lower left ventricular ejection fraction (LVEF) when compared to those without MACE-3M (all P values ≤.05). By receiver–operator characteristic (ROC) curve analysis, 265 mU/mg for Plt-GGT, 30 U/L for serum GGT, and 45% for LVEF were determined as cutoff values to discriminate MACEs. Platelet GGT activity >265 mU/mg, TIMI risk score >4, and family history of CAD were independent predictors of MACE-3M (all P values <.05). Platelet GGT activity was as an independent predictor for MACEs in patients with ACS during the 3 months follow-up.
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Affiliation(s)
- Koray Demirtaş
- Department of Cardiology, Türkiye Yüksek Ihtisas Education and Research Hospital, Ankara, Turkey
| | - Çağri Yayla
- Department of Cardiology, Türkiye Yüksek Ihtisas Education and Research Hospital, Ankara, Turkey
| | - Leyla Elif Sade
- Faculty of Medicine, Department of Cardiology, Baskent University, Ankara, Turkey
| | - Aylin Yildirir
- Faculty of Medicine, Department of Cardiology, Baskent University, Ankara, Turkey
| | - Mehmet Bülent Özin
- Faculty of Medicine, Department of Cardiology, Baskent University, Ankara, Turkey
| | - Ayşegül Haberal
- Faculty of Medicine, Department of Biochemistry, Baskent University, Ankara, Turkey
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Alexander KS, Zakai NA, Lidofsky SD, Callas PW, Judd SE, Tracy RP, Cushman M. Non-alcoholic fatty liver disease, liver biomarkers and stroke risk: The Reasons for Geographic and Racial Differences in Stroke cohort. PLoS One 2018; 13:e0194153. [PMID: 29529073 PMCID: PMC5847237 DOI: 10.1371/journal.pone.0194153] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Accepted: 02/26/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND PURPOSE Liver disease, particularly non-alcoholic fatty liver disease (NAFLD), is a risk factor for cardiovascular disease, but little is known about its relationship with ischemic stroke. METHODS In the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of 30,239 American black and white adults, we assessed baseline NAFLD as fatty liver index (FLI) >60, and assessed liver biomarkers aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), and the AST/ALT ratio and risk of incident ischemic stroke over 5.8 years using a case-cohort study design. RESULTS Considering 572 strokes and a 1,017-person cohort sample, NAFLD was inversely associated with stroke risk in men (HR: 0.50; 95% CI: 0.26, 0.96), as was being in the highest ALT quintile versus the lowest (HR: 0.39; 95% CI: 0.19, 0.78) and the highest versus lowest GGT quintile (HR: 0.45, 95% CI: 0.24, 0.85), but not in women. Conversely, FLI score above the 90th percentile was associated with increased stroke risk among women (HR: 2.26; 95% CI: 1.14-4.47), but not men. AST was not associated with stroke risk in either sex. AST/ALT ratio >2 was strongly associated with increased stroke risk in whites, but not blacks (HRs: 3.64; 95% CI: 1.42-9.35 and 0.97; 95% CI: 0.45-1.99, respectively; p for interaction = 0.03). CONCLUSIONS The relationships between NAFLD, liver biomarkers, and ischemic stroke are complex, and sex and race differences we observed require further study and confirmation.
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Affiliation(s)
- Kristine S. Alexander
- Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont, United States of America
| | - Neil A. Zakai
- Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont, United States of America
- Department of Pathology and Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont, United States of America
| | - Steven D. Lidofsky
- Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont, United States of America
| | - Peter W. Callas
- Department of Mathematics and Statistics, University of Vermont, Burlington, Vermont, United States of America
| | - Suzanne E. Judd
- Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
| | - Russell P. Tracy
- Department of Pathology and Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont, United States of America
- Department of Biochemistry, Larner College of Medicine at the University of Vermont, Burlington, Vermont, United States of America
| | - Mary Cushman
- Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont, United States of America
- Department of Pathology and Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont, United States of America
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Choi KM, Han K, Park S, Chung HS, Kim NH, Yoo HJ, Seo JA, Kim SG, Kim NH, Baik SH, Park YG, Kim SM. Implication of liver enzymes on incident cardiovascular diseases and mortality: A nationwide population-based cohort study. Sci Rep 2018; 8:3764. [PMID: 29491346 PMCID: PMC5830612 DOI: 10.1038/s41598-018-19700-8] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Accepted: 01/05/2018] [Indexed: 12/14/2022] Open
Abstract
Although liver enzymes, such as γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), have recently been suggested as risk factors for cardiovascular diseases (CVD), impact on mortality after myocardial infarction (MI) or ischemic stroke (IS) was not previously examined. Using a population-based, nationwide cohort database, we explored the implication of GGT and aminotransferases on the development of CVD and all-cause mortality during a median 9.1 years of follow-up. Among 16,624,006 Korean adults, both GGT and aminotransferases exhibited a positive relationship with MI, IS, and mortality in a multivariate adjusted model. ALT and AST showed U-shaped associations with mortality, whereas GGT showed a positive linear relationship with mortality. The risk of 1-year mortality after MI or IS was significantly higher in the highest quartile of GGT compared to the lowest quartile (HR, 1.46; 95% CI, 1.40-1.52). The implication of GGT on MI, IS, and mortality persisted regardless of traditional cardiovascular risk parameters. This study demonstrated the unique pattern of association of ALT, AST, and GGT with the development of CVD and all-cause mortality in the Korean population. In particular, GGT showed the most robust linear relationship with mortality before and after cardiovascular events independent of risk factors.
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Affiliation(s)
- Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Kyungdo Han
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sanghyun Park
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hye Soo Chung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Nam Hoon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Hye Jin Yoo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Ji-A Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Sin Gon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Nan Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Sei Hyun Baik
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Yong Gyu Park
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seon Mee Kim
- Department of Family Medicine, College of Medicine, Korea University, Seoul, Korea.
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Bozkus F, Dikmen N, Demir LS. Gamma-glutamyl transferase activity as a predictive marker for severity of obstructive sleep apnea syndrome and concomitant hypertension. CLINICAL RESPIRATORY JOURNAL 2018; 12:1964-1973. [PMID: 29330970 DOI: 10.1111/crj.12765] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Revised: 11/01/2017] [Accepted: 01/09/2018] [Indexed: 12/30/2022]
Abstract
BACKGROUND Chronic intermittent hypia, inflammation and oxidative stress are involved in resultant obstructive sleep apnea syndrome (OSAS), which may affect numerous regulatory mechanisms that play a role in the regulation of blood pressure. Gamma-glutamyl transferase (GGT) is a novel marker in the prediction of cardiovascular risk. OBJECTIVE The objective of this study was to investigate the correlation of serum levels of GGT with hypertension and the degree of the upper airway obstruction in subjects with OSAS. METHODS A total of 270 subjects that met the inclusion criteria were enrolled in the study. The subjects were divided into four separate groups according to the apnea-hypopnea index (AHI) scores as the control group (AHI < 5), mild OSAS group (AHI 5-15), moderate OSAS group (AHI 16-30) and severe OSAS group (AHI >30). A further classification of the OSAS subjects was made in two groups based on the presence of hypertension. RESULTS The study included 43 control individuals and 59 subjects with mild, 54 subjects with moderate and 114 subjects with severe OSAS. The serum levels of GGT were found to be significantly correlated with OSAS severity (control group: 18 ± 3.3, mild OSAS: 23.6 ± 7.3, moderate OSAS: 26.4 ± 7.5 and severe OSAS: 39.8 ± 12). Serum levels of GGT were found to be significantly higher in OSAS subjects with concomitant hypertension than in the group without associated hypertension (P < .05). The results showed that the adjusted mean GGT under OSA without hypertension (Madj = 28.76, SE = 0.71) was significantly lower than in cases with OSA with hypertension (Madj = 42.79, SE = 1.19). CONCLUSION The present study indicated a strong correlation between high serum levels of GGT and concomitant hypertension in subjects with obstructive sleep apnea. This biomarker may be helpful in grading the severity of obstructive sleep apnea and correlated with hypertension in this population.
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Affiliation(s)
- Fulsen Bozkus
- Department of Chest Diseases, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey
| | - Nursel Dikmen
- Department of Chest Diseases, Necip Fazıl State Hospital, Kahramanmaras, Turkey
| | - Lutfu Saltuk Demir
- Department of Public Health, Necmettin Erbakan University, Konya, Turkey
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Yang W, Kim CK, Kim DY, Jeong HG, Lee SH. Gamma-glutamyl transferase predicts future stroke: A Korean nationwide study. Ann Neurol 2018; 83:375-386. [DOI: 10.1002/ana.25158] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2017] [Revised: 01/22/2018] [Accepted: 01/23/2018] [Indexed: 12/21/2022]
Affiliation(s)
- Wookjin Yang
- Department of Neurology; Seoul National University Hospital
- Korean Cerebrovascular Research Institute
| | - Chi Kyung Kim
- Korean Cerebrovascular Research Institute
- Department of Neurology; Korea University Guro Hospital and Korea University College of Medicine; Seoul Republic of Korea
| | - Do Yeon Kim
- Department of Neurology; Seoul National University Hospital
- Korean Cerebrovascular Research Institute
| | - Han-Gil Jeong
- Department of Neurology; Seoul National University Hospital
- Korean Cerebrovascular Research Institute
| | - Seung-Hoon Lee
- Department of Neurology; Seoul National University Hospital
- Korean Cerebrovascular Research Institute
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Ndrepepa G, Colleran R, Kastrati A. Gamma-glutamyl transferase and the risk of atherosclerosis and coronary heart disease. Clin Chim Acta 2018; 476:130-138. [DOI: 10.1016/j.cca.2017.11.026] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Revised: 11/21/2017] [Accepted: 11/23/2017] [Indexed: 02/08/2023]
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Song JL, Yang J, Yan LN, Yang JY, Wen TF, Li B, Zeng Y, Wu H, Wang WT, Xu MQ, Chen ZY, Wei YG, Jiang L. A new index predicts early allograft dysfunction following living donor liver transplantation: A propensity score analysis. Dig Liver Dis 2017; 49:1225-1232. [PMID: 28750872 DOI: 10.1016/j.dld.2017.06.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 06/08/2017] [Accepted: 06/12/2017] [Indexed: 01/10/2023]
Abstract
OBJECTIVE/AIM The aim of this study was to identify a new index to predict early allograft dysfunction following living donor liver transplantation. METHODS The study enrolled 260 adult living donor liver transplantation recipients. Postoperative laboratory variables were assessed for their association with the prevalence of early allograft dysfunction using the inverse probability of treatment weighting and propensity-score matching (n=93 pairs) analysis. RESULTS Forty-seven recipients (18.1%) developed early allograft dysfunction. In multivariable analysis, the alanine aminotransferase and gamma-glutamyl transpeptidase levels on postoperative day 1 were independent predictors of early allograft dysfunction. The alanine aminotransferase to gamma-glutamyl transpeptidase ratio (AGR) was developed. All cases were divided into two groups (Group 1 [AGR≥8.47, n=103] and Group 2 [AGR<8.47, n=157]). AGR≥8.47 (OR 10.345, 95%CI 4.502-23.772, p<0.001), hepatorenal syndrome (OR 3.016, 95%CI 1.119-8.125, p=0.029), and graft to recipient weight ratio <0.8% (OR 2.155, 95%CI 1.004-4.624, p=0.049) were independent risk factors for early allograft dysfunction. The prevalence of early allograft dysfunction was higher in group 1 (after adjusting for inverse probability of treatment weighting [n=39; 37.9% vs n=8; 5.1%] and propensity-score matching [n=33; 35.5% vs n=2; 2.2%]) than that in group 2 (p<0.001). CONCLUSIONS The postoperative AGR is a practical index for predicting early allograft dysfunction after living donor liver transplantation.
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Affiliation(s)
- Jiu-Lin Song
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Jian Yang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Lu-Nan Yan
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Jia-Yin Yang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Tian-Fu Wen
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Bo Li
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Yong Zeng
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Hong Wu
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Wen-Tao Wang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Ming-Qing Xu
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Zhe-Yu Chen
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Yong-Gang Wei
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Li Jiang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
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Yadav D, Lee MY, Kim JY, Ryu H, Huh JH, Bae KS, Ahn SV, Chung CH, Park JT, Koh SB. Combined Effect of Initial and Longitudinal Increases in γ-Glutamyltransferase on Incident Metabolic Syndrome: ARIRANG Study. Yonsei Med J 2017; 58:763-769. [PMID: 28540989 PMCID: PMC5447107 DOI: 10.3349/ymj.2017.58.4.763] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Revised: 02/03/2017] [Accepted: 02/06/2017] [Indexed: 01/14/2023] Open
Abstract
PURPOSE Although γ-glutamyltransferase (GGT) is well known to be associated with metabolic syndrome (MS), prospective data on baseline and longitudinal changes in GGT levels and incident cases of MS are limited. We aimed to examine prospective associations between changes in GGT levels over time, as well as at baseline, and incident MS in Korean adults. MATERIALS AND METHODS A total of 2579 Korean adults free of MS were followed up for 2.6 years. Data were collected from 2005-2008 (baseline) and from 2008-2011 (follow-up). Serum GGT levels were determined by enzymatic methods. RESULTS During follow-up, 558 participants (21.6%) developed MS. A gradual increase in the incidence of MS was observed across GGT quartiles. After adjustment for confounding factors, the odds ratio and 95% confidence interval (CI) for new onset MS, comparing the highest to the lowest quartiles of baseline GGT, was 2.07 (95% CI: 1.52-2.80). The odds ratio for the highest GGT changes (>4 IU/L increase) in comparison to the lowest GGT changes (<-5 IU/L decrease) was 1.75 (95% CI: 1.32-2.33). Among participants with baseline GGT concentrations <the median, the odds ratio for incident MS, comparing participants with the highest GGT changes with the lowest GGT changes, was 1.52 (95% CI: 1.01-2.31). Among participants with baseline GGT concentration ≥the median, the corresponding odds ratio was 2.75 (95% CI: 1.84-4.10). CONCLUSION High initial GGT concentration and increases in GGT concentration over time should be considered independent predictors of and to have a combined effect on incident MS.
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Affiliation(s)
- Dhananjay Yadav
- Department of Preventive Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Mi Young Lee
- Department of Interanl Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Jang Young Kim
- Department of Interanl Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
| | - Hoon Ryu
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Ji Hye Huh
- Department of Interanl Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Keum Seok Bae
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Song Vogue Ahn
- Department of Preventive Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Choon Hee Chung
- Department of Interanl Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Jong Taek Park
- Department of Anesthesiology and Pain Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
| | - Sang Baek Koh
- Department of Preventive Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
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Ryu S, Chang Y, Kang J, Kwon MJ, Yun KE, Jung HS, Kim CW, Shin H, Sung KC. Relationship Between γ-Glutamyltransferase Levels and Left Ventricular Diastolic Dysfunction. Circ J 2017; 81:823-830. [PMID: 28228613 DOI: 10.1253/circj.cj-16-1084] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND The goal of this study was to examine the association of serum γ-glutamyltransferase (GGT) levels with left ventricular (LV) diastolic dysfunction and LV hypertrophy. METHODS AND RESULTS A cross-sectional study of 79,459 Korean men and women who underwent an echocardiography as part of a comprehensive health examination between March 2011 and December 2014. The presence of LV diastolic dysfunction and LV hypertrophy was determined using echocardiography. Of the subjects, 5,447 had LV diastolic dysfunction and 2,070 had LV hypertrophy. Both LV diastolic dysfunction and LV hypertrophy were associated with higher levels of serum GGT. Multivariable-adjusted odds ratios (95% confidence interval) for LV diastolic dysfunction comparing serum GGT quartiles 2-4 with quartile 1 were 1.25 (1.08-1.44), 1.65 (1.43-1.91) and 2.23 (1.92-2.58), respectively (P for trend <0.001). Multivariable-adjusted odds ratios (95% CI) for LV hypertrophy comparing serum GGT quartiles 2-4 with quartile 1 were 1.13 (0.94-1.36), 1.14 (0.93-1.40) and 1.33 (1.07-1.65), respectively (P for trend 0.01). These associations of serum GGT levels with LV diastolic dysfunction and LV hypertrophy were modified by age (P for interaction <0.05). CONCLUSIONS This study demonstrated a positive association between serum GGT levels and LV diastolic dysfunction and LV hypertrophy in a large cohort of middle-aged men and women independent of potential confounders.
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Affiliation(s)
- Seungho Ryu
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University
| | - Yoosoo Chang
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University
| | - Jeonggyu Kang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
| | - Min-Jung Kwon
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
- Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
| | - Kyung Eun Yun
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
| | - Hyun-Suk Jung
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
| | - Chan-Won Kim
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
| | - Hocheol Shin
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
- Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
| | - Ki-Chul Sung
- Division of Cardiology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
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Spoto B, Mattace-Raso F, Sijbrands EJ, D'Arrigo G, Tripepi G, Volpato S, Bandinelli S, Ferrucci L, Zoccali C. Oxidized LDL, Gamma-Glutamyltransferase and Adverse Outcomes in Older Adults. J Am Geriatr Soc 2017; 65:e77-e82. [PMID: 28422277 DOI: 10.1111/jgs.14566] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES Gamma-glutamyltransferase (GGT) is a biomarker of liver disease and oxidative stress which was associated with all-cause and cardiovascular (CV) mortality in the general population and in patients with high risk conditions. This study aims at assessing whether oxLDL modifies the relationship between GGT, all-cause, and CV mortality in elderly individuals from the general population. DESIGN Observational longitudinal study. SETTING Population-based cohort of older individuals (>65 years) free of liver disease. PARTICIPANTS One thousand and thirty-eight individuals from the Invecchiare in Chianti (InCHIANTI) study. MEASUREMENTS Serum GGT level, oxidized low-density lipoprotein (oxLDL), CV comorbidities, all-cause and CV mortality. RESULTS The median age of the study population (n = 1,038) was 74 years (inter-quartile range: 69-79), 152 individuals (15%) had past CV events. During a median follow-up of 9 years, 401 individuals died, 168 of them (42%) for CV causes. In adjusted analyses, GGT predicted all-cause mortality (HR for 20 U/L increase in serum GGT: 1.11, 95% CI: 1.02-1.21, P = .02) and CV mortality (HR: 1.17, 95% CI: 1.03-1.33; P = .02). Furthermore, in an analysis for interaction circulating oxLDL amplified the effect of GGT on all-cause mortality (P = .003). CONCLUSION Circulating oxLDL amplifies the effect of GGT on mortality in the elderly. The mechanism for this association remains unknown and requires further research, including studying the potential role of GGT in oxidative stress. These results are consistent with the hypothesis of a causal role of GGT in the CV morbidity and mortality in older individuals and indicate that oxLDL plays a crucial role in the interpretation of the link between GGT and the risk of adverse clinical events in this population.
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Affiliation(s)
- Belinda Spoto
- National Council of Research and Institute of Clinical Physiology CNR-IFC, Reggio Calabria Unit, Reggio Calabria, Italy
| | - Francesco Mattace-Raso
- Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Eric J Sijbrands
- Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Graziella D'Arrigo
- National Council of Research and Institute of Clinical Physiology CNR-IFC, Reggio Calabria Unit, Reggio Calabria, Italy
| | - Giovanni Tripepi
- National Council of Research and Institute of Clinical Physiology CNR-IFC, Reggio Calabria Unit, Reggio Calabria, Italy
| | - Stefano Volpato
- Department of Science and Medicine, University of Ferrara, Ferrara, Italy
| | | | - Luigi Ferrucci
- Longitudinal Studies Section, National Institute on Aging, Baltimore, Maryland
| | - Carmine Zoccali
- National Council of Research and Institute of Clinical Physiology CNR-IFC, Reggio Calabria Unit, Reggio Calabria, Italy
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Caravaca-Fontán F, Azevedo L, Bayo MÁ, Gonzales-Candia B, Luna E, Caravaca F. Niveles séricos elevados de gamma-glutamil transferasa y fosfatasa alcalina son predictores independientes de mortalidad en la enfermedad renal crónica estadio 4-5. Nefrologia 2017. [DOI: 10.1016/j.nefro.2016.11.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
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Abstract
AIM OF THE STUDY The aim of the study was to determine the excess risk of all-cause and cardiovascular mortality in older people with elevated liver enzymes [alanine transaminase (ALT) and gamma glutamyltransferase (GGT)]. METHODS We utilized data from a large, prospective, population based study of 2061 people aged 50 to 99 years with linkage to a National Death Registry. Participants were categorized as having elevated liver enzymes using standard thresholds (for males, GGT>51 and ALT>40 IU/L, and GGT>33 and ALT>31 IU/L for females). Adjusted Cox proportional hazards models assessed the association of elevated liver enzymes and mortality with long duration follow-up. RESULTS Over a median follow-up of 10 years (20,145 person years), 701 people died, including 203 (34%) from cardiovascular disease. Cox regression models adjusted for sex, age, smoking, and alcohol intake indicated that people with elevated liver enzymes had an increased risk of all-cause mortality that was modified by age (test for interaction P=0.01). Age-stratified analyses demonstrated no increased risk at younger ages [age 59 y and below; hazard ratio (HR): 0.46; 95% confidence interval, 0.06-3.49], but increased risk with age; age 60 to 69, HR: 1.05 (0.53-2.07), age 70 to 79 years, HR: 1.54 (0.81 to 2.93), and age 80 years and above, HR: 3.53 (1.55 to 8.04). Similarly, the risk of cardiovascular mortality with elevated liver enzymes was also modified by, and increased with age (test for interaction P=0.02); age 70 to 79, HR: 3.15 (1.37 to 7.23), age 80 years and above, HR: 6.86 (2.44 to 19.30). CONCLUSIONS In community-dwelling elderly persons, an elevation in both ALT and GGT are associated with an excess risk of all-cause and cardiovascular mortality which increases with age.
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Lee SH, Kim KM, Kim KN. Combined effect of serum gamma-glutamyltransferase and uric acid on incidence of diabetes mellitus: A longitudinal study. Medicine (Baltimore) 2017; 96:e6901. [PMID: 28489802 PMCID: PMC5428636 DOI: 10.1097/md.0000000000006901] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Gamma-glutamyltransferase (GGT) and uric acid (UA) are novel diabetes risk factors. However, little is known about the combined effects of GGT and UA on the development of diabetes. Here, we assessed the combined effects of GGT and UA on the development of diabetes in a Korean population.We evaluated 1983 women and 2687 men without diabetes. From the baseline health screening to the follow-up examination, the development of diabetes, based on changes in GGT and UA quartile levels, was analyzed. Furthermore, the quartile of GGT and quartile of UA were analyzed together to determine any synergistic effect from the 4th quartile of GGT and UA on the development of diabetes.In women, the development of diabetes gradually increased with an increase in the circulating levels of GGT and UA. For the highest quartile of GGT and UA, hazard ratios of diabetes compared with the lowest quartile were 3.88 (95% confidence interval [CI]: 1.12-13.43, P = .032) and 7.58 (95% CI: 2.17-26.42, P = .002) after adjusting for confounders, respectively. Hazard ratios of diabetes after combining both 4th quartiles of GGT and UA were 5.29 (95% CI: 1.87-15.18, P = .002), as compared with the first and second quartiles. In men, however, the development of diabetes was not significantly different among the quartiles of UA.GGT and UA levels can synergize in predicting the development of diabetes in Korean women.
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Seo Y, Aonuma K. Gamma-Glutamyl Transferase as a Risk Biomarker of Cardiovascular Disease - Does It Have Another Face? Circ J 2017; 81:783-785. [PMID: 28450670 DOI: 10.1253/circj.cj-17-0409] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Yoshihiro Seo
- Department of Cardiology, Faculty of Medicine, University of Tsukuba
| | - Kazutaka Aonuma
- Department of Cardiology, Faculty of Medicine, University of Tsukuba
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Bharani V, Ramesh V, Rao RN, Tewari S. Evaluation of gamma glutamyl transferase as a marker of cardiovascular risk, in 200 angiographically proven coronary artery disease patients. Indian Heart J 2017. [PMID: 28648423 PMCID: PMC5485402 DOI: 10.1016/j.ihj.2017.03.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Gamma glutamyl transferase (GGT) is emerging as a promising marker for assessing cardiovascular risk. GGT predicts cardiovascular mortality in the population and is positively associated with traditional risk factors for coronary artery disease (CAD). This study was undertaken on 200 north Indian CAD patients diagnosed with coronary angiography to study relation of GGT with risk factors for CAD and severity of CAD. GGT values ranged from 5 to 69U/L and were divided in 4 quartiles. GGT was positively associated with triglyceride (p=0.008) and VLDL cholesterol (p=0.002) in our subjects. Also an increase in total cholesterol from GGT quartile I to quartile IV (p=0.28) was noted.
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Affiliation(s)
- Vani Bharani
- Dept. of Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - V Ramesh
- Dept. of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Ram Nawal Rao
- Dept. of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Satyendra Tewari
- Dept of Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Gamma-glutamyl transferase and atrial fibrillation in patients with coronary artery disease. Clin Chim Acta 2017; 465:17-21. [DOI: 10.1016/j.cca.2016.12.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Revised: 12/02/2016] [Accepted: 12/02/2016] [Indexed: 11/19/2022]
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Kasapoglu B, Turkay C, Yalcın KS, Carlioglu A, Koktener A. Role of γ-glutamyl transferase levels in prediction of high cardiovascular risk among patients with non-alcoholic fatty liver disease. Indian J Med Res 2017; 143:30-6. [PMID: 26997011 PMCID: PMC4822365 DOI: 10.4103/0971-5916.178585] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND & OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is an important cause of elevated liver functions. There is evidence showing an association between NAFLD and subclinical atherosclerosis independent of traditional risk factors. We undertook this retrospective study to determine the association of Framingham cardiovascular risk scoring system with liver function tests and inflammatory markers and to find the role of liver function tests in determination of CVD risk among non-obese and non-diabetic subjects with non-alcoholic fatty liver disease. METHODS A total of 2058 patients were included in the study. Framingham cardiovascular risk scoring was done of all patients according to the age, gender, systolic blood pressure, serum total cholesterol and HDL cholesterol levels, smoking and antihypertensive medication history. Liver function test, lipid profile, insulin, uric acid, ferritin levels, etc. were determined. RESULTS According to the ultrasonography findings, patients were grouped as without any fatty infiltration of the liver (control group) (n=982), mild (n= 473), moderate (n=363) and severe fatty liver disease (n= 240) groups. In severe fatty liver disease group, the mean Framingham cardiovascular risk score was significantly higher than that of other groups. t0 here was a positive correlation between GGT, uric acid and ferritin levels with Framingham cardiovascular score. In multivariate analysis, high GGT levels were positively associated with high-risk disease presence (OR: 3.02, 95% CI: 2.62-3.42) compared to low GGT levels independent of the age and sex. INTERPRETATION & CONCLUSIONS Cardiovascular disease risk increases with the presence and stage of fatty liver disease. Our findings showed a positive correlation between elevated GGT levels and Framingham cardiovascular risk scoring system among non-diabetic, non-obese adults which could be important in clinical practice. Though in normal limits, elevated GGT levels among patients with fatty liver disease should be regarded as a sign of increased cardiovascular disease risk. Larger studies are warranted to elucidate the role of GGT in prediction of cardiovascular risk.
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Affiliation(s)
- Benan Kasapoglu
- Turgut Ozal University Medical School, Department of Internal Medicine, Division of Gastroenterology, Ankara, Turkey
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Ndrepepa G, Kastrati A. Gamma-glutamyl transferase and cardiovascular disease. ANNALS OF TRANSLATIONAL MEDICINE 2016; 4:481. [PMID: 28149843 DOI: 10.21037/atm.2016.12.27] [Citation(s) in RCA: 83] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Gamma-glutamyl transferase (GGT) is an enzyme located on the external surface of cellular membranes. GGT contributes in maintaining the physiological concentrations of cytoplasmic glutathione and cellular defense against oxidative stress via cleavage of extracellular glutathione and increased availability of amino acids for its intracellular synthesis. Increased GGT activity is a marker of antioxidant inadequacy and increased oxidative stress. Ample evidence suggests that elevated GGT activity is associated with increased risk of cardiovascular disease (CVD) such as coronary heart disease (CHD), stroke, arterial hypertension, heart failure, cardiac arrhythmias and all-cause and CVD-related mortality. The evidence is weaker for an association between elevated GGT activity and acute ischemic events and myocardial infarction. The risk for CVD or CVD-related mortality mediated by GGT may be explained by the close correlation of GGT with conventional CVD risk factors and various comorbidities, particularly non-alcoholic fatty liver disease, alcohol consumption, oxidative stress, metabolic syndrome, insulin resistance and systemic inflammation. The finding of GGT activity in atherosclerotic plaques and correlation of intra-plaque GGT activity with histological indexes of plaque instability may suggest a participation of GGT in the pathophysiology of CVD, particularly atherosclerosis. However, whether GGT has a direct role in the pathophysiology of CVD or it is an epiphenomenon of coexisting CVD risk factors or comorbidities remains unknown and Hill's criteria of causality relationship between GGT and CVD are not fulfilled. The exploration whether GGT provides prognostic information on top of the information provided by known cardiovascular risk factors regarding the CVD or CVD-related outcome and exploration of molecular mechanisms of GGT involvement in the pathophysiology of CVD and eventual use of interventions to reduce circulating GGT activity remain a duty of future studies.
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Affiliation(s)
- Gjin Ndrepepa
- Department of Adult Cardiology, Deutsches Herzzentrum München, Technische Universität, Munich, Germany
| | - Adnan Kastrati
- Department of Adult Cardiology, Deutsches Herzzentrum München, Technische Universität, Munich, Germany;; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
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Brea Á, Pintó X, Ascaso JF, Blasco M, Díaz Á, González-Santos P, Hernández Mijares A, Mantilla T, Millán J, Pedro-Botet J. Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment. (I). Nonalcoholic fatty liver disease and its association with cardiovascular disease. CLINICA E INVESTIGACION EN ARTERIOSCLEROSIS 2016; 29:141-148. [PMID: 27692633 DOI: 10.1016/j.arteri.2016.06.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Accepted: 06/29/2016] [Indexed: 12/27/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the association of NAFLD with cardiovascular disease.
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Affiliation(s)
- Ángel Brea
- Unidad de Lípidos, Servicio de Medicina Interna, Hospital San Pedro, Logroño, España.
| | - Xavier Pintó
- Unidad de Lípidos y Riesgo Vascular, Servicio de Medicina Interna, Hospital Universitario de Bellvitge, Idibell. CiberObn, L'Hospitalet de Llobregat, Barcelona, España
| | - Juan F Ascaso
- Servicio de Endocrinología, Hospital Clínico , Valencia, España
| | - Mariano Blasco
- Atención Primaria, Área Sanitaria de Delicias, Zaragoza, España
| | - Ángel Díaz
- Centro de Salud de Bembibre, Bembibre, León, España
| | | | - Antonio Hernández Mijares
- Servicio de Endocrinología, Hospital Universitario Dr. Peset, Universitat de València , Valencia, España
| | - Teresa Mantilla
- Atención Primaria, Centro de Salud de Prosperidad, Madrid, España
| | - Jesús Millán
- Unidad de Lípidos, Servicio de Medicina Interna, Hospital General Universitario Gregorio Marañón, Universidad Complutense , Madrid, España
| | - Juan Pedro-Botet
- Unidad de Lípidos y Riesgo Vascular, Servicio de Endocrinología y Nutrición, Hospital del Mar, Universitat Autònoma de Barcelona , Barcelona, España
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Ortakoyluoglu A, Boz B, Dizdar OS, Avcı D, Cetinkaya A, Baspınar O. The association of serum gamma-glutamyl transpeptidase level and other laboratory parameters with blood pressure in hypertensive patients under ambulatory blood pressure monitoring. Ther Clin Risk Manag 2016; 12:1395-401. [PMID: 27660457 PMCID: PMC5019468 DOI: 10.2147/tcrm.s116603] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Hypertension is a very important cause of morbidity and mortality. Serum gamma-glutamyl transpeptidase (GGT) is a biomarker of oxidative stress and associated with increased risk of hypertension and diabetes. The aim of this study was to evaluate the association of serum GGT level, which is an early marker of inflammation and endothelial dysfunction, with the deterioration of the diurnal rhythm of the blood pressure. METHODS A total of 171 patients with hypertension were included in this study. Patients whose nighttime mean blood pressure, measured via ambulatory blood pressure monitoring, decreased between 10% and 20% compared with the daytime mean blood pressure were defined as "dippers", whereas patients with a nighttime blood pressure decrease lower than 10% were defined as "non-dippers". RESULTS A total of 99 hypertensive patients (65 females/34 males) were classified as dippers and 72 patients (48 females/24 males) as non-dippers. The mean age of the non-dipper group was significantly greater than the dipper group. Serum GGT, C-reactive protein and uric acid levels were significantly higher among patients in the non-dipper group. Negative correlations were detected between GGT levels and diurnal systolic and diastolic blood pressure decreases. CONCLUSION Our findings revealed that GGT level was higher in the non-dipper group, and was negatively correlated with the nighttime decrease of diurnal blood pressure. C-reactive protein and uric acid levels were also higher in the non-dipper group. However, future randomized controlled prospective studies with larger patient populations are necessary to confirm our findings.
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Affiliation(s)
- Adile Ortakoyluoglu
- Department of Internal Medicine, Kayseri Training and Research Hospital, Kayseri, Turkey
| | - Betul Boz
- Department of Internal Medicine, Kayseri Training and Research Hospital, Kayseri, Turkey
| | - Oguzhan Sıtkı Dizdar
- Department of Internal Medicine, Kayseri Training and Research Hospital, Kayseri, Turkey
| | - Deniz Avcı
- Department of Internal Medicine, Kayseri Training and Research Hospital, Kayseri, Turkey
| | - Ali Cetinkaya
- Department of Internal Medicine, Kayseri Training and Research Hospital, Kayseri, Turkey
| | - Osman Baspınar
- Department of Internal Medicine, Kayseri Training and Research Hospital, Kayseri, Turkey
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Oxidative Stress as Estimated by Gamma-Glutamyl Transferase Levels Amplifies the Alkaline Phosphatase-Dependent Risk for Mortality in ESKD Patients on Dialysis. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:8490643. [PMID: 27525053 PMCID: PMC4976170 DOI: 10.1155/2016/8490643] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Revised: 06/06/2016] [Accepted: 06/14/2016] [Indexed: 01/02/2023]
Abstract
Alkaline phosphatase (Alk-Phos) is a powerful predictor of death in patients with end-stage kidney disease (ESKD) and oxidative stress is a strong inducer of Alk-Phos in various tissues. We tested the hypothesis that oxidative stress, as estimated by a robust marker of systemic oxidative stress like γ-Glutamyl-Transpeptidase (GGT) levels, may interact with Alk-Phos in the high risk of death in a cohort of 993 ESKD patients maintained on chronic dialysis. In fully adjusted analyses the HR for mortality associated with Alk-Phos (50 IU/L increase) was progressively higher across GGT quintiles, being minimal in patients in the first quintile (HR: 0.89, 95% CI: 0.77–1.03) and highest in the GGT fifth quintile (HR: 1.13, 95% CI: 1.03–1.2) (P for the effect modification = 0.02). These findings were fully confirmed in sensitivity analyses excluding patients with preexisting liver disease, excessive alcohol intake, or altered liver disease biomarkers. GGT amplifies the risk of death associated with high Alk-Phos levels in ESKD patients. This observation is compatible with the hypothesis that oxidative stress is a strong modifier of the adverse biological effects of high Alk-Phos in this population.
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Pisa P, Kruger A, Vorster H, Margetts B, Loots Du T. Alcohol consumption and cardiovascular disease risk in an African population in transition: the Prospective Urban and Rural Epidemiology (PURE) study. SOUTH AFRICAN JOURNAL OF CLINICAL NUTRITION 2016. [DOI: 10.1080/16070658.2010.11734299] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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