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1
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Yang J, Wang T, Li K, Wāng Y. Associations between per- and polyfluoroalkyl chemicals and abdominal aortic calcification in middle-aged and older adults. J Adv Res 2025; 70:203-222. [PMID: 38705256 PMCID: PMC11976567 DOI: 10.1016/j.jare.2024.04.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 03/11/2024] [Accepted: 04/24/2024] [Indexed: 05/07/2024] Open
Abstract
INTRODUCTION Per- and polyfluoroalkyl substances (PFAS) have infiltrated countless everyday products, raising concerns about potential effects on human health, specifically on the cardiovascular system and the development of abdominal aortic calcification (AAC). However, our understanding of this relationship is still limited. OBJECTIVES This study aims to investigate the effects of PFAS on AAC using machine learning algorithms. METHODS Leveraging the power of machine learning technique, extreme gradient boosting (XGBoost), we assessed the relationship between PFAS exposure and AAC risk. We focused on three PFAS compounds, perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) through multiple logistic regression, restricted cubic spline (RCS), and quantile g-computation (QGC) models. To get more insight into the underlying mechanisms, mediation analyses are used to investigate the potential mediating role of fatty acids and blood cell fractions in AAC. RESULTS Our findings indicate that elevated serum levels of PFHxS and PFDeA are associated with the increased risk of AAC. The QGC analyses underscore the overall positive association between the PFAS mixture and AAC risk, with PFHxS carrying the greatest weight, followed by PFDeA. The RCS analyses reveal a dose-dependent increase between serum PFHxS concentration and AAC risk in an inverted V-shape way. Moreover, age and PFHxS exposure are identified as the primary factors contributing to abdominal aortic calcification risk in SHapley Additive exPlanation (SHAP) summary plot combined with XGBoost technique. Although PFAS significantly change the profile of fatty acids, we do not find any mediating roles of them in AAC. Despite strong associations between PFAS exposure and hematological indicators, our analysis does not find evidence that these indicators mediate the development of AAC. CONCLUSIONS In summary, our study highlights the detrimental impact of PFAS on abdominal aortic health and emphasizes the need for further research to understand the underlying mechanisms involved.
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Affiliation(s)
- Jijingru Yang
- Research Center for Translational Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China; The Second School of Clinical Medicine, Anhui Medical University, Hefei, 230032, China
| | - Tian Wang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Kai Li
- School of Public Health, Shanxi Medical University, Taiyuan 030001, China
| | - Yán Wāng
- Research Center for Translational Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China; Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China; Department of Toxicology, School of Public Health, Anhui Medical University, Hefei 230032, China.
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Chew NW, Muthiah MD, Sanyal AJ. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: pathophysiology and implications for cardiovascular disease. CARDIOVASCULAR ENDOCRINOLOGY AND METABOLISM 2023:137-173. [DOI: 10.1016/b978-0-323-99991-5.00003-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Chi ZC. Research status and progress of metabolic associated fatty liver disease. Shijie Huaren Xiaohua Zazhi 2022; 30:1-16. [DOI: 10.11569/wcjd.v30.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Metabolic associated fatty liver disease (MAFLD) is a more appropriate general predicate to describe non-alcoholic fatty liver disease. The new definition lists metabolic dysfunction as an important cause of liver disease, demonstrates the high heterogeneity of this condition, and speeds up the transformation path to new treatment. The incidence of extrahepatic complications and related diseases of MAFLD far exceed that of the liver disease itself, which seriously threatens human health. In view of the current insufficient understanding of its severity, and the imperfect understanding of the disease scope, pathogenesis, and diagnosis of extrahepatic complications, especially the lack of effective drug treatment, this paper introduces and reviews the research status and progress of extrahepatic complications of MAFLD.
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Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
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Yardeni D, Toledano R, Novack V, Shalev A, Wolak A, Rotman Y, Etzion O. The Association of Alanine Aminotransferase Levels With Myocardial Perfusion Imaging and Cardiovascular Morbidity. J Cardiovasc Pharmacol Ther 2022; 27:10742484221074585. [PMID: 35077243 PMCID: PMC8840806 DOI: 10.1177/10742484221074585] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
INTRODUCTION Studies suggest that non-alcoholic fatty liver disease (NAFLD) is associated with an independent risk of cardiovascular disease (CVD). We utilized a large cohort of patients undergoing myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) to determine the association between alanine aminotransferase (ALT) as a surrogate marker for presumed NAFLD, and the presence of myocardial ischemia and mortality. METHODS We retrospectively assessed SPECT-MPI results and medical records of individuals evaluated between 1997 and 2008. We excluded patients with known non-NAFLD liver diseases, ALT values <17 or >340 U/L and absent liver tests. Elevated ALT cases were classified as presumed NAFLD. The primary endpoint was abnormal SPECT-MPI. Secondary endpoints included cardiac death, acute myocardial infarction and all-cause mortality. RESULTS Of 26,034 patients who underwent SPECT-MPI, 11,324 met inclusion criteria. 1635 (14.4%) patients had elevated ALT. SPECT-MPI results did not differ significantly between subjects with elevated ALT and controls. Elevated ALT was associated with increased risk for the composite endpoint of cardiac death or acute myocardial infarction at 5-year follow-up (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.01-1.67) and in all-cause mortality (HR 1.27, CI 1.02-1.58) but only in patients with normal SPECT-MPI. CONCLUSIONS The long-term mortality of patients with abnormal SPECT-MPI is not modulated by ALT, likely reflecting an already high risk and established CVD. However, patients with normal SPECT-MPI are at increased risk for a future cardiac event if they have an elevated ALT level, suggesting an important role for NAFLD in earlier stages of CVD.
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Affiliation(s)
- David Yardeni
- Department of Gastroenterology and Liver Diseases, Soroka University Medical Center, Beer-Sheva, Israel
| | - Ronen Toledano
- Clinical Research Center, Soroka University Medical Center, Beer-Sheva, Israel
| | - Victor Novack
- Clinical Research Center, Soroka University Medical Center, Beer-Sheva, Israel
| | - Aryeh Shalev
- Cardiology Department, Soroka University Medical Center, Beer-Sheva, Israel
| | - Arik Wolak
- Cardiology Department, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Yaron Rotman
- Liver & Energy Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Ohad Etzion
- Department of Gastroenterology and Liver Diseases, Soroka University Medical Center, Beer-Sheva, Israel
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Wong MYZ, Yap JJL, Sultana R, Cheah M, Goh GBB, Yeo KK. Association between non-alcoholic fatty liver disease and subclinical atherosclerosis in Western and Asian cohorts: an updated meta-analysis. Open Heart 2021; 8:openhrt-2021-001850. [PMID: 34933963 PMCID: PMC8693165 DOI: 10.1136/openhrt-2021-001850] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 10/25/2021] [Indexed: 11/16/2022] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is a well-established risk factor for cardiovascular disease, with ethnic and regional differences noted. With the recent surge of research within this field, we re-examine the evidence associating NAFLD with subclinical atherosclerosis, and investigate potential regional differences. Methods This is a systematic review and meta-analysis. PubMed and EMBASE were systematically searched for publications from January 1967 to July 2020 using standardised criteria. Original, observational studies investigating the association between NAFLD and either carotid intima-media thickness (CIMT) and/or coronary artery calcification (CAC) were included. Key outcomes included differences in mean CIMT, the presence of increased CIMT, the presence of CAC and the development/progression of CAC. Pooled ORs and pooled standard differences in means were calculated using random-effects models. Between-study heterogeneity was quantified using the Q statistic and I². Subgroup analyses stratified by region of study (Asian vs Western) were also conducted. Results 64 studies involving a total of 172 385 participants (67 404 with NAFLD) were included. 44 studies assessed the effect of NAFLD on CIMT, with the presence of NAFLD associated with increased CIMT (OR 2.00, 95% CI 1.56 to 2.56). 22 studies assessed the effects of NAFLD on CAC score, with the presence of NAFLD associated with the presence of any coronary calcification (OR 1.21, 95% CI 1.12 to 1.32), and the development/progression of CAC (OR 1.26, 95% CI 1.04 to 1.52). When stratified by region, these associations remained consistent across both Asian and Western populations (p>0.05). The majority (n=39) of studies were classified as ‘high quality’, with the remaining 25 of ‘moderate quality’. Conclusions There is a significant positive association between various measures of subclinical atherosclerosis and NAFLD, seen across both Western and Asian populations. These results re-emphasise the importance of early risk evaluation and prophylactic intervention measures to preclude progression to clinical cardiovascular disease in patients with NAFLD.
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Affiliation(s)
| | - Jonathan Jiunn Liang Yap
- Department of Cardiology, National Heart Center Singapore, Singapore.,Duke-NUS Medical School, Singapore
| | | | - Mark Cheah
- Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore
| | - George Boon Bee Goh
- Duke-NUS Medical School, Singapore.,Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore
| | - Khung Keong Yeo
- Department of Cardiology, National Heart Center Singapore, Singapore .,Duke-NUS Medical School, Singapore
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Pennisi G, Di Marco V, Buscemi C, Mazzola G, Randazzo C, Spatola F, Craxì A, Buscemi S, Petta S. Interplay between non-alcoholic fatty liver disease and cardiovascular risk in an asymptomatic general population. J Gastroenterol Hepatol 2021; 36:2389-2396. [PMID: 33871081 DOI: 10.1111/jgh.15523] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 11/07/2020] [Accepted: 12/03/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIMS Non-alcoholic fatty liver (NAFLD) is a major cause of liver disease worldwide leading also to a higher risk of cardiovascular events. We aimed to evaluate the impact of fatty liver and fibrosis on cardiovascular risk in a general population. METHODS Five hundred and forty-two subjects included in the community-based ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study were recruited. Steatosis (controlled attenuation parameter > 288 dB/m) and severe fibrosis (low risk, liver stiffness measurement [LSM] < 7.9 KPa with M probe and < 5.7 KPa with XL probe; intermediate risk, LSM 7.9-9.5 KPa with M probe and 5.7-9.2 KPa with XL probe; high risk, LSM ≥ 9.6 KPa with M probe and ≥ 9.3 KPa with XL probe) were assessed with FibroScan. Cardiovascular risk was evaluated by the atherosclerotic cardiovascular disease (ASCVD) risk estimator and defined low if < 5%, borderline if 5-7.4%, intermediate if 7.5-19.9% and high if ≥ 20%. Intima-media thickness (IMT) was measured with ultrasound. RESULTS Prevalence of steatosis and of severe fibrosis in this cohort was 31.7% and 4.8%, respectively. ASCVD score was evaluated in patients with and without steatosis and according to the risk of severe fibrosis. By ordinal regression analysis, both steatosis (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.13-2.33, P = 0.009) and severity of fibrosis (OR 1.67, 95% CI 1.18-2.36, P = 0.003) were independent risk factors for a higher ASCVD risk after adjusting for obesity. Subjects with NAFLD, when compared with those without, did not differ for IMT (0.75 vs 0.72 mm; P = 0.11) and IMT ≥ 1 mm (15.6% vs 12.1%; P = 0.24). Higher prevalence of IMT ≥ 1 mm was found in patients at high or intermediate risk of severe fibrosis (24% and 28.6%, respectively) compared with those at low risk (12.1%) (P = 0.03); this association was maintained after adjusting for confounders (OR 2.70, 95% CI 1.01-2.86, P = 0.04). CONCLUSION In the setting of a general adult population, the presence of NAFLD and severe fibrosis are associated with to a higher cardiovascular risk profile, pointing towards the need for specific preventive measures.
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Affiliation(s)
- Grazia Pennisi
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Maternal and Childhood, Internal and Specialized Medicine of Excellence (PROMISE), University of Palermo, Palermo, Italy
| | - Vito Di Marco
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Maternal and Childhood, Internal and Specialized Medicine of Excellence (PROMISE), University of Palermo, Palermo, Italy
| | - Carola Buscemi
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Maternal and Childhood, Internal and Specialized Medicine of Excellence (PROMISE), University of Palermo, Palermo, Italy
| | - Giovanni Mazzola
- Infectious Diseases Unit, Department of Health Promotion Sciences and Mother Child Care "Giuseppe D'Alessandro", University of Palermo, Palermo, Italy
| | - Cristiana Randazzo
- Endocrine Diseases, Replacement and Nutrition Unit, Policlinico P. Giaccone Palermo, Palermo, Italy
| | - Federica Spatola
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Maternal and Childhood, Internal and Specialized Medicine of Excellence (PROMISE), University of Palermo, Palermo, Italy
| | - Antonio Craxì
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Maternal and Childhood, Internal and Specialized Medicine of Excellence (PROMISE), University of Palermo, Palermo, Italy
| | - Silvio Buscemi
- Endocrine Diseases, Replacement and Nutrition Unit, Policlinico P. Giaccone Palermo, Palermo, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Maternal and Childhood, Internal and Specialized Medicine of Excellence (PROMISE), University of Palermo, Palermo, Italy
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Jung DH, Lee YJ, Park B. Longitudinal Effect of Hemoglobin Concentration With Incident Ischemic Heart Disease According to Hepatic Steatosis Status Among Koreans. Front Cardiovasc Med 2021; 8:677040. [PMID: 34124205 PMCID: PMC8193037 DOI: 10.3389/fcvm.2021.677040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 05/07/2021] [Indexed: 02/06/2023] Open
Abstract
Background: An increased hemoglobin (Hb) level may have detrimental effects on hepatic steatosis (HS) as well as cardiovascular disease (CVD). We investigated Hb's effect on incident ischemic heart disease (IHD) risk in the context of hepatic steatosis (HS). Methods: We assessed 17,521 non-diabetic participants and retrospectively screened for IHD using the Korea National Health Insurance data. High Hb was defined as Hb levels ≥16.3 g/dL in men and 13.9 g/dL in women (>75th percentile). The participants were divided into five groups: reference (group 1), mild HS only (group 2), mild HS and high Hb (group 3), severe HS only (group 4), and severe HS and high Hb (group 5). We assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional hazards regression models over 50 months from the baseline survey. Results: During the follow-up period, 330 (1.9%) participants developed IHD (310 angina pectoris and 20 myocardial infarction). Compared with the reference group (group 1), the HRs for IHD were 1.04 (95% CI, 0.75–1.46) in group 2, 1.14 (95% CI, 0.70–1.85) in group 3, 1.58 (95% CI, 1.08–2.32) in group 4, and 1.79 (95% CI, 1.15–2.80) in group 5, after adjusting for IHD risk factors. Conclusions: We found the combined effect of HS and Hb levels on the incidence of IHD.
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Affiliation(s)
- Dong Hyuk Jung
- Department of Family Medicine, Yongin Severance Hospital, Yongin, South Korea.,Department of Family Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Yong Jae Lee
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, South Korea.,Department of Family Medicine, Gangnam Severance Hospital, Seoul, South Korea
| | - Byoungjin Park
- Department of Family Medicine, Yongin Severance Hospital, Yongin, South Korea.,Department of Family Medicine, Yonsei University College of Medicine, Seoul, South Korea
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8
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Chi ZC. Relationship between non-alcoholic fatty liver disease and cardiovascular disease. Shijie Huaren Xiaohua Zazhi 2020; 28:313-329. [DOI: 10.11569/wcjd.v28.i9.313] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
With the in-depth study of non-alcoholic fatty liver disease (NAFLD), it has been found in recent years that NAFLD is closely related to cardiovascular disease (CVD). It has been proved that NAFLD is not only an important risk factor for CVD, but it is also an important mechanism of atherosclerosis, coronary heart disease, and hypertension in young people. This article reviews the recent progress in the understanding of the relationship between NAFLD and CVD, with an aim to improve the knowledge of CVD physicians on liver disease and provide reference for prevention and treatment of these conditions.
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Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
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Ismaiel A, Dumitraşcu DL. Cardiovascular Risk in Fatty Liver Disease: The Liver-Heart Axis-Literature Review. Front Med (Lausanne) 2019; 6:202. [PMID: 31616668 PMCID: PMC6763690 DOI: 10.3389/fmed.2019.00202] [Citation(s) in RCA: 112] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 08/27/2019] [Indexed: 12/14/2022] Open
Abstract
According to the World Health Organization, cardiovascular disease (CVD) remains the leading cause of death worldwide, accounting for approximately 18 million deaths per year. Nevertheless, the worldwide prevalence of metabolic diseases, such as type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease (NAFLD), also known to be common risk factors for CVD, have dramatically increased over the last decades. Chronic alcohol consumption is a major cause of chronic liver diseases (CLD) as well as being a major health care cost expenditure accounting for the spending of tremendous amounts of money annually. NAFLD has become one of the major diseases plaguing the world while standing as the most common cause of liver disease in the Western countries by representing about 75% of all CLD. Currently, the most common cause of death in NAFLD remains to be CVD. Several mechanisms have been suggested to be responsible for associating FLD with CVD through several mechanisms including low-grade systemic inflammation, oxidative stress, adipokines, endoplasmic reticulum stress, lipotoxicity and microbiota dysbiosis which may also be influenced by other factors such as genetic and epigenetic variations. Despite of all this evidence, the exact mechanisms of how FLD can causally contribute to CVD are not fully elucidated and much remains unknown. Moreover, the current literature supports the increasing evidence associating FLD with several cardiovascular (CV) adverse events including coronary artery disease, increased subclinical atherosclerosis risk, structural alterations mainly left ventricular hypertrophy, increased epicardial fat thickness, valvular calcifications including aortic valve sclerosis and mitral annular calcification and functional cardiac modifications mainly diastolic dysfunction in addition to cardiac arrhythmias such as atrial fibrillation and ventricular arrythmias and conduction defects including atrioventricular blocks and bundle branch blocks. Patients with FLD should be evaluated and managed accordingly in order to prevent further complications. Possible management methods include non-pharmacological strategies including life style modifications, pharmacological therapies as well as surgical management. This review aims to summarize the current state of knowledge regarding the pathophysiological mechanisms linking FLD with an increased CV risk, in addition to associated CV adverse events and current management modalities.
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Affiliation(s)
- Abdulrahman Ismaiel
- Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.,2nd Department of Internal Medicine, Cluj-Napoca, Romania
| | - Dan L Dumitraşcu
- Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.,2nd Department of Internal Medicine, Cluj-Napoca, Romania
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is an important cause of chronic hepatic disease and liver transplant in Western societies. The increasing prevalence is related to dietary changes and sedentarism and follows the increasing frequency of obesity and type 2 diabetes mellitus. Growing evidence of association of NAFLD with cardiovascular diseases (CVD), independent of cardiovascular risk factors, has prompted the clarification of whether the liver is mainly a key-effector or a target-organ of the metabolic disarrangements in the metabolic syndrome. The therapeutic strategies able to alter liver disease progression and, through this, reduce the cardiovascular risk have also been tested in the last 2 decades. This review focus on the possible interactions between hepatic disease, metabolic syndrome, and CVD, and on their implications for clinical practice.
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Affiliation(s)
- Elisabete Martins
- Department of Medicine, Faculty of Medicine.,Instituto de Investigação e Inovação em Saúde (i3s), University of Porto.,Department of Cardiology
| | - Ana Oliveira
- Department of Nuclear Medicine, São João Hospital Center, Porto, Portugal
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Kapuria D, Takyar VK, Etzion O, Surana P, O'Keefe JH, Koh C. Association of Hepatic Steatosis With Subclinical Atherosclerosis: Systematic Review and Meta-Analysis. Hepatol Commun 2018; 2:873-883. [PMID: 30094399 PMCID: PMC6078218 DOI: 10.1002/hep4.1199] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 04/24/2018] [Accepted: 04/24/2018] [Indexed: 12/19/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming common in the United States and throughout the world and can progress to cirrhosis, hepatocellular carcinoma, and death. There is a strong association between coronary artery disease and NAFLD due to common risk factors, such as metabolic syndrome, obesity, and diabetes mellitus. Subclinical atherosclerosis, defined as coronary artery calcification in asymptomatic patients, has been shown to have a higher incidence in patients with NAFLD. We performed a meta‐analysis to examine the association of NAFLD with subclinical atherosclerosis measured by coronary artery calcium (CAC) scoring. Data were extracted from 12 studies selected using a predefined search strategy. NAFLD was diagnosed by abdominal ultrasound or computed tomography scans. The rate of coronary artery calcification was analyzed using random effects models, and publication bias was assessed using Egger's regression test. A total of 42,410 subjects were assessed, including 16,883 patients with NAFLD. Mean CAC score was significantly higher in subjects with NAFLD compared to those without NAFLD (odds ratio with random effects model, 1.64; 95% confidence inteval, 1.42‐1.89). This association remained significant through subgroup analyses for studies with >1,000 subjects and a higher CAC score cutoff of >100. Higher aspartate aminotransferase levels were also associated with increased subclinical atherosclerosis (mean difference 1.77; 95% confidence interval, 1.19‐2.34). Conclusion: There is an increased prevalence of subclinical atherosclerosis in patients with NAFLD, where subclinical atherosclerosis is defined using a “real world” clinical biomarker, namely the CAC score. Prospective studies are needed to establish a causative link between NAFLD and coronary artery disease. (Hepatology Communications 2018; 00:000‐000)
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Affiliation(s)
- Devika Kapuria
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda MD
| | - Varun K Takyar
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda MD
| | - Ohad Etzion
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda MD
| | - Pallavi Surana
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda MD
| | - James H O'Keefe
- Department of Cardiology Saint Luke's Mid-America Heart Institute Kansas City MO
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda MD
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Cheng SQ. Influence of non-pathological factors on ALT measurements. Shijie Huaren Xiaohua Zazhi 2017; 25:3005-3020. [DOI: 10.11569/wcjd.v25.i34.3005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Alanine transaminase (ALT) is still the most sensitive marker for evaluating the damage of liver cells. ALT measurements may be affected by common non-pathological factors such as gender, age, pregnancy, different physiological conditions, circadian rhythm, diet, drinking, smoking, strenuous exercise, metabolic factors, drugs, blood collection methods, and specimen collection, transmission, and preservation. It is important to emphasize the definition of limits of normal ALT and the influence of the above-mentioned non-pathological factors on its test results.
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Affiliation(s)
- Shu-Quan Cheng
- Department of Hepatology, the Third People's Hospital of Guilin, Guilin 541002, Guangxi Zhuang Autonomous Region, China
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13
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Jaruvongvanich V, Wirunsawanya K, Sanguankeo A, Upala S. Nonalcoholic fatty liver disease is associated with coronary artery calcification: A systematic review and meta-analysis. Dig Liver Dis 2016; 48:1410-1417. [PMID: 27697419 DOI: 10.1016/j.dld.2016.09.002] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 08/20/2016] [Accepted: 09/04/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is associated increased cardiovascular events and mortality. Coronary artery calcium scanning (CAC) is the robust predictor of coronary events in the asymptomatic individuals. Several recent studies have investigated the association between NAFLD and this surrogate marker. Thus, we conducted a systematic review and meta-analysis to better characterize the association between NAFLD and CAC. METHODS MEDLINE and EMBASE were searched through May 2016. Primary outcome was the association between NAFLD and CAC. Pooled odds ratio (OR) and 95% confidence interval (CI) from multivariable-adjusted estimates were calculated using a random-effects model. The between-study heterogeneity of effect-size was quantified using the Q statistic and I2. RESULTS Data were extracted from 16 studies (all cross-sectional studies) involving 16,433 NAFLD patients and 41,717 controls. NAFLD is significantly associated with CAC score >0 and CAC score >100 with pooled OR of 1.41 (95%CI 1.26-1.57, Pheterogeneity=0.07, I2=66%) and 1.24 (95%CI 1.02-1.52, Pheterogeneity=0.10, I2=42%). CONCLUSIONS NAFLD is associated with increased coronary artery calcification independent of traditional risk factors. The assessment of coronary artery calcium may be useful in identifying NAFLD patients at risk of future cardiovascular events.
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Affiliation(s)
- Veeravich Jaruvongvanich
- Department of Internal Medicine, University of Hawaii, Honolulu, HI, USA; Department of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
| | | | - Anawin Sanguankeo
- Department of Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY, USA; Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Sikarin Upala
- Department of Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY, USA; Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
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Jacobs K, Brouha S, Bettencourt R, Barrett-Connor E, Sirlin C, Loomba R. Association of Nonalcoholic Fatty Liver Disease With Visceral Adiposity but Not Coronary Artery Calcification in the Elderly. Clin Gastroenterol Hepatol 2016; 14:1337-1344.e3. [PMID: 26820400 DOI: 10.1016/j.cgh.2016.01.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 12/13/2015] [Accepted: 01/14/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is related closely to risk factors for coronary artery disease, but it is unclear whether NAFLD independently contributes to atherosclerosis. We investigated the association between NAFLD and coronary artery calcium (CAC) scores, determined based on noncontrast cardiac computed tomography data, in an elderly cohort. METHODS We conducted a longitudinal, cross-sectional study of data from 250 participants (mean age, 67.6 ± 7.0 y; 43.2% men) in the Rancho Bernardo Study-a prospective population-based study of mostly white adults in suburban Southern California. We compared CAC scores, liver-to-spleen attenuation ratio, and volumes of visceral adipose tissue (VAT) at baseline and after a 5-year follow-up period. RESULTS We assigned participants to groups based on CAC scores (0, 0-10, 11-100, 101-400, and >400). Among groups, the liver-to-spleen attenuation ratio did not vary significantly, but VAT increased with CAC score (median and interquartile range values were as follows: 50.0 [33.3-77.4] cm(3), 63.0 [33.9-93.1] cm(3), 66.1 [48.2-80.2] cm(3), 69.1 [48.1-85.0] cm(3), 76.1 [53.1-108.5] cm(3) for CAC groups; P = .0054). In multivariable regression analysis, NAFLD at baseline was not associated with an increased risk of a CAC score greater than 0. Longitudinal analysis showed that visceral fat, but not hepatic steatosis, increased in participants with increasing CAC scores (interquartile range 57.1-92.4) vs 55.2 cm(3) in patients without (interquartile range 36.5-81.1, P = .0401). The proportion of patients with NAFLD decreased after the 5-year follow-up period (from 29.3% before to 14.1% afterward; P = .0081), despite increased mean CAC scores and VAT volume in patients. CONCLUSIONS In adults age 67.6 ± 7.0 years, the proportion with NAFLD decreased despite increasing CAC score and VAT with age. There was no clear association between NAFLD and CAC score. However, VAT was associated with baseline and increasing CAC scores. Visceral adiposity therefore might be a risk factor for coronary artery disease.
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Affiliation(s)
- Kathleen Jacobs
- Department of Radiology, University of California San Diego, La Jolla, California
| | - Sharon Brouha
- Department of Radiology, University of California San Diego, La Jolla, California
| | - Ricki Bettencourt
- Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California; Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California
| | - Elizabeth Barrett-Connor
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California
| | - Claude Sirlin
- Department of Radiology, University of California San Diego, La Jolla, California
| | - Rohit Loomba
- Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California; Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California; NAFLD Translational Research Unit, University of California San Diego, La Jolla, California.
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Kim BJ, Cheong ES, Kang JG, Kim BS, Kang JH. Relationship of epicardial fat thickness and nonalcoholic fatty liver disease to coronary artery calcification: From the CAESAR study. J Clin Lipidol 2016; 10:619-626.e1. [PMID: 27206950 DOI: 10.1016/j.jacl.2016.01.008] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Revised: 01/21/2016] [Accepted: 01/26/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Epicardial fat and nonalcoholic fatty liver disease (NAFLD) are associated with subclinical atherosclerosis; however, the combined effect of both EAT and NAFLD on coronary artery calcium (CAC) is unclear. OBJECTIVE The present study was performed to evaluate the association of both epicardial fat thickness (EFT) and NAFLD with CAC. METHODS Among 2277 individuals enrolled in the CArdiometabolic risk, Epicardial fat, and Subclinical Atherosclerosis Registry (CAESAR) Study, 1473 individuals (1242 men, mean age, 44 ± 9 years) were included for analysis. Echocardiographic EFT and ultrasonographic fatty liver were measured. Individuals were divided into 4 groups according to EFT and NAFLD (group I: low EFT and without NAFLD; group II: low EFT and with NAFLD; group III: high EFT and without NAFLD; and group IV: high EFT and with NAFLD). RESULTS The median EFT value (interquartiles) was 3.17 mm (2.58 mm, 3.85 mm), and the prevalence of NAFLD and CACS >0 was 46.0% and 16.8%, respectively. The prevalence of CACS >0 was 7.9%, 16.8%, 18.0%, and 26.0% in group I, II, III, and IV, respectively (P < .001). On multivariate regression after adjusting for variables with a univariate relationship (P < .20), group IV had a significantly higher OR for CACS >0, and the OR in group III was marginally significant, compared to group I (1.458 [0.795, 2.672], 1.744 [0.999, 3.046], and 1.864 [1.041, 3.337] for groups II, III, and IV, respectively). CONCLUSION This study shows that both increased EFT and presence of NAFLD are associated with coronary artery calcification, and that increased EFT is more strongly related to CAC than NAFLD, in spite of NAFLD having greater cardiometabolic risk than EFT.
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Affiliation(s)
- Byung Jin Kim
- Division of Cardiology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Eun Sun Cheong
- Division of Cardiology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jung Gyu Kang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Bum Soo Kim
- Division of Cardiology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jin Ho Kang
- Division of Cardiology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Lazo M, Rubin J, Clark JM, Coresh J, Schneider ALC, Ndumele C, Hoogeveen RC, Ballantyne CM, Selvin E. The association of liver enzymes with biomarkers of subclinical myocardial damage and structural heart disease. J Hepatol 2015; 62:841-7. [PMID: 25433159 PMCID: PMC4373587 DOI: 10.1016/j.jhep.2014.11.024] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Revised: 11/14/2014] [Accepted: 11/18/2014] [Indexed: 12/28/2022]
Abstract
BACKGROUND & AIMS Patients with non-alcoholic fatty liver disease (NAFLD) are thought to be at increased risk of cardiovascular morbidity and mortality. However, the relationships between NAFLD and subclinical myocardial injury or structural heart disease are unknown. METHODS We conducted a cross-sectional analysis of 8668 participants from the Atherosclerosis Risk in Communities (ARIC) Study, who showed no clinical evidence of cardiovascular disease. We used levels of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST] and gamma-glutamyl transpeptidase [GGT]), in the context of no history of elevated alcohol consumption as non-invasive surrogates of NAFLD. We used highly sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-Brain natriuretic peptide (NT-proBNP) as biomarkers of myocardial damage and function. RESULTS In this population-based study (mean age 63 years, 60% women, 78% white), higher levels of ALT, AST, and GGT, even within the normal range, were significantly and independently associated with detectable (hs-cTnT >3 ng/L) and elevated (hs-cTnT ⩾14 ng/L) concentrations of hs-cTnT. The adjusted odds ratios (95% confidence interval) for elevated liver enzymes (vs. normal levels) with elevated hs-cTnT were: 1.65 (1.28-2.14) for ALT, 1.90 (1.36-2.68) for AST, and 1.55 (1.13-2.12) for GGT. Furthermore, there was evidence for inverse associations of ALT and AST with NT-proBNP. CONCLUSIONS Our results suggest that elevated liver enzyme levels in the absence of elevated alcohol consumption may be associated with subclinical myocardial injury. The inverse association between NT-proBNP and both ALT and AST supports the recently described metabolic role of natriuretic peptides.
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Affiliation(s)
- Mariana Lazo
- Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United States; Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
| | - Jonathan Rubin
- Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United States; Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - Jeanne M Clark
- Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United States; Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - Josef Coresh
- Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United States; Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - Andrea L C Schneider
- Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United States
| | - Chiadi Ndumele
- Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United States; Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - Ron C Hoogeveen
- Department of Medicine, Section of Atherosclerosis and Vascular Medicine, Baylor College of Medicine, Houston, TX, United States
| | - Christie M Ballantyne
- Department of Medicine, Section of Atherosclerosis and Vascular Medicine, Baylor College of Medicine, Houston, TX, United States
| | - Elizabeth Selvin
- Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United States; Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
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Kwak MS, Yim JY, Kim D, Park MJ, Lim SH, Yang JI, Chung GE, Kim YS, Yang SY, Kim MN, Lee CH, Yoon JH, Lee HS. Nonalcoholic fatty liver disease is associated with coronary artery calcium score in diabetes patients with higher HbA1c. Diabetol Metab Syndr 2015; 7:28. [PMID: 25844093 PMCID: PMC4384364 DOI: 10.1186/s13098-015-0025-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Accepted: 03/18/2015] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND In patients with diabetes, studies investigating the association between nonalcoholic fatty liver disease (NAFLD) and coronary artery calcium score (CACS) have shown conflicting results. The aim of this study was to evaluate the association between NAFLD and CACS in diabetic patients. METHODS This is the cohort study performed in Seoul National University Hospital Gangnam Healthcare Center. NAFLD was defined as cases with the typical ultrasonographic findings without excessive alcohol consumption, medications causing hepatic steatosis or other chronic liver diseases. CACS was evaluated using the Agatston method. Diabetes was defined as cases with fasting serum glucose ≥ 126 mg/dl, glycated hemoglobin (HbA1c) ≥ 6.5%, or those taking anti-diabetic medications. Multivariate linear regression analyses were performed with use of the interaction term of NAFLD × glycemic level and other confounders of CACS such as age, sex, hypertension, body mass index, waist circumference, HDL cholesterol and triglyceride. RESULTS A total of 213 participants with diabetes were included in the study. As 77 subjects (36.2%) had CACS 0, causing left sided skewness, CACS was analyzed after log transformation to Ln (CACS + 1). A statistically significant interaction was observed between NAFLD and HbA1c ≥ 7% (P for interaction = 0.014). While NAFLD was not associated with CACS in the group with HbA1c < 7% (P = 0.229), it was significantly associated in the group with HbA1c ≥ 7% (P = 0.010) after adjusting for covariates in multivariate analyses. CONCLUSIONS This study demonstrated an effect modification of glycemic level on the association between NAFLD and CACS. NAFLD was independently associated with CACS only in diabetes patients with higher HbA1c, after adjustment for confounders.
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Affiliation(s)
- Min-Sun Kwak
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Jeong Yoon Yim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Donghee Kim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Min Jung Park
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Seon Hee Lim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Jong In Yang
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Goh Eun Chung
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Young Sun Kim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Sun Young Yang
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Mi Na Kim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Chang-Hoon Lee
- />Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jung-Hwan Yoon
- />Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyo-Suk Lee
- />Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Ballestri S, Lonardo A, Bonapace S, Byrne CD, Loria P, Targher G. Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease. World J Gastroenterol 2014; 20:1724-45. [PMID: 24587651 PMCID: PMC3930972 DOI: 10.3748/wjg.v20.i7.1724] [Citation(s) in RCA: 197] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Revised: 10/30/2013] [Accepted: 11/18/2013] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health problem of epidemic proportions worldwide. Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease (CHD), abnormalities of cardiac function and structure (e.g., left ventricular dysfunction and hypertrophy, and heart failure), valvular heart disease (e.g., aortic valve sclerosis) and arrhythmias (e.g., atrial fibrillation). Experimental evidence suggests that NAFLD itself, especially in its more severe forms, exacerbates systemic/hepatic insulin resistance, causes atherogenic dyslipidemia, and releases a variety of pro-inflammatory, pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications. Collectively, these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications. The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular, cardiac and arrhythmic complications, to briefly examine the putative biological mechanisms underlying this association, and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.
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Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in western countries and is closely related to the metabolic syndrome. When NAFLD is associated with hepatocellular damage and inflammation (non-alcoholic steatohepatitis [NASH]) it can lead to severe liver disease. However, it has become clear that NAFLD is also associated with an increased risk of cardiovascular disease (CVD), independently of classical known risk factors for the latter. In the current review we briefly summarise the current clinical evidence on the role of NAFLD in CVD and discuss the potential mechanisms by which NAFLD can be linked to the pathophysiology of CVD.
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Affiliation(s)
- Sven M Francque
- Department of Gastroenterology Hepatology, University Hospital Antwerp & Laboratory of Experimental Medicine and Paediatrics, Division of Gastroenterology Hepatology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
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Arjmand Shabestari A. Coronary artery calcium score: a review. IRANIAN RED CRESCENT MEDICAL JOURNAL 2013; 15:e16616. [PMID: 24693399 PMCID: PMC3955514 DOI: 10.5812/ircmj.16616] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2013] [Revised: 09/25/2013] [Accepted: 09/27/2013] [Indexed: 02/06/2023]
Abstract
Context Coronary artery disease (CAD) is the foremost cause of death in many countries and hence, its early diagnosis is usually concerned as a major healthcare priority. Coronary artery calcium scoring (CACS) using either electron beam computed tomography (EBCT) or multislice computed tomography (MSCT) has been applied for more than 20 years to provide an early CAD diagnosis in clinical routine practice. Moreover, its association with other body organs has been a matter of vast research. Evidence Acquisition In this review article, techniques of CACS using EBCT and MSCT scanners as well as clinical and research indications of CACS are searched from PubMed, ISI Web of Science, Google Scholar and Scopus databases in a time period between late 1970s through July 2013 and following appropriate selection, dealt with. Moreover, the previous and ongoing research subjects and their results are discussed. Results The CACS is vastly applied in early detection of CAD and in many other research fields. Conclusions CACS has remarkably changed the screening techniques to detect CAD earlier than before and is generally accepted as a standard of reference for determination of risk of further cardiac events.
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Affiliation(s)
- Abbas Arjmand Shabestari
- Radiology Department, Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran, IR Iran
- Corresponding Author: Abbas Arjmand Shabestari, Corresponding Author: Abbas Arjmand Shabestari, Radiology Department, Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran, Tel.: +98-21-22083111, +98-21-88336335, Fax: +98-2122074101, E-mail:
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Chhabra R, O'Keefe JH, Patil H, O'Keefe E, Thompson RC, Ansari S, Kennedy KF, Lee LW, Helzberg JH. Association of coronary artery calcification with hepatic steatosis in asymptomatic individuals. Mayo Clin Proc 2013; 88:1259-65. [PMID: 24138963 DOI: 10.1016/j.mayocp.2013.06.025] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Revised: 06/17/2013] [Accepted: 06/21/2013] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To determine the association of coronary artery calcification with hepatic steatosis in asymptomatic volunteers. PATIENTS AND METHODS The study group comprised 400 asymptomatic volunteers, enrolled from April 1, 2011, to September 30, 2012, without known coronary artery disease who were self-referred for screening noncontrast computed tomography to determine coronary calcium score (CCS). Computed tomographic images were used to determine the presence of hepatic steatosis. An a priori model was created to predict a CCS of 100 Agatston units (AU) or higher on the basis of Framingham risk factors, diabetes mellitus, and metabolic syndrome. Hepatic steatosis was then added to this model. Computation of the odds ratio (OR) for hepatic steatosis predicting a CCS of 100 AU or higher was performed. Finally, the OR for a CCS of 100 AU or higher being associated with hepatic steatosis was calculated. RESULTS When hepatic steatosis was added to traditional coronary risk factors, it was independently associated with a CCS of 100 AU or higher (OR, 2.85). This was greater than the OR of Framingham factors, diabetes mellitus, or metabolic syndrome. A CCS of 100 AU or higher was independently associated with an increased risk for hepatic steatosis (OR, 2.4). This OR was higher than traditional hepatic steatosis risk factors or metabolic syndrome. CONCLUSION Hepatic steatosis is a strong independent predictor of a CCS of 100 AU or higher in asymptomatic patients. It is associated with an increased risk of coronary artery disease beyond that expected from traditional coronary risk factors and/or metabolic syndrome. Additional studies are needed to clarify the role of hepatic steatosis as a possible independent risk factor for the development of coronary artery disease.
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Affiliation(s)
- Rajiv Chhabra
- Department of Gastroenterology and Hepatology, Saint Luke's Hospital of Kansas City, Kansas City, MO; Liver Disease Management Center and Division of Gastroenterology, Department of Medicine, Saint Luke's Hospital, Kansas City, MO; School of Medicine, Department of Medicine, University of Missouri-Kansas City, Kansas City, MO
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Oni ET, Agatston AS, Blaha MJ, Fialkow J, Cury R, Sposito A, Erbel R, Blankstein R, Feldman T, Al-Mallah MH, Santos RD, Budoff MJ, Nasir K. A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care? Atherosclerosis 2013; 230:258-67. [PMID: 24075754 DOI: 10.1016/j.atherosclerosis.2013.07.052] [Citation(s) in RCA: 265] [Impact Index Per Article: 22.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2013] [Revised: 07/19/2013] [Accepted: 07/31/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is an emerging disease and a leading cause of chronic liver disease. The prevalence in the general population is approximately 15-30% and it increases to 70-90% in obese or diabetic populations. NAFLD has been linked to increased cardiovascular disease (CVD) risk. It is therefore critical to evaluate the relationship between markers of subclinical CVD and NAFLD. METHOD An extensive search of databases; including the National Library of Medicine and other relevant databases for research articles meeting inclusion criteria: observational or cohort, studies in adult populations and clearly defined NAFLD and markers of subclinical CVD. RESULTS Twenty-seven studies were included in the review; 16 (59%) presented the association of NAFLD and carotid intima-media thickness (CIMT), 7 (26%) the association with coronary calcification and 7 (26%) the effect on endothelial dysfunction and 6 (22%) influence on arterial stiffness. CIMT studies showed significant increases among NAFLD patients compared to controls. These were independent of traditional risk factors and metabolic syndrome. The association was similar in coronary calcification studies. The presence of NAFLD is associated with the severity of the calcification. Endothelial dysfunction and arterial stiffness showed significant independent associations with NAFLD. Two studies argued the associations were not significant; however, these studies were limited to diabetic populations. CONCLUSION There is evidence to support the association of NAFLD with subclinical atherosclerosis independent of traditional risk factors and metabolic syndrome. However, there is need for future longitudinal studies to review this association to ascertain causality and include other ethnic populations.
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Affiliation(s)
- Ebenezer T Oni
- Center for Prevention and Wellness Research, Baptist Health Medical Group, Miami Beach, FL, USA
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Vilar CP, Cotrim HP, Florentino GS, Barreto CP, Florentino AVA, Bragagnoli G, Schwingel PA. Association between nonalcoholic fatty liver disease and coronary artery disease. Rev Assoc Med Bras (1992) 2013; 59:290-7. [DOI: 10.1016/j.ramb.2012.11.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2012] [Revised: 10/22/2012] [Accepted: 11/23/2012] [Indexed: 01/22/2023] Open
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Feitosa MF, Reiner AP, Wojczynski MK, Graff M, North KE, Carr JJ, Borecki IB. Sex-influenced association of nonalcoholic fatty liver disease with coronary heart disease. Atherosclerosis 2013; 227:420-4. [PMID: 23390892 PMCID: PMC3602396 DOI: 10.1016/j.atherosclerosis.2013.01.013] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2012] [Revised: 12/28/2012] [Accepted: 01/10/2013] [Indexed: 12/15/2022]
Abstract
OBJECTIVE This study investigated whether nonalcoholic fatty liver disease (NAFLD) predicts prevalent coronary heart disease (CHD). METHODS Epidemiologic studies have used various definitions for NAFLD. Here, we considered both liver fat burden measured by CT (FL) and the non-specific measure of hepatic inflammation -alanine aminotransferase (ALT). The association of FL and ALT with CHD (self report of coronary bypass, myocardial infarction, or percutaneous transluminal coronary angioplasty) was investigated in 2756 European-American participants of the Family Heart Study. RESULTS FL (p = 0.0084) and ALT (≥40 U/L, p = 0.014) were each individually associated with prevalent CHD. However, when accounting for traditional metabolic risk factors in a multivariate model FL had no predictive value for CHD in either men or women; whereas ALT was a significant predictor of CHD in men, and the association strengthened among non-diabetic men. In non-diabetic women, neither FL nor ALT was associated with CHD. CONCLUSIONS ALT (≥40 U/L) was a predictor of prevalent CHD in men but not in women, while CT measured FL was not significant in either sex. The failure to account for traditional risk factors, heterogeneity by sex, and varying definitions of NAFLD may account for some of the conflicting evidence in the literature regarding the association between NAFLD and coronary disease.
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Affiliation(s)
- Mary F Feitosa
- Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, 4444 Forest Park Blvd, Saint Louis, MO 63108-2212, Campus Box 8506, USA.
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Sung KC, Wild SH, Kwag HJ, Byrne CD. Fatty liver, insulin resistance, and features of metabolic syndrome: relationships with coronary artery calcium in 10,153 people. Diabetes Care 2012; 35:2359-64. [PMID: 22829522 PMCID: PMC3476919 DOI: 10.2337/dc12-0515] [Citation(s) in RCA: 111] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2012] [Accepted: 05/14/2012] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) coexists with insulin resistance (IR), but it is uncertain whether NAFLD and IR contribute independently to atherosclerosis. We tested whether fatty liver, IR, and metabolic syndrome (MetS) features (waist, glucose, triglyceride, HDL cholesterol [HDL-C], and blood pressure) were associated with a marker of atherosclerosis (coronary artery calcium [CAC] score >0), independently of cardiovascular risk factors and cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS Data were analyzed from a South Korean occupational cohort of 10,153 people who all received ultrasound measurements of fatty liver and a cardiac computed tomography CAC score. IR was defined by homeostasis model assessment of IR (HOMA-IR) ≥75th percentile. Odds ratios (ORs) (95% CIs) for the presence of a CAC score >0 were estimated using logistic regression. RESULTS There were 915 people with a CAC score >0. MetS features were increased (glucose, blood pressure, triglyceride, and waist) or decreased (HDL-C) among people with a CAC score >0 (all comparisons against CAC score ≤0; P < 0.0001). Of subjects with a CAC score >0, 55% had fatty liver and 33.7% were insulin resistant. Fatty liver (OR 1.21 [95% CI 1.01-1.45]; P = 0.04) and HOMA-IR (1.10 [1.02-1.18]; P = 0.02) were associated with CAC score >0, independently of all MetS features, conventional cardiovascular risk factors, and prior evidence of CVD. The presence of IR and fatty liver combined was associated with CAC score >0 (1.53 [1.20-1.95]; P = 0.001). CONCLUSIONS Fatty liver and HOMA-IR are both associated with a CAC score >0 (independently of each other), features of MetS, conventional cardiovascular risk factors, and existing CVD.
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Affiliation(s)
- Ki-Chul Sung
- Division of Cardiology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sarah H. Wild
- Centre for Population Health Sciences, University of Edinburgh, Edinburgh, U.K
| | - Hyon Joo Kwag
- Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Christopher D. Byrne
- Endocrinology and Metabolism Unit, Southampton General Hospital, University of Southampton, Southampton, U.K
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Kim D, Choi SY, Park EH, Lee W, Kang JH, Kim W, Kim YJ, Yoon JH, Jeong SH, Lee DH, Lee HS, Larson J, Therneau TM, Kim WR. Nonalcoholic fatty liver disease is associated with coronary artery calcification. Hepatology 2012; 56:605-13. [PMID: 22271511 PMCID: PMC3830979 DOI: 10.1002/hep.25593] [Citation(s) in RCA: 247] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2011] [Accepted: 12/26/2011] [Indexed: 12/13/2022]
Abstract
UNLABELLED Nonalcoholic fatty liver disease (NAFLD) is related to risk factors of coronary artery disease, such as dyslipidemia, diabetes, and metabolic syndrome, which are closely linked with visceral adiposity. The aim of this study was to investigate whether NAFLD was associated with coronary artery calcification (CAC), which is used as a surrogate marker for coronary atherosclerosis independent of computed tomography (CT)-measured visceral adiposity. Out of 5,648 subjects who visited one of our health screening centers between 2003 and 2008, we enrolled 4,023 subjects (mean age, 56.9 ± 9.4 years; 60.7% males) without known liver disease or a history of ischemic heart disease. CAC score was evaluated using the Agatston method. On univariate analysis, the presence of CAC (score >0) was significantly associated with age, sex, body mass index, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, triglycerides, and increased risk of diabetes, hypertension, smoking, and NAFLD. Increasing CAC scores (0, <10, 10-100, ≥ 100) were associated with higher prevalence of NAFLD (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.61-2.10; P<0.001). Multivariable ordinal regression analysis was adjusted for traditional risk factors, and CT-measured visceral adipose tissue area in a subgroup of subjects showed that the increased CAC scores were significantly associated with the presence of NAFLD (OR, 1.28, 95% CI, 1.04-1.59; P = 0.023) independent of visceral adiposity. CONCLUSION Patients with NAFLD are at increased risk for coronary atherosclerosis independent of classical coronary risk factors, including visceral adiposity. These data suggest that NAFLD might be an independent risk factor for coronary artery disease.
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Affiliation(s)
- Donghee Kim
- Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea.
| | - Su-Yeon Choi
- Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
| | - Eun Ha Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Whal Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Jin Hwa Kang
- Department of Radiology, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Yoon Jun Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sook Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyo-suk Lee
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Joseph Larson
- Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Terry M. Therneau
- Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - W. Ray Kim
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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27
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Pacana T, Fuchs M. The cardiovascular link to nonalcoholic fatty liver disease: a critical analysis. Clin Liver Dis 2012; 16:599-613. [PMID: 22824483 DOI: 10.1016/j.cld.2012.05.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries and can progress from simple steatosis to nonalcoholic steatohepatitis and finally to liver cirrhosis. NAFLD is considered to be the hepatic manifestation of the metabolic syndrome because both share common features, which implicates a role of NAFLD in the development and progression of cardiovascular disease (CVD). The diagnosis of NAFLD deserves special attention in clinical practice for cardiovascular risk screening and surveillance strategies to allow for early targeted intervention in selected individuals at risk of future cardiovascular events.
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Affiliation(s)
- Tommy Pacana
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, 23298-0341, USA.
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28
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Coronary artery calcium scoring and its impact on the clinical practice in the era of multidetector CT. Int J Cardiovasc Imaging 2011; 27 Suppl 1:9-25. [PMID: 22012492 DOI: 10.1007/s10554-011-9964-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2011] [Accepted: 10/07/2011] [Indexed: 10/16/2022]
Abstract
With the suggestion of coronary artery calcium as an indicator of coronary artery disease 30 years ago, intense and controversial discussion regarding coronary artery calcium has been ongoing. Diverse techniques for evaluation of coronary artery calcium were suggested and validation of its feasibility has been followed up. Following establishment of reference standards, coronary artery calcium became widely utilized in clinical practice and scientific research. Originally coronary artery calcium scoring techniques were developed for prediction of cardiovascular risk. Additionally, coronary artery calcium scoring has been utilized as an indicator for other medical events. Recently, coronary artery calcium scoring used to be applied as a reference standard during scientific research. In this article, the topic of coronary artery calcium, from its introduction to its current usefulness, was discussed from the viewpoints of coronary artery calcium scoring techniques, imaging modalities, validation of the techniques, clinical feasibility of coronary artery calcium scoring beyond traditional cardiovascular risk prediction, and utilization of coronary artery calcium scoring as a reference standard. Popular coronary calcium scoring techniques comprises of Agatston, volume, and mass scores. Through validation of these techniques, pros and cons of each technique were analyzed and proper utility could be suggested. In parallel, the reference standards for Agatston and volume scores were established by age, sex, and race. Through the vigorous controversies, nowadays, the clinical feasibility of coronary artery calcium score as a surrogate marker of cardiovascular risk was acknowledged in the literature.
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29
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Targher G. Relationship of hepatic steatosis and alanine aminotransferase with coronary calcification. Clin Chem Lab Med 2011; 49:741. [DOI: 10.1515/cclm.2011.104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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