|
1
|
Choque Vargas C, Cáceres F, Landeira G, Perez S, Marchi L, Ruffillo G, Tevez S, Puga-Tejada M, Fassio E. Cardiovascular events and incident diabetes in 220 patients with MASLD according to basal liver fibrosis: a 10-year follow-up historic cohort. Eur J Gastroenterol Hepatol 2025; 37:660-667. [PMID: 39975992 DOI: 10.1097/meg.0000000000002943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
AIM The aim of this study is to analyze association between liver fibrosis with CVE, incident diabetes, and cirrhosis complications. METHODS Historic cohort of biopsy-proven MASLD patients, divided into two groups: F0-F2 vs F3-F4 fibrosis. Baseline data included metabolic traits and liver function tests. Patients were contacted and scheduled for laboratory analysis and elastography. Endpoints were (a) CVE, defined as any of acute myocardial infarction, coronary stenting, ischemic cardiopathy, and stroke; (b) incident diabetes; (c) cirrhosis complications. Baseline data were collected at the time of liver biopsy, while follow-up data were recovered through personal interview or medical records. A stepwise logistic regression determined predictive variables for each endpoint. RESULTS Study population included 220 patients with median age 53 years, and 145 were women; baseline fibrosis was F0-F2 in 165 patients and F3-F4 in 55 patients; median follow-up was 9.9 years. A higher percentage of F3-F4 patients had CVE (29.4%) than F0-F2 ones (13.1%) (hazard ratio 2.42; 95% CI: 1.26-4.6; P = 0.008). Incident diabetes occurred in 53.3% of F3-F4 and 20.2% of F0-F2 cohort (hazard ratio 3.04; 95% CI: 1.99-4.86; P < 0.001); cirrhosis complications occurred in 9/55 F3-F4 patients and in 1/165 F0-F2 ones (hazard ratio 26.3; 95% CI: 3.3-208.3; P = 0.002). Multivariate analysis confirmed liver fibrosis as an independent predictor of incident diabetes and cirrhosis complications. CVE were associated with baseline diabetes and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio. CONCLUSION In a cohort of 220 MASLD patients followed for 9.9 years, baseline F3-F4 was associated with incident diabetes and cirrhosis complications. AST/ALT ratio and diabetes were associated with CVE.
Collapse
Affiliation(s)
- Cinthia Choque Vargas
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Francisco Cáceres
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Graciela Landeira
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Soledad Perez
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Laura Marchi
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Gabriela Ruffillo
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Silvina Tevez
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Miguel Puga-Tejada
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
- División de Investigación Médica & Bioestadística, Instituto Ecuatoriano de Enfermedades Digestivas, Guayaquil, Ecuador
| | - Eduardo Fassio
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| |
Collapse
|
|
2
|
Alkhouri N, Beyer C, Shumbayawonda E, Andersson A, Yale K, Rolph T, Chung RT, Vuppalanchi R, Cusi K, Loomba R, Pansini M, Dennis A. Decreases in cT1 and liver fat content reflect treatment-induced histological improvements in MASH. J Hepatol 2025; 82:438-445. [PMID: 39326675 DOI: 10.1016/j.jhep.2024.08.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 08/26/2024] [Accepted: 08/29/2024] [Indexed: 09/28/2024]
Abstract
BACKGROUND & AIMS MRI biomarkers of liver disease are robust and reproducible alternatives to liver biopsy. Emerging data suggest that absolute reduction in iron-corrected T1 (cT1) of ≥80 ms and relative reduction in liver fat content (LFC) of 30% reflect histological improvement. We aimed to validate the associations of changes to these non-invasive biomarkers with histological improvement, specifically the resolution of steatohepatitis. METHODS We performed a retrospective analysis of participants from three interventional clinical trials who underwent multiparametric MRI to measure liver cT1 and LFC (LiverMultiScan) alongside biopsies at baseline and end of study. Responders were defined as those achieving resolution of steatohepatitis with no worsening in fibrosis. Differences in the magnitude of change in cT1 and LFC between responders and non-responders were assessed. RESULTS Individual patient data from 150 participants were included. There was a significant decrease in liver cT1 (-119 ms vs. -49 ms) and LFC (-65% vs. -29%) in responders compared to non-responders (p <0.001), respectively. The diagnostic accuracy to identify responders was 0.72 (AUC) for both. The Youden's index for cT1 to separate responders from non-responders was -82 ms and for liver fat was a 58% relative reduction. Those achieving a ≥80 ms reduction in cT1 were 5-fold more likely to achieve histological response (sensitivity 0.68; specificity 0.70). Those achieving a 30% relative reduction in liver fat were ∼4-fold more likely to achieve a histological response (sensitivity 0.77; specificity 0.53). CONCLUSIONS These results, from a pooled analysis of three drug trials, demonstrate that changes in multiparametric MRI markers of liver health (cT1 and LFC) can predict histological response for steatohepatitis following therapeutic intervention. IMPACT AND IMPLICATIONS We investigated the utility of two MRI-derived non-invasive tests, iron-corrected T1 mapping (cT1) and liver fat content from proton density fat fraction (PDFF), to predict histological improvement in patients who had undergone experimental treatment for metabolic dysfunction-associated steatohepatitis. Using data from 150 people who participated in one of three clinical trials, we observed that a reduction in cT1 by over 80 ms and a relative reduction in PDFF of over 58% were the optimal thresholds for change that predicted resolution of steatohepatitis on histology. PDFF as a marker of liver fat, and cT1 as a specific measure of liver disease activity, are both effective at identifying those who are likely responding to drug interventions and experiencing improvements in overall liver health. CLINICAL TRIAL NUMBER(S) NCT02443116, NCT03976401, NCT03551522.
Collapse
Affiliation(s)
| | | | | | | | - Kitty Yale
- Akero Therapeutics Inc., South San Francisco, California, USA
| | - Timothy Rolph
- Akero Therapeutics Inc., South San Francisco, California, USA
| | - Raymond T Chung
- Liver Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Raj Vuppalanchi
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA
| | - Rohit Loomba
- MASLD Research Center, University of California at San Diego, La Jolla, CA, USA
| | - Michele Pansini
- Clinica Di Radiologia EOC, Istituto Di Imaging Della Svizzera Italiana (IIMSI), Ente Ospedaliero Cantonale, Via Tesserete 46, 6900, Lugano, Switzerland; John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, OX3 0AG, Oxford, UK
| | | |
Collapse
|
|
3
|
Karady J, Mayrhofer T, Foldyna B, Lu MT, Meyersohn N, Hoffmann U, Balogon O, Pagidipati N, Shah S, Douglas PS, Ferencik M, Corey K. Coronary Artery Disease and Major Adverse Cardiovascular Events in People With Hepatic Steatosis at Low Atherosclerotic Cardiovascular Disease Risk. Aliment Pharmacol Ther 2025; 61:558-569. [PMID: 39610294 DOI: 10.1111/apt.18415] [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: 06/12/2024] [Revised: 06/28/2024] [Accepted: 11/14/2024] [Indexed: 11/30/2024]
Abstract
BACKGROUND Hepatic steatosis (HS) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥ 7.5% are associated with increased risk for cardiovascular events. AIM To assess underlying coronary artery disease (CAD) and major adverse cardiovascular event (MACE) among those with and without HS at different ASCVD risk. METHODS We evaluated stable chest pain patients receiving coronary computed tomography (CT) in the PROMISE trial. HS and CAD endpoints were defined on coronary CT. MACE was defined as unstable angina, non-fatal myocardial infarction, and all-cause death. Multivariable Cox regression, adjusting for CAD characteristics, assessed the association of HS with MACE for ASCVD < 7.5%. RESULTS One thousand two hundred and four of 3702 (32.5%) patients were at ASCVD < 7.5% and 20.3% (244/1204) of them had HS. Individuals with HS were younger (54.3 ± 5.2 vs. 55.8 ± 5.2; p < 0.001), more often males (40.2% [98/244] vs. 27.1% [260/960]; p < 0.001), had more risk factors/person (2.06 ± 0.89 vs. 1.93 ± 0.91; p = 0.047). CAD characteristics were similar between HS vs. non-HS patients at ASCVD < 7.5% and ASCVD ≥ 7.5% (all p > 0.05). Patients with HS had greater MACE rate compared to non-HS patients (ASCVD < 7.5%: 3.75%[9/244] vs. 1.5% [14/960]; p = 0.027 and ASCVD ≥ 7.5%: 4.7% [33/696] vs. 3.1% [56/1802]; p = 0.043). In patients without HS, MACE rate was higher in the ASCVD ≥ 7.5% vs. < 7.5% (3.1% [56/1802] vs. 1.5% [14/960]; p = 0.011). In patients with HS, MACE rates were not significantly different between ASCVD ≥ 7.5% vs. < 7.5% (4.7% [33/696] vs. 3.7% [9/244]; p = 0.484). In ASCVD < 7.5%, HS predicted MACE (aHR:2.34, 95%CI:1.01-5.43; p = 0.048), independent of CAD characteristics. CONCLUSIONS Individuals with HS at ASCVD < 7.5% risk had similar CAD characteristics as patients without HS at < 7.5% ASCVD risk, yet experienced comparable MACE rates as those at ASCVD ≥ 7.5%.
Collapse
Affiliation(s)
- Julia Karady
- Cardiovascular Imaging Research Center, Harvard Medical School-Massachusetts General Hospital, Boston, Massachusetts, USA
- Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Thomas Mayrhofer
- Cardiovascular Imaging Research Center, Harvard Medical School-Massachusetts General Hospital, Boston, Massachusetts, USA
- School of Business Studies, Stralsund University of Applied Sciences, Stralsund, Germany
| | - Borek Foldyna
- Cardiovascular Imaging Research Center, Harvard Medical School-Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Michael T Lu
- Cardiovascular Imaging Research Center, Harvard Medical School-Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Nandini Meyersohn
- Cardiovascular Imaging Research Center, Harvard Medical School-Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Udo Hoffmann
- Cardiovascular Imaging Research Center, Harvard Medical School-Massachusetts General Hospital, Boston, Massachusetts, USA
- Cleerly Inc., Denver, Colorado, USA
| | - Oluwafemi Balogon
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Neha Pagidipati
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Svati Shah
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
- Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA
| | - Pamela S Douglas
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Maros Ferencik
- Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA
| | - Kathleen Corey
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| |
Collapse
|
|
4
|
Mladenova IL, Tan EF, Ng JY, Sharma P. Non-alcoholic fatty liver disease (NAFLD) and its association to cardiovascular disease: A comprehensive meta-analysis. JRSM Cardiovasc Dis 2025; 14:20480040251325929. [PMID: 40123646 PMCID: PMC11930486 DOI: 10.1177/20480040251325929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 11/13/2024] [Accepted: 11/18/2024] [Indexed: 03/25/2025] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) affects up to nearly a third of the Western population and has been inconsistently associated with cardiovascular diseases (CVDs). Therefore, we conducted a comprehensive meta-analysis to quantify the correlation of NAFLD with all major vascular diseases, acute coronary syndrome (ACS), subclinical atherosclerosis and endothelial dysfunction. Methods We searched PubMed and Embase for studies looking at the relationship between NAFLD and cardiovascular diseases published through September 2023. The parameters we used to assess cardiovascular diseases include acute coronary syndrome, brachial flow-mediated dilatation (FMD), serum asymmetric dimethylarginine (ADMA), carotid intima-media thickness (CIMT), and carotid stenosis (>50%). Data from these studies were then collected and meta-analysis was performed using the random effects model. RevMan v5.4 was used for statistical analysis. Results We interrogated a total of 114 publications which met our inclusion criteria. NAFLD patients showed statistically significant reduction in FMD% [MD: -4.83 (95% CI: -5.84 to 3.81, p < .00001)] and increased serum ADMA [MD: 0.08 (95% CI: 0.05-0.11, p < .00001)]. Mean CIMT was also increased in NAFLD patients [MD 0.13 (95% CI: 0.12-0.14, p < .00001)]. NAFLD showed a higher prevalence of pathological CIMT [MD: 0.11 (95% CI: 0.10-0.12, p < .00001)] and increased carotid plaques [OR: 2.08 (95% CI: 1.52-2.86, p < .00001)]. Furthermore, we demonstrated statistically significant increase in cardiovascular diseases among NAFLD patients compared to controls [OR: 1.92 (95% CI: 1.53-2.41, p < .00001)]. Conclusion NAFLD is a strong predictor for endothelial dysfunction, subclinical atherosclerosis and cardiovascular disease. Further studies are required to determine whether incidental findings of fatty liver on abdominal ultrasonography should prompt the need for detailed assessment of other CVD risk factors.
Collapse
Affiliation(s)
| | - Eu Fon Tan
- Queen Mary University of London, London, UK
| | | | - Pankaj Sharma
- Institute of Cardiovascular Research, Royal Holloway University, Egham, Greater London, UK
| |
Collapse
|
|
5
|
Dehghani Firouzabadi M, Poopak A, Sheikhy A, Dehghani Firouzabadi F, Moosaie F, Rabizadeh S, Momtazmanesh S, Nakhjavani M, Esteghamati A. Nonalcoholic Fatty Liver Disease as a Potential Risk Factor for Cardiovascular Disease in Patients with Type 2 Diabetes: A Prospective Cohort Study. Int J Endocrinol 2024; 2024:5328965. [PMID: 38962375 PMCID: PMC11221952 DOI: 10.1155/2024/5328965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 06/11/2024] [Accepted: 06/15/2024] [Indexed: 07/05/2024] Open
Abstract
Methods and Results In this prospective cohort study, 1197 patients with type 2 diabetes (T2D) were divided into two groups (360 patients with NAFLD and 847 without NAFLD) and were followed for a median of 5 years for the incidence of CVD. Cox regression analysis was used to assess the association between NAFLD, liver enzyme level, aspartate aminotransferase to platelet ratio index (APRI), and the incidence risk of CVD and its subgroups (i.e., myocardial infarction, chronic heart disease, coronary artery bypass grafting, and percutaneous coronary intervention). There was a significant positive association between CVD incidence and NAFLD (HR = 1.488, 95% CI = 1.041-2.124, p value = 0.029). Although patients with NAFLD had higher levels of ALT and AST levels (p value = <0.001), there was no significant association between liver enzymes and the incidence risk of CVD when adjusted for different variables. Furthermore, NAFLD was associated with NAFLD APRI Q (2), APRI Q (3), and APRIQ (4) (1.365 (1.046-1.781), 1.623 (1.234-2.135), and 3.373 (2.509-4.536)), respectively. Conclusion NAFLD increased the incidence risk of CVD in T2D. However, there was no association between liver enzymes (ALT, AST, ALK-P, and GGT) and a higher incidence risk of CVD in T2D when adjusted for confounding variables.
Collapse
Affiliation(s)
- Mohammad Dehghani Firouzabadi
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Poopak
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Ali Sheikhy
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
- Department of Radiology and Imaging SciencesClinical CenterNational Institutes of Health, Bethesda, USA
| | - Fatemeh Dehghani Firouzabadi
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
- Department of Radiology and Imaging SciencesClinical CenterNational Institutes of Health, Bethesda, USA
| | - Fatemeh Moosaie
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Soghra Rabizadeh
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Sara Momtazmanesh
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Manouchehr Nakhjavani
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Alireza Esteghamati
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
6
|
Karady J, McGarrah RW, Nguyen M, Giamberardino SN, Meyersohn N, Lu MT, Staziaki PV, Puchner SB, Bittner DO, Foldyna B, Mayrhofer T, Connelly MA, Tchernof A, White PJ, Nasir K, Corey K, Voora D, Pagidipati N, Ginsburg GS, Kraus WE, Hoffmann U, Douglas PS, Shah SH, Ferencik M. Lipoprotein subclasses are associated with Hepatic steatosis: insights from the prospective multicenter imaging study for the evaluation of chest pain (PROMISE) clinical trial. Am J Prev Cardiol 2024; 18:100680. [PMID: 38764778 PMCID: PMC11101949 DOI: 10.1016/j.ajpc.2024.100680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 04/12/2024] [Accepted: 04/27/2024] [Indexed: 05/21/2024] Open
Abstract
Objectives To determine the relationship between lipoprotein particle size/number with hepatic steatosis (HS), given its association with traditional lipoproteins and coronary atherosclerosis. Methods Individuals with available CT data and blood samples enrolled in the PROMISE trial were studied. HS was defined based on CT attenuation. Lipoprotein particle size/number were measured by nuclear magnetic resonance spectroscopy. Principal components analysis (PCA) was used for dimensionality reduction. The association of PCA factors and individual lipoprotein particle size/number with HS were assessed in multivariable regression models. Associations were validated in an independent cohort of 59 individuals with histopathology defined HS. Results Individuals with HS (n=410/1,509) vs those without (n=1,099/1,509), were younger (59±8 vs 61±8 years) and less often females (47.6 % vs 55.9 %). All PCA factors were associated with HS: factor 1 (OR:1.36, 95 %CI:1.21-1.53), factor 3 (OR:1.75, 95 %CI:1.53-2.02) and factor 4 (OR:1.49; 95 %CI:1.32-1.68) were weighted heavily with small low density lipoprotein (LDL) and triglyceride-rich (TRL) particles, while factor 2 (OR:0.86, 95 %CI:0.77-0.97) and factor 5 (OR:0.74, 95 %CI:0.65-0.84) were heavily loaded with high density lipoprotein (HDL) and larger LDL particles. These observations were confirmed with the analysis of individual lipoprotein particles in PROMISE. In the validation cohort, association between HS and large TRL (OR: 8.16, 95 %CI:1.82-61.98), and mean sizes of TRL- (OR: 2.82, 95 %CI:1.14-9.29) and HDL (OR:0.35, 95 %CI:0.13-0.72) were confirmed. Conclusions Large TRL, mean sizes of TRL-, and HDL were associated with radiographic and histopathologic HS. The use of lipoprotein particle size/number could improve cardiovascular risk assessment in HS.
Collapse
Affiliation(s)
- Julia Karady
- Cardiovascular Imaging Research Center, Harvard Medical School - Massachusetts General Hospital, MA, USA
- MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Robert W McGarrah
- Duke Molecular Physiology Institute, Duke University, Durham, NC, USA
| | - Maggie Nguyen
- Duke Molecular Physiology Institute, Duke University, Durham, NC, USA
| | | | - Nandini Meyersohn
- Cardiovascular Imaging Research Center, Harvard Medical School - Massachusetts General Hospital, MA, USA
| | - Michael T Lu
- Cardiovascular Imaging Research Center, Harvard Medical School - Massachusetts General Hospital, MA, USA
| | - Pedro V Staziaki
- Cardiovascular Imaging Research Center, Harvard Medical School - Massachusetts General Hospital, MA, USA
- University of Vermont Medical Center, Robert Larner College of Medicine at the University of Vermont, Burlington, VT, USA
| | - Stefan B Puchner
- Cardiovascular Imaging Research Center, Harvard Medical School - Massachusetts General Hospital, MA, USA
- Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Daniel O Bittner
- Cardiovascular Imaging Research Center, Harvard Medical School - Massachusetts General Hospital, MA, USA
- Friedrich-Alexander University Erlangen-Nürnberg, Department of Cardiology, University Hospital Erlangen, Germany
| | - Borek Foldyna
- Cardiovascular Imaging Research Center, Harvard Medical School - Massachusetts General Hospital, MA, USA
| | - Thomas Mayrhofer
- Cardiovascular Imaging Research Center, Harvard Medical School - Massachusetts General Hospital, MA, USA
- School of Business Studies, Stralsund University of Applied Sciences, Stralsund, Germany
| | | | - Andre Tchernof
- Quebec Heart and Lung Institute, School of Nutrition, Laval University, Canada; Institute of Nutrition and Functional Foods, Laval University, Canada
| | - Phillip J White
- Duke Molecular Physiology Institute, Duke University, Durham, NC, USA
- Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, Duke University, Durham, NC, USA
- Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA
| | - Khurram Nasir
- Division of Cardiovascular Prevention and Wellness, Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, Houston, TX, USA
| | - Kathleen Corey
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Deepak Voora
- Duke Precision Medicine Program, Duke University School of Medicine, Durham, NC, USA
| | - Neha Pagidipati
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
| | - Geoffrey S Ginsburg
- All of Us Research Program, National Institutes of Health, MD Innovative Imaging, Bethesda, USA
| | - William E Kraus
- Duke Molecular Physiology Institute, Duke University, Durham, NC, USA
| | - Udo Hoffmann
- Cardiovascular Imaging Research Center, Harvard Medical School - Massachusetts General Hospital, MA, USA
- Consulting LLC, Waltham, MA, USA
- Cleerly Inc., Denver, CO, USA
| | - Pamela S Douglas
- Duke Molecular Physiology Institute, Duke University, Durham, NC, USA
| | - Svati H Shah
- Duke Molecular Physiology Institute, Duke University, Durham, NC, USA
| | - Maros Ferencik
- Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA
| |
Collapse
|
|
7
|
Piña P, Lorenzatti D, Castagna F, Miles J, Kuno T, Scotti A, Arce J, Feinberg A, Huang D, Gilman J, Leiderman E, Daich J, Ippolito P, Gongora CA, Schenone AL, Zhang L, Rodriguez CJ, Blaha MJ, Dey D, Berman DS, Virani SS, Levsky JM, Garcia MJ, Slipczuk L. Association of cardiometabolic and vascular atherosclerosis phenotypes on non-contrast chest CT with incident heart failure in patients with severe hypercholesterolemia. J Clin Lipidol 2024; 18:e403-e412. [PMID: 38368138 DOI: 10.1016/j.jacl.2024.02.001] [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: 06/16/2023] [Revised: 11/16/2023] [Accepted: 02/01/2024] [Indexed: 02/19/2024]
Abstract
BACKGROUND Coronary artery calcium (CAC), thoracic aorta calcification (TAC), non-alcoholic fatty liver disease (NAFLD), and epicardial adipose tissue (EAT) are associated with atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF). OBJECTIVES We aimed to determine whether these cardiometabolic and atherosclerotic risk factors identified by non-contrast chest computed tomography (CT) are associated with HF hospitalizations in patients with LDL-C≥ 190 mg/dL. METHODS We conducted a retrospective cohort analysis of patients with LDL-C ≥190 mg/dL, aged ≥40 years without established ASCVD or HF, who had a non-contrast chest CT within 3 years of LDL-C measurement. Ordinal CAC, ordinal TAC, EAT, and NAFLD were measured. Kaplan-Meier curves and multivariable Cox regression models were built to ascertain the association with HF hospitalization. RESULTS We included 762 patients with median age 60 (53-68) years, 68% (n=520) female, and median LDL-C level of 203 (194-216) mg/dL. Patients were followed for 4.7 (interquartile range 2.75-6.16) years, and 107 (14%) had a HF hospitalization. Overall, 355 (47%) patients had CAC=0, 210 (28%) had TAC=0, 116 (15%) had NAFLD, and median EAT was 79 mL (49-114). Moderate-Severe CAC (log-rank p<0.001) and TAC (log-rank p=0.006) groups were associated with increased HF hospitalizations. This association persisted when considering myocardial infarction (MI) as a competing risk. NAFLD and EAT volume were not associated with HF. CONCLUSIONS In patients without established ASCVD and LDL-C≥190 mg/dL, CAC was independently associated with increased HF hospitalizations while TAC, NAFLD, and EAT were not.
Collapse
Affiliation(s)
- Pamela Piña
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk); Division of Cardiology, CEDIMAT, Santo Domingo, Dominican Republic (Dr Piña)
| | - Daniel Lorenzatti
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Francesco Castagna
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Jeremy Miles
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Toshiki Kuno
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Andrea Scotti
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Javier Arce
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Ari Feinberg
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Dou Huang
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Jake Gilman
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Ephraim Leiderman
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Jonathan Daich
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Paul Ippolito
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Carlos A Gongora
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Aldo L Schenone
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Lili Zhang
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Carlos J Rodriguez
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Michael J Blaha
- Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA (Dr Blaha)
| | - Damini Dey
- Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, CA, USA (Drs Dey and Berman)
| | - Daniel S Berman
- Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, CA, USA (Drs Dey and Berman)
| | - Salim S Virani
- Section of Cardiology, Department of Medicine, The Aga Khan University, Karachi, Pakistan. Section of Cardiology, Texas Heart Institute & Baylor College of Medicine, Houston, TX, USA (Dr Virani)
| | - Jeffrey M Levsky
- Division of Radiology, Montefiore Medical Center/Albert Einstein College of Medicine. Bronx, NY, USA (Dr Levsky)
| | - Mario J Garcia
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk)
| | - Leandro Slipczuk
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA (Drs Piña, Lorenzatti, Castagna, Miles, Kuno, Scotti, Arce, Feinberg, Huang, Gilman, Leiderman, Daich, Ippolito, Gongora, Schenone, Zhang, Rodriguez, Garcia, and Slipczuk).
| |
Collapse
|
|
8
|
Yang W, Wen D, Li S, Zhao H, Xu J, Liu J, Chang Y, Xu J, Zheng M. Prognostic Value of Non-alcoholic Fatty Liver Disease and RCA Pericoronary Adipose Tissue CT Attenuation in Patients with Acute Chest Pain. Acad Radiol 2024; 31:1773-1783. [PMID: 38160090 DOI: 10.1016/j.acra.2023.12.001] [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: 09/24/2023] [Revised: 11/22/2023] [Accepted: 12/01/2023] [Indexed: 01/03/2024]
Abstract
RATIONALE AND OBJECTIVES Pericoronary adipose tissue (PCAT) CT attenuation of right coronary artery (RCA) and non-alcoholic fatty liver disease (NAFLD) have prognostic value for major adverse cardiovascular events (MACE) in patients with coronary artery disease. However, the superior prognostic value between RCA PCAT CT attenuation and NAFLD remains unclear in patients with acute chest pain. This study is to evaluate the prognostic value of NAFLD for MACE, and further assess the incremental prognostic value of NAFLD over PCAT CT attenuation. MATERIALS AND METHODS Between January 2011 and December 2021, all consecutive emergency patients with acute chest pain referred for coronary CT angiography (CCTA) were retrospectively enrolled. MACE included unstable angina requiring hospitalization, coronary revascularization, non-fatal myocardial infarction, and all-cause death. Patients' baseline and CCTA characteristics, RCA PCAT CT attenuation, and the presence of NAFLD were used to evaluate risk factors of MACE using multivariable Cox regression analysis. The prognostic value of NAFLD compared to RCA PCAT CT attenuation was analyzed. RESULTS A total of 514 patients were enrolled (mean age, 58.36 ± 13.05 years; 310 men). During a median follow-up of 31 months, 60 patients (11.67%) experienced MACE. NAFLD (HR = 2.599, 95% CI: 1.207, 5.598, P = 0.015) and RCA PCAT CT attenuation (HR = 1.026, 95% CI: 1.001, 1.051, P = 0.038) were independent predictors of MACE. The global Chi-square analysis showed that NAFLD improved the risk of MACE more than that using clinical risk factors and CCTA metrics (59.51 vs 54.44, P = 0.024) or combined with RCA PCAT CT attenuation (63.75 vs 59.51, P = 0.040). CONCLUSION NAFLD and RCA PCAT CT attenuation were predictors of MACE. NAFLD had an incremental prognostic value beyond RCA PCAT CT attenuation for MACE in patients with acute chest pain. Adding CT-FFR into the risk prediction of patients with acute chest pain is worth considering.
Collapse
Affiliation(s)
- Wenxuan Yang
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, 127# Changle West Road, Xi'an, 710032, China (W.Y., D.W., S.L., M.Z.)
| | - Didi Wen
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, 127# Changle West Road, Xi'an, 710032, China (W.Y., D.W., S.L., M.Z.)
| | - Shuangxin Li
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, 127# Changle West Road, Xi'an, 710032, China (W.Y., D.W., S.L., M.Z.)
| | - Hongliang Zhao
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, 127# Changle West Road, Xi'an, 710032, China (W.Y., D.W., S.L., M.Z.)
| | - Jingji Xu
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, 127# Changle West Road, Xi'an, 710032, China (W.Y., D.W., S.L., M.Z.)
| | - Jiali Liu
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, 127# Changle West Road, Xi'an, 710032, China (W.Y., D.W., S.L., M.Z.)
| | - Yingjuan Chang
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, 127# Changle West Road, Xi'an, 710032, China (W.Y., D.W., S.L., M.Z.)
| | - Jian Xu
- Interventional Surgery Center, Xijing Hospital, Fourth Military Medical University, 127# Changle West Road, Xi'an, 710032, China (H.Z., J.X., J.L., Y.C., J.X.)
| | - Minwen Zheng
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, 127# Changle West Road, Xi'an, 710032, China (W.Y., D.W., S.L., M.Z.).
| |
Collapse
|
|
9
|
Muñoz-Restrepo AM, Navas MC, Daza J, Girala M, Ridruejo E, Gerken G, Teufel A. Prevention in Hepatology. J Pers Med 2024; 14:132. [PMID: 38392566 PMCID: PMC10890057 DOI: 10.3390/jpm14020132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Revised: 01/01/2024] [Accepted: 01/09/2024] [Indexed: 02/24/2024] Open
Abstract
The prevention of liver disease has improved significantly in the last few decades, to the point that it can now be considered a true success story. The wide variety of interventions, including comprehensive vaccination strategies, novel medications, lifestyle changes, and even preventive surgeries, have reduced the morbidity and mortality of chronic liver diseases. However, the prevalence of chronic liver diseases is increasing worldwide. Currently, fatty liver disease alone is estimated to be present in as much as 30% of the adult population. Furthermore, there is a trend towards increasing incidences of chronic hepatitis B, and a global lack of success in efforts to eliminate chronic hepatitis C. Thus, improving and efficiently rolling out existing and successful prevention strategies for chronic liver diseases will play an essential role in healthcare throughout the upcoming decades. In this review, we summarize the current options and concepts for preventing chronic liver diseases, highlight their limitations, and provide an outlook on probable future developments to improve awareness, integrated care, and the analysis of big data.
Collapse
Affiliation(s)
- Ana-Maria Muñoz-Restrepo
- Department of Medicine II, Division of Hepatology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (A.-M.M.-R.); (J.D.)
- Grupo Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, UdeA, Calle 70 # 52-21, Medellin 050010, Colombia;
| | - Maria-Cristina Navas
- Grupo Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, UdeA, Calle 70 # 52-21, Medellin 050010, Colombia;
| | - Jimmy Daza
- Department of Medicine II, Division of Hepatology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (A.-M.M.-R.); (J.D.)
| | - Marcos Girala
- Department of Hepatology, Universidad Nacional de Asunción, San Lorenzo 111421, Paraguay;
| | - Ezequiel Ridruejo
- Hepatology Section, Department of Medicine, Center for Medical Education and Clinical Research, Norberto Quirno CEMIC, Buenos Aires 1431, Argentina;
| | - Guido Gerken
- Department of Gastroenterology, University Hospital Essen, 45147 Essen, Germany;
| | - Andreas Teufel
- Department of Medicine II, Division of Hepatology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (A.-M.M.-R.); (J.D.)
- Clinical Cooperation Unit Healthy Metabolism, Center for Preventive Medicine, and Digital Health (CPD), Medical Faculty Mannheim, Heidelberg University, 69117 Mannheim, Germany
| |
Collapse
|
|
10
|
Thomaides-Brears H, Banerjee R, Banerjee A. Reply to: "Reassessing the causal relationship between liver diseases and cardiovascular outcomes" and "From liver to heart: Enhancing the understanding of cardiovascular outcomes in the UK Biobank". J Hepatol 2024; 80:e24-e25. [PMID: 37821017 DOI: 10.1016/j.jhep.2023.09.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 09/29/2023] [Indexed: 10/13/2023]
Affiliation(s)
| | | | - Amitava Banerjee
- University College London Hospitals National Health Service Trust, London, United Kingdom; Institute of Health Informatics, University College London, London, United Kingdom; Barts Health National Health Service Trust, The Royal London Hospital, London, United Kingdom.
| |
Collapse
|
|
11
|
Yang K, Song M. New Insights into the Pathogenesis of Metabolic-Associated Fatty Liver Disease (MAFLD): Gut-Liver-Heart Crosstalk. Nutrients 2023; 15:3970. [PMID: 37764755 PMCID: PMC10534946 DOI: 10.3390/nu15183970] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/11/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
Metabolism-associated fatty liver disease (MAFLD) is a multifaceted disease that involves complex interactions between various organs, including the gut and heart. It is defined by hepatic lipid accumulation and is related to metabolic dysfunction, obesity, and diabetes. Understanding the intricate interplay of the gut-liver-heart crosstalk is crucial for unraveling the complexities of MAFLD and developing effective treatment and prevention strategies. The gut-liver crosstalk participates in the regulation of the metabolic and inflammatory processes through host-microbiome interactions. Gut microbiota have been associated with the development and progression of MAFLD, and its dysbiosis contributes to insulin resistance, inflammation, and oxidative stress. Metabolites derived from the gut microbiota enter the systemic circulation and influence both the liver and heart, resulting in the gut-liver-heart axis playing an important role in MAFLD. Furthermore, growing evidence suggests that insulin resistance, endothelial dysfunction, and systemic inflammation in MAFLD may contribute to an increased risk of cardiovascular disease (CVD). Additionally, the dysregulation of lipid metabolism in MAFLD may also lead to cardiac dysfunction and heart failure. Overall, the crosstalk between the liver and heart involves a complex interplay of molecular pathways that contribute to the development of CVD in patients with MAFLD. This review emphasizes the current understanding of the gut-liver-heart crosstalk as a foundation for optimizing patient outcomes with MAFLD.
Collapse
Affiliation(s)
| | - Myeongjun Song
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
| |
Collapse
|
|
12
|
Zhang Z, Zheng M, Lei H, Jiang Z, Chen Y, He H, Zhao G, Huang H. A clinical study of the correlation between metabolic-associated fatty liver disease and coronary plaque pattern. Sci Rep 2023; 13:7224. [PMID: 37142746 PMCID: PMC10160090 DOI: 10.1038/s41598-023-34462-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 04/30/2023] [Indexed: 05/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome (MetS) and has been correlated with coronary atherosclerosis (CAS). Since NAFLD was renamed metabolic-associated fatty liver disease(MAFLD) in 2020, no studies have evaluated the correlation between MAFLD and CAS. The aim of this study was to evaluate the relationship between MAFLD and CAS. A total of 1330 patients underwent continuous coronary computed tomography angiography (CCTA) and abdominal ultrasound as part of a routine physical examination. Ultrasonography was used to assess fatty liver, and CCTA was used to assess coronary artery plaques, degree of stenosis, and diseased blood vessels. Univariate and multivariate logistic regression analyses were performed with plaque type and degree of stenosis as dependent variables and MAFLD and traditional cardiovascular risk factors as independent variables to analyze the correlation between MAFLD and CAS. Among the 1164 patients, 680 (58.4%) were diagnosed with MAFLD through a combination of ultrasound and auxiliary examinations. Compared with the non-MAFLD group, the MAFLD group had more cardiovascular risk factors,and the MAFLD group had more likely to have coronary atherosclerosis, coronary stenosis and multiple coronary artery stenosis.In the univariate logistic regression, MAFLD was significantly correlated with overall plaque, calcified plaques, noncalcified plaques, mixed plaques,and significant stenosis in the coronary arteries.(p < 0.05). After adjusting for cardiovascular risk factors , MAFLD was correlated with noncalcified plaques (1.67; 95% confidence interval (CI) 1.15-2.43; p = 0.007) and mixed plaques (1.54; 95% CI 1.10-2.16; p = 0.011). In this study, MAFLD group had more cardiovascular risk factors, MAFLD was correlated with coronary atherosclerosis,and significant stenosis.Further study found independent associations between MAFLD and noncalcified plaques and mixed plaques, which suggest a clinically relevant link between MAFLD and coronary atherosclerosis.
Collapse
Affiliation(s)
- Zhijiao Zhang
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Avenue, Wuhua District, Kunming City, 650000, China
| | - Mengyao Zheng
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Avenue, Wuhua District, Kunming City, 650000, China
| | - Hongtao Lei
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Avenue, Wuhua District, Kunming City, 650000, China
| | - Zimeng Jiang
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Avenue, Wuhua District, Kunming City, 650000, China
| | - Yuhang Chen
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Avenue, Wuhua District, Kunming City, 650000, China
| | - Haiyu He
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Avenue, Wuhua District, Kunming City, 650000, China
| | - Gongfang Zhao
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Avenue, Wuhua District, Kunming City, 650000, China.
| | - Hua Huang
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Avenue, Wuhua District, Kunming City, 650000, China
| |
Collapse
|
|
13
|
Li X, Guo D, Zhou W, Hu Y, Zhou H, Chen Y. The Potential Prognostic, Diagnostic and Therapeutic Targets for Recurrent Arrhythmias in Patients with Coronary Restenosis and Reocclusions After Coronary Stenting. Curr Pharm Des 2022; 28:3500-3512. [PMID: 36424794 DOI: 10.2174/1381612829666221124110445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 10/07/2022] [Accepted: 10/13/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND The interplay of oxidative stress, proinflammatory microparticles, and proinflammatory cytokines in recurrent arrhythmias is unknown in elderly patients with coronary restenosis and reocclusions after coronary stenting. OBJECTIVE This research sought to investigate the potential diagnostic and therapeutic targets for recurrent arrhythmias in patients with coronary restenosis and reocclusions after coronary stenting. METHODS We examined whether oxidative stress, proinflammatory microparticles, and proinflammatory cytokines could have effects that lead to recurrent arrhythmias in elderly patients with coronary restenosis and reocclusions. We measured the levels of malondialdehyde (MDA), CD31 + endothelial microparticle (CD31 EMP), CD62E + endothelial microparticle (CD62E + EMP), high-sensitivity C-reactive protein (hs-CRP), interleukin- 1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α), as well as oxidized low-density lipoprotein (OX-LDL), and assessed the effects of relationship between oxidative stress, proinflammatory microparticles, and proinflammatory cytokines on recurrent atrial and ventricular arrhythmias in elderly patients with coronary restenosis and reocclusions after coronary stenting. RESULTS The levels of CD31 + EMP, CD62E + EMP, MDA, hs-CRP, IL-1β, IL-6, IL-8, TNF-α and OX-LDL were found to be increased significantly in coronary restenosis + recurrent atrial arrhythmia group compared to without coronary restenosis and coronary restenosis + without recurrent atrial arrhythmia groups, respectively (P < 0.001). Patients in the coronary reocclusion + recurrent ventricular arrhythmia group also exhibited significantly increased levels of CD31 + EMP, CD62E + EMP, MDA, hs-CRP, IL-1β, IL-6, IL-8, TNF-α and OXLDL compared to without coronary reocclusion and coronary reocclusion + without recurrent ventricular arrhythmia groups, respectively (P < 0.001). CONCLUSION Proinflammatory microparticles, proinflammatory cytokines, and oxidative stress might act as potential targets for recurrent arrhythmias in patients with coronary restenosis and reocclusions after coronary stenting.
Collapse
Affiliation(s)
- Xia Li
- Department of Geriatrics, Second People's Hospital of Huai'an, Xiamen Road Branch Hospital, The Affiliated Huaian Hospital of Xuzhou Medical University, Huai'an 223002, China
| | - Dianxuan Guo
- Department of Geriatrics, Second People's Hospital of Huai'an, Xiamen Road Branch Hospital, The Affiliated Huaian Hospital of Xuzhou Medical University, Huai'an 223002, China
| | - Wenhang Zhou
- Department of Geriatrics, Second People's Hospital of Huai'an, Xiamen Road Branch Hospital, The Affiliated Huaian Hospital of Xuzhou Medical University, Huai'an 223002, China
| | - Youdong Hu
- Department of Geriatrics, Second People's Hospital of Huai'an, Xiamen Road Branch Hospital, The Affiliated Huaian Hospital of Xuzhou Medical University, Huai'an 223002, China
| | - Hualan Zhou
- Department of Geriatrics, Second People's Hospital of Huai'an, Xiamen Road Branch Hospital, The Affiliated Huaian Hospital of Xuzhou Medical University, Huai'an 223002, China
| | - Ying Chen
- Department of Geriatrics, Second People's Hospital of Huai'an, Xiamen Road Branch Hospital, The Affiliated Huaian Hospital of Xuzhou Medical University, Huai'an 223002, China
| |
Collapse
|
|
14
|
Josloff K, Beiriger J, Khan A, Gawel RJ, Kirby RS, Kendrick AD, Rao AK, Wang RX, Schafer MM, Pearce ME, Chauhan K, Shah YB, Marhefka GD, Halegoua-DeMarzio D. Comprehensive Review of Cardiovascular Disease Risk in Nonalcoholic Fatty Liver Disease. J Cardiovasc Dev Dis 2022; 9:419. [PMID: 36547416 PMCID: PMC9786069 DOI: 10.3390/jcdd9120419] [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: 10/22/2022] [Revised: 11/16/2022] [Accepted: 11/23/2022] [Indexed: 11/29/2022] Open
Abstract
Nonalcoholic Fatty Liver Disease (NAFLD) is a growing global phenomenon, and its damaging effects in terms of cardiovascular disease (CVD) risk are becoming more apparent. NAFLD is estimated to affect around one quarter of the world population and is often comorbid with other metabolic disorders including diabetes mellitus, hypertension, coronary artery disease, and metabolic syndrome. In this review, we examine the current evidence describing the many ways that NAFLD itself increases CVD risk. We also discuss the emerging and complex biochemical relationship between NAFLD and its common comorbid conditions, and how they coalesce to increase CVD risk. With NAFLD's rising prevalence and deleterious effects on the cardiovascular system, a complete understanding of the disease must be undertaken, as well as effective strategies to prevent and treat its common comorbid conditions.
Collapse
Affiliation(s)
- Kevan Josloff
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Jacob Beiriger
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Adnan Khan
- Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Richard J. Gawel
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Richard S. Kirby
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Aaron D. Kendrick
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Abhinav K. Rao
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Roy X. Wang
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Michelle M. Schafer
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Margaret E. Pearce
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Kashyap Chauhan
- Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Yash B. Shah
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Gregary D. Marhefka
- Department of Internal Medicine, Division of Cardiology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Dina Halegoua-DeMarzio
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| |
Collapse
|
|
15
|
Outcomes of Liver Transplantation in Patients with Preexisting Coronary Artery Disease. Transplantation 2022; 107:933-940. [PMID: 36397734 DOI: 10.1097/tp.0000000000004402] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND Advances in surgical and medical technology over the years has made liver transplantation possible for older and higher risk patients. Despite rigorous preoperative cardiac testing, cardiovascular events remain a major cause of death after orthotopic liver transplantation (OLT). However, there are little data on the outcomes of OLT in patients with preexisting coronary artery disease (CAD). This study aimed to compare all-cause and cardiovascular mortality of patients with and without history of CAD undergoing OLT. METHODS Six hundred ninety-three adult patients with cirrhosis underwent liver transplantation between July 2013 and December 2018 (female n = 243, male n = 450; median age 59). RESULTS During the study period of 5 y (median follow-up, 24.1 mo), 92 of 693 patients (13.3%) died. All-cause mortality in the CAD group was significantly higher than in the non-CAD group (26.7% versus 9.6%; P <0.01). Cardiovascular events accounted for 52.5% of deaths (n = 21) in patients with CAD compared with 36.5% (n = 19) in non-CAD patients. At 6 mo, patients with combined nonalcoholic steatohepatitis (NASH)/CAD had significantly worse survival than those with CAD or NASH alone ( P <0.01). After 6 mo, patients with CAD alone had similar survival to those with combined NASH/CAD. CONCLUSIONS Patients with preexisting CAD before liver transplantation are at higher risk of death from any cause, specifically cardiovascular-related death. This risk increases with coexisting NASH. The presence of NASH and CAD at the time of liver transplant should prompt the initiation of aggressive risk factor modification for patients with CAD.
Collapse
|
|
16
|
A Meta-Analysis on the Global Prevalence, Risk factors and Screening of Coronary Heart Disease in Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol 2022; 20:2462-2473.e10. [PMID: 34560278 DOI: 10.1016/j.cgh.2021.09.021] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/04/2021] [Accepted: 09/10/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Cardiovascular disease remains the leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Studies examining the association of coronary heart disease (CHD) and NAFLD are cofounded by various cardiometabolic factors, particularly diabetes and body mass index. Hence, we seek to explore such association by investigating the global prevalence, independent risk factors, and influence of steatosis grade on manifestation of CHD among patients with NAFLD. METHODS Two databases, Embase and Medline, were utilized to search for articles relating to NAFLD and CHD. Data including, but not limited to, continent, diagnostic methods, baseline characteristics, prevalence of CHD, CHD severity, NAFLD severity, and risk factors were extracted. RESULTS Of the 38 articles included, 14 reported prevalence of clinical coronary artery disease (CAD) and 24 subclinical CAD. The pooled prevalence of CHD was 44.6% (95% confidence interval [CI], 36.0%-53.6%) among 67,070 patients with NAFLD with an odds ratio of 1.33 (95% CI, 1.21%-1.45%; P < .0001). The prevalence of CHD was higher in patients with moderate to severe steatosis (37.5%; 95% CI, 15.0%-67.2%) than those with mild steatosis (29.6%; 95% CI, 13.1%-54.0%). The pooled prevalence of subclinical and clinical CAD was 38.7% (95% CI, 29.8%-48.5%) and 55.4% (95% CI, 39.6%-70.1%), respectively. CONCLUSION Steatosis was found to be related with CHD involvement, with moderate to severe steatosis related to clinical CAD. Early screening and prompt intervention for CHD in NAFLD are warranted for holistic care in NAFLD.
Collapse
|
|
17
|
Karády J, Ferencik M, Mayrhofer T, Meyersohn NM, Bittner DO, Staziaki PV, Szilveszter B, Hallett TR, Lu MT, Puchner SB, Simon TG, Foldyna B, Ginsburg GS, McGarrah RW, Voora D, Shah SH, Douglas PS, Hoffmann U, Corey KE. Risk factors for cardiovascular disease among individuals with hepatic steatosis. Hepatol Commun 2022; 6:3406-3420. [PMID: 36281983 PMCID: PMC9701472 DOI: 10.1002/hep4.2090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 07/25/2022] [Accepted: 08/08/2022] [Indexed: 01/21/2023] Open
Abstract
Cardiovascular disease (CVD) is the leading cause of mortality in adults with hepatic steatosis (HS). However, risk factors for CVD in HS are unknown. We aimed to identify factors associated with coronary artery disease (CAD) and incident major adverse cardiovascular events (MACE) in individuals with HS. We performed a nested cohort study of adults with HS detected on coronary computed tomography in the PROspective Multicenter Imaging Study for Evaluation of chest pain (PROMISE) trial. Obstructive CAD was defined as ≥50% coronary stenosis. MACE included hospitalization for unstable angina, nonfatal myocardial infarction, or all-cause death. Multivariate modeling, adjusted for age, sex, atherosclerotic CVD (ASCVD) risk score and body mass index, identified factors associated with obstructive CAD. Cox regression, adjusted for ASCVD risk score, determined the predictors of MACE. A total of 959 of 3,756 (mean age 59.4 years, 55.0% men) had HS. Obstructive CAD was present in 15.2% (145 of 959). Male sex (adjusted odds ratio [aOR] = 1.83, 95% confidence interval [CI] 1.18-1.2.84; p = 0.007), ASCVD risk score (aOR = 1.05, 95% CI 1.03-1.07; p < 0.001), and n-terminal pro-b-type natriuretic peptide (NT-proBNP; aOR = 1.90, 95% CI 1.38-2.62; p < 0.001) were independently associated with obstructive CAD. In the 25-months median follow-up, MACE occurred in 4.4% (42 of 959). Sedentary lifestyle (adjusted hazard ratio [aHR] = 2.53, 95% CI 1.27-5.03; p = 0.008) and NT-proBNP (aOR = 1.50, 95% CI 1.01-2.25; p = 0.046) independently predicted MACE. Furthermore, the risk of MACE increased by 3% for every 1% increase in ASCVD risk score (aHR = 1.03, 95% CI 1.01-1.05; p = 0.02). Conclusion: In individuals with HS, male sex, NT-pro-BNP, and ASCVD risk score are associated with obstructive CAD. Furthermore, ASCVD, NT-proBNP, and sedentary lifestyle are independent predictors of MACE. These factors, with further validation, may help risk-stratify adults with HS for incident CAD and MACE.
Collapse
Affiliation(s)
- Julia Karády
- Cardiovascular Imaging Research CenterHarvard Medical School, Massachusetts General HospitalBostonMassachusettsUSA,MTA‐SE Cardiovascular Imaging Research GroupHeart and Vascular Center, Semmelweis UniversityBudapestHungary
| | - Maros Ferencik
- Cardiovascular Imaging Research CenterHarvard Medical School, Massachusetts General HospitalBostonMassachusettsUSA,Knight Cardiovascular InstituteOregon Health and Science UniversityPortlandOregonUSA
| | - Thomas Mayrhofer
- Cardiovascular Imaging Research CenterHarvard Medical School, Massachusetts General HospitalBostonMassachusettsUSA,School of Business StudiesStralsund University of Applied SciencesStralsundGermany
| | - Nandini M. Meyersohn
- Cardiovascular Imaging Research CenterHarvard Medical School, Massachusetts General HospitalBostonMassachusettsUSA
| | - Daniel O. Bittner
- Cardiovascular Imaging Research CenterHarvard Medical School, Massachusetts General HospitalBostonMassachusettsUSA,Department of CardiologyFriedrich‐Alexander University Erlangen‐Nürnberg (FAU)ErlangenGermany
| | - Pedro V. Staziaki
- Cardiovascular Imaging Research CenterHarvard Medical School, Massachusetts General HospitalBostonMassachusettsUSA
| | - Balint Szilveszter
- Cardiovascular Imaging Research CenterHarvard Medical School, Massachusetts General HospitalBostonMassachusettsUSA,MTA‐SE Cardiovascular Imaging Research GroupHeart and Vascular Center, Semmelweis UniversityBudapestHungary
| | - Travis R. Hallett
- Cardiovascular Imaging Research CenterHarvard Medical School, Massachusetts General HospitalBostonMassachusettsUSA
| | - Michael T. Lu
- Cardiovascular Imaging Research CenterHarvard Medical School, Massachusetts General HospitalBostonMassachusettsUSA
| | - Stefan B. Puchner
- Cardiovascular Imaging Research CenterHarvard Medical School, Massachusetts General HospitalBostonMassachusettsUSA,Department of Biomedical Imaging and Image‐Guided TherapyMedical University of ViennaViennaAustria
| | - Tracey G. Simon
- Division of GastroenterologyMassachusetts General Hospital, Harvard Medical SchoolBostonMassachusettsUSA
| | - Borek Foldyna
- Cardiovascular Imaging Research CenterHarvard Medical School, Massachusetts General HospitalBostonMassachusettsUSA
| | | | - Robert W. McGarrah
- Duke Molecular Physiology InstituteDuke UniversityDurhamNorth CarolinaUSA
| | - Deepak Voora
- Duke Center for Applied Genomics & Precision MedicineDuke University School of MedicineDurhamNorth CarolinaUSA
| | - Svati H. Shah
- Duke Molecular Physiology InstituteDuke UniversityDurhamNorth CarolinaUSA,Duke Clinical Research InstituteDuke University School of MedicineDurhamNorth CarolinaUSA
| | - Pamela S. Douglas
- Duke Clinical Research InstituteDuke University School of MedicineDurhamNorth CarolinaUSA
| | - Udo Hoffmann
- Cardiovascular Imaging Research CenterHarvard Medical School, Massachusetts General HospitalBostonMassachusettsUSA
| | - Kathleen E. Corey
- Division of GastroenterologyMassachusetts General Hospital, Harvard Medical SchoolBostonMassachusettsUSA
| |
Collapse
|
|
18
|
Taylan G, Ebik M, Solak S, Kaya Ç, Yalta K. Risk of premature coronary atherosclerosis in patients with nonalcoholic fatty liver disease. Rev Assoc Med Bras (1992) 2022; 68:1428-1433. [PMID: 36417648 DOI: 10.1590/1806-9282.20220514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 07/12/2022] [Indexed: 11/23/2022] Open
|
|
19
|
Cazac GD, Lăcătușu CM, Mihai C, Grigorescu ED, Onofriescu A, Mihai BM. New Insights into Non-Alcoholic Fatty Liver Disease and Coronary Artery Disease: The Liver-Heart Axis. Life (Basel) 2022; 12:1189. [PMID: 36013368 PMCID: PMC9410285 DOI: 10.3390/life12081189] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 07/28/2022] [Accepted: 07/29/2022] [Indexed: 12/17/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents the hepatic expression of the metabolic syndrome and is the most prevalent liver disease. NAFLD is associated with liver-related and extrahepatic morbi-mortality. Among extrahepatic complications, cardiovascular disease (CVD) is the primary cause of mortality in patients with NAFLD. The most frequent clinical expression of CVD is the coronary artery disease (CAD). Epidemiological data support a link between CAD and NAFLD, underlain by pathogenic factors, such as the exacerbation of insulin resistance, genetic phenotype, oxidative stress, atherogenic dyslipidemia, pro-inflammatory mediators, and gut microbiota. A thorough assessment of cardiovascular risk and identification of all forms of CVD, especially CAD, are needed in all patients with NAFLD regardless of their metabolic status. Therefore, this narrative review aims to examine the available data on CAD seen in patients with NAFLD, to outline the main directions undertaken by the CVD risk assessment and the multiple putative underlying mechanisms implicated in the relationship between CAD and NAFLD, and to raise awareness about this underestimated association between two major, frequent and severe diseases.
Collapse
Affiliation(s)
- Georgiana-Diana Cazac
- Unit of Diabetes, Nutrition and Metabolic Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Cristina-Mihaela Lăcătușu
- Unit of Diabetes, Nutrition and Metabolic Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Cătălina Mihai
- Institute of Gastroenterology and Hepatology, “Sf. Spiridon” Emergency Hospital, 700111 Iași, Romania
- Unit of Medical Semiology and Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Elena-Daniela Grigorescu
- Unit of Diabetes, Nutrition and Metabolic Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Alina Onofriescu
- Unit of Diabetes, Nutrition and Metabolic Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Bogdan-Mircea Mihai
- Unit of Diabetes, Nutrition and Metabolic Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| |
Collapse
|
|
20
|
Association between Coronary Artery Plaque Progression and Liver Fibrosis Biomarkers in Population with Low Calcium Scores. Nutrients 2022; 14:nu14153163. [PMID: 35956339 PMCID: PMC9370134 DOI: 10.3390/nu14153163] [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: 07/10/2022] [Revised: 07/28/2022] [Accepted: 07/29/2022] [Indexed: 11/17/2022] Open
Abstract
Background: The severity of nonalcoholic fatty liver disease (NAFLD) has been found to be associated with atherosclerosis burden. However, whether liver fibrosis scores can be used to predict atherosclerosis progression, especially for patients with low calcium scores, remains undetermined. Methods: A total of 165 subjects who underwent repeated coronary computed tomography angiography (CCTA) and had low calcium scores (<100) were enrolled. The segment stenosis score (SSS) from the CCTA was measured, and the association between SSS progression and biochemical parameters was analyzed in addition to liver fibrosis scores, including nonalcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), and Forns score. Results: When compared with those without plaque at baseline (SSS = 0), subjects with plaque had higher blood pressure, higher coronary artery calcium (CAC) scores, and higher liver fibrosis scores, including Forns score, Fib-4, and NFS. During the medium follow-up interval of 24.7 months, 60 (39.4%) patients displayed SSS progression, while the remaining 105 (63.6%) patients showed no CAD progression. In a multivariate analysis, being male having a high diastolic blood pressure (DBP), and having a high NFS liver fibrosis score were independently associated with the odds ratio for SSS progression. Conclusions: Higher baseline blood pressure and liver fibrosis markers are associated with the presence of coronary artery disease (CAD) plaques in subjects in early CAD stages. For disease progression, the male gender, DBP, and NFS appear to be independently associated with coronary atherosclerosis plaque progression in subjects with low calcium scores.
Collapse
|
|
21
|
Han D, Zhang H, Liu S, Zhuang L, Zhao Z, Ding H, Xin Y. Association between the LRP5 rs556442 gene polymorphism and the risks of NAFLD and CHD in a Chinese Han population. BMC Gastroenterol 2022; 22:305. [PMID: 35733105 PMCID: PMC9219200 DOI: 10.1186/s12876-022-02385-9] [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: 12/31/2021] [Accepted: 06/10/2022] [Indexed: 12/20/2022] Open
Abstract
Background Multiple studies have demonstrated the involvement of low-density lipoprotein receptor-related protein 5 (LRP5) in metabolism-related diseases. This study explored the relationship between the LRP5 rs556442 gene polymorphism and the risks of non-alcoholic fatty liver disease (NAFLD) and coronary heart disease (CHD) in a Chinese Han population. Methods This retrospective case–control study included 247 patients with NAFLD, 200 patients with CHD, 118 patients with both NAFLD and CHD, and 339 healthy controls from June 2018 to June 2019 at Qingdao Municipal Hospital. Basic information and clinical characteristics were collected for all subjects. The genotype and allele frequency of LRP5 rs556442 were determined. Results The genotype distributions of LRP5 rs556442 differed significantly between the CHD and NAFLD + CHD groups (P < 0.05). The LRP5 rs556442 GG genotype markedly promoted the risk of NAFLD in CHD patients [odds ratio (OR) = 2.857, 95% confidence interval (CI): 1.196–6.824, P = 0.018). After adjustment for sex, age, and body mass index (BMI), this association remained significant (OR = 3.252, 95% CI: 1.306–8.102, P = 0.011). In addition, the LRP5 rs556442 AA + AG genotype was associated with an increased BMI in obese NAFLD patients (OR = 1.526, 95% CI: 1.004–2.319, P = 0.048). However, after adjustment for sex and age, this association was no longer significant (OR = 1.504, 95% CI: 0.991–2.282, P = 0.055). Conclusions This study found that the LRP5 rs556442 GG genotype increased the risk of NAFLD in CHD patients and AA + AG genotype may be associated with an increased BMI in obese NAFLD patients among a Chinese Han population. Trial registration ChiCTR, ChiCTR1800015426. Registered 28 March 2018—Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=26239.
Collapse
Affiliation(s)
- Dongli Han
- Department of Infectious Disease, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, 266011, Shandong Province, China.,Department of Gastroenterology, Zhumadian Central Hospital, Zhumadian, China
| | - Haiying Zhang
- Health Management Center, Qingdao Central Hospital, Qingdao, China
| | - Shousheng Liu
- Clinical Research Center, Qingdao Municipal Hospital, Qingdao, China
| | - Likun Zhuang
- Clinical Research Center, Qingdao Municipal Hospital, Qingdao, China
| | - Zhenzhen Zhao
- Clinical Research Center, Qingdao Municipal Hospital, Qingdao, China
| | - Hongguang Ding
- Second Department of General Surgery, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, 266011, Shandong Province, China.
| | - Yongning Xin
- Department of Infectious Disease, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, 266011, Shandong Province, China. .,Digestive Disease Key Laboratory of Qingdao, Qingdao, China.
| |
Collapse
|
|
22
|
Duell PB, Welty FK, Miller M, Chait A, Hammond G, Ahmad Z, Cohen DE, Horton JD, Pressman GS, Toth PP. Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol 2022; 42:e168-e185. [PMID: 35418240 DOI: 10.1161/atv.0000000000000153] [Citation(s) in RCA: 323] [Impact Index Per Article: 107.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition that is believed to affect >25% of adults worldwide. Unless specific testing is done to identify NAFLD, the condition is typically silent until advanced and potentially irreversible liver impairment occurs. For this reason, the majority of patients with NAFLD are unaware of having this serious condition. Hepatic complications from NAFLD include nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. In addition to these serious complications, NAFLD is a risk factor for atherosclerotic cardiovascular disease, which is the principal cause of death in patients with NAFLD. Accordingly, the purpose of this scientific statement is to review the underlying risk factors and pathophysiology of NAFLD, the associations with atherosclerotic cardiovascular disease, diagnostic and screening strategies, and potential interventions.
Collapse
|
|
23
|
Sharma D, Gotlieb N, Farkouh ME, Patel K, Xu W, Bhat M. Machine Learning Approach to Classify Cardiovascular Disease in Patients With Nonalcoholic Fatty Liver Disease in the UK Biobank Cohort. J Am Heart Assoc 2022; 11:e022576. [PMID: 34927450 PMCID: PMC9075189 DOI: 10.1161/jaha.121.022576] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 11/12/2021] [Indexed: 12/18/2022]
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide. Cardiovascular disease (CVD) is the leading cause of mortality among patients with NAFLD. The aim of our study was to develop a machine learning algorithm integrating clinical, lifestyle, and genetic risk factors to identify CVD in patients with NAFLD. Methods and Results We created a cohort of patients with NAFLD from the UK Biobank, diagnosed according to proton density fat fraction from magnetic resonance imaging data sets. A total of 400 patients with NAFLD with subclinical atherosclerosis or clinical CVD, defined by disease codes, constituted cases and 446 NAFLD cases with no CVD constituted controls. We evaluated 7 different supervised machine learning approaches on clinical, lifestyle, and genetic variables for identifying CVD in patients with NAFLD. The most significant clinical and lifestyle variables observed by the predictive modeling were age (59 years [54.00-63.00 years]), hypertension (145 mm Hg [134.0-156.0 mm Hg] and 85 mm Hg [79.00-93.00 mm Hg]), waist circumference (98 cm [95.00-105.00 cm]), and sedentary lifestyle, defined as time spent watching TV >4 h/d. In the genetic data, single-nucleotide polymorphisms in IL16 and ANKLE1 gene were most significant. Our proposed ensemble-based integrative machine learning model achieved an area under the curve of 0.849 using the random forest modeling for CVD prediction. Conclusions We propose a machine learning algorithm that identifies CVD in patients with NAFLD through integration of significant clinical, lifestyle, and genetic risk factors. These patients with NAFLD at higher risk of CVD should be flagged for screening and aggressive treatment of their cardiometabolic risk factors to prevent cardiovascular morbidity and mortality.
Collapse
Affiliation(s)
- Divya Sharma
- Department of BiostatisticsPrincess Margaret Cancer CentreUniversity Health NetworkTorontoOntarioCanada
| | - Neta Gotlieb
- Division of Adult GastroenterologyUniversity Health NetworkToronto General HospitalTorontoOntarioCanada
| | - Michael E. Farkouh
- Peter Munk Cardiac Centre, Heart and Stroke Richard Lewar CentreUniversity of TorontoOntarioCanada
| | - Keyur Patel
- Division of GastroenterologyUniversity Health NetworkToronto General HospitalTorontoOntarioCanada
| | - Wei Xu
- Department of BiostatisticsPrincess Margaret Cancer CentreUniversity Health NetworkTorontoOntarioCanada
- Biostatistics DivisionDalla Lana School of Public HealthUniversity of TorontoOntarioCanada
| | - Mamatha Bhat
- Department of MedicineMulti‐Organ Transplant ProgramToronto General HospitalTorontoOntarioCanada
| |
Collapse
|
|
24
|
Bhatti S, Lizaola-Mayo B, Al-Shoha M, Garcia-Saenz-de-Sicilia M, Habash F, Ayoub K, Karr M, Ahmed Z, Borja-Cacho D, Duarte-Rojo A. Use of Computed Tomography Coronary Calcium Score for Coronary Artery Disease Risk Stratification During Liver Transplant Evaluation. J Clin Exp Hepatol 2022; 12:319-328. [PMID: 35535104 PMCID: PMC9077224 DOI: 10.1016/j.jceh.2021.08.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 08/14/2021] [Indexed: 12/12/2022] Open
Abstract
Background End-stage liver disease (ESLD) is not considered a risk factor for atherosclerotic cardiovascular disease (ASCVD). However, lifestyle characteristics commonly associated with increased ASCVD risk are highly prevalent in ESLD. Emerging literature shows a high burden of asymptomatic coronary artery disease (CAD) in patients with ESLD and a high ASCVD risk in liver transplantation (LT) recipients. Coronary artery calcium score (CAC) is a noninvasive test providing reliable CAD risk stratification. We implemented an LT evaluation protocol with CAC playing a central role in triaging and determining the need for further CAD assessment. Here, we inform our results from this early experience. Methods Patients with ESLD referred for LT evaluation were prospectively studied. We compared accuracy of CAC against that of CAD risk factors/scores, troponin I, dobutamine stress echocardiogram (DSE), and single-photon emission computed tomography (SPECT) to detect coronary stenosis ≥70 (CAD ≥ 70) per left heart catheterization (LHC). Thirty-day post-LT cardiac outcomes were also analyzed. Results One hundred twenty-four of 148 (84%) patients underwent CAC, 106 (72%) DSE/SPECT, and 50 (34%) LHC. CAC ≥ 400 was found in 35 (28%), 100 to 399 in 17 (14%), and <100 in 72 (58%). LHC identified CAD ≥ 70% in 8 of 29 (28%), 2 of 9 (22%), and 0 of 4, respectively. Two acute coronary syndromes occurred after LT in a patient with CAC 811 (CAD < 70%), and one with CAC 347 (CAD ≥ 70%). No patients with CAC < 100 presented with acute coronary syndrome after LT. When using CAD ≥ 70% as primary endpoint of LT evaluation, CAC ≥ 346 was the only test showing predictive usefulness (negative predictive value 100%). Conclusions CAC is a promising tool to guide CAD risk stratification and need for LHC during LT evaluation. Patients with a CAC < 100 can safely undergo LT without the need for LHC or cardiac stress testing, whereas a CAC < 346 accurately rules out significant CAD stenosis (≥70%) on LHC, outperforming other CAD risk-stratification strategies.
Collapse
Key Words
- ACS, Acute coronary syndromes
- ALD, alcoholic liver disease
- ASCVD, Atherosclerotic cardiovascular disease
- ASCVD, atherosclerosis cardiovascular disease risk
- BMI, Body mass index
- CABG, Coronary angioplasty bypass surgery
- CAC, Coronary calcium score
- CAD, Coronary artery disease
- CKD, chronic kidney disease
- DSE/SPECT, Dobutamine stress echocardiogram or single-photon emission computed tomography
- ESLD, End-stage liver disease
- HCV, hepatitis C virus
- IQR, Interquartile range
- LCx, left circumflex
- LHC, Left heart catheterization
- LT, liver transplantation
- MELD, model for end stage liver disease
- MESA, Multi-Ethnic Study of Atherosclerosis
- METs, Metabolic equivalents
- NPV, negative predictive value
- OM, obtuse marginal
- OPTN, Organ Procurement and Transplantation Network
- PCI, Percutaneous coronary intervention
- PDA, posterior descending artery
- POBA, plain old balloon angioplasty
- PPV, positive predictive value
- RCA, right coronary artery
- RI, ramus intermedius
- ROC, Receiver operating characteristic
- RPL, right posterolateral
- SD, Standard deviation
- VT, Ventricular tachycardia
- agatston score
- angiogram
- cardiac stress test
- cirrhosis
- end-stage liver disease
Collapse
Affiliation(s)
- Sabha Bhatti
- Division of Cardiology, University of Arkansas for Medical Sciences, 4301 W. Markham Slot #567, Little Rock, AR, 70205, United States
| | - Blanca Lizaola-Mayo
- Division of Gastroenterology and Hepatology, Mayo Clinic, 13400 East Shea Blvd, Scottsdale, AZ, 85259, United States
| | - Mohammad Al-Shoha
- Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, 4301 W. Markham Slot #567, Little Rock, AR, 70205, United States
| | | | - Fuad Habash
- Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham Slot #567, Little Rock, AR, 70205, United States
| | - Karam Ayoub
- Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham Slot #567, Little Rock, AR, 70205, United States
| | - Michael Karr
- Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham Slot #567, Little Rock, AR, 70205, United States
| | - Zubair Ahmed
- Division of Cardiology, University of Arkansas for Medical Sciences, 4301 W. Markham Slot #567, Little Rock, AR, 70205, United States
| | - Daniel Borja-Cacho
- Division of Transplant Surgery, Northwestern University, 676 N Saint Clair, Chicago, IL, 60611, United States
| | - Andres Duarte-Rojo
- Division of Cardiology, University of Arkansas for Medical Sciences, 4301 W. Markham Slot #567, Little Rock, AR, 70205, United States
- Thomas E. Starzl Transplantation Institute and Division of Gastroenterology, Hepatology and Nutrition; University of Pittsburgh Medical Center, 3471 Fifth Avenue, Suite 916, Pittsburgh, PA, 15213, United States
- Address for correspondence: Andres Duarte-Rojo, MD, MS, DSc, Starzl Transplantation Institute and Center for Liver Diseases, University of Pittsburgh Medical Center, 3471 Fifth Avenue, Suite 916, Pittsburgh, PA, 15213, United States. Tel.: +1 412 647-1170; fax: +1 412 647 9268
| |
Collapse
|
|
25
|
Istanbuly S, Matetic A, Mohamed MO, Panaich S, Velagapudi P, Elgendy IY, Paul TK, Alkhouli M, Mamas MA. Comparison of Outcomes of Patients With Versus Without Chronic Liver Disease Undergoing Percutaneous Coronary Intervention. Am J Cardiol 2021; 156:32-38. [PMID: 34348842 DOI: 10.1016/j.amjcard.2021.06.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 06/12/2021] [Accepted: 06/15/2021] [Indexed: 02/07/2023]
Abstract
There are limited data on the outcomes of chronic liver disease (CLD) patients admitted for percutaneous coronary intervention (PCI). All PCI hospitalizations from the Nationwide Inpatient Sample (2004 to 2015) were analyzed and stratified by the presence, cause and severity of CLD, as well as the indication for PCI. Multivariable logistic regression analysis was performed to determine the adjusted odds ratios (aOR) of in-hospital adverse outcomes in patients with CLD compared with those without CLD. Among 7,296,679 PCI admissions, 54,368 (0.7%) had a CLD diagnosis. Among patients with CLD, 36,853 (67.8%) had severe CLD. Patients with CLD had higher likelihood of adverse outcomes including major adverse cardiovascular and cerebrovascular events (MACCE) (aOR 1.25, 95%CI 1.20 to 1.30), mortality (aOR 1.43, 95%CI 1.35 to 1.51), major bleeding (aOR 2.22, 95%CI 2.12 to 2.32). When accounting for severity, only severe CLD subgroup was more likely to have MACCE and all-cause mortality compared to no-CLD patients (p <0.001). Among CLD etiologic subgroups, those with 'alcohol-related liver disease' and 'other CLD' were consistently more likely to develop MACCE, all-cause mortality and major bleeding in comparison to no-CLD patients, while 'chronic viral hepatitis' subgroup had only increased odds of major bleeding (p <0.001). In conclusion, CLD patients admitted for PCI are more likely to have worse in-hospital outcomes, particularly in the severe CLD subgroup and 'alcohol-related liver disease' and 'other CLD' etiologic subgroups.
Collapse
Affiliation(s)
- Sedralmontaha Istanbuly
- Faculty of Medicine, University of Aleppo, Aleppo, Syrian Arab Republic; Keele Cardiovascular Research Group, Keele University, Stoke on Trent, United Kingdom
| | - Andrija Matetic
- Keele Cardiovascular Research Group, Keele University, Stoke on Trent, United Kingdom; Department of Cardiology, University Hospital of Split, Split, Croatia
| | - Mohamed O Mohamed
- Keele Cardiovascular Research Group, Keele University, Stoke on Trent, United Kingdom
| | | | | | - Islam Y Elgendy
- Division of Cardiology, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Timir K Paul
- Department of Medicine, Division of Cardiology, East Tennessee State University, Johnson City, Tennessee
| | - Mohamad Alkhouli
- Department of Cardiovascular Disease, Mayo Clinic School of Medicine, Rochester, Minnesota
| | - Mamas A Mamas
- Keele Cardiovascular Research Group, Keele University, Stoke on Trent, United Kingdom; Department of Cardiology, Thomas Jefferson University, Philadelphia, Pennsylvania.
| |
Collapse
|
|
26
|
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.
Collapse
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
| |
Collapse
|
|
27
|
Dongiovanni P, Paolini E, Corsini A, Sirtori CR, Ruscica M. Nonalcoholic fatty liver disease or metabolic dysfunction-associated fatty liver disease diagnoses and cardiovascular diseases: From epidemiology to drug approaches. Eur J Clin Invest 2021; 51:e13519. [PMID: 33583033 DOI: 10.1111/eci.13519] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/10/2021] [Accepted: 02/11/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND A consensus of experts has proposed to replace the term nonalcoholic fatty liver disease (NAFLD), whose global prevalence is 25%, with metabolic dysfunction-associated fatty liver disease (MAFLD), to describe more appropriately the liver disease related to metabolic derangements. MAFLD is closely intertwined with type 2 diabetes, obesity, dyslipidaemia, all linked to a rise in the risk of cardiovascular disease (CVDs). Since controversy still stands on whether or not NAFLD/MAFLD raises the odds of CVD, the present review aims to evaluate the impact of NAFLD/MAFLD aetiologies on CV health and the potential correction by dietary and drug approaches. RESULTS Epidemiological studies indicate that NAFLD raises risk of fatal or non-fatal CVD events. NAFLD patients have a higher prevalence of arterial plaques and stiffness, coronary calcification, and endothelial dysfunction. Although genetic and environmental factors strongly contribute to NAFLD pathogenesis, a Mendelian randomization analysis indicated that the PNPLA3 genetic variant leading to NAFLD may not be causally associated with CVD risk. Among other genetic variants related to NAFLD, TM6SF2 appears to be protective, whereas MBOAT7 may favour venous thromboembolism. CONCLUSIONS NAFLD is correlated to a higher CVD risk which may be ameliorated by dietary interventions. This is not surprising, since new criteria defining MAFLD include other metabolic risk abnormalities fuelling development of serious adverse extrahepatic outcomes, for example CVD. The present lack of a targeted pharmacological approach makes the identification of patients with liver disease at higher CVD risk (eg diabetes, hypertension, obesity or high levels of C-reactive protein) of major clinical interest.
Collapse
Affiliation(s)
- Paola Dongiovanni
- General Medicine and Metabolic Diseases, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Erika Paolini
- General Medicine and Metabolic Diseases, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.,Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
| | - Alberto Corsini
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.,Multimedica IRCCS, Sesto San Giovanni (MI), Milan, Italy
| | - Cesare R Sirtori
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
| | - Massimiliano Ruscica
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
| |
Collapse
|
|
28
|
Meyersohn NM, Mayrhofer T, Corey KE, Bittner DO, Staziaki PV, Szilveszter B, Hallett T, Lu MT, Puchner SB, Simon TG, Foldyna B, Voora D, Ginsburg GS, Douglas PS, Hoffmann U, Ferencik M. Association of Hepatic Steatosis With Major Adverse Cardiovascular Events, Independent of Coronary Artery Disease. Clin Gastroenterol Hepatol 2021; 19:1480-1488.e14. [PMID: 32707340 PMCID: PMC7855524 DOI: 10.1016/j.cgh.2020.07.030] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 07/12/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Hepatic steatosis has been associated with increased risk of major adverse cardiovascular events (MACE) but it is not clear whether steatosis is independently associated with risk of MACE. We investigated whether steatosis is associated with risk of MACE independently of the presence and extent of baseline coronary artery disease, assessed by comprehensive contrast-enhanced computed tomography angiography (CTA). METHODS We conducted a nested cohort study of 3756 subjects (mean age, 60.6 years; 48.4% men) who underwent coronary CTA at 193 sites in North America, from July 2010 through September 2013, as part of the PROMISE study, which included noninvasive cardiovascular analyses of symptomatic outpatients without coronary artery disease. Independent core laboratory readers measured hepatic and splenic attenuation, using non-contrast computed tomography images to identify steatosis, and evaluated coronary plaques and stenosis in coronary CTA images. We collected data on participants' cardiovascular risk factors, presence of metabolic syndrome, and body mass index. The primary endpoint was an adjudicated composite of MACE (death, myocardial infarction, or unstable angina) during a median follow-up time of 25 months. RESULTS Among the 959 subjects who had steatosis (25.5% of the cohort), 42 had MACE (4.4%), whereas among the 2797 subjects without steatosis, 73 had MACE (2.6%) (hazard ratio [HR] for MACE in subjects with steatosis, 1.69; 95% CI, 1.16-2.48; P = .006 for MACE in subjects with vs without steatosis). This association remained after adjustment for atherosclerotic cardiovascular disease risk scores, significant stenosis, and metabolic syndrome (adjusted HR, 1.72; 95% CI, 1.16-2.54; P = .007) or obesity (adjusted HR, 1.75; 95% CI, 1.19-2.59; P = .005). Steatosis remained independently associated with MACE after adjustment for all CTA measures of plaques and stenosis. CONCLUSIONS Hepatic steatosis is associated with MACE independently of other cardiovascular risk factors or extent of coronary artery disease. Strategies to reduce steatosis might reduce risk of MACE. ClinicalTrials.gov no: NCT01174550.
Collapse
Affiliation(s)
- Nandini M. Meyersohn
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, MA
| | - Thomas Mayrhofer
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, MA,School of Business Studies, Stralsund University of Applied Sciences, Stralsund, Germany
| | - Kathleen E. Corey
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA
| | - Daniel O. Bittner
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, MA,Friedrich-Alexander University Erlangen-Nürnberg, Department of Cardiology, University Hospital Erlangen, Germany
| | - Pedro V. Staziaki
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, MA
| | - Balint Szilveszter
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, MA
| | - Travis Hallett
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, MA
| | - Michael T. Lu
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, MA
| | - Stefan B. Puchner
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, MA,Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Tracey G. Simon
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA
| | - Borek Foldyna
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, MA
| | - Deepak Voora
- Duke Center for Applied Genomics & Precision Medicine, Duke University School of Medicine, Durham, NC
| | - Geoffrey S. Ginsburg
- Duke Center for Applied Genomics & Precision Medicine, Duke University School of Medicine, Durham, NC
| | - Pamela S. Douglas
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC
| | - Udo Hoffmann
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, MA
| | - Maros Ferencik
- Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, MA,Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR
| |
Collapse
|
|
29
|
Ramadan MS, Russo V, Nigro G, Durante-Mangoni E, Zampino R. Interplay between Heart Disease and Metabolic Steatosis: A Contemporary Perspective. J Clin Med 2021; 10:1569. [PMID: 33917867 PMCID: PMC8068259 DOI: 10.3390/jcm10081569] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 03/26/2021] [Accepted: 04/03/2021] [Indexed: 12/12/2022] Open
Abstract
The liver-heart axis is a growing field of interest owing to rising evidence of complex bidirectional interplay between the two organs. Recent data suggest non-alcoholic fatty liver disease (NAFLD) has a significant, independent association with a wide spectrum of structural and functional cardiac diseases, and seems to worsen cardiovascular disease (CVD) prognosis. Conversely, the effect of cardiac disease on NAFLD is not well studied and data are mostly limited to cardiogenic liver disease. We believe it is important to further investigate the heart-liver relationship because of the tremendous global health and economic burden the two diseases pose, and the impact of such investigations on clinical decision making and management guidelines for both diseases. In this review, we summarize the current knowledge on NAFLD diagnosis, its systemic manifestations, and associations with CVD. More specifically, we review the pathophysiological mechanisms that govern the interplay between NAFLD and CVD and evaluate the relationship between different CVD treatments and NAFLD progression.
Collapse
Affiliation(s)
- Mohammad Said Ramadan
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
| | - Vincenzo Russo
- Department of Translational Medical Sciences, AORN Ospedali dei Colli-Monaldi Hospital, 80131 Naples, Italy; (V.R.); (G.N.)
- Cardiology Unit, AORN Ospedali dei Colli-Monaldi Hospital, 80131 Naples, Italy
| | - Gerardo Nigro
- Department of Translational Medical Sciences, AORN Ospedali dei Colli-Monaldi Hospital, 80131 Naples, Italy; (V.R.); (G.N.)
- Cardiology Unit, AORN Ospedali dei Colli-Monaldi Hospital, 80131 Naples, Italy
| | - Emanuele Durante-Mangoni
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
- Infectious and Transplant Medicine Unit, AORN Ospedali dei Colli-Monaldi Hospital, 80131 Naples, Italy;
| | - Rosa Zampino
- Infectious and Transplant Medicine Unit, AORN Ospedali dei Colli-Monaldi Hospital, 80131 Naples, Italy;
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| |
Collapse
|
|
30
|
El Amrousy D, Elgendy E, Awad MED, El Razaky O. Three-dimensional speckle tracking echocardiography for early detection of left ventricular dysfunction in children with non-alcoholic fatty liver diseases. Cardiol Young 2021; 31:562-567. [PMID: 33300483 DOI: 10.1017/s104795112000445x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVES To detect early left ventricular dysfunction in children with non-alcoholic fatty liver disease using three-dimensional speckle tracking echocardiography. METHODS Forty obese children with non-alcoholic fatty liver disease were included as group I. Another 40 obese children without non-alcoholic fatty liver disease of matched age, sex, and weight were included as group II. Forty healthy controls of matched age and sex served as a control group. Anthropometric measurements, laboratory investigations, and echocardiographic examinations including three-dimensional speckle tracking echocardiography were measured for all included children. RESULTS Abnormal lipid profile was detected in children with non-alcoholic fatty liver disease. Troponin I levels were significantly higher in children with non-alcoholic fatty liver disease compared to obese children without non-alcoholic fatty liver disease and to healthy controls. Three-dimensional speckle tracking echocardiography examination revealed a significant reduction of left ventricular global longitudinal strain, circumferential strain, radial strain, and area strain in children with non-alcoholic fatty liver disease inspite of normal left ventricular fraction shortening measured by conventional echocardiography. All strains were negatively correlated with the grade of non-alcoholic fatty liver disease. CONCLUSION Non-alcoholic fatty liver disease is associated with subclinical left ventricular dysfunction. Three-dimensional speckle tracking echocardiography can be helpful in identifying early left ventricular dysfunction in children with non-alcoholic fatty liver disease even in the presence of normal left ventricular ejection fraction.
Collapse
Affiliation(s)
- Doaa El Amrousy
- Pediatric Department, Faculty of Medicine, Tanta University, Egypt
| | - Esam Elgendy
- Pediatric Department, Faculty of Medicine, Tanta University, Egypt
| | | | - Osama El Razaky
- Pediatric Department, Faculty of Medicine, Tanta University, Egypt
| |
Collapse
|
|
31
|
Kirby RS, Halegoua-DeMarzio D. Coronary artery disease and non-alcoholic fatty liver disease: Clinical correlation using computed tomography coronary calcium scans. JGH Open 2021; 5:390-395. [PMID: 33732887 PMCID: PMC7936612 DOI: 10.1002/jgh3.12509] [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: 11/13/2020] [Revised: 01/28/2021] [Accepted: 02/08/2021] [Indexed: 12/30/2022]
Abstract
Background and Aim Non‐alcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) have been explored using coronary angiography, which showed a link between severe NAFLD and cardiovascular disease risk. This study's aim is to determine if computed tomography (CT) coronary artery calcium (CAC) scores used to determine CAD severity in asymptomatic populations can help predict the presence of NAFLD. Methods This was a retrospective cross‐sectional study of positive CT CAC scores and liver imaging with either CT; ultrasound; magnetic resonance imaging of the abdomen; or CT of the chest, which included liver images. Drinking 7 or 14 drinks per week for a female or male, respectively, and chronic viral hepatitis diagnosis were the exclusion criteria. CT CAC scores, hepatic steatosis, age, gender, lipid and liver panels, weight, blood pressure, F‐4/BARD scores, and hemoglobin A1c were correlated to CAD severity and NAFLD by logistic regression. Results A total of 134 patients with a mean age of 62.3 years (σ = 9.1), with 65% males, body mass index 28.5 (σ = 6.0), and 8% diabetics, were recruited. CAD severity was not associated with the presence of hepatic steatosis (odds ratio 1.96 [95% confidence interval, confidence interval 0.74–5.23] P = 0.36). Adjusted for variables, a link between hepatic steatosis, CAD severity, body mass index over 30 (odds ratio 6.77 [95% confidence interval 1.40–32.66] P = 0.02), and diabetes (odds ratio 9.60 [95% confidence interval 0.56–165.5] P = 0.01) was observed. Conclusions In patients with CAD detected using a positive CT CAC scan, we determined that BMI over 30 and diabetes were correlated with the presence of NAFLD. There was no direct relationship between CAD presence and hepatic steatosis presence.
Collapse
Affiliation(s)
- Richard S Kirby
- Sidney Kimmel Medical College Thomas Jefferson University Philadelphia Pennsylvania USA
| | - Dina Halegoua-DeMarzio
- Department of Medicine, Division of Gastroenterology and Hepatology Thomas Jefferson University Philadelphia Pennsylvania USA
| |
Collapse
|
|
32
|
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is caused by the accumulation of fat in over 5% of hepatocytes in the absence of alcohol consumption. NAFLD is considered the hepatic manifestation of metabolic syndrome (MS). Recently, an expert consensus suggested as more appropriate the term MAFLD (metabolic-associated fatty liver disease). Insulin resistance (IR) plays a key role in the development of NAFLD, as it causes an increase in hepatic lipogenesis and an inhibition of adipose tissue lipolysis. Beyond the imbalance of adipokine levels, the increase in the mass of visceral adipose tissue also determines an increase in free fatty acid (FFA) levels. In turn, an excess of FFA is able to determine IR through the inhibition of the post-receptor insulin signal. Adipocytes secrete chemokines, which are able to enroll macrophages inside the adipose tissue, responsible, in turn, for the increased levels of TNF-α. The latter, as well as resistin and other pro-inflammatory cytokines such as IL-6, enhances insulin resistance and correlates with endothelial dysfunction and an increased cardiovascular (CV) risk. In this review, the role of diet, intestinal microbiota, genetic and epigenetic factors, low-degree chronic systemic inflammation, mitochondrial dysfunction, and endoplasmic reticulum stress on NAFLD have been addressed. Finally, the clinical impact of NAFLD on cardiovascular and renal outcomes, and its direct link with type 2 diabetes have been discussed.
Collapse
|
|
33
|
Yan X, Jin W, Zhang J, Wang M, Liu S, Xin Y. Association of TCF7L2 rs7903146 Gene Polymorphism with the Risk of NAFLD and CAD in the Chinese Han Population. J Clin Transl Hepatol 2020; 8:371-376. [PMID: 33447519 PMCID: PMC7782105 DOI: 10.14218/jcth.2020.00071] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 08/25/2020] [Accepted: 09/24/2020] [Indexed: 12/13/2022] Open
Abstract
Background and Aims: Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD). Previous studies have suggested that TCF7L2 rs7903146 was related to the risk of developing NAFLD but the conclusions are not consistent and no related study has been conducted in Chinese populations. The aim of this study was to investigate the association between TCF7L2 rs7903146 and the risk of developing NAFLD and CAD in a Chinese Han population. Methods: TCF7L2 rs7903146 genotypes were measured by the MALDI-TOF-MS from 143 NAFLD patients, 159 CAD patients, 131 NAFLD + CAD patients, and 212 healthy controls. The demographic data and serum lipid profiles of all subjects were collected. The distributions of genotype and allele frequency in each group were also tested. Logistic regression was used to investigate the risk of TCF7L2 rs7903146 with NAFLD and CAD. All statistical analyses were conducted using SPSS 23.0. Results: There were no significant differences in the distributions of TCF7L2 rs7903146 genotype and allele frequency in each of the two groups, and the TCF7L2 rs7903146 CT + TT genotype did not increase the risk of developing NAFLD, CAD, and NAFLD + CAD. Except for body mass index in the control group, the differences of clinical parameters between the TCF7L2 rs7903146 T allele carriers and non-carriers in each group were not significant. In the non-obese group, the TCF7L2 rs7903146 CT + TT genotype was a protective factor for the development of NAFLD in the non-obese subjects (odds ratio=0.359, 95% confidence interval: 0.134-0.961, p = 0.041). Conclusions: TCF7L2 rs7903146 was not associated with the risk of developing NAFLD, CAD, and NAFLD + CAD in the Chinese Han population. In the non-obese population, the TCF7L2 rs7903146 CT + TT genotype was a protective factor against the development of NAFLD.
Collapse
Affiliation(s)
- Xin Yan
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, Shandong, China
- Dalian Medical University, Dalian, Liaoning, China
| | - Wenwen Jin
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, Shandong, China
| | - Jie Zhang
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, Shandong, China
| | - Mengke Wang
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, Shandong, China
| | - Shousheng Liu
- Clinical Research Center, Qingdao Municipal Hospital, Qingdao, Shandong, China
- Digestive Disease Key Laboratory of Qingdao, Qingdao, Shandong, China
- Correspondence to: Yongning Xin, Department of Infectious Disease, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong 266011, China. Tel: +86-532-82789463, Fax: +86-532-85968434, E-mail: ; Shousheng Liu, Clinical Research Center, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong 266011, China. Tel: +86-532-88905831, Fax: +86-532-88905293, E-mail:
| | - Yongning Xin
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, Shandong, China
- Clinical Research Center, Qingdao Municipal Hospital, Qingdao, Shandong, China
- Digestive Disease Key Laboratory of Qingdao, Qingdao, Shandong, China
- Correspondence to: Yongning Xin, Department of Infectious Disease, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong 266011, China. Tel: +86-532-82789463, Fax: +86-532-85968434, E-mail: ; Shousheng Liu, Clinical Research Center, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong 266011, China. Tel: +86-532-88905831, Fax: +86-532-88905293, E-mail:
| |
Collapse
|
|
34
|
Translational insight into prothrombotic state and hypercoagulation in nonalcoholic fatty liver disease. Thromb Res 2020; 198:139-150. [PMID: 33340925 DOI: 10.1016/j.thromres.2020.12.002] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 11/17/2020] [Accepted: 12/07/2020] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an emerging and threatening pathological condition, ranging from fatty liver (FL) to chronic steatohepatitis (NASH), liver cirrhosis, and eventually to hepatocellular carcinoma (HCC). Recent findings suggest that patients with NAFLD have a higher risk of cardiovascular events and thromboembolism and that this risk is independent of metabolic diseases that are frequently associated with NAFLD, such as diabetes, hyperlipidaemia, and obesity. The vascular involvement of NAFLD might be considered its systemic burden, conditioning higher mortality in patients affected by the disease. These clinical findings suggested the existence of a prothrombotic state in NAFLD, which is partially unexplored and whose underlying mechanisms are to date not completely understood. Here, we review the mechanisms involved in the pathogenesis of the prothrombotic state in NAFLD across the progression from the healthy liver through the different stages of the disease. We focused on the possible role of several metabolic features of NAFLD possibly leading to hypercoagulation other than endothelial and platelet activation, such as insulin-resistance, nitric oxide production regulation, and gut microbiota homeostasis. Also, we analysed the involvement of plasminogen activator inhibitor-1 (PAI-1) and thromboinflammation taking place in NAFLD. Finally, we described factors striking a prothrombotic imbalance in NASH cirrhosis, with a particular focus on the pathogenesis of portal vein thrombosis.
Collapse
|
|
35
|
Bae YS, Ko YS, Yun JM, Eo AY, Kim H. Association and Prediction of Subclinical Atherosclerosis by Nonalcoholic Fatty Liver Disease in Asymptomatic Patients. Can J Gastroenterol Hepatol 2020; 2020:8820445. [PMID: 33354557 PMCID: PMC7735832 DOI: 10.1155/2020/8820445] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 11/09/2020] [Accepted: 11/11/2020] [Indexed: 12/30/2022] Open
Abstract
Background The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing in the general population. This study evaluated the association between NAFLD and significant coronary stenosis in asymptomatic adults and evaluated sex-based differences. Methods We performed a retrospective cross-sectional study in participants without previous cardiovascular diseases who visited the Seoul National University Hospital Health Promotion Center for a health checkup between January 1, 2010, and December 31, 2015. NAFLD was diagnosed on sonography, while coronary artery stenosis (CAS) was assessed on coronary computed tomography angiography (CCTA). Results We obtained 3,693 participants who met the inclusion criteria, and 3,449 of them had no significant stenosis. Among the participants with significant stenosis, the prevalence of NAFLD was 59.4% (145 patients). The prevalence of NAFLD was 47.26% in male participants, which was higher than that in female participants. The association between NAFLD and significant CAS persisted after adjusting for age, body mass index, glycated hemoglobin, and Framingham risk factors. The correlation between NAFLD and significant coronary stenosis appeared to be stronger in women than in men, but the absolute risk was higher in men than in women. Conclusion NAFLD was strongly associated with CAS. We should be alert about an increased cardiovascular risk in patients with NAFLD and more intensively provide primary prevention by performing tests to detect subclinical atherosclerosis.
Collapse
Affiliation(s)
- Ye Seul Bae
- Department of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea
- Office of Hospital Information, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yeon Seo Ko
- Department of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jae Moon Yun
- Department of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Ah Young Eo
- Department of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - HaJin Kim
- Department of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| |
Collapse
|
|
36
|
Sasson A, Kristoferson E, Batista R, McClung JA, Abraham NG, Peterson SJ. The pivotal role of heme Oxygenase-1 in reversing the pathophysiology and systemic complications of NAFLD. Arch Biochem Biophys 2020; 697:108679. [PMID: 33248947 DOI: 10.1016/j.abb.2020.108679] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 11/03/2020] [Accepted: 11/12/2020] [Indexed: 02/06/2023]
Abstract
The pathogenesis and molecular pathways involved in non-alcoholic fatty liver disease (NAFLD) are reviewed, as well as what is known about mitochondrial dysfunction that leads to heart disease and the progression to steatohepatitis and hepatic fibrosis. We focused our discussion on the role of the antioxidant gene heme oxygenase-1 (HO-1) and its nuclear coactivator, peroxisome proliferator-activated receptor-gamma coactivator (PGC1-α) in the regulation of mitochondrial biogenesis and function and potential therapeutic benefit for cardiac disease, NAFLD as well as the pharmacological effect they have on the chronic inflammatory state of obesity. The result is increased mitochondrial function and the conversion of white adipocyte tissue to beige adipose tissue ("browning of white adipose tissue") that leads to an improvement in signaling pathways and overall liver function. Improved mitochondrial biogenesis and function is essential to preventing the progression of hepatic steatosis to NASH and cirrhosis as well as preventing cardiovascular complications.
Collapse
Affiliation(s)
- Ariel Sasson
- Department of Medicine, New York Medical College, Valhalla, NY, 10595, USA; Department of Pharmacology, New York Medical College, Valhalla, NY, 10595, USA
| | - Eva Kristoferson
- Department of Medicine, New York Medical College, Valhalla, NY, 10595, USA
| | - Rogerio Batista
- The Mount Sinai Bone Program, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - John A McClung
- Department of Medicine, New York Medical College, Valhalla, NY, 10595, USA
| | - Nader G Abraham
- Department of Medicine, New York Medical College, Valhalla, NY, 10595, USA; Department of Pharmacology, New York Medical College, Valhalla, NY, 10595, USA; Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, 25701, USA
| | - Stephen J Peterson
- Department of Medicine, Weill Cornell Medicine, New York, NY, 10065, USA; New York Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY, 11215, USA.
| |
Collapse
|
|
37
|
Arslan U, Yenerçağ M. Relationship between non-alcoholic fatty liver disease and coronary heart disease. World J Clin Cases 2020; 8:4688-4699. [PMID: 33195636 PMCID: PMC7642538 DOI: 10.12998/wjcc.v8.i20.4688] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 09/17/2020] [Accepted: 09/25/2020] [Indexed: 02/05/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease and considered a liver manifestation of metabolic syndrome. It is in close relationship with insulin resistance, obesity, diabetes mellitus, all of which increase risk of cardiovascular disease (CVD). Besides, many studies point out that NAFLD independently contributes to the development of atherosclerosis and CHD. On the other hand, CVDs are the leading cause of death in NAFLD patients. Many pathophysiological changes and molecular mechanisms play an important role in NAFLD for CVD formation. Atherosclerosis is common in NAFLD, which also mainly contributes to the CVD formation and CHD. Many studies linking atherosclerotic CHD and NAFLD are present in the literature. Subclinical CHD, mainly detected by coronary computed tomography views, have been detected more common in NAFLD patients. Presence of NAFLD has been found to be more common in patients with severe CHD and in stable CHD, NAFLD has been found to be associated with more diffuse disease. In acute coronary syndromes, especially in acute myocardial infarction, patients with NAFLD have been found to have poor prognosis when compared with NAFLD free patients. In this review, our aim is to evaluate the relationship between NAFLD and CHD in detail and go over the pathophysiological mechanisms underlying this relationship.
Collapse
Affiliation(s)
- Ugur Arslan
- Department of Cardiology, University of Health Sciences Samsun Training and Research Hospital, Samsun 55400, Turkey
| | - Mustafa Yenerçağ
- Department of Cardiology, University of Health Sciences Samsun Training and Research Hospital, Samsun 55400, Turkey
| |
Collapse
|
|
38
|
Castaldo L, Laguzzi F, Strawbridge RJ, Baldassarre D, Veglia F, Vigo L, Tremoli E, de Faire U, Eriksson P, Smit AJ, Aubrecht J, Leander K, Pirro M, Giral P, Ritieni A, Di Minno G, Mälarstig A, Gigante B. Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease Do Not Associate with Measures of Sub-Clinical Atherosclerosis: Results from the IMPROVE Study. Genes (Basel) 2020; 11:genes11111243. [PMID: 33105679 PMCID: PMC7690395 DOI: 10.3390/genes11111243] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 10/16/2020] [Accepted: 10/21/2020] [Indexed: 01/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and atherosclerosis-related cardiovascular diseases (CVD) share common metabolic pathways. We explored the association between three NAFLD-associated single nucleotide polymorphisms (SNPs) rs738409, rs10401969, and rs1260326 with sub-clinical atherosclerosis estimated by the carotid intima-media thickness (c-IMT) and the inter-adventitia common carotid artery diameter (ICCAD) in patients free from clinically overt NAFLD and CVD. The study population is the IMPROVE, a multicenter European study (n = 3711). C-IMT measures and ICCAD were recorded using a standardized protocol. Linear regression with an additive genetic model was used to test for association of the three SNPs with c-IMT and ICCAD. In secondary analyses, the association of the three SNPs with c-IMT and ICCAD was tested after stratification by alanine aminotransferase levels (ALT). No associations were found between rs738409, rs1260326, rs10401969, and c-IMT or ICCAD. Rs738409-G and rs10401969-C were associated with ALT levels (p < 0.001). In patients with ALT levels above 28 U/L (highest quartile), we observed an association between rs10401969-C and c-IMT measures of c-IMTmax and c-IMTmean-max (p = 0.018 and 0.021, respectively). In conclusion, NAFLD-associated SNPs do not associate with sub-clinical atherosclerosis measures. However, our results suggest a possible mediating function of impaired liver function on atherosclerosis development.
Collapse
Affiliation(s)
- Luigi Castaldo
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80138 Naples, Italy;
- Department of Pharmacy, University of Naples “Federico II”, 80138 Naples, Italy;
- Correspondence: ; Tel.: +39-081-678116
| | - Federica Laguzzi
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden; (F.L.); (U.d.F.); (K.L.)
| | - Rona J. Strawbridge
- Mental Health and Wellbeing, Institute of Health and Wellbeing, University of Glasgow, Glasgow G12-8QQ, UK;
- Health Data Research University of Glasgow, College of Medicine, Veterinarian and Life Sciences, Glasgow G12-8RZ, UK
- Cardiovascular Medicine, Department of Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden; (P.E.); (A.M.); (B.G.)
| | - Damiano Baldassarre
- Centro Cardiologico Monzino, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Via Parea 4, 20138 Milan, Italy; (D.B.); (F.V.); (L.V.); (E.T.)
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milano MI, Italy
| | - Fabrizio Veglia
- Centro Cardiologico Monzino, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Via Parea 4, 20138 Milan, Italy; (D.B.); (F.V.); (L.V.); (E.T.)
| | - Lorenzo Vigo
- Centro Cardiologico Monzino, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Via Parea 4, 20138 Milan, Italy; (D.B.); (F.V.); (L.V.); (E.T.)
| | - Elena Tremoli
- Centro Cardiologico Monzino, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Via Parea 4, 20138 Milan, Italy; (D.B.); (F.V.); (L.V.); (E.T.)
| | - Ulf de Faire
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden; (F.L.); (U.d.F.); (K.L.)
| | - Per Eriksson
- Cardiovascular Medicine, Department of Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden; (P.E.); (A.M.); (B.G.)
| | - Andries J. Smit
- Department of Medicine, Division of vascular medicine University Medical Center Groningen, 9713 GZ Groningen, The Netherlands;
| | - Jiri Aubrecht
- Takeda Pharmaceuticals International Co., Cambridge, 02139 MA, USA;
| | - Karin Leander
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden; (F.L.); (U.d.F.); (K.L.)
| | - Matteo Pirro
- Unit of Internal Medicine, Department of Medicine, University of Perugia, 06123 Perugia PG, Italy;
| | - Philippe Giral
- Assistance Publique—Hopitaux de Paris; Service Endocrinologie-Metabolisme, Groupe Hôpitalier Pitie-Salpetriere, Unités de Prévention Cardiovasculaire, 75013 Paris, France;
| | - Alberto Ritieni
- Department of Pharmacy, University of Naples “Federico II”, 80138 Naples, Italy;
| | - Giovanni Di Minno
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80138 Naples, Italy;
| | - Anders Mälarstig
- Cardiovascular Medicine, Department of Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden; (P.E.); (A.M.); (B.G.)
| | - Bruna Gigante
- Cardiovascular Medicine, Department of Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden; (P.E.); (A.M.); (B.G.)
| |
Collapse
|
|
39
|
de Roos A, Lamb HJ. Exploring the Interaction between Liver and Heart Disease. Radiology 2020; 297:62-63. [PMID: 32813598 DOI: 10.1148/radiol.2020203112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Albert de Roos
- From the Department of Radiology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333ZA, the Netherlands
| | - Hildo J Lamb
- From the Department of Radiology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333ZA, the Netherlands
| |
Collapse
|
|
40
|
Chin J, Mori TA, Adams LA, Beilin LJ, Huang RC, Olynyk JK, Ayonrinde OT. Association between remnant lipoprotein cholesterol levels and non-alcoholic fatty liver disease in adolescents. JHEP Rep 2020; 2:100150. [PMID: 32984791 PMCID: PMC7495103 DOI: 10.1016/j.jhepr.2020.100150] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 06/15/2020] [Accepted: 07/13/2020] [Indexed: 12/19/2022] Open
Abstract
Background & Aims Remnant lipoprotein cholesterol (RLP-C) is an atherogenic lipid profile associated with non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). With increased rates of CVD seen in adults with NAFLD, RLP-C has the potential to identify individuals with NAFLD who are at increased risk of CVD. This study examined in adolescents sex-different associations among RLP-C, NAFLD, and cardiometabolic risk factors, and whether RLP-C is associated with NAFLD beyond traditional cardiometabolic risk factors. Methods Adolescents in the Raine Study had anthropometry, clinical, biochemistry and arterial stiffness measurements recorded at 17 years of age. Fatty liver, subcutaneous and visceral adipose thickness were assessed using abdominal ultrasound. Relationships among RLP-C, NAFLD, liver biochemistry, insulin resistance, adipokines, adiposity and arterial stiffness were assessed. Results NAFLD was diagnosed in 15.1% (19.6% females and 10.7% males) of adolescents. Increasing RLP-C levels were associated with increasing severity of hepatic steatosis and metabolic syndrome. Adolescents with NAFLD and serum RLP-C levels in the highest quartile compared with the lowest quartile, had higher serum leptin, homeostatic model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein, low-density-lipoprotein cholesterol, triglycerides, BMI, subcutaneous and visceral adipose thickness, systolic blood pressure and arterial stiffness, but lower adiponectin and high-density-lipoprotein cholesterol. Using multivariable logistic regression, RLP-C in the lowest quartile compared with the highest quartile was associated with 85% lower odds of NAFLD in males and 55% in females, after adjusting for waist circumference, leptin, ALT, adiponectin and HOMA-IR. Conclusions There is an association between RLP-C and NAFLD beyond traditional risk factors of adiposity and insulin resistance in adolescents. Although raised serum RLP-C levels were associated with the severity of hepatic steatosis and markers of cardiometabolic risk, lower serum RLP-C might reflect reduced cardiovascular risk. Lay summary Remnant lipoprotein cholesterol (RLP-C) is a part of the blood cholesterol that is linked with heart disease and non-alcoholic fatty liver disease (NAFLD) in adults. In the Raine Study, teenagers with high RLP-C levels had more severe fat accumulation in their liver. Thus, RLP-C might be the hidden link between NAFLD and future risk of heart disease.
Non-alcoholic fatty liver disease (NAFLD) and heart disease share risk factors. Serum remnant lipoprotein cholesterol (RLP-C) is linked with severity of liver fat. Males with NAFLD have higher cardiometabolic risk. RLP-C may contribute to risk of cardiovascular disease in people with NAFLD.
Collapse
Key Words
- AIx, Aortic Augmentation Index
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- Adiposity
- Arterial stiffness
- C-AGPH-HR75, Central Augmentation Pressure/Pulse Height Ratio at Heart Rate 75
- Cardiometabolic risk
- GGT, gamma-glutamyl transpeptidase
- HDL-C, high-density lipoprotein cholesterol
- HOMA-IR, homeostatic model assessment of insulin resistance
- IDF, International Diabetes Federation
- LDL-C, low-density lipoprotein cholesterol
- Lipids
- Metabolic syndrome
- NAFLD
- NAFLD, non-alcoholic fatty liver disease
- OR, odds ratio
- Q1, lowest (first) quartile
- Q2, second quartile
- Q3, third quartile
- Q4, top (fourth) quartile
- RLP-C, remnant lipoprotein cholesterol
- Raine study
- T2DM, type 2 diabetes mellitus
- TG, triglycerides
- VLDL, very-low-density lipoprotein
- hsCRP, high-sensitivity C-reactive protein
Collapse
Affiliation(s)
- Justin Chin
- Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, WA, Australia
| | - Trevor A Mori
- School of Medicine and Pharmacology, The University of Western Australia, Perth, WA, Australia
| | - Leon A Adams
- School of Medicine and Pharmacology, The University of Western Australia, Perth, WA, Australia.,Department of Hepatology and Liver Transplantation, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
| | - Lawrence J Beilin
- School of Medicine and Pharmacology, The University of Western Australia, Perth, WA, Australia
| | - Rae-Chi Huang
- Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia
| | - John K Olynyk
- Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, WA, Australia.,School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
| | - Oyekoya T Ayonrinde
- Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, WA, Australia.,School of Medicine and Pharmacology, The University of Western Australia, Perth, WA, Australia.,Faculty of Health Sciences, Curtin University, Bentley, WA, Australia
| |
Collapse
|
|
41
|
Motamed N, Ajdarkosh H, Ahmadi M, Perumal D, Ashrafi GH, Nikkhah M, Faraji AH, Maadi M, Khoonsari M, Rezaie N, Farahani B, Safarnezhad Tameshkel F, Ameli M, Panahi M, Karbalaie Niya MH, Zamani F. Non-alcoholic fatty liver disease is not independent risk factor for cardiovascular disease event: A cohort study. World J Hepatol 2020; 12:323-331. [PMID: 32742574 PMCID: PMC7364326 DOI: 10.4254/wjh.v12.i6.323] [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: 02/09/2020] [Revised: 04/08/2020] [Accepted: 05/14/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND There are no consistent results between previous studies for an independent association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) events.
AIM To determine if there is an independent association between NAFLD and CVD events.
METHODS In the present study, valid outcome data of 4808 subjects were available for phase 2 of our cohort study. These subjects had been followed up for seven years from phase 1, beginning in 2009-2010 to phase 2 during 2016-2017. Simple and multiple Cox proportional models were used to determine the association between NAFLD in the primary phase of the cohort and subsequent fatal and non-fatal CVD events during follow-up.
RESULTS The incidence of non-fatal CVD events in males with NAFLD was significantly higher (P = 0.004) than in males without NAFLD. A positive association was demonstrated between NAFLD and non-fatal CVD events in males (Hazard ratio = 1.606; 95%CI: 1.166-2.212; P = 0.004) by the simple Cox proportional hazard model, but no independent association was detected between these in the multiple Cox models.
CONCLUSION No independent association was detected between NAFLD and CVD. It is likely that diabetes mellitus and age may be the principle mediators in this regard.
Collapse
Affiliation(s)
- Nima Motamed
- Department of Social Medicine, Zanjan University of Medical Sciences, Zanjan 1449614535, Iran
| | - Hossein Ajdarkosh
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran 1449614535, Iran
| | - Maral Ahmadi
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran 1449614535, Iran
| | - Dhayaneethie Perumal
- Faculty of Science, Engineering and Computing, Kingston University, Kingston, London KT1 2EE, United Kingdom
| | - G Hossein Ashrafi
- Cancer Theme SEC Faculty Penrhyn Road, Kingston University, London KT1 2EE, United Kingdom
| | - Mehdi Nikkhah
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran 1449614535, Iran
| | - Amir Hossein Faraji
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran 1449614535, Iran
| | - Mansooreh Maadi
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran 1449614535, Iran
| | - Mahmoodreza Khoonsari
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran 1449614535, Iran
| | - Nader Rezaie
- Department of Pulmonology, Firouzgar Hospital, Iran University of Medical Sciences, Tehran 1449614535, Iran
| | - Behzad Farahani
- Department of Cardiology, Iran University of Medical Sciences, Tehran 1449614535, Iran
| | | | - Mitra Ameli
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran 1449614535, Iran
| | - Mahshid Panahi
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran 1449614535, Iran
| | - Mohammad Hadi Karbalaie Niya
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran 1449614535, Iran
| | - Farhad Zamani
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran 1449614535, Iran
| |
Collapse
|
|
42
|
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.
Collapse
Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
| |
Collapse
|
|
43
|
Lee H, Kim G, Choi YJ, Huh BW, Lee BW, Kang ES, Cha BS, Lee EJ, Lee YH, Huh KB. Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus. Diabetes Metab J 2020; 44:267-276. [PMID: 30877708 PMCID: PMC7188976 DOI: 10.4093/dmj.2019.0001] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 01/16/2019] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Impaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM. METHODS We analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography. RESULTS LV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%, P=0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively; P for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34; P=0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51; P=0.002). CONCLUSIONS Liver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.
Collapse
Affiliation(s)
- Hokyou Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Gyuri Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young Ju Choi
- Huh's Diabetes Center and the 21st Century Diabetes and Vascular Research Institute, Seoul, Korea
| | - Byung Wook Huh
- Huh's Diabetes Center and the 21st Century Diabetes and Vascular Research Institute, Seoul, Korea
| | - Byung Wan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Seok Kang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Bong Soo Cha
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Jig Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Yong Ho Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
- Department of Systems Biology, Glycosylation Network Research Center, Yonsei University, Seoul, Korea.
| | - Kap Bum Huh
- Huh's Diabetes Center and the 21st Century Diabetes and Vascular Research Institute, Seoul, Korea
| |
Collapse
|
|
44
|
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.
Collapse
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
| |
Collapse
|
|
45
|
El Hadi H, Di Vincenzo A, Vettor R, Rossato M. Relationship between Heart Disease and Liver Disease: A Two-Way Street. Cells 2020; 9:cells9030567. [PMID: 32121065 PMCID: PMC7140474 DOI: 10.3390/cells9030567] [Citation(s) in RCA: 92] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 02/23/2020] [Accepted: 02/25/2020] [Indexed: 12/18/2022] Open
Abstract
In clinical practice, combined heart and liver dysfunctions coexist in the setting of the main heart and liver diseases because of complex cardiohepatic interactions. It is becoming increasingly crucial to identify these interactions between heart and liver in order to ensure an effective management of patients with heart or liver disease to provide an improvement in overall prognosis and therapy. In this review, we aim to summarize the cross-talk between heart and liver in the setting of the main pathologic conditions affecting these organs. Accordingly, we present the clinical manifestation, biochemical profiles, and histological findings of cardiogenic ischemic hepatitis and congestive hepatopathy due to acute and chronic heart failure, respectively. In addition, we discuss the main features of cardiac dysfunction in the setting of liver cirrhosis, nonalcoholic fatty liver disease, and those following liver transplantation.
Collapse
Affiliation(s)
- Hamza El Hadi
- Internal Medicine 3, Department of Medicine—DIMED, University of Padova, Via Giustiniani 2, 35100 Padova, Italy; (H.E.H.); (A.D.V.); (R.V.)
- Department of Medicine, Klinikum Rheine, 48431 Rheine, Germany
| | - Angelo Di Vincenzo
- Internal Medicine 3, Department of Medicine—DIMED, University of Padova, Via Giustiniani 2, 35100 Padova, Italy; (H.E.H.); (A.D.V.); (R.V.)
| | - Roberto Vettor
- Internal Medicine 3, Department of Medicine—DIMED, University of Padova, Via Giustiniani 2, 35100 Padova, Italy; (H.E.H.); (A.D.V.); (R.V.)
| | - Marco Rossato
- Internal Medicine 3, Department of Medicine—DIMED, University of Padova, Via Giustiniani 2, 35100 Padova, Italy; (H.E.H.); (A.D.V.); (R.V.)
- Correspondence: ; Tel.: +39-049-8218747; Fax: +39049-8213332
| |
Collapse
|
|
46
|
VanWagner LB, Wilcox JE, Ning H, Lewis CE, Carr JJ, Rinella ME, Shah SJ, Lima JAC, Lloyd-Jones DM. Longitudinal Association of Non-Alcoholic Fatty Liver Disease With Changes in Myocardial Structure and Function: The CARDIA Study. J Am Heart Assoc 2020; 9:e014279. [PMID: 32067588 PMCID: PMC7070184 DOI: 10.1161/jaha.119.014279] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background Non‐alcoholic fatty liver disease (NAFLD) is associated with high cardiovascular morbidity/mortality, including heart failure. Abnormalities in left ventricular (LV) structure/function are associated with heart failure risk. Methods and Results Participants from the population‐based CARDIA (Coronary Artery Risk Development in Young Adults) study year 25 exam (2010–2011, aged 43–55 years, 61% women, 48% black) with computed tomography measured liver fat and comprehensive echocardiography were included. Echocardiography was repeated at year 30 follow‐up (aged 47–62 years, N=1827). NAFLD was defined as liver attenuation ≤40 HU after exclusions. LV geometry was classified into normal and abnormal by integrating relative wall thickness and LV mass index. Diastolic function was defined using Doppler and tissue Doppler imaging. Systolic function was assessed with myocardial strain measured by speckle tracking. NAFLD prevalence was 8.7% (n=159). NAFLD participants had higher LV mass, relative wall thickness, incident LV hypertrophy and abnormal LV geometry versus non‐NAFLD (P<0.02). NAFLD participants had impaired LV relaxation (E/A ratio 1.1 versus 1.2), higher LV filling pressures (E/e′ ratio 7.9 versus 7.2), worse longitudinal strain (−13.9% versus −15.3%), and lower LV ejection fraction (58.9% versus 60.2%, P<0.01). In multivariable analyses adjusted for heart failure risk factors, NAFLD was independently associated with incident LV hypertrophy (odds ratio: 1.9, 95% CI: 1.1–3.4), abnormal LV geometry (odds ratio: 1.9, 1.1–3.3) and greater change in strain (odds ratio: 2.2, 1.1–4.7). Adjustment for body mass index attenuated associations to non‐significance. Conclusions NAFLD is associated with subclinical changes over time in LV structure/function and obesity explains much of the association. Presence of obesity in mid‐life may identify an important at‐risk population in whom to focus preventive heart failure strategies.
Collapse
Affiliation(s)
- Lisa B VanWagner
- Division of Gastroenterology & Hepatology Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL.,Department of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago IL
| | - Jane E Wilcox
- Department of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago IL.,Department of Medicine Division of Cardiology Northwestern University Feinberg School of Medicine Chicago IL
| | - Hongyan Ning
- Department of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago IL
| | - Cora E Lewis
- Department of Epidemiology University of Alabama Birmingham School of Public Health Birmingham AL
| | - John Jeffrey Carr
- Departments of Radiology, Cardiovascular Medicine and Biomedical Informatics Vanderbilt University School of Medicine Nashville TN
| | - Mary E Rinella
- Division of Gastroenterology & Hepatology Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL
| | - Sanjiv J Shah
- Department of Medicine Division of Cardiology Northwestern University Feinberg School of Medicine Chicago IL
| | - Joao A C Lima
- Departments of Medicine and Radiology Johns Hopkins University School of Medicine Baltimore MD
| | - Donald M Lloyd-Jones
- Department of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago IL.,Department of Medicine Division of Cardiology Northwestern University Feinberg School of Medicine Chicago IL
| |
Collapse
|
|
47
|
THE INFLUENCE OF CHRONIC NON–CALCULOUS CHOLECYSTITIS ON THE COURSE OF CORONARY HEART DISEASE. WORLD OF MEDICINE AND BIOLOGY 2020. [DOI: 10.26724/2079-8334-2020-4-74-20-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
|
|
48
|
Dong Y, Li G. Cardiac abnormalities in patients with nonalcoholic fatty liver disease : Insights from auxiliary examinations. Herz 2019; 46:158-163. [PMID: 31538216 DOI: 10.1007/s00059-019-04855-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 08/19/2019] [Accepted: 08/26/2019] [Indexed: 12/16/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease in developed countries and is associated with type 2 diabetes mellitus, obesity, hypertension, dyslipidemia, and metabolic syndrome. It is defined as steatosis in over 5% of hepatocytes. The disease spectrum of NAFLD ranges from simple fatty liver to nonalcoholic steatohepatitis, liver fibrosis, even hepatic cirrhosis. The disease affects various extra-hepatic systems such as the cardiovascular system and urinary system. Heart-related disease is identified as the leading cause of mortality in NAFLD patients rather than liver-related disease. In this review, we summarize the cardiac abnormalities (structural, functional, arrhythmic cardiac complications etc.) seen in NAFLD patients with the assistance of auxiliary examinations, such as electrocardiography, echocardiography, computed tomography, magnetic resonance imaging etc. In addition, the epidemiology of NAFLD and how NAFLD affects the myocardium are also discussed.
Collapse
Affiliation(s)
- Yu Dong
- Department of Ultrasound, the Second Affiliated Hospital, Dalian Medical University, 116027, Dalian, China
| | - Guangsen Li
- Department of Ultrasound, the Second Affiliated Hospital, Dalian Medical University, 116027, Dalian, China.
| |
Collapse
|
|
49
|
Turan Y. The Nonalcoholic Fatty Liver Disease Fibrosis Score Is Related to Epicardial Fat Thickness and Complexity of Coronary Artery Disease. Angiology 2019; 71:77-82. [DOI: 10.1177/0003319719844933] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of the metabolic syndrome and is associated with cardiovascular disease (CVD). The NAFLD Fibrosis Score (NFS) is an index used for the detection of liver fibrosis. We investigated the relationship between NFS and complexity of coronary artery disease (CAD). In this cross-sectional study, 109 patients with CAD and 50 patients without CAD were enrolled. Demographic data, laboratory parameters, epicardial fat thickness (EFT), NFS, and Synergy between percutaneous coronary intervention with Taxus and cardiac surgery (SYNTAX) score were recorded. Waist circumference, fasting glucose, low-density lipoprotein cholesterol (LDL-C), EFT, and NFS were significantly higher in the CAD group ( P < .05). High-density lipoprotein cholesterol (HDL-C) and ejection fraction were significantly lower in the CAD group ( P < .05). The SYNTAX score was positively correlated with fasting glucose, LDL-C, EFT, and NFS and negatively correlated with HDL-C ( P < .05). The NFS was positively correlated with EFT ( P = .019). Multivariate linear regression analysis revealed that NFS ( P = .012), EFT ( P < .001), and LDL-C ( P = .001) were independently associated with the SYNTAX score. In conclusion, NFS, as a marker of NAFLD, could identify patients at higher risk of CVD.
Collapse
Affiliation(s)
- Yaşar Turan
- Division of Cardiology, School of Medicine, Bozok University, Yozgat, Turkey
| |
Collapse
|
|
50
|
Park HE, Lee H, Choi SY, Kwak MS, Yang JI, Yim JY, Chung GE. Clinical significance of hepatic steatosis according to coronary plaque morphology: assessment using controlled attenuation parameter. J Gastroenterol 2019; 54:271-280. [PMID: 30284617 DOI: 10.1007/s00535-018-1516-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 09/27/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) plays a significant role in coronary atherosclerosis, independent of shared metabolic risk factors. The measurement of the controlled attenuation parameter (CAP) has shown to allow early and noninvasive detection of NAFLD at subclinical stage. We evaluated the significance of CAP-defined NAFLD in association with the presence of any type of coronary plaques and different plaque compositions. METHODS We conducted a retrospective cohort of apparently healthy subjects who had liver Fibroscan and coronary computed tomography during health screening exams. RESULTS A greater number of subjects with CAP-defined NAFLD was found in group with coronary plaques (61.3% vs. 73.5%, p = 0.005 without vs. with any type of plaque). From multivariate regression model, CAP ≥ 222 dB/m was an independent and significant parameter associated with the presence of coronary plaques, after adjusting possible confounders (OR 1.624, 95% 1.047-2.518, p = 0.030). Interestingly, CAP ≥ 222 dB/m was significantly associated with non-calcified plaque (adjusted OR 3.528, 95% CI 1.463-8.511, p = 0.005), whereas it was not significant in calcified plaques (p = 0.171). CONCLUSION CAP-defined NAFLD is independently associated with coronary plaques, especially non-calcified plaques. The association between NAFLD and non-calcified plaques suggests that particular attention should be given to the subjects with NAFLD for primary prevention.
Collapse
Affiliation(s)
- Hyo Eun Park
- Division of Cardiology, Department of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - Heesun Lee
- Division of Cardiology, Department of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - Su-Yeon Choi
- Division of Cardiology, Department of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - Min-Sun Kwak
- Division of Gastroenterology, Department of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL. Gangnam Finance Center 737, Yeoksam-Dong, Gangnam-Gu, Seoul, 135-984, Korea
| | - Jong In Yang
- Division of Gastroenterology, Department of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL. Gangnam Finance Center 737, Yeoksam-Dong, Gangnam-Gu, Seoul, 135-984, Korea
| | - Jeong Yoon Yim
- Division of Gastroenterology, Department of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL. Gangnam Finance Center 737, Yeoksam-Dong, Gangnam-Gu, Seoul, 135-984, Korea
| | - Goh Eun Chung
- Division of Gastroenterology, Department of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL. Gangnam Finance Center 737, Yeoksam-Dong, Gangnam-Gu, Seoul, 135-984, Korea.
| |
Collapse
|