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      Non-alcoholic fatty liver disease is a strong predictor of coronary artery calcification in metabolically healthy subjects: A cross-sectional, population-based study in middle-aged subjects

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          Abstract

          Objectives

          This study aims to estimate the relationship between non-alcoholic fatty liver disease (NAFLD) and measures of atherosclerotic cardiovascular disease (ASCVD), and to determine to what extent such relationships are modified by metabolic risk factors.

          Methods

          The study was conducted in the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort (n = 1015, age 50–64 years, 51.2% women). NAFLD was defined as computed tomography liver attenuation ≤40 Hounsfield Units, excluding other causes of liver fat. Coronary artery calcification score (CACS) was assessed using the Agatston method. Carotid plaques and intima media thickness (IMT) were measured by ultrasound. Metabolic status was based on assessments of glucose homeostasis, serum lipids, blood pressure and inflammation. A propensity score model was used to balance NAFLD and non NAFLD groups with regards to potential confounders and associations between NAFLD status and ASCVD variables in relation to metabolic status were examined by logistic and generalized linear regression models.

          Results

          NAFLD was present in 106 (10.4%) of the subjects and strongly associated with obesity-related traits. NAFLD was significantly associated with CACS after adjustment for confounders and metabolic risk factors (OR 1.77, 95% CI 1.07–2.94), but not with carotid plaques and IMT. The strongest association between NAFLD and CACS was observed in subjects with few metabolic risk factors (n = 612 [60% of all] subjects with 0–1 out of 7 predefined metabolic risk factors; OR 5.94, 95% CI 2.13–16.6).

          Conclusions

          NAFLD was independently associated with coronary artery calcification but not with measures of carotid atherosclerosis in this cohort. The association between NAFLD and CACS was most prominent in the metabolically healthy subjects.

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          Most cited references37

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          Coronary calcium as a predictor of coronary events in four racial or ethnic groups.

          In white populations, computed tomographic measurements of coronary-artery calcium predict coronary heart disease independently of traditional coronary risk factors. However, it is not known whether coronary-artery calcium predicts coronary heart disease in other racial or ethnic groups. We collected data on risk factors and performed scanning for coronary calcium in a population-based sample of 6722 men and women, of whom 38.6% were white, 27.6% were black, 21.9% were Hispanic, and 11.9% were Chinese. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 3.8 years. There were 162 coronary events, of which 89 were major events (myocardial infarction or death from coronary heart disease). In comparison with participants with no coronary calcium, the adjusted risk of a coronary event was increased by a factor of 7.73 among participants with coronary calcium scores between 101 and 300 and by a factor of 9.67 among participants with scores above 300 (P<0.001 for both comparisons). Among the four racial and ethnic groups, a doubling of the calcium score increased the risk of a major coronary event by 15 to 35% and the risk of any coronary event by 18 to 39%. The areas under the receiver-operating-characteristic curves for the prediction of both major coronary events and any coronary event were higher when the calcium score was added to the standard risk factors. The coronary calcium score is a strong predictor of incident coronary heart disease and provides predictive information beyond that provided by standard risk factors in four major racial and ethnic groups in the United States. No major differences among racial and ethnic groups in the predictive value of calcium scores were detected. Copyright 2008 Massachusetts Medical Society.
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            Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus

            (2002)
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              Mannheim Carotid Intima-Media Thickness and Plaque Consensus (2004–2006–2011)

              Intima-media thickness (IMT) provides a surrogate end point of cardiovascular outcomes in clinical trials evaluating the efficacy of cardiovascular risk factor modification. Carotid artery plaque further adds to the cardiovascular risk assessment. It is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. The scientific basis for use of IMT in clinical trials and practice includes ultrasound physics, technical and disease-related principles as well as best practice on the performance, interpretation and documentation of study results. Comparison of IMT results obtained from epidemiological and interventional studies around the world relies on harmonization on approaches to carotid image acquisition and analysis. This updated consensus document delineates further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT. Standardized methods will foster homogenous data collection and analysis, improve the power of randomized clinical trials incorporating IMT and plaque measurements and facilitate the merging of large databases for meta-analyses. IMT results are applied to individual patients as an integrated assessment of cardiovascular risk factors. However, this document recommends against serial monitoring in individual patients.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – review & editing
                Role: Data curationRole: MethodologyRole: SoftwareRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: Data curationRole: MethodologyRole: Writing – review & editing
                Role: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 August 2018
                2018
                : 13
                : 8
                : e0202666
                Affiliations
                [1 ] Department of Clinical Pathology and Genetics, Sahlgrenska University Hospital, Gothenburg, Sweden
                [2 ] Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
                [3 ] Health Metrics Unit, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
                [4 ] Department of Surgical Sciences, Section of Radiology, Uppsala University, Uppsala, Sweden
                [5 ] Antaros Medical, Mölndal, Sweden
                [6 ] Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
                [7 ] Gastroenterology Division, Department of Clinical Sciences, Lund University, University Hospital Skåne, Malmö, Sweden
                [8 ] Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden
                [9 ] Section of Occupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
                [10 ] Department of Radiology, Sahlgrenska University Hospital, Gothenburg, Sweden
                Medizinische Fakultat der RWTH Aachen, GERMANY
                Author notes

                Competing Interests: J.K. is cofounder and employee of Antaros Medical, Sweden. S.L. has received fees from Intercept Pharmaceuticals for lecturing and advisory board participation. A.G. is a part time employee at Antaros Medical, Sweden. All other authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0003-0024-960X
                Article
                PONE-D-18-14425
                10.1371/journal.pone.0202666
                6105021
                30133541
                18067a2b-575c-4045-baac-9514418d93ed
                © 2018 Gummesson et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 May 2018
                : 7 August 2018
                Page count
                Figures: 3, Tables: 3, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003793, Hjärt-Lungfonden;
                Award ID: 254002157
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004359, Vetenskapsrådet;
                Award ID: 254002165
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100005761, Sahlgrenska Akademin;
                Award ID: 70290
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100007212, Västra Götalandsregionen;
                Award ID: 70370
                Award Recipient :
                The main funding body of The Swedish CArdioPulmonary bioImage Study (SCAPIS) is the Swedish Heart and Lung Foundation ( www.hjart-lungfonden.se). In addition, the SCAPIS Pilot study received support from the Swedish Research Council ( www.vr.se), the Sahlgrenska Academy at University of Gothenburg (sahlgrenska.gu.se) and Region Västra Götaland ( www.vgregion.se). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Fatty Liver
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Vascular Medicine
                Atherosclerosis
                Biology and Life Sciences
                Anatomy
                Cardiovascular Anatomy
                Blood Vessels
                Arteries
                Coronary Arteries
                Medicine and Health Sciences
                Anatomy
                Cardiovascular Anatomy
                Blood Vessels
                Arteries
                Coronary Arteries
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Calcification
                Medicine and Health Sciences
                Physiology
                Physiological Processes
                Calcification
                Biology and Life Sciences
                Biochemistry
                Lipids
                Fats
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Hypertension
                Custom metadata
                The data underlying the findings in our study are not freely and directly available in the manuscript, supplemental files, or in a public repository because the original approval by the regional ethics board and the informed consent from the subjects participating in the studies do not include such a direct, free access. If a reader wants access to the data underlying the present article, please contact Swedish National Data Service with a direct link to this study ( https://snd.gu.se/en/catalogue/study/EXT0054).

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