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      Mucosal Healing and the Risk of Ischemic Heart Disease or Atrial Fibrillation in Patients with Celiac Disease; A Population-Based Study

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          Abstract

          Background

          Patients with celiac disease (CD), characterized histologically by villous atrophy (VA) of the small intestine, have an increased risk of ischemic heart disease (IHD) and atrial fibrillation (AF), risks that persist for years after commencing the gluten-free diet. It is unknown whether persistent VA on follow-up biopsy, rather than mucosal healing, affects the risk of IHD or AF.

          Methods

          We identified patients with histologic evidence of CD diagnosed at all 28 pathology departments in Sweden. Among patients who underwent a follow-up small intestinal biopsy, we compared patients with persistent VA to those who showed histologic improvement, with regard to the development of IHD (angina pectoris or myocardial infarction) or AF.

          Results

          Among patients with CD and a follow-up biopsy (n = 7,440), the median age at follow-up biopsy was 25 years, with 1,063 (14%) patients who were ≥60 years at the time of follow-up biopsy. Some 196 patients developed IHD and 205 patients developed AF. After adjusting for age, gender, duration of CD, calendar period, and educational attainment, there was no significant effect of persistent VA on IHD (adjusted HR 0.97; 95%CI 0.73–1.30). Adjusting for diabetes had a negligible effect (adjusted HR 0.98; 95%CI 0.73–1.31). There was no significant association between persistent VA and the risk of AF (adjusted HR 0.98; 95%CI 0.74–1.30).

          Conclusions

          In this population-based study of patients with CD, persistent VA on follow-up biopsy was not associated with an increased risk of IHD or AF. Failed mucosal healing does not influence the risk of these cardiac events.

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          Most cited references26

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          The histopathology of coeliac disease: time for a standardized report scheme for pathologists.

          G Oberhuber, G Granditsch, H Vogelsang (1999)
          In this paper, we review the histological features of coeliac disease and propose a standardized report scheme based on the Marsh classification. Furthermore, terms used by pathologists are defined. The most important histological differential diagnoses are given, as well as a definition of the different clinical forms of coeliac disease such as symptomatic, silent, latent, potential, treated and refractory coeliac disease.
          Article 0 comments Cited 270 times – based on 0 reviews     Review now
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            All-cause mortality in 272 186 patients hospitalized with incident atrial fibrillation 1995–2008: a Swedish nationwide long-term case–control study

            Tommy Andersson, Anders Magnuson, Ing-Liss Bryngelsson … (2013)
            Aims To evaluate long-term all-cause risk of mortality in women and men hospitalized for the first time with atrial fibrillation (AF) compared with matched controls. Methods and results A total of 272 186 patients (44% women) ≤85 years at the time of hospitalization with incidental AF 1995–2008 and 544 344 matched controls free of in-hospital diagnosis of AF were identified. Patients were followed via record linkage of the Swedish National Patient Registry and the Cause of Death Registry. Using Cox regression models, the long-term relative all-cause mortality risk, adjusted for concomitant diseases, in women vs. controls was 2.15, 1.72, and 1.44 (P < 0.001) in the age categories ≤65, 65–74, and 75–85 years, respectively. The corresponding figures for men were 1.76, 1.36, and 1.24 (P < 0.001). Among concomitant diseases, neoplasm, chronic renal failure, and chronic obstructive pulmonary disease contributed most to the increased all-cause mortality vs. controls. In patients with AF as the primary diagnosis, the relative risk of mortality was 1.63, 1.46, and 1.28 (P < 0.001) in women and 1.45, 1.17, and 1.10 (P < 0.001) in men. Conclusion Atrial fibrillation was an independent risk factor of all-cause mortality in patients with incident AF. The concomitant diseases that contributed most were found outside the thromboembolic risk scores. The highest relative risk of mortality was seen in women and in the youngest patients compared with controls, and the differences between genders in each age category were statistically significant.
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              Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet.

              Brian D. Lahr, Michael J. Murray, Alberto Mudarra-Rubio … (2010)
              Clinical response is typically observed in most adults with celiac disease (CD) after treatment with a gluten-free diet (GFD). The rate of mucosal recovery is less certain. The aims of this study were (1) to estimate the rate of mucosal recovery after GFD in a cohort of adults with CD, and (2) to assess the clinical implications of persistent mucosal damage after GFD. The study group included adults with biopsy-proven CD evaluated at the Mayo Clinic who had duodenal biopsies at diagnosis and at least one follow-up intestinal biopsy to assess mucosal recovery after starting a GFD. The primary outcomes of interest were mucosal recovery and all-cause mortality. Of 381 adults with biopsy-proven CD, 241 (73% women) had both a diagnostic and follow-up biopsy available for re-review. Among these 241, the Kaplan-Meier rate of confirmed mucosal recovery at 2 years following diagnosis was 34% (95% confidence interval (CI): 27-40%), and at 5 years was 66% (95% CI: 58-74%). Most patients (82%) had some clinical response to GFD, but it was not a reliable marker of mucosal recovery (P=0.7). Serological response was associated with confirmed mucosal recovery (P=0.01). Poor compliance to GFD (P<0.01), severe CD defined by diarrhea and weight loss (P<0.001), and total villous atrophy at diagnosis (P<0.001) were strongly associated with persistent mucosal damage. There was a trend toward an association between achievement of mucosal recovery and a reduced rate of all-cause mortality (hazard ratio=0.13, 95% CI: 0.02-1.06, P=0.06), adjusted for gender and age. Mucosal recovery was absent in a substantial portion of adults with CD after treatment with a GFD. There was a borderline significant association between confirmed mucosal recovery (vs. persistent damage) and reduced mortality independent of age and gender. Systematic follow-up with intestinal biopsies may be advisable in patients diagnosed with CD as adults.
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                Author and article information

                Contributors
                Larisa G. Tereshchenko: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 30 January 2015
                Publication date Collection: 2015
                Volume: 10
                Issue: 1
                Electronic Location Identifier: e0117529
                Affiliations
                [1 ]Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, United States of America
                [2 ]Department of Medical Epidemiology and Biostatistics, Karolinska University Hospital and Karolinska Institute, Stockholm, Swede0060045
                [3 ]Primary care research unit, Vårdcentralen Värmlands Nysäter, Värmland County, and the Department of Medicine, Örebro University, Örebro, Sweden
                [4 ]Department of Cardiology, Örebro University Hospital, Örebro, Sweden
                [5 ]Division of Cardiology, Department of Medicine, and Department of Radiology, Columbia University College of Physicians and Surgeons and New York-Presbyterian Hospital, New York, New York, United States of America
                [6 ]Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
                Johns Hopkins University SOM, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: BL LE OF AJE PHRG JFL. Analyzed the data: BL JFL. Wrote the paper: BL LE OF AJE PHRG JFL. Collected data: JFL. Supervision: JFL.

                Article
                Publisher ID: PONE-D-14-22926
                DOI: 10.1371/journal.pone.0117529
                PMC ID: 4312018
                PubMed ID: 25635403
                SO-VID: 6797afaf-7c0a-44c1-8810-40808c1f1645
                Copyright statement: Copyright @ 2015
                License:

                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
                Date received : 1 June 2014
                Date accepted : 15 November 2014
                Page count
                Figures: 0, Tables: 5, Pages: 14
                Funding
                This work was supported by grants to BL from the National Center for Advancing Translational Sciences, National Institutes of Health (UL1 TR000040); and to JFL from Örebro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, the Swedish Research Council—Medicine (522-2A09-195) and the Swedish Celiac Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Custom metadata
                Data Availability The data cannot be made freely and publicly available for ethical and legal reasons, as stipulated by the Swedish Secrecy Act. As described in the paper, the authors obtained the data from the 28 pathology departments in Sweden, the Swedish Patient Registry, and the Swedish Cause of Death Registry.

                ScienceOpen disciplines: Uncategorized
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