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  • 1.
    Emilsson, Louise
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden. Primary Care Res Unit, Värmlands Nysäter, Värmland County Council, Karlstad, Sweden.
    James, Stefan
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ischaemic heart disease in first-degree relatives to coeliac patients2014In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 44, no 4, p. 359-364Article in journal (Refereed)
    Abstract [en]

    Objective: Coeliac disease (CD) has been linked to an increased risk of ischaemic heart disease (IHD). We examined the risk of IHD in first-degree relatives and spouses to coeliac patients to ascertain the genetic contribution to IHD excess risk.

    Study design and setting: Coeliac disease was defined as having a biopsy-verified villous atrophy (Marsh grade 3) in 1969-2008 (n=29096). Coeliac patients were matched to 144522 controls. Through Swedish registers, we identified all first-degree relatives and spouses to coeliac patients and their controls, in total 87622 unique coeliac relatives and 432655 unique control relatives. Our main outcome measure was IHD defined according to relevant international classification of disease codes in the Swedish Inpatient Registry or in the Cause of Death Registry. Hazard ratios (HR) and confidence intervals (CI) were estimated through Cox regression adjusted for sex, age-group and calendar year at study entry of the relative.

    Result: During a median follow-up of 108 years, 2880 coeliac relatives and 13817 control relatives experienced IHD. First-degree relatives of coeliac patients were at increased risk of IHD (HR=105; 95% CI=100-109, P-value=004), while spouses were at no increased risk (HR=099; 95% CI=087-112). The excess risk of IHD in coeliac first-degree relatives aged 40-59years was 70/100000 person-years.

    Conclusion: First-degree relatives to coeliac patients seem to be at an increased risk of IHD but the excess risk is so small that it has little clinical relevance.

  • 2.
    Emilsson, Louise
    et al.
    Primary Care Res Unit Vårdcentralen Värmlands Nysäter, Värmland County, Karlstad, Sweden; Inst Hlth & Soc, Dept Hlth Management & Hlth Econ, Univ Oslo, Oslo, Norway.
    Lebwohl, Benjamin
    Dept Med, Celiac Dis Ctr, Columbia Univ Coll Phys & Surg, New York NY, USA; Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden.
    Sundstrom, Johan
    Uppsala Clin Res Ctr, Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden; Dept Pediat, Örebro University Hospital, Örebro, Sweden.
    Cardiovascular disease in patients with coeliac disease: A systematic review and meta-analysis2015In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 47, no 10, p. 847-852Article in journal (Refereed)
    Abstract [en]

    Background: Coeliac disease has been associated with an increased risk of cardiovascular disease in some studies, whereas other studies have shown no association. We performed a systematic review and meta-analysis of cardiovascular disease in celiac disease. Methods: Pubmed, Cinahl, EMBASE and Medline via Ovid were searched for relevant articles published until January 5, 2015. English-language articles on studies with more than 20 patients were included, and were quality rated using the GRADE risk of bias tool. We used random-effects models and assessed heterogeneity using the I-2 statistic. Results: Ten studies were relevant, reporting the risk of myocardial infarction, cardiovascular death and stroke in 33,128/32,903/32,466 coeliac disease patients respectively. Only one study examined celiac disease and a composite measure of cardiovascular disease and this study found a hazard ratio of 1.10 (95% CI 1.03-1.28). In a meta-analysis, we observed an increased risk of stroke (OR 1.11; 95% CI 1.02-1.20). The risks of myocardial infarction (OR 1.12; 95% CI 0.83-1.40) and cardiovascular death (OR 1.12; 95% CI 0.96-1.29) were similar but were estimated with less certainty. Heterogeneity was low for all outcomes except for myocardial infarction where it was moderate. Conclusion: Coeliac disease was associated with a modestly increased risk of cardiovascular disease, but the evidence base is limited.

  • 3.
    Emilsson, Louise
    et al.
    Primary Care Res Unit, Vårdcentralen (Medical Care Center) Värmlands Nysäter, Värmland County, Värmlands Nysäter, Sweden; Inst Hlth & Soc, Dept Hlth Management & Hlth Econ, Univ Oslo, Oslo, Norway.
    Sultan, Alyshah Abdul
    Div Epidemiol & Publ Hlth, City Hosp, Univ Nottingham, Nottingham, England; Biomed Res Unit, Nottingham Digest Dis Ctr, Natl Inst Hlth Res, Nottingham Univ Hosp NHS Trust, Nottingham, England; Univ Nottingham, Nottingham, England.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Dept Med Epidemiol & Biostat, Karolinska Institute, Stockholm, Sweden; Dept Pediat, Örebro University Hospital, Örebro, Sweden.
    No increased mortality in 109,000 first-degree relatives of celiac individuals2016In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 48, no 4, p. 376-380Article in journal (Refereed)
    Abstract [en]

    Background: Several studies have shown an excess mortality in individuals with celiac disease (CD). However, it is unknown if also first-degree relatives (FDRs) to celiac patients are at increased risk of death. Aim: We aimed to assess mortality in FDRs to celiac patients. Methods: Individuals with CD were identified through biopsy reports (equal to Marsh grade III). Each celiac individual was matched on sex, age, county and calendar year with up to five control individuals. Through Swedish healthcare registries we identified all FDRs (father, mother, sibling, offspring) of CD individuals and controls. Through Cox regression we calculated hazard ratios (HRs) for mortality (all-cause death, circulatory, cancer and other). Results: We identified 109,309 FDRs of celiac individuals and 549,098 FDRs of controls. Overall mortality was increased in FDRs to celiac individuals (HR = 1.02, 95%CI = 1.00-1.04, p = 0.03). This corresponded to an excess risk of 5.9 deaths per 100,000 person-years of follow-up. When limiting follow-up to time since celiac diagnosis in the index individual, we found no increased risk of death (HR = 1.01; 95%CI = 0.98-1.03). Conclusion: FDRs to individuals with CD are at increased risk of death. This excess risk is however minimal and unlikely to be of any clinical importance to the individual. (C) 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  • 4.
    Emilsson, Louise
    et al.
    Primary Care Res Unit Vårdctr Värmlands Nysäter, Värmland County, Karlstad, Sweden; Inst Hlth & Soc, Dept Hlth Management & Hlth Econ, Univ Oslo, Oslo, Norway.
    Wijmenga, Cisca
    Dept Genet, Univ Med Ctr Groningen, Univ Groningen, Groningen, Netherlands.
    Murray, Joseph A.
    Dept Internal Med, Div Gastroenterol & Hepatol, Mayo Clin, Rochester MN, USA.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden; Dept Pediat, Örebro University Hospital, Örebro, Sweden.
    Autoimmune Disease in First-Degree Relatives and Spouses of Individuals With Celiac Disease2015In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 13, no 7, p. 1271-1277.e2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: First-degree relatives of individuals with celiac disease are at increased risk for this disorder, but little is known about their risk for other autoimmune diseases. We assessed the risk of nonceliac autoimmune disease in first-degree relatives and spouses of people with celiac disease. METHODS: We identified individuals with celiac disease by searching computerized duodenal and jejunal biopsies, collected from 1969 through 2008, at 28 pathology departments in Sweden. Celiac disease was identified based on biopsy reports of villous atrophy (equal to Marsh grade 3; n = 29,096). Individuals with celiac disease were matched with up to 5 controls (people without celiac disease) for sex, age, county, and calendar year (total, 144,522 controls). Through Swedish health care registries, we identified all first-degree relatives (fathers, mothers, siblings, and offspring) and spouses of individuals with celiac disease (n = 84,648) and controls (n = 430,942). We used Cox regression analysis to calculate hazard ratios (HRs) for nonceliac autoimmune disease (Crohn's disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, or ulcerative colitis) in these groups. RESULTS: During the follow-up period (median, 10.8 y), 3333 of the first-degree relatives of patients with celiac disease (3.9%) and 12,860 relatives of controls (3.0%) had an autoimmune disease other than celiac disease. First-degree relatives of people with celiac disease were at increased risk of nonceliac autoimmune disease, compared with controls (HR, 1.28; 95% confidence interval, 1.23-1.33), as were spouses (HR, 1.20; 95% confidence interval, 1.06-1.35). Risk estimates for nonceliac autoimmune disease did not differ between first-degree relatives and spouses of individuals with celiac disease (interaction test: P =.11). HRs for nonceliac autoimmune disease were highest in the first 2 years of follow-up evaluation. CONCLUSIONS: First-degree relatives and spouses of individuals with celiac disease are at increased risk of nonceliac autoimmune disease. In addition to genetic factors, environmental factors and ascertainment bias might contribute to the increased risk of autoimmunity in first-degree relatives of individuals with celiac disease.

  • 5.
    Ludvigsson, Jonas F.
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA.
    Choung, Rok Seon
    Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, USA.
    Marietta, Eric V.
    Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, USA.
    Murray, Joseph A.
    Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, USA.
    Emilsson, Louise
    Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Oslo, Norway; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Centre for clinical research & Vårdcentralen Värmlands Nysäter, County council of Värmland, Sweden.
    Increased risk of herpes zoster in patients with coeliac disease - nationwide cohort study2018In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 46, no 8, p. 859-866Article in journal (Refereed)
    Abstract [en]

    Background and aims: Clinical experience suggests that patients with coeliac disease (CD) are more prone to develop herpes zoster (HZ), but robust studies are lacking.

    Methods: We identified 29,064 patients with CD 1969-2008 using biopsy report data from Sweden's 28 pathology departments. CD was equalled to villous atrophy (Marsh histopathology grade III). Each patient was matched on age, sex, calendar year and county of residence to up to five reference individuals (n=144,342) from the general population. We then used Cox regression to estimate hazard ratios (HRs) for future HZ (defined as having a hospital-based inpatient or outpatient record of this diagnosis in the Swedish Patient Register).

    Results: During follow-up, 154 (0.53%) individuals with CD and 499 (0.35%) reference individuals developed HZ. Among individuals aged >= 60 years, 1.06% of CD individuals and 0.85% of reference individuals had a lifetime record of HZ. Overall, CD was associated with a 1.62-fold increased risk of HZ (95% CI=1.35-1.95), and was seen also when we considered comorbidity with lymphoproliferative disease, systemic lupus erythematosus, type 1 diabetes, thyroid disease, rheumatoid disease and excluded individuals with a record of dermatitis herpetiformis. The increased risk remained significant after more than five years of follow-up (1.46; 1.16-1.84)

    Conclusions: CD is associated with HZ, the increased relative risk persists over time from celiac diagnosis but the absolute risk is small.

  • 6.
    Ludvigsson, Jonas F.
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, City Hospital, Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Jarrick, Simon
    Örebro University, School of Medical Sciences. Department of Paediatrics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Murray, Joseph A.
    Department of Immunology, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester MN, USA.
    Emilsson, Louise
    Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Oslo, Norway; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA, USA; Primary Care Research Unit, Vårdcentralen Värmlands Nysäter, Värmland County, Sweden.
    Celiac Disease and Risk of Henoch-Schonlein Purpura Population-based Cohort Study2018In: Journal of Clinical Gastroenterology, ISSN 0192-0790, E-ISSN 1539-2031, Vol. 52, no 2, p. 141-145Article in journal (Refereed)
    Abstract [en]

    Background and Aims: A recent study found a 10-fold increased risk of celiac disease (CD) in individuals with Henoch-Schonlein purpura (HSP), but the confidence interval (CI) was wide.

    Methods: The retrospective cohort study of all patients with CD in Sweden, diagnosed through small intestinal biopsy from 1969 to 2008 (n = 29,077). Each individual with CD was matched to up to 5 controls (n = 144,433). Data on study participants were linked to diagnostic codes for HSP in the National Patient Registry. Through Cox regression we estimated hazard ratios for CD and later HSP. Through logistic regression we calculated odds ratios for HSP preceding CD.

    Results: During follow-up 19 individuals with CD and 99 controls developed HSP. This corresponded to a hazard ratio of 0.96 (95% CI, 0.59-1.56). Looking backward, we found no increased risk of earlier HSP in patients with CD (odds ratio = 1.02; 95% CI, 0.601.72).

    Conclusions: In this study of more than 29,000 patients with CD, we found no increased risk of HSP before or after CD.

  • 7.
    Ludvigsson, Jonas F.
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, City Hospital, Nottingham, UK; Department of Medicine, Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York City, USA.
    Lebwohl, Benjamin
    Department of Medicine, Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York City, USA.
    Chen, Qi
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bröms, Gabriella
    Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden; Department of Internal Medicine, Danderyd Hospital, Stockholm, Sweden; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston Massachusetts, USA.
    Wolf, Randi L.
    Department of Health & Behavior Studies, Program in Nutrition, Teachers College, Columbia University, New York City, USA.
    Green, Peter H. R.
    Department of Medicine, Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York City, USA.
    Emilsson, Louise
    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston Massachusetts, USA; Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Oslo, Norway; Centre for Clinical Research, Vårdcentralen Värmlands Nysäter, Värmlands Nysäter, Sweden.
    Anxiety after coeliac disease diagnosis predicts mucosal healing: a population-based study2018In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 48, no 10, p. 1091-1098Article in journal (Refereed)
    Abstract [en]

    Background: Coeliac disease has been linked to anxiety and depression. However, their association with mucosal healing is unknown.

    Aim: To examine the relationship between anxiety, depression and mucosal healing in coeliac disease.

    Methods: Between 1969 and 2008, we collected data on all small intestinal biopsies with villous atrophy from Sweden's 28 pathology departments. We restricted our cohort to individuals with data on follow-up biopsy (either persistent villous atrophy [n = 3317] or mucosal healing [n = 4331]). Through Cox regression, we estimated hazard ratios (HRs) for anxiety or depression.

    Results: Conclusion APPENDIX During follow-up, 123 (2.8/1000 person-years) individuals with mucosal healing had developed anxiety, compared to 94 (2.1/1000 person-years) with persistent villous atrophy. Mucosal healing was hence associated with a higher risk of future anxiety (HR = 1.49; 95% CI = 1.12-1.96). Similarly, 167 (3.8/1000 person-years) individuals with mucosal healing developed depression, compared to 148 (3.3/1000 person-years) with persistent villous atrophy, corresponding to a HR of 1.25 (95% CI = 0.99-1.59). Mucosal healing was more common in individuals with prior diagnoses of anxiety or depression before follow-up biopsy. Anxiety diagnosed between diagnostic and follow-up biopsy for coeliac disease was associated with an almost nine-fold increased chance of mucosal healing (odds ratio = 8.94; 95%CI = 2.03-39.27).

    Conclusion: Anxiety and depression are more common in coeliac disease patients with mucosal healing, both before and after follow-up biopsy, an association potentially mediated through more vigilant compliance with a gluten-free diet. This finding raises concern that achieving the goal of mucosal healing may come at a cost of an increased risk of mood disorders.

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