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Cardiac complications in celiac disease
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Celiac disease (CD) is an immune-mediated enteropathy induced by dietary gluten that affects about 1% of western populations. CD has been associated to an increased risk of cardiovascular mortality in some studies; however associations to cardiovascular diseases have not been broadly researched.

Aim: The aim of this thesis was to examine the associations between CD and some cardiovascular diseases, namely; atrial fibrialltion, dilated cardiomyopathy and risk factors of ischemic heart disease.Methods: We used computerized data on all Swedish patients with biopsy-verified CD equal to villous atrophy from 1969 to 31st of December 2008. All CD patients were matched on age, sex, county and calendar year with up to five reference individuals. Altogether we had data on 29,096 CD patients and 144,522 reference individuals. Data were linked to different Swedish national registries and the Swedish quality and cardiac care registry SWEDEHEART. Main outcomes in the studies were: I: atrial fibrillation registered in the national patient registry or the cause of death registry, II: chart validated idiopathic dilated cardiomyopathy, III: different risk factors, clinical presentation and parameters in patients with first myocardial infarction (MI) registered in SWEDEHEART and IV: follow-up parameters, 6-10 weeks and one year after MI, registered in SWEDEHEART.

Result: We showed a 34% increased risk of atrial fibrillation in CD and a 73% increased risk of dilated cardiomyopathy, the latter only of borderline significance, p=0.052. In the third study we showed that CD patients with MI had a more beneficial cardiovascular risk factor profile, better left ventricular ejection fraction and fewer stenoses on coronary angiography compared to reference individuals with MI. The fourth study showed that follow-up after MI does not differ from follow-up in reference individuals.

Conclusion: This thesis supports an association of cardiovascular diseases in CD. Potential mechanisms include shared risk factors and chronic in-flammation.

Place, publisher, year, edition, pages
Örebro: Örebro universitet , 2013. , p. 82
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 92
Keywords [en]
atrial fibrillation, autoimmune, celiac disease, cohort, dilated cardiomyopathy, inflammation, myocardial infarction, registry
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
URN: urn:nbn:se:oru:diva-28977Libris ID: 14181560ISBN: 978-91-7668-955-4 (print)OAI: oai:DiVA.org:oru-28977DiVA, id: diva2:619790
Public defence
2013-10-11, Wilandersalen, Universitetssjukhuset, Södra Grev Rosengatan, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2013-05-06 Created: 2013-05-06 Last updated: 2017-10-17Bibliographically approved
List of papers
1. Increased risk of atrial fibrillation in patients with coeliac disease: a nationwide cohort study
Open this publication in new window or tab >>Increased risk of atrial fibrillation in patients with coeliac disease: a nationwide cohort study
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2011 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 32, no 19, p. 2430-7Article in journal (Refereed) Published
Abstract [en]

Aims: Inflammatory markers are established risk factors for atrial fibrillation (AF), but the role of autoimmune diseases is unknown. The aim of the study was to examine the association between coeliac disease (CD) and AF in a large cohort of patients with biopsy-verified CD.

Metods and results: We identified 28,637 patients with CD through biopsy reports (defined as Marsh 3: villous atrophy) from all pathology departments (n = 28) in Sweden. Biopsies had been performed between 1969 and 2008. Age- and sex-matched reference individuals (n = 141,731) were identified from the Swedish Total Population Register. Data on AF were obtained from the Swedish Hospital Discharge Register, the Hospital Outpatient Register, and the Cause of Death Register. Hazard ratios (HRs) for AF were estimated using Cox regression. In the CD cohort, 941 individuals developed AF (vs. 2918 reference individuals) during a median follow-up of 9 years. The corresponding adjusted HR for AF was 1.34 (95% CI = 1.24-1.44). The absolute risk of AF in CD was 321 of 100,000 person-years, with an excess risk of 81 of 100,000. A prior AF diagnosis was also associated with an increased risk of subsequent CD (odds ratio = 1.45, 95% CI = 1.31-1.62).

Conclusions Atrial fibrillation is more common both before and after CD diagnosis in patients with CD though the excess risk is small. Potential explanations for the increased risk of AF in CD include chronic inflammation and shared risk factors, but ascertainment bias may also have contributed.

CLINICAL IMPLICATIONS: Coeliac disease affects 1-2% of the Western population. Our results indicate that patients with coeliac disease, verified by intestinal biopsy, are at increased risk of atrial fibrillation. This observation is consistent with previous findings that elevation of inflammatory markers predicts atrial fibrillation. Additional studies are needed to clarify the mechanistic link between atrial fibrillation and autoimmune diseases such as coeliac disease.

Place, publisher, year, edition, pages
Oxford, United Kingdom: Oxford University Press, 2011
Keywords
Autoimmunity, Coeliac, Inflammation, Atrial fibrillation
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-32520 (URN)10.1093/eurheartj/ehr167 (DOI)000295684300023 ()21653560 (PubMedID)2-s2.0-80054052563 (Scopus ID)
Available from: 2013-11-25 Created: 2013-11-25 Last updated: 2018-05-05Bibliographically approved
2. Risk of idiopathic dilated cardiomyopathy in 29 000 patients with celiac disease
Open this publication in new window or tab >>Risk of idiopathic dilated cardiomyopathy in 29 000 patients with celiac disease
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2012 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 1, no 3, article id e001594Article in journal (Refereed) Published
Abstract [en]

Background: Dilated cardiomyopathy (DCM) is a rare disease of largely unknown origin. Previous studies have suggested an increased prevalence of celiac disease (CD) in patients with DCM. These studies, however, were based on a maximum of 5 patients with both CD and DCM. In the present large Swedish population-based cohort study, we examined the risk of idiopathic DCM in patients with CD determined by small-intestinal histopathology.

Methods and Results: From 2006 to 2008, we collected duodenal/jejunal biopsy data on CD (equal to villous atrophy, Marsh stage 3, n=29 071 unique individuals) from (all) 28 pathology departments in Sweden. These individuals were compared with 144 429 reference individuals matched for age, sex, calendar year, and county. Data on DCM were obtained through the National Patient Register and confirmed by patient charts and echocardiography data. During follow-up, 17 patients with CD and 52 reference individuals developed idiopathic DCM. Thus, patients with CD were at an increased risk of idiopathic DCM (hazard ratio, 1.73; 95% confidence interval, 1.00 to 3.00), although the risk estimate failed to attain statistical significance (P=0.052).

Conclusion: This nationwide study found a moderately but not statistically significantly increased risk of idiopathic DCM in patients with biopsy-verified CD.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell, 2012
Keywords
Autoimmunity, celiac disease, cohort studies, heart, inflammation, dilatation
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:oru:diva-32521 (URN)10.1161/JAHA.112.001594 (DOI)000326333700005 ()23130142 (PubMedID)
Available from: 2013-11-25 Created: 2013-11-25 Last updated: 2018-09-11Bibliographically approved
3. The characterisation and risk factors of ischaemic heart disease in patients with coeliac disease
Open this publication in new window or tab >>The characterisation and risk factors of ischaemic heart disease in patients with coeliac disease
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2013 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 37, no 9, p. 905-914Article in journal (Refereed) Published
Abstract [en]

Background: Studies have shown an increased risk of ischaemic heart disease (IHD) in patients with coeliac disease (CD), despite the patients' lack of traditional IHD risk factors.

Aim: To characterise IHD according to CD status.

Methods: Data on duodenal or jejunal biopsies were collected in 20062008 from all 28 pathology departments in Sweden and were used to define CD (equal to villous atrophy; Marsh stage 3). We used the Swedish cardiac care register SWEDEHEART to identify IHD and to obtain data on clinical status and risk factors at time of first myocardial infarction for this case-only comparison. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). CD patients were compared with general population reference individuals.

Results: We identified 1075 CD patients and 4142 reference individuals with subsequent IHD. CD patients with myocardial infarction had lower body mass index (P<0.001) and cholesterol values (P<0.001) and were less likely to be active smokers (OR=0.74; 95% CI=0.560.98) than reference individuals with myocardial infarction. CD patients had less extensive coronary artery disease at angiography (any stenosis: OR=0.80; 95% CI=0.660.97; three-vessel disease: OR=0.73; 95% CI=0.570.94); but there was no difference in the proportions of CD patients with positive biochemical markers of myocardial infarction (CD: 92.2% vs. reference individuals: 91.5%, P=0.766).

Conclusion: Despite evidence of an increased risk of IHD and higher cardiovascular mortality, patients with coeliac disease with IHD have a more favourable cardiac risk profile compared with IHD in reference individuals.

National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-29001 (URN)10.1111/apt.12271 (DOI)000317065600006 ()23451861 (PubMedID)
Available from: 2013-05-14 Created: 2013-05-13 Last updated: 2018-05-17Bibliographically approved
4. Follow-up of ischaemic heart disease in patients with coeliac disease
Open this publication in new window or tab >>Follow-up of ischaemic heart disease in patients with coeliac disease
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2015 (English)In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 1, p. 83-90Article in journal (Refereed) Published
Abstract [en]

Patients with coeliac disease and myocardial infarction have a more favourable atherosclerotic risk factor profile than controls with myocardial infarction (MI). Therefore, MI prognosis and treatment may differ according to coeliac status. This paper reports on the study of Swedish MI patients with and without coeliac disease (equal to villous atrophy; Marsh histopathology stage 3) based on duodenal or jejunal biopsy data. We used the Swedish Quality Register (SWEDEHEART) to identify individuals with a record of MI from 2005 to 2008 and to obtain data on medication, coronary interventions, and clinical and laboratory parameters at 6–10 weeks and one year after first MI. One-year mortality and coronary interventions were assessed for 430 coeliac patients and 1988 controls. For other outcome variables, we compared 42 coeliac patients with MI and 201 general population controls with MI. Odds ratios (ORs) were calculated by logistic regression. The results showed that compared with controls with MI, coeliac individuals with MI had significantly higher one-year all-cause mortality (OR = 1.43; 95% confidence interval (CI) = 1.04–1.95) but less often underwent a percutaneous coronary intervention (OR = 0.77; 95% CI = 0.61–0.96). Coeliac patients were more often prescribed warfarin but less often aspirin and statins. The readmission rate due to cardiac events in coeliac patients was 15.2% vs. 12.6% in controls (p-value  = 0.69). Other clinical and laboratory parameters were similar. We conclude that the follow up of MI does not seem to differ between coeliac patients and controls, and is unlikely to explain the excess mortality from cardiovascular disease noted in Swedish patients with CD.

Place, publisher, year, edition, pages
London, United Kingdom: Sage Publications, 2015
Keywords
Autoimmunity, coeliac, inflammation, riskfactors, myocardialinfarction
National Category
Medical and Health Sciences Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:oru:diva-32523 (URN)10.1177/2047487313502446 (DOI)000346557500007 ()23963400 (PubMedID)2-s2.0-84918493520 (Scopus ID)
Funder
Swedish Research Council, 522-2A09-195
Note

Funding Agencies:

Swedish Society of Medicine

Swedish Celiac Society

Värmland County

Available from: 2013-11-25 Created: 2013-11-25 Last updated: 2018-06-26Bibliographically approved

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