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Association Between Celiac Disease and Mortality Risk in a Swedish Population
Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, USA; Mailman School of Public Health, Department of Epidemiology, Columbia University, New York, USA.
Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, USA.
Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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2020 (English)In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 323, no 13, p. 1277-1285Article in journal (Refereed) Published
Abstract [en]

Question: Is celiac disease associated with increased mortality?

Findings: In this population-based cohort study of 49 & x202f;829 patients in Sweden with celiac disease followed up for a median of 12.5 years, the mortality rate compared with general population controls was 9.7 vs 8.6 deaths per 1000 person-years, a difference that was statistically significant.

Meaning: In a Swedish population, celiac disease was associated with a small but statistically significant increased mortality risk.

Importance: Celiac disease may be associated with a modest but persistent increased long-term mortality risk. It is uncertain whether this risk has changed in the era of wider diagnosis rates, less severe clinical disease, and more widespread availability of gluten-free food.

Objective: To evaluate the association between celiac disease and mortality risk in a population-based cohort in Sweden.

Design, Setting, and Participants: All individuals in Sweden with celiac disease diagnosed between 1969 and 2017 were identified through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort. Participants (n = 49 & x202f;829) were observed starting on the day of the biopsy. The final date of follow-up was December 31, 2017.

Exposures: Celiac disease was defined by the presence of small intestinal villus atrophy on histopathology specimens during the years 1969-2017 from Sweden's 28 pathology departments. Each individual was matched with as many as 5 control participants in the general population by age, sex, county, and calendar period.

Main Outcomes and Measures: The primary outcome was all-cause mortality, and the secondary outcome was cause-specific mortality. Patients with celiac disease were compared with controls using stratified Cox proportional modeling, stratifying by year of diagnosis.

Results: There were 49 & x202f;829 patients with celiac disease, including 24% who were diagnosed between the years 2010 and 2017. The mean (SD) age at diagnosis was 32.2 (25.2) years and 62.4% were women. During a median follow-up time of 12.5 years, 13.2% (n = 6596) died. Compared with controls (n = 246 & x202f;426), overall mortality was increased in those with celiac disease (9.7 vs 8.6 deaths per 1000 person-years; absolute difference, 1.2 per 1000 person-years; hazard ratio [HR], 1.21 [95% CI, 1.17-1.25]). The relative increase in mortality risk was present in all age groups and was greatest in those diagnosed in the age range of 18 to 39 years (1.9 vs 1.1 per 1000 person-years; HR, 1.69 [95% CI, 1.47-1.94]; P values for heterogeneity comparing 18-39 years with 40-59 years and with >= 60 years were both <.001). Individuals with celiac disease were at increased risk of death from cardiovascular disease (3.5 vs 3.4 per 1000 person-years; HR, 1.08 [95% CI, 1.02-1.13]), cancer (2.7 vs 2.2 per 1000 person-years; HR, 1.29 [95% CI, 1.22-1.36]), and respiratory disease (0.6 vs 0.5 per 1000 person-years; HR, 1.21 [95% CI, 1.08-1.37]). When compared with controls, the overall mortality risk was greatest in the first year after diagnosis (15.3 vs 6.5 per 1000 person-years; HR, 2.34 [95% CI, 2.14-2.55]) but persisted beyond 10 years after diagnosis (10.5 vs 10.1 per 1000 person-years; HR, 1.15 [95% CI, 1.10-1.20]). The mortality risk was likewise present for patients diagnosed during the years 2010-2017 (7.5 vs 5.5 per 1000 person-years; HR, 1.35 [95% CI, 1.21-1.51]).

Conclusions and Relevance: In a Swedish population studied between 1969 and 2017, a diagnosis of celiac disease compared with the general population was associated with a small but statistically significant increased mortality risk. This population epidemiology study used Swedish histopathology registry data to estimate mortality risk in patients with vs without celiac disease.

Place, publisher, year, edition, pages
American Medical Association , 2020. Vol. 323, no 13, p. 1277-1285
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-81804DOI: 10.1001/jama.2020.1943ISI: 000526602700017PubMedID: 32259229Scopus ID: 2-s2.0-85083022834OAI: oai:DiVA.org:oru-81804DiVA, id: diva2:1429649
Funder
Swedish Research Council
Note

Funding Agencies:

Celiac Disease Foundation Young Investigator Research Grant Award  

Louis and Gloria Flanzer Philanthropic Trust 

Available from: 2020-05-12 Created: 2020-05-12 Last updated: 2020-12-01Bibliographically approved

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Ludvigsson, Jonas F.

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