Association Between Celiac Disease and Mortality Risk in a Swedish Population | Gastroenterology | JAMA | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 35.170.64.36. Please contact the publisher to request reinstatement.
1.
Lebwohl  B, Sanders  DS, Green  PHR.  Coeliac disease.   Lancet. 2018;391(10115):70-81. doi:10.1016/S0140-6736(17)31796-8PubMedGoogle ScholarCrossref
2.
Rubio-Tapia  A, Kyle  RA, Kaplan  EL,  et al.  Increased prevalence and mortality in undiagnosed celiac disease.   Gastroenterology. 2009;137(1):88-93. doi:10.1053/j.gastro.2009.03.059PubMedGoogle ScholarCrossref
3.
Corrao  G, Corazza  GR, Bagnardi  V,  et al.  Mortality in patients with coeliac disease and their relatives.   Lancet. 2001;358(9279):356-361. doi:10.1016/S0140-6736(01)05554-4PubMedGoogle ScholarCrossref
4.
Grainge  MJ, West  J, Card  TR, Holmes  GKT.  Causes of death in people with celiac disease spanning the pre- and post-serology era.   Am J Gastroenterol. 2011;106(5):933-939. doi:10.1038/ajg.2010.506PubMedGoogle ScholarCrossref
5.
Ludvigsson  JF, Montgomery  SM, Ekbom  A, Brandt  L, Granath  F.  Small-intestinal histopathology and mortality risk in celiac disease.   JAMA. 2009;302(11):1171-1178. doi:10.1001/jama.2009.1320PubMedGoogle ScholarCrossref
6.
Catassi  C, Fabiani  E, Corrao  G,  et al.  Risk of non-Hodgkin lymphoma in celiac disease.   JAMA. 2002;287(11):1413-1419. doi:10.1001/jama.287.11.1413PubMedGoogle ScholarCrossref
7.
Ludvigsson  JF, Michaelsson  K, Ekbom  A, Montgomery  SM.  Coeliac disease and the risk of fractures—a general population-based cohort study.   Aliment Pharmacol Ther. 2007;25(3):273-285. doi:10.1111/j.1365-2036.2006.03203.xPubMedGoogle ScholarCrossref
8.
Elfström  P, Sundström  J, Ludvigsson  JF.  Systematic review with meta-analysis: associations between coeliac disease and type 1 diabetes.   Aliment Pharmacol Ther. 2014;40(10):1123-1132. doi:10.1111/apt.12973PubMedGoogle ScholarCrossref
9.
Ludvigsson  JF, Lindelöf  B, Zingone  F, Ciacci  C.  Psoriasis in a nationwide cohort study of patients with celiac disease.   J Invest Dermatol. 2011;131(10):2010-2016. doi:10.1038/jid.2011.162PubMedGoogle ScholarCrossref
10.
Zingone  F, Swift  GL, Card  TR, Sanders  DS, Ludvigsson  JF, Bai  JC.  Psychological morbidity of celiac disease: a review of the literature.   United European Gastroenterol J. 2015;3(2):136-145. doi:10.1177/2050640614560786PubMedGoogle ScholarCrossref
11.
Ludvigsson  JF.  Mortality and malignancy in celiac disease.   Gastrointest Endosc Clin N Am. 2012;22(4):705-722. doi:10.1016/j.giec.2012.07.005PubMedGoogle ScholarCrossref
12.
Choung  RS, Unalp-Arida  A, Ruhl  CE, Brantner  TL, Everhart  JE, Murray  JA.  Less hidden celiac disease but increased gluten avoidance without a diagnosis in the United States.   Mayo Clin Proc. Published online December 5, 2016. doi:10.1016/j.mayocp.2016.10.012PubMedGoogle Scholar
13.
Abdul Sultan  A, Crooks  CJ, Card  T, Tata  LJ, Fleming  KM, West  J.  Causes of death in people with coeliac disease in England compared with the general population.   Gut. 2015;64(8):1220-1226. doi:10.1136/gutjnl-2014-308285PubMedGoogle ScholarCrossref
14.
Holmes  GKT, Muirhead  A.  Mortality in coeliac disease.   BMJ Open Gastroenterol. 2018;5(1):e000201. doi:10.1136/bmjgast-2018-000201PubMedGoogle Scholar
15.
Quarpong  W, Card  TR, West  J, Solaymani-Dodaran  M, Logan  RF, Grainge  MJ.  Mortality in people with coeliac disease.   United European Gastroenterol J. 2019;7(3):377-387. doi:10.1177/2050640618814662PubMedGoogle ScholarCrossref
16.
Ludvigsson  JF, Lashkariani  M.  Cohort profile: ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden).   Clin Epidemiol. 2019;11:101-114. doi:10.2147/CLEP.S191914PubMedGoogle ScholarCrossref
17.
Ludvigsson  JF, Brandt  L, Montgomery  SM, Granath  F, Ekbom  A.  Validation study of villous atrophy and small intestinal inflammation in Swedish biopsy registers.   BMC Gastroenterol. 2009;9:19. doi:10.1186/1471-230X-9-19PubMedGoogle ScholarCrossref
18.
Brooke  HL, Talbäck  M, Hörnblad  J,  et al.  The Swedish cause of death register.   Eur J Epidemiol. 2017;32(9):765-773. doi:10.1007/s10654-017-0316-1PubMedGoogle ScholarCrossref
19.
Ludvigsson  JF, Almqvist  C, Bonamy  A-KE,  et al.  Registers of the Swedish total population and their use in medical research.   Eur J Epidemiol. 2016;31(2):125-136. doi:10.1007/s10654-016-0117-yPubMedGoogle ScholarCrossref
20.
Husby  S, Koletzko  S, Korponay-Szabó  IR,  et al.  European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease.   J Pediatr Gastroenterol Nutr. 2012;54(1):136-160. doi:10.1097/MPG.0b013e31821a23d0PubMedGoogle ScholarCrossref
21.
Lebwohl  B, Granath  F, Ekbom  A,  et al.  Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study.   Ann Intern Med. 2013;159(3):169-175. doi:10.7326/0003-4819-159-3-201308060-00006PubMedGoogle ScholarCrossref
22.
Lebwohl  B, Michaëlsson  K, Green  PHR, Ludvigsson  JF.  Persistent mucosal damage and risk of fracture in celiac disease.   J Clin Endocrinol Metab. 2014;99(2):609-616. doi:10.1210/jc.2013-3164PubMedGoogle ScholarCrossref
23.
Lebwohl  B, Granath  F, Ekbom  A,  et al.  Mucosal healing and mortality in coeliac disease.   Aliment Pharmacol Ther. 2013;37(3):332-339. doi:10.1111/apt.12164PubMedGoogle ScholarCrossref
24.
Marsh  MN.  Gluten, major histocompatibility complex, and the small intestine: a molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’).   Gastroenterology. 1992;102(1):330-354. doi:10.1016/0016-5085(92)91819-PPubMedGoogle ScholarCrossref
25.
Kaptoge  S, Di Angelantonio  E, Lowe  G,  et al.  C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality.   Lancet. 2010;375(9709):132-140. doi:10.1016/S0140-6736(09)61717-7PubMedGoogle ScholarCrossref
26.
Lohi  S, Mustalahti  K, Kaukinen  K,  et al.  Increasing prevalence of coeliac disease over time.   Aliment Pharmacol Ther. 2007;26(9):1217-1225. doi:10.1111/j.1365-2036.2007.03502.xPubMedGoogle ScholarCrossref
27.
Thomas  HJ, Wotton  CJ, Yeates  D, Ahmad  T, Jewell  DP, Goldacre  MJ.  Pneumococcal infection in patients with coeliac disease.   Eur J Gastroenterol Hepatol. 2008;20(7):624-628. doi:10.1097/MEG.0b013e3282f45764PubMedGoogle ScholarCrossref
28.
Zingone  F, Abdul Sultan  A, Crooks  CJ, Tata  LJ, Ciacci  C, West  J.  The risk of community-acquired pneumonia among 9803 patients with coeliac disease compared to the general population: a cohort study.   Aliment Pharmacol Ther. 2016;44(1):57-67. doi:10.1111/apt.13652PubMedGoogle ScholarCrossref
29.
Ludvigsson  JF, Bai  JC, Biagi  F,  et al; BSG Coeliac Disease Guidelines Development Group; British Society of Gastroenterology.  Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology.   Gut. 2014;63(8):1210-1228. doi:10.1136/gutjnl-2013-306578PubMedGoogle ScholarCrossref
30.
Schiepatti  A, Biagi  F, Fraternale  G,  et al.  Short article: mortality and differential diagnoses of villous atrophy without coeliac antibodies.   Eur J Gastroenterol Hepatol. 2017;29(5):572-576. doi:10.1097/MEG.0000000000000836PubMedGoogle ScholarCrossref
31.
Tio  M, Cox  MR, Eslick  GD.  Meta-analysis: coeliac disease and the risk of all-cause mortality, any malignancy and lymphoid malignancy.   Aliment Pharmacol Ther. 2012;35(5):540-551. doi:10.1111/j.1365-2036.2011.04972.xPubMedGoogle ScholarCrossref
32.
Biagi  F, Corazza  GR.  Do different patients with coeliac disease have different mortality rates?   Gut. 2015;64(8):1187-1188. doi:10.1136/gutjnl-2014-308567PubMedGoogle ScholarCrossref
Original Investigation
April 7, 2020

Association Between Celiac Disease and Mortality Risk in a Swedish Population

Author Affiliations
  • 1Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, New York
  • 2Mailman School of Public Health, Department of Epidemiology, Columbia University, New York, New York
  • 3Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 4Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden
JAMA. 2020;323(13):1277-1285. doi:10.1001/jama.2020.1943
Key Points

Question  Is celiac disease associated with increased mortality?

Findings  In this population-based cohort study of 49 829 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.

Abstract

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 = 49 829) 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 49 829 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 = 246 426), 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.

×