In an evaluation of Swedes diagnosed with celiac disease from 1969 to 2017, researchers found a small but significant association between celiac disease and increased mortality risk, according to the results of a cohort study published in JAMA.1
Previous studies have reported a 1.3- to 2-fold increased risk of mortality among patients with celiac disease.2 However, according to the investigators, many of these studies were performed before 2000, when widespread awareness and testing of the disease began. The current study was designed to evaluate the link in patients diagnosed before and after 2000.
Gastrointestinal histopathology reports were provided by the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO), which consists of histopathology specimens submitted from patients to all pathology departments in Sweden. All specimens submitted from 1969 to 2017 with topography codes corresponding to the small intestine were identified. From there, patients with a clinical diagnosis of celiac disease were matched to 5 control participants from the general population by Statistics Sweden.
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The primary outcome was all-cause mortality. Individuals with celiac disease and controls were linked to the Swedish Cause of Death Register. Secondary outcomes included cause-specific mortality due to cardiovascular disease, cancer, respiratory disease, and other causes. Patients with celiac disease were compared with controls using stratified Cox proportional modeling.
A total of 49,829 individuals with celiac disease were matched to 246,426 controls. The mean age of celiac disease diagnosis was 32 years; 62% of patients were female. The majority of celiac patients (64%) were diagnosed after 2000 including 24% diagnosed after 2010. Autoimmune comorbidities (type 1 diabetes, thyroid disease, rheumatoid arthritis, and inflammatory bowel disease) were more common in patients with celiac disease than in the control group.
During a median follow-up time of 12.5 years, 6596 (13.2%) of patients with celiac disease died; 9.7 vs 8.6 deaths per 1000 person years in the control group. The risk of cause-specific mortality was increased in those with celiac disease compared with controls for cardiovascular disease (3.5 vs 3.4 per 1000 person-years), cancer (2.7 vs 2.2 per 1000 person-years), respiratory disease (0.6 vs 0.5 per 1000 person-years), and other causes (2.9 vs 2.3 per 1000 person-years).
Although the mortality risk remained elevated throughout the study period, the increase in risk was greatest for those diagnosed with celiac disease as young adults (aged 18 to 39 years; 1.9 vs 1.1 per 1000 person-years). Mortality risk was most elevated in the first year after diagnosis compared with controls (15.3 vs 6.5 per 1000 person-years) but persisted beyond 10 years after diagnosis (10.5 vs 10.1 per 1000 person-years). The mortality risk was likewise present for patients diagnosed during the years 2010 to 2017 (7.5 vs 5.5 per 1000 person-years).
“The mechanism by which celiac disease is associated with increased mortality risk is unknown, though it is plausible that chronic inflammation, a driver of mortality in other contexts, may be the underlying cause in this population,” the authors concluded.
References
1. Lebwohl B, Green PHR, Söderling J, Roelstraete B, Ludvigsson JF. Association between celiac disease and mortality risk in a Swedish population. JAMA. 2020;323(13):1277-1285.
2. Ludvigsson JF. Mortality and malignancy in celiac disease. Gastrointest Endosc Clin N Am. 2012;22(4):705-722.
