Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, New York.
Mailman School of Public Health, Department of Epidemiology, Columbia University, New York, New York.
JAMA. 2020 Apr 7;323(13):1277-1285. doi: 10.1001/jama.2020.1943.
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.
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.
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.
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.
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]).
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.
乳糜泻可能与适度但持续存在的长期死亡率增加相关。目前尚不确定在诊断率更高、临床疾病较轻、无麸质食品更广泛的时代，这种风险是否已经发生了变化。
评估在瑞典的基于人群队列中，乳糜泻与死亡率风险之间的关联。
设计、设置和参与者：通过瑞典流行病学强化病理报告（ESPRESSO）队列，确定了 1969 年至 2017 年间诊断为乳糜泻的所有瑞典患者。参与者（n=49829）从活检之日开始观察。随访的最后日期是 2017 年 12 月 31 日。
通过 1969-2017 年瑞典 28 个病理科的小肠绒毛萎缩的组织病理学标本，定义了乳糜泻。每位患者都可以通过年龄、性别、县和日历期与最多 5 名普通人群中的对照相匹配。
主要结局是全因死亡率，次要结局是病因特异性死亡率。使用分层 Cox 比例模型比较乳糜泻患者和对照组，按诊断年份分层。
有 49829 例乳糜泻患者，其中 24%的患者在 2010 年至 2017 年间诊断。诊断时的平均（SD）年龄为 32.2（25.2）岁，62.4%为女性。在中位随访时间 12.5 年期间，13.2%（n=6596）死亡。与对照组（n=246426）相比，乳糜泻患者的总体死亡率升高（每 1000 人年 9.7 例死亡 vs 8.6 例死亡；绝对差异，1.2 例/1000 人年；危险比[HR]，1.21[95%CI，1.17-1.25]）。在所有年龄组中，死亡率风险的相对增加，在 18 至 39 岁年龄组中最大（每 1000 人年 1.9 例死亡 vs 1.1 例死亡；HR，1.69[95%CI，1.47-1.94]；比较 18-39 岁与 40-59 岁和≥60 岁的年龄组之间的异质性检验 P 值均<0.001）。乳糜泻患者死于心血管疾病（每 1000 人年 3.5 例死亡 vs 3.4 例死亡；HR，1.08[95%CI，1.02-1.13]）、癌症（每 1000 人年 2.7 例死亡 vs 2.2 例死亡；HR，1.29[95%CI，1.22-1.36]）和呼吸系统疾病（每 1000 人年 0.6 例死亡 vs 0.5 例死亡；HR，1.21[95%CI，1.08-1.37]）的风险增加。与对照组相比，诊断后第一年的总死亡率最高（每 1000 人年 15.3 例死亡 vs 6.5 例死亡；HR，2.34[95%CI，2.14-2.55]），但在诊断后 10 年以上仍持续存在（每 1000 人年 10.5 例死亡 vs 10.1 例死亡；HR，1.15[95%CI，1.10-1.20]）。在 2010-2017 年诊断的患者中也存在死亡率风险（每 1000 人年 7.5 例死亡 vs 5.5 例死亡；HR，1.35[95%CI，1.21-1.51]）。
在 1969 年至 2017 年期间研究的瑞典人群中，与普通人群相比，乳糜泻诊断与死亡率风险小但具有统计学意义的增加相关。
