All-cause and Cause-specific Mortality in Achalasia: A Nationwide Matched Cohort Study

Abstract

Background & aims: Achalasia has been linked to increased mortality, but evidence from large population-based cohorts is scarce. We aimed to assess mortality in individuals with achalasia.

Methods: This nationwide cohort study included all adults in Sweden with incident achalasia (n = 704; 1969-2017; follow-up until December 31, 2021) without any other prior esophageal conditions. Achalasia was defined through International Classification of Disease codes in the Swedish National Patient Register in individuals who underwent endoscopic esophageal examination including biopsy as recorded in the histopathology cohort ESPRESSO. Individuals with achalasia were matched by age, sex, birth year, and county to up to 5 reference individuals (n = 3348) from the general population. In a secondary analysis, full siblings were used as secondary reference individuals. Mortality incidence rates (IRs) and multivariable-adjusted hazard ratios (aHRs) with 95% confidence intervals [Cis] for all-cause and cause-specific mortality were calculated using Cox proportional hazards modeling.

Results: During a median follow-up of 9.1 years, there were 270 deaths in individuals with achalasia, and 1023 in reference individuals (IR, 69.4 vs 51.9/1000 person-years). This corresponded to a 1.42-fold increased risk of death (95% CI, 1.21-1.65); or 1 extra death per every 6 individuals with achalasia followed for 10 years. Risk increases were seen for death from any cancer (IR, 17.4 vs 11.8; aHR, 1.65; 95% CI, 1.21-2.23), esophageal cancer (IR, 2.7 vs 0.2; aHR, 23.19; 95% CI, 3.27-164.55), and respiratory disease (IR, 7.4 vs 3.9; aHR, 2.22; 95% CI, 1.28-3.87), but not from cardiovascular disease (IR, 22.7 vs 19.6; aHR, 1.10; 95% CI, 0.84-1.45). Results remained robust across sensitivity analyses, including sibling comparisons.

Conclusions: Individuals with achalasia had a 42% increased mortality rate compared with the general population. The elevated mortality risk indicates a need for long-term follow-up.

Keywords: Achalasia; Epidemiology; Esophageal Cancer; Mortality.