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α1-Antitrypsin deficiency and increased risk of atrial fibrillation in two large population-based cohorts

Sine V Winther1,2, Eskild M Landt1,2, Børge G Nordestgaard2,3,4

  • 1Department of Clinical Biochemistry, Zealand University Hospital, Køge, Denmark.

ERJ Open Research
|October 29, 2025
PubMed

Insights

Individuals with alpha-1 antitrypsin deficiency face significantly higher risks of atrial fibrillation, including hospitalizations, medication use, and related mortality. This genetic condition impacts cardiovascular health, underscoring the need for targeted screening and management.

Area of Science:

  • Cardiology
  • Genetics
  • Pulmonology

Background:

  • Alpha-1 antitrypsin deficiency (AATD) is linked to potential cardiac tissue remodeling.
  • AATD may increase susceptibility to atrial fibrillation (AF).

Purpose of the Study:

  • To investigate the association between AATD and the risk of developing AF.
  • To quantify the risk of AF-related outcomes in individuals with AATD.

Main Methods:

  • Nationwide nested study in Denmark (2,233 AATD cases vs. 22,133 controls).
  • Population-based cohort study (102,481 individuals) and Danish AATD Registry (187 individuals).
  • Follow-up for AF hospitalizations, digoxin use, and AF-related mortality over a median of 67 years.

Main Results:

  • AATD associated with increased AF hospitalization risk (aHR 1.99 nationwide, aHR 1.51 population-based).
  • AATD linked to higher digoxin use (aHR 2.11 nationwide).
  • AATD showed increased risk of AF-related death (aHR 2.60 nationwide).

Conclusions:

  • Individuals with AATD exhibit 2- to 3-fold increased risks for AF hospitalization, digoxin use, and AF-related mortality.
  • AATD is a significant risk factor for atrial fibrillation and its complications.
  • Findings highlight the importance of considering AATD in AF risk assessment.
Abstract

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