Background: Individuals with severe α1-antitrypsin deficiency (AATD) have increased elastase activity resulting in continuous degradation of elastin and an early onset of chronic obstructive pulmonary disease. It has been suggested that the increased elastase activity over time also affects the elastic properties of other organs, for instance the heart.

Aims and objectives: We tested whether severe AATD is associated with susceptibility to heart failure in the Danish population.

Methods: In a nationwide nested study of 2,209 patients with AATD and 21,871 controls without AATD, we recorded admissions and deaths due to heart failure during follow-up. We validated our findings in a population-based cohort of 102,295 individuals from the Copenhagen General Population Study and 187 patients from the Danish α1-antitrypsin deficiency registry. There was no overlap between the two cohorts.

Results: Individuals with severe AATD versus those without had increased risks of heart failure hospitalization during follow-up in the nationwide cohort (HR adjusted: 2.38, 95%CI: 2.03-2.79) and population-based cohort (1.77, 1.14-2.74). The hazard ratio of heart failure hospitalization was attenuated but remained increased among patients with myocardial infarction (1.49, 1.08-2.06), hypertension (1.67, 1.29-2.16) and atrial fibrillation (1.42, 1.07-1.89) in the nationwide cohort. The hazard ratios of heart failure-specific mortality in individuals with severe AATD versus those without were 2.14 (1.47-3.11) in the nationwide cohort study and 2.59 (0.81-8.30) in the population-based cohort.

Conclusion: Individuals with severe AATD have an increased risk of heart failure in the Danish general population.