Cause-specific mortality in individuals with severe alpha 1-antitrypsin deficiency in comparison with the general population in Sweden.

Background: Severe alpha 1-antitrypsin deficiency (PiZZ) predisposes to morbidity and mortality due to early-onset emphysema and liver disease. The risk of death from other causes, including cardiovascular disease and cancer, has not been well investigated. We aimed to analyze cause-specific mortality in PiZZ individuals compared with the general Swedish population.

Methods: Data on 1,561 PiZZ individuals from the Swedish National AAT Deficiency Register, prospectively followed from 1991 to 2014, were analyzed. Causes of death according to the Swedish National Causes of Death Register for the study group were compared with those for the general Swedish population matched for age, sex, and calendar year, with the excess mortality expressed as standardized mortality ratios (SMRs) with 95% confidence intervals (CIs).

Results: There were 524 deaths during the follow-up period. PiZZ individuals had excess all-cause mortality compared with the Swedish general population (SMR 3.6, 95% CI 3.3-3.9). SMR for ischemic heart disease (IHD) was 0.5 (95% CI 0.3-0.8) and was similar for never and ever-smokers, and in males and females. SMR for lung cancer was 0.9 (95% CI 0.4-1.7). PiZZ individuals had increased mortality compared with the general population for the following diseases: respiratory disease, SMR 48.4 (95% CI 43.0-54.5); primary liver carcinoma, SMR 90.0 (95% CI 59.3-130.9); complicated colon diverticulitis, SMR 20.8 (95% CI 6.7-48.6); and pulmonary embolism, SMR 6.9 (95% CI 3.3-12.7).

Conclusion: PiZZ individuals had a reduced mortality risk of IHD. Mortality due to respiratory, hepatic disease, diverticulitis, and pulmonary embolism was markedly increased compared with the age- and sex-matched Swedish population.