Decreased Risk of Ischemic Heart Disease in Individuals with Severe Alpha 1-Antitrypsin Deficiency (PiZZ) in Comparison with the General Population.

Background: Severe alpha-1-antitrypsin deficiency (AATD) is an established risk factor for chronic obstructive pulmonary disease (COPD) and liver disease, but the effect on the incidence of ischemic heart disease (IHD) is not well known. The aim was to evaluate the risk of incident IHD in patients with severe AATD compared with a random sample of the general population, with known smoking habits. Methods: AAT-deficient individuals, phenotype PiZZ (n=1545), were included in the Swedish National AATD Register. Controls (n=5883) were selected from population-based cohorts in Northern Sweden. Data on IHD and comorbidities were obtained by nationwide cross-linkage with the Swedish National Patient Register. Risk factors for incident IHD were analyzed using Cox regression, adjusted for age, gender, smoking status and the presence of COPD, hypertension, hyperlipidemia and diabetes. Results: At inclusion, 46% of the PiZZ individuals and 53% of the controls were never-smokers. During follow-up (median 16 years; range 0.2-23), 8% (n=123) of PiZZ individuals and 12% (n=690) of controls developed IHD. The controls had a significantly higher risk for incident IHD than the PiZZ individuals, with adjusted hazard ratio (HR) of 1.8 (95% CI 1.4-2.3). The risk was higher for controls in both ever-smokers (HR 2.1; 95% CI 1.5-2.9) and never-smokers (HR 1.5; 95% CI 1.1-2.2). Conclusion: PiZZ individuals have a lower risk of developing incident ischemic heart disease than the control subjects with known smoking habits, who had been randomly selected from population-based cohorts.