Severe α(1)-antitrypsin deficiency associated with lower blood pressure and reduced risk of ischemic heart disease: a cohort study of 91,540 individuals and a meta-analysis

BACKGROUND: Increased elastase activity in α(1)-antitrypsin deficiency may affect elasticity of the arterial walls, and thereby blood pressure and susceptibility to cardiovascular disease. We hypothesized that severe α(1)-antitrypsin deficiency is associated with reduced blood pressure and susceptibility to cardiovascular disease. METHODS: We genotyped 91,353 adults randomly selected from the Danish general population and 187 patients from the Danish α(1)-Antitrypsin Deficiency Registry and recorded baseline blood pressure, baseline plasma lipids and cardiovascular events during follow-up. 185 participants carried the ZZ genotype, 207 carried the SZ genotype and 91,148 carried the MM genotype. RESULTS: α(1)-Antitrypsin deficiency was associated with decreases in blood pressure of up to 5 mmHg for systolic blood pressure and up to 2 mmHg for diastolic blood pressure, in ZZ vs SZ vs MM individuals (trend test, P’s ≤ 0.01). Plasma triglycerides and remnant cholesterol were reduced in ZZ individuals compared with MM individuals (t-test, P’s < 0.001). α(1)-Antitrypsin deficiency was associated with lower risk of myocardial infarction (trend test P = 0.03), but not with ischemic heart disease, ischemic cerebrovascular disease or hypertension (trend test, P’s ≥ 0.59). However, when results for ischemic heart disease were summarized in meta-analysis with results from four previous studies, individuals with versus without α(1)-antitrypsin deficiency had an odds ratio for ischemic heart disease of 0.66 (95% CI:0.53–0.84). CONCLUSIONS: Individuals with severe α(1)-antitrypsin deficiency have lower systolic and diastolic blood pressure, lower plasma triglycerides and remnant cholesterol, reduced risk of myocardial infarction, and a 34% reduced risk of ischemic heart disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-01973-3.