Hypertension Prevalence in the US Population Varies with Differences in Alpha-1 Antitrypsin Genotype: A Cross Sectional Study

Background: The prevalence of hypertension (HTN) associated with alpha-1 antitrypsin deficiency (AATD) has been studied with indeterminate results. The aim of the study was to prospectively compare the prevalence of HTN before testing in 3 groups of individuals with subsequently normal, moderately deficient, and severely deficient genotypes of AATD with adjustment for differences in demographics and clinical variables.
Methods: We performed a cross sectional study using data from the Alpha-1 Coded Testing (ACT) study. The univariate demographic and clinical factors associated with HTN were further analyzed by logistic regression analysis.
Results: The prevalence of HTN was 27.2%, 20.6%, and 27.9% for individuals with normal, moderate and severe AATD, respectively (p<0.02). The prevalence of HTN increased with age and an interaction between age, alpha-1 antitrypsin deficiency genotype and HTN was identified. The relative risk of HTN among young moderately deficient individuals was 0.53 (95% CI 0.37-0.76) the risk of young PiMM and PiMS (normal genotype) individuals. There was no significant difference in the risk in older moderately deficient individuals 1.02 (95% CI 0.76-1.37) and individuals with severe AATD 1.10 (95% CI 0.71-1.68) when compared to normal genotypes.
Conclusion: Moderate deficiency genotypes (PiMZ, PiSS, PiMNull) have less HTN than normal or severe deficiency genotypes, particularly in young individuals. We speculate that protease inhibitor deficiency over a lifetime allows unopposed proteolysis of vascular connective tissue.Measured comorbidities do not explain these findings. Validation of this data should occur in other AATD cohorts.