1. 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.
- Author
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Winther SV, Ahmed D, Al-Shuweli S, Landt EM, Nordestgaard BG, Seersholm N, and Dahl M
- Subjects
- Denmark epidemiology, Female, Genotype, Humans, Male, Meta-Analysis as Topic, Middle Aged, Myocardial Ischemia diagnosis, Myocardial Ischemia epidemiology, Odds Ratio, Phenotype, RNA genetics, Risk Factors, alpha 1-Antitrypsin biosynthesis, alpha 1-Antitrypsin Deficiency complications, alpha 1-Antitrypsin Deficiency physiopathology, Blood Pressure physiology, Gene Expression Regulation, Myocardial Ischemia etiology, Registries, Risk Assessment methods, alpha 1-Antitrypsin genetics, alpha 1-Antitrypsin Deficiency genetics
- Abstract
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 α1 -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 α1 -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: α1 -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). α1 -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 α1 -antitrypsin deficiency had an odds ratio for ischemic heart disease of 0.66 (95% CI:0.53-0.84)., Conclusions: Individuals with severe α1 -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., (© 2022. The Author(s).)- Published
- 2022
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