TY - JOUR
T1 - Severe α1-antitrypsin deficiency associated with lower blood pressure and reduced risk of ischemic heart disease
T2 - a cohort study of 91,540 individuals and a meta-analysis
AU - Winther, Sine Voss
AU - Ahmed, Dunia
AU - Al-Shuweli, Suzan
AU - Landt, Eskild Morten
AU - Nordestgaard, Børge Grønne
AU - Seersholm, Niels
AU - Dahl, Morten
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - Background: Increased elastase activity in α1-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.
AB - Background: Increased elastase activity in α1-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.
KW - Blood pressure
KW - Cardiovascular disease
KW - Epidemiology
KW - Genetics
KW - Lipids
KW - SERPINA1
KW - α-Antitrypsin deficiency
U2 - 10.1186/s12931-022-01973-3
DO - 10.1186/s12931-022-01973-3
M3 - Journal article
C2 - 35264159
AN - SCOPUS:85126078127
VL - 23
JO - Respiratory Research (Print)
JF - Respiratory Research (Print)
SN - 1465-9921
IS - 1
M1 - 55
ER -