Severe α1-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

Abstract

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.

Implications of Inflammatory and Oxidative Stress Markers in the Attenuation of Nocturnal Blood Pressure Dipping

“…The presence of isolated systolic AHT, lower DBP, PP widening, and excessive nDBP dipping are important features in arterial stiffness [ 13 ]. Some studies also support that low levels of some alpha-1-globulins are associated with lower BP figures and fewer cardiovascular events whereas some alpha-2-globulins have been associated with greater arterial stiffness [ 36 , 37 , 38 ].…”

α1-Antitrypsin deficiency associated with increased risk of heart failure

“…For our validation cohort we used individuals from the Copenhagen General Population Study and 187 patients from the Danish α 1 -Antitrypsin Deficiency Registry [ 6 ]. Since cases in these two populations did not differ significantly for the heart failure outcomes studied (p-values for interaction ≥0.94), the two studies were combined yielding a total population of 102 481, within which 185 carried the ZZ genotype, 205 the SZ genotype, 5259 the MZ genotype, 93 the SS genotype, 5591 the MS genotype and 91 148 the MM genotype.…”

Quantitative Lipid Profiling Reveals Major Differences between Liver Organoids with Normal Pi*M and Deficient Pi*Z Variants of Alpha-1-antitrypsin

“…Recent studies described lipid alterations in Pi*ZZ patients with liver diseases. Specifically, serum levels of triglyceride and cholesterol levels were found to be lower in AATD in comparison to non-AATD patients [12,13]. Transgenic mice expressing the human Z allele also showed alterations in hepatic lipid metabolism, namely increased levels of hepatic triglycerides and cholesterol [14], and high numbers of lipid droplets [12].…”