Department of Clinical Biochemistry, Zealand University Hospital, Køge, Denmark.
Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark.
Respir Res. 2022 Mar 9;23(1):55. doi: 10.1186/s12931-022-01973-3.
Increased elastase activity in α-antitrypsin deficiency may affect elasticity of the arterial walls, and thereby blood pressure and susceptibility to cardiovascular disease. We hypothesized that severe α-antitrypsin deficiency is associated with reduced blood pressure and susceptibility to cardiovascular disease.
We genotyped 91,353 adults randomly selected from the Danish general population and 187 patients from the Danish α-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.
α-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-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-antitrypsin deficiency had an odds ratio for ischemic heart disease of 0.66 (95% CI:0.53-0.84).
Individuals with severe α-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.
α-1 抗胰蛋白酶缺乏症中弹性蛋白酶活性的增加可能会影响动脉壁的弹性，从而影响血压和心血管疾病的易感性。我们假设严重的α-1 抗胰蛋白酶缺乏症与血压降低和心血管疾病易感性降低有关。
我们对丹麦普通人群中随机抽取的 91353 名成年人和丹麦α-1 抗胰蛋白酶缺乏症登记处的 187 名患者进行了基因分型，并记录了基线血压、基线血浆脂质和随访期间的心血管事件。185 名参与者携带 ZZ 基因型，207 名携带 SZ 基因型，91148 名携带 MM 基因型。
α-1 抗胰蛋白酶缺乏症与收缩压降低 5mmHg 以下和舒张压降低 2mmHg 以下有关，在 ZZ 个体与 SZ 个体与 MM 个体之间（趋势检验，P 值均≤0.01）。与 MM 个体相比，ZZ 个体的血浆甘油三酯和残余胆固醇降低（t 检验，P 值均<0.001）。与心肌梗死风险降低相关（趋势检验 P=0.03），但与缺血性心脏病、缺血性脑血管病或高血压无关（趋势检验，P 值均≥0.59）。然而，当将缺血性心脏病的结果与之前四项研究的结果进行汇总的荟萃分析时，患有与不患有α-1 抗胰蛋白酶缺乏症的个体发生缺血性心脏病的比值比为 0.66（95%CI：0.53-0.84）。
严重的α-1 抗胰蛋白酶缺乏症患者的收缩压和舒张压较低，血浆甘油三酯和残余胆固醇较低，心肌梗死风险降低，缺血性心脏病风险降低 34%。
