Ambrosino Pasquale, Marcuccio Giuseppina, Lombardi Carmen, D'Anna Silvestro Ennio, Sanduzzi Zamparelli Stefano, Mancusi Costantino, Spedicato Giorgio Alfredo, Motta Andrea, Maniscalco Mauro
Istituti Clinici Scientifici Maugeri IRCCS, Directorate of Telese Terme Institute, 82037 Telese Terme, Italy.
Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of Telese Terme Institute, 82037 Telese Terme, Italy.
J Clin Med. 2023 Oct 12;12(20):6490. doi: 10.3390/jcm12206490.
Alpha-1 antitrypsin deficiency (AATD) can result in severe liver and respiratory disorders. The uninhibited elastase activity on the elastic tissue of arterial walls suggests that AATD may also impact vascular health. Thus, we performed a meta-analysis of the studies evaluating cardiovascular risk in individuals with AATD and non-AATD controls.
A systematic literature search was conducted in the main scientific databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Differences between cases and controls were expressed as odds ratios (OR) with 95% confidence intervals (95%CI). The protocol was registered on PROSPERO under the identification number CRD42023429756.
The analysis of eight studies showed that, with a prevented fraction of disease of 15.0% and a corresponding OR of 0.779 (95%CI: 0.665-0.912; = 0.002), a total of 24,428 individuals with AATD exhibited a significantly lower risk of ischemic heart disease compared to 534,654 non-AATD controls. Accordingly, given a prevented fraction of disease of 19.5%, a lower risk of acute myocardial infarction was documented when analyzing four studies on 21,741 cases and 513,733 controls (OR: 0.774; 95%CI: 0.599-0.999; = 0.049). Sensitivity and subgroup analyses substantially confirmed results. Meta-regression models suggested that these findings were not influenced by AATD genotypes or prevalence of chronic obstructive pulmonary disease (COPD) among cases and controls, while higher differences in the prevalence of male sex (Z-score: 3.40; < 0.001), hypertension (Z-score: 2.31; = 0.021), and diabetes (Z-score: 4.25; < 0.001) were associated with a lower effect size.
Individuals with AATD may exhibit a reduced risk of ischemic heart disease, even in the presence of mild deficiency of the serine protease inhibitor. Although caution is warranted due to the observational nature of the data, future pharmacological and rehabilitation strategies should also take this controversial relationship into account.
α-1抗胰蛋白酶缺乏症（AATD）可导致严重的肝脏和呼吸系统疾病。动脉壁弹性组织上不受抑制的弹性蛋白酶活性表明，AATD可能也会影响血管健康。因此，我们对评估AATD个体和非AATD对照者心血管风险的研究进行了荟萃分析。
根据系统评价和荟萃分析的首选报告项目（PRISMA）指南，在主要科学数据库中进行了系统的文献检索。病例与对照之间的差异以比值比（OR）及其95%置信区间（95%CI）表示。该方案已在PROSPERO上注册，识别号为CRD42023429756。
对八项研究的分析表明，在疾病预防率为15.0%且相应OR为0.779（95%CI：0.665 - 0.912；P = 0.002）的情况下，与534,654名非AATD对照者相比，总共24,428名AATD个体患缺血性心脏病的风险显著更低。相应地，在分析针对21,741例病例和513,733名对照者的四项研究时，鉴于疾病预防率为19.5%，记录到急性心肌梗死风险较低（OR：0.774；95%CI：0.599 - 0.999；P = 0.049）。敏感性分析和亚组分析基本证实了结果。荟萃回归模型表明，这些发现不受病例和对照者中AATD基因型或慢性阻塞性肺疾病（COPD）患病率的影响，而男性患病率（Z值：3.40；P < 0.001）、高血压患病率（Z值：2.31；P = 0.021）和糖尿病患病率（Z值：4.25；P < 0.001）的较大差异与较小的效应量相关。
即使存在丝氨酸蛋白酶抑制剂轻度缺乏的情况，AATD个体患缺血性心脏病的风险可能也会降低。尽管由于数据的观察性质需要谨慎，但未来的药物和康复策略也应考虑到这种有争议的关系。
