Cardiovascular Risk Associated with Alpha-1 Antitrypsin Deficiency (AATD) Genotypes: A Meta-Analysis with Meta-Regressions

Author:

Ambrosino Pasquale1ORCID,Marcuccio Giuseppina2,Lombardi Carmen2,D’Anna Silvestro Ennio2,Sanduzzi Zamparelli Stefano3ORCID,Mancusi Costantino4ORCID,Spedicato Giorgio Alfredo5ORCID,Motta Andrea6ORCID,Maniscalco Mauro23ORCID

Affiliation:

1. Istituti Clinici Scientifici Maugeri IRCCS, Directorate of Telese Terme Institute, 82037 Telese Terme, Italy

2. Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of Telese Terme Institute, 82037 Telese Terme, Italy

3. Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy

4. Department of Advanced Biomedical Science, Federico II University, 80131 Naples, Italy

5. Department of Statistics and Quantitative Methods, Milano-Bicocca University, 20126 Milan, Italy

6. Institute of Biomolecular Chemistry, National Research Council, 80078 Pozzuoli, Italy

Abstract

Background. 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. Methods. 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. Results. 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; p = 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; p = 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; p < 0.001), hypertension (Z-score: 2.31; p = 0.021), and diabetes (Z-score: 4.25; p < 0.001) were associated with a lower effect size. Conclusions. 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.

Funder

“Ricerca Corrente” funding scheme of the Italian Ministry of Health

Publisher

MDPI AG

Subject

General Medicine

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