PMID- 37892629
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231030
IS  - 2077-0383 (Print)
IS  - 2077-0383 (Electronic)
IS  - 2077-0383 (Linking)
VI  - 12
IP  - 20
DP  - 2023 Oct 12
TI  - Cardiovascular Risk Associated with Alpha-1 Antitrypsin Deficiency (AATD) 
      Genotypes: A Meta-Analysis with Meta-Regressions.
LID - 10.3390/jcm12206490 [doi]
LID - 6490
AB  - 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.
FAU - Ambrosino, Pasquale
AU  - Ambrosino P
AUID- ORCID: 0000-0002-9398-0428
AD  - Istituti Clinici Scientifici Maugeri IRCCS, Directorate of Telese Terme 
      Institute, 82037 Telese Terme, Italy.
FAU - Marcuccio, Giuseppina
AU  - Marcuccio G
AD  - Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of 
      Telese Terme Institute, 82037 Telese Terme, Italy.
FAU - Lombardi, Carmen
AU  - Lombardi C
AD  - Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of 
      Telese Terme Institute, 82037 Telese Terme, Italy.
FAU - D'Anna, Silvestro Ennio
AU  - D'Anna SE
AD  - Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of 
      Telese Terme Institute, 82037 Telese Terme, Italy.
FAU - Sanduzzi Zamparelli, Stefano
AU  - Sanduzzi Zamparelli S
AUID- ORCID: 0000-0003-3336-7290
AD  - Department of Clinical Medicine and Surgery, Federico II University, 80131 
      Naples, Italy.
FAU - Mancusi, Costantino
AU  - Mancusi C
AUID- ORCID: 0000-0001-6690-1408
AD  - Department of Advanced Biomedical Science, Federico II University, 80131 Naples, 
      Italy.
FAU - Spedicato, Giorgio Alfredo
AU  - Spedicato GA
AUID- ORCID: 0000-0002-0315-8888
AD  - Department of Statistics and Quantitative Methods, Milano-Bicocca University, 
      20126 Milan, Italy.
FAU - Motta, Andrea
AU  - Motta A
AUID- ORCID: 0000-0002-8643-658X
AD  - Institute of Biomolecular Chemistry, National Research Council, 80078 Pozzuoli, 
      Italy.
FAU - Maniscalco, Mauro
AU  - Maniscalco M
AUID- ORCID: 0000-0001-6751-9921
AD  - Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of 
      Telese Terme Institute, 82037 Telese Terme, Italy.
AD  - Department of Clinical Medicine and Surgery, Federico II University, 80131 
      Naples, Italy.
LA  - eng
PT  - Journal Article
DEP - 20231012
PL  - Switzerland
TA  - J Clin Med
JT  - Journal of clinical medicine
JID - 101606588
PMC - PMC10607733
OTO - NOTNLM
OT  - alpha-1 antitrypsin deficiency
OT  - cardiovascular disease
OT  - chronic disease
OT  - chronic obstructive pulmonary disease
OT  - disability
OT  - exercise
OT  - ischemic heart disease
OT  - outcome
OT  - rehabilitation
COIS- The authors declare no conflict of interest.
EDAT- 2023/10/28 11:44
MHDA- 2023/10/28 11:45
PMCR- 2023/10/12
CRDT- 2023/10/28 01:05
PHST- 2023/08/31 00:00 [received]
PHST- 2023/10/05 00:00 [revised]
PHST- 2023/10/09 00:00 [accepted]
PHST- 2023/10/28 11:45 [medline]
PHST- 2023/10/28 11:44 [pubmed]
PHST- 2023/10/28 01:05 [entrez]
PHST- 2023/10/12 00:00 [pmc-release]
AID - jcm12206490 [pii]
AID - jcm-12-06490 [pii]
AID - 10.3390/jcm12206490 [doi]
PST - epublish
SO  - J Clin Med. 2023 Oct 12;12(20):6490. doi: 10.3390/jcm12206490.