Alpha-1 antitrypsin deficiency: From the lung to the heart?

Ivan Curjuric, Medea Imboden, Robert Bettschart, Seraina Caviezel, Julia Dratva, Marco Pons, Thomas Rothe, Arno Schmidt-Trucksäss, Daiana Stolz, Gian Andri Thun, Arnold von Eckardstein, Florian Kronenberg, Ilaria Ferrarotti, Nicole M. Probst-Hensch

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background and aims: Alpha-1 antitrypsin (A1AT) is the most abundant serine protease inhibitor in human blood and exerts important anti-inflammatory and immune-modulatory effects. In combination with smoking or other long-term noxious exposures such as occupational dust and fumes, genetic A1AT deficiency can cause chronic obstructive pulmonary disease, a condition with elevated cardiovascular risk. The effects of A1AT deficiency on cardiovascular risk have hardly been studied today. Methods: Using data from 2614 adults from the population-based SAPALDIA cohort, we tested associations of serum A1AT and SERPINA1 mutations with carotid intima-media thickness (CIMT, measured by B-mode ultrasonography) or self-reported arterial hypertension or cardiovascular disease in multiple regression models using a Mendelian Randomization like analysis design. Mutations Pi-S and Pi-Z were coded as ordinal genotype score (MM, MS, MZ/SS, SZ and ZZ), according to their progressive biological impact. Results: Serum A1AT concentration presented a u-shaped association with CIMT. At the lower end of the A1AT distribution, an analogous, linear association between SERPINA1 score and higher CIMT was observed, resulting in an estimated 1.2% (95%-confidence interval -0.1-2.5) increase in CIMT per unit (p = 0.060). Genotype score was significantly associated with arterial hypertension with an odds ratio (OR) of 1.2 (1.0–1.5) per unit (p = 0.028). The association with cardiovascular disease was not significant (OR 1.3 (0.9–1.9)). Conclusions: Our results support a possible causal relationship between genetic A1AT deficiency and increased cardiovascular risk, which needs to be better taken into account for the management of affected patients and first-degree relatives.

Original languageEnglish
Pages (from-to)166-172
Number of pages7
JournalAtherosclerosis
Volume270
DOIs
Publication statusPublished - Mar 1 2018

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alpha 1-Antitrypsin Deficiency
alpha 1-Antitrypsin
Lung
Mendelian Randomization Analysis
Cardiovascular Diseases
Odds Ratio
Genotype
Hypertension
Carotid Intima-Media Thickness
Mutation
Serine Proteinase Inhibitors
Dust
Serum
Chronic Obstructive Pulmonary Disease
Ultrasonography
Anti-Inflammatory Agents
Smoking
Confidence Intervals
Autosomal Recessive alpha-1-Antitrypsin Deficiency
Population

Keywords

  • Alpha-1 antitrypsin deficiency
  • Cardiovascular diseases
  • Cohort study
  • Mendelian randomization analysis
  • MESH): carotid intima-media thickness

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Curjuric, I., Imboden, M., Bettschart, R., Caviezel, S., Dratva, J., Pons, M., ... Probst-Hensch, N. M. (2018). Alpha-1 antitrypsin deficiency: From the lung to the heart? Atherosclerosis, 270, 166-172. https://doi.org/10.1016/j.atherosclerosis.2018.01.042

Alpha-1 antitrypsin deficiency : From the lung to the heart? / Curjuric, Ivan; Imboden, Medea; Bettschart, Robert; Caviezel, Seraina; Dratva, Julia; Pons, Marco; Rothe, Thomas; Schmidt-Trucksäss, Arno; Stolz, Daiana; Thun, Gian Andri; von Eckardstein, Arnold; Kronenberg, Florian; Ferrarotti, Ilaria; Probst-Hensch, Nicole M.

In: Atherosclerosis, Vol. 270, 01.03.2018, p. 166-172.

Research output: Contribution to journalArticle

Curjuric, I, Imboden, M, Bettschart, R, Caviezel, S, Dratva, J, Pons, M, Rothe, T, Schmidt-Trucksäss, A, Stolz, D, Thun, GA, von Eckardstein, A, Kronenberg, F, Ferrarotti, I & Probst-Hensch, NM 2018, 'Alpha-1 antitrypsin deficiency: From the lung to the heart?', Atherosclerosis, vol. 270, pp. 166-172. https://doi.org/10.1016/j.atherosclerosis.2018.01.042
Curjuric I, Imboden M, Bettschart R, Caviezel S, Dratva J, Pons M et al. Alpha-1 antitrypsin deficiency: From the lung to the heart? Atherosclerosis. 2018 Mar 1;270:166-172. https://doi.org/10.1016/j.atherosclerosis.2018.01.042
Curjuric, Ivan ; Imboden, Medea ; Bettschart, Robert ; Caviezel, Seraina ; Dratva, Julia ; Pons, Marco ; Rothe, Thomas ; Schmidt-Trucksäss, Arno ; Stolz, Daiana ; Thun, Gian Andri ; von Eckardstein, Arnold ; Kronenberg, Florian ; Ferrarotti, Ilaria ; Probst-Hensch, Nicole M. / Alpha-1 antitrypsin deficiency : From the lung to the heart?. In: Atherosclerosis. 2018 ; Vol. 270. pp. 166-172.
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abstract = "Background and aims: Alpha-1 antitrypsin (A1AT) is the most abundant serine protease inhibitor in human blood and exerts important anti-inflammatory and immune-modulatory effects. In combination with smoking or other long-term noxious exposures such as occupational dust and fumes, genetic A1AT deficiency can cause chronic obstructive pulmonary disease, a condition with elevated cardiovascular risk. The effects of A1AT deficiency on cardiovascular risk have hardly been studied today. Methods: Using data from 2614 adults from the population-based SAPALDIA cohort, we tested associations of serum A1AT and SERPINA1 mutations with carotid intima-media thickness (CIMT, measured by B-mode ultrasonography) or self-reported arterial hypertension or cardiovascular disease in multiple regression models using a Mendelian Randomization like analysis design. Mutations Pi-S and Pi-Z were coded as ordinal genotype score (MM, MS, MZ/SS, SZ and ZZ), according to their progressive biological impact. Results: Serum A1AT concentration presented a u-shaped association with CIMT. At the lower end of the A1AT distribution, an analogous, linear association between SERPINA1 score and higher CIMT was observed, resulting in an estimated 1.2{\%} (95{\%}-confidence interval -0.1-2.5) increase in CIMT per unit (p = 0.060). Genotype score was significantly associated with arterial hypertension with an odds ratio (OR) of 1.2 (1.0–1.5) per unit (p = 0.028). The association with cardiovascular disease was not significant (OR 1.3 (0.9–1.9)). Conclusions: Our results support a possible causal relationship between genetic A1AT deficiency and increased cardiovascular risk, which needs to be better taken into account for the management of affected patients and first-degree relatives.",
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AU - Dratva, Julia

AU - Pons, Marco

AU - Rothe, Thomas

AU - Schmidt-Trucksäss, Arno

AU - Stolz, Daiana

AU - Thun, Gian Andri

AU - von Eckardstein, Arnold

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AU - Probst-Hensch, Nicole M.

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