Serum A-1 Antitrypsin As a Novel Biomarker in Chronic Heart Failure

Overview

Journal ESC Heart Fail

Date 2023 Jul 7

PMID 37417425

Authors

Ying-Ying Zheng

Ting-Ting Wu

Xian-Geng Hou

Hai-Tao Yang

Yi Yang

Wen-Juan Xiu

Ying Pan

Yi-Tong Ma

Ailiman Mahemuti

Xiang Xie

Affiliations

Soon will be listed here.

Abstract

Aims: Chronic heart failure (CHF) remains a major health issue worldwide. In the present study, we aimed to identify novel circulating biomarkers for CHF using serum proteomics technology and to validate the biomarker in three independent cohorts.

Methods And Results: The isobaric tags for relative and absolute quantitation technology was utilized to identify the potential biomarkers of CHF. The validation was conducted in three independent cohort. Cohort A included 223 patients with ischaemic heart disease (IHD) and 321 patients with ischaemic heart failure (IHF) from the CORFCHD-PCI study. Cohort B recruited 817 patients with IHD and 1139 patients with IHF from the PRACTICE study. Cohort C enrolled 559 non-ischaemic heart disease patients with CHF (n = 316) or without CHF (n = 243). We found the expression of a-1 antitrypsin (AAT) was elevated significantly in patients with CHF compared with that in the patients with stable IHD using statistical and bioinformatics analyses. In a validation study, there was a significant difference between patients with stable IHD and patients with IHF in AAT concentration either in cohort A (1.35 ± 0.40 vs. 1.64 ± 0.56, P < 0.001) or in cohort B (1.37 ± 0.42 vs. 1.70 ± 0.48, P < 0.001). The area under the receiver operating characteristic curve was 0.70 [95% confidence interval (CI): 0.66 to 0.74, P < 0.001] in cohort A and 0.74 (95% CI: 0.72 to 0.76, P < 0.001) in cohort B. Furthermore, AAT was negative correlated with left ventricular ejection fraction (r = -0.261, P < 0.001). After adjusting for confounders using a multivariate logistic regression analysis, AAT remained an independent association with CHF in both cohort A (OR = 3.14, 95% CI: 1.667 to 5.90, P < 0.001) and cohort B (OR = 4.10, 95% CI: 2.97 to 5.65, P < 0.001). This association was also validated in cohort C (OR = 1.86, 95% CI: 1.02 to 3.38, P = 0.043).

Conclusions: The present study suggests that serum AAT is a reliable biomarker for CHF in a Chinese population.

Citing Articles

Serum a-1 antitrypsin as a novel biomarker in chronic heart failure.

Zheng Y, Wu T, Hou X, Yang H, Yang Y, Xiu W ESC Heart Fail. 2023; 10(5):2865-2874.

PMID: 37417425 PMC: 10567649. DOI: 10.1002/ehf2.14451.

References

Nelson D, Teckman J, Di Bisceglie A, Brenner D . Diagnosis and management of patients with α1-antitrypsin (A1AT) deficiency. Clin Gastroenterol Hepatol. 2011; 10(6):575-80. PMC: 3360829. DOI: 10.1016/j.cgh.2011.12.028. View

Batra G, Aktaa S, Benson L, Dahlstrom U, Hage C, Savarese G . Association between heart failure quality of care and mortality: a population-based cohort study using nationwide registries. Eur J Heart Fail. 2022; 24(11):2066-2077. PMC: 10099535. DOI: 10.1002/ejhf.2725. View

Zheng Y, Wu T, Hou X, Yang H, Yang Y, Xiu W . Serum a-1 antitrypsin as a novel biomarker in chronic heart failure. ESC Heart Fail. 2023; 10(5):2865-2874. PMC: 10567649. DOI: 10.1002/ehf2.14451. View

Bojic M, Koller L, Cejka D, Niessner A, Bielesz B . Propensity for Calcification in Serum Associates With 2-Year Cardiovascular Mortality in Ischemic Heart Failure With Reduced Ejection Fraction. Front Med (Lausanne). 2021; 8:672348. PMC: 8249741. DOI: 10.3389/fmed.2021.672348. View

Tyers M, Mann M . From genomics to proteomics. Nature. 2003; 422(6928):193-7. DOI: 10.1038/nature01510. View

Mastorci F, Sabatino L, Vassalle C, Pingitore A . Cardioprotection and Thyroid Hormones in the Clinical Setting of Heart Failure. Front Endocrinol (Lausanne). 2020; 10:927. PMC: 6997485. DOI: 10.3389/fendo.2019.00927. View

Booth R, Hill S, Don-Wauchope A, Santaguida P, Oremus M, McKelvie R . Performance of BNP and NT-proBNP for diagnosis of heart failure in primary care patients: a systematic review. Heart Fail Rev. 2014; 19(4):439-51. DOI: 10.1007/s10741-014-9445-8. View

Savarese G, Becher P, Lund L, Seferovic P, Rosano G, Coats A . Global burden of heart failure: a comprehensive and updated review of epidemiology. Cardiovasc Res. 2022; 118(17):3272-3287. DOI: 10.1093/cvr/cvac013. View

Xiu W, Yang H, Zheng Y, Wu T, Hou X, Jiang Z . ALB-dNLR Score Predicts Mortality in Coronary Artery Disease Patients After Percutaneous Coronary Intervention. Front Cardiovasc Med. 2022; 9:709868. PMC: 8965023. DOI: 10.3389/fcvm.2022.709868. View

10.

Packer M, Chowdhary V, Lung G, Cheng L, Aratyn-Schaus Y, Leboeuf D . Evaluation of cytosine base editing and adenine base editing as a potential treatment for alpha-1 antitrypsin deficiency. Mol Ther. 2022; 30(4):1396-1406. PMC: 9077367. DOI: 10.1016/j.ymthe.2022.01.040. View

11.

Zheng Y, Wu T, Guo Q, Chen Y, Ma X, Ma Y . Long-term dual antiplatelet-induced intestinal injury resulting in translocation of intestinal bacteria into blood circulation increased the incidence of adverse events after PCI in patients with coronary artery disease. Atherosclerosis. 2021; 328:1-10. DOI: 10.1016/j.atherosclerosis.2021.04.012. View

12.

Santaguida P, Don-Wauchope A, Oremus M, McKelvie R, Ali U, Hill S . BNP and NT-proBNP as prognostic markers in persons with acute decompensated heart failure: a systematic review. Heart Fail Rev. 2014; 19(4):453-70. DOI: 10.1007/s10741-014-9442-y. View

13.

Lubrano V, Balzan S . Role of oxidative stress-related biomarkers in heart failure: galectin 3, α1-antitrypsin and LOX-1: new therapeutic perspective?. Mol Cell Biochem. 2019; 464(1-2):143-152. DOI: 10.1007/s11010-019-03656-y. View

14.

Dixit N, Ziaeian B, Fonarow G . SGLT2 Inhibitors in Heart Failure: Early Initiation to Achieve Rapid Clinical Benefits. Heart Fail Clin. 2022; 18(4):587-596. DOI: 10.1016/j.hfc.2022.03.003. View

15.

Maggioni A, Clark A, Barrios V, Damy T, Drozdz J, Fonseca C . Outcomes with sacubitril/valsartan in outpatients with heart failure and reduced ejection fraction: The ARIADNE registry. ESC Heart Fail. 2022; 9(6):4209-4218. PMC: 9773755. DOI: 10.1002/ehf2.14014. View

16.

Puetz A, Artati A, Adamski J, Schuett K, Romeo F, Stoehr R . Non-targeted metabolomics identify polyamine metabolite acisoga as novel biomarker for reduced left ventricular function. ESC Heart Fail. 2021; 9(1):564-573. PMC: 8788009. DOI: 10.1002/ehf2.13713. View

17.

Lee K, Doudesis D, Anwar M, Astengo F, Chenevier-Gobeaux C, Claessens Y . Development and validation of a decision support tool for the diagnosis of acute heart failure: systematic review, meta-analysis, and modelling study. BMJ. 2022; 377:e068424. PMC: 9189738. DOI: 10.1136/bmj-2021-068424. View

18.

Zhang C, Jiang L, Xu L, Tian J, Liu J, Zhao X . Implications of N-terminal pro-B-type natriuretic peptide in patients with three-vessel disease. Eur Heart J. 2019; 40(41):3397-3405. DOI: 10.1093/eurheartj/ehz394. View

19.

Wu T, Zheng Y, Hou X, Yang Y, Ma X, Ma Y . Red blood cell distribution width as long-term prognostic markers in patients with coronary artery disease undergoing percutaneous coronary intervention. Lipids Health Dis. 2019; 18(1):140. PMC: 6560761. DOI: 10.1186/s12944-019-1082-8. View

20.

Moore L, Fan D, Basu R, Kandalam V, Kassiri Z . Tissue inhibitor of metalloproteinases (TIMPs) in heart failure. Heart Fail Rev. 2011; 17(4-5):693-706. DOI: 10.1007/s10741-011-9266-y. View