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05-04-2024 | Cardiac Amyloidosis | Original Article

Serum alpha 1 antitrypsin potent act as an early diagnostic biomarker for cardiac amyloidosis

Authors: Ye Zhu, Haitao Yuan, Huiting Qu

Published in: Heart and Vessels

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Abstract

Cardiac amyloidosis is a refractory cardiomyopathy with a poor prognosis and lacks effective treatments. N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T are poor prognostic factors for myocardial amyloidosis. However, NT-proBNP and troponin also serve as markers of heart failure and myocardial infarction, lacking specificity. Whether abnormal elevation of alpha-1 antitrypsin in myocardial amyloidosis also predicts the poor prognosis of patients remains unknown. We conducted a retrospective single-center case–control study to analyze the serological and physical examination data of 83 cardiac amyloidosis patients and 68 healthy controls matched by gender and age. We aimed to explore the onset and prognostic factors of cardiac amyloidosis. The serum alpha-1 antitrypsin level (169.78 ± 39.59 mg/dl) in patients with cardiac amyloidosis was significantly higher than that in the normal control (125.92 ± 18.26 mg/dl). Logistic regression results showed that alpha-1 antitrypsin, free sialic acid, high-density lipoprotein cholesterol, apolipoprotein A/B ratio, and homocysteine were predictors of cardiac amyloidosis. Multivariable logistic regression showed that only alpha 1 antitrypsin was an independent risk factor for cardiac amyloidosis. Receiver operating characteristic curve analysis based on the Mayo stage and troponin level showed the cut-off value of 140.55 mg/dl for alpha-1 antitrypsin in predicting cardiac amyloidosis with 81.7% sensitivity and 83.9% specificity. Elevated alpha-1 antitrypsin levels may be an early diagnostic biomarker for cardiac amyloidosis.
Literature
1.
go back to reference Bhogal S, Ladia V, Sitwala P, Cook E, Bajaj K, Ramu V, Lavie CJ, Paul TK (2018) Cardiac amyloidosis: an updated review with emphasis on diagnosis and future directions. Curr Probl Cardiol 43(1):10–34CrossRefPubMed Bhogal S, Ladia V, Sitwala P, Cook E, Bajaj K, Ramu V, Lavie CJ, Paul TK (2018) Cardiac amyloidosis: an updated review with emphasis on diagnosis and future directions. Curr Probl Cardiol 43(1):10–34CrossRefPubMed
2.
go back to reference Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, Plante-Bordeneuve V, Barroso FA, Merlini G, Obici L, Scheinberg M, Brannagan TH 3rd, Litchy WJ, Whelan C, Drachman BM, Adams D, Heitner SB, Conceicao I, Schmidt HH, Vita G, Campistol JM, Gamez J, Gorevic PD, Gane E, Shah AM, Solomon SD, Monia BP, Hughes SG, Kwoh TJ, McEvoy BW, Jung SW, Baker BF, Ackermann EJ, Gertz MA, Coelho T (2018) Inotersen treatment for patients with hereditary transthyretin amyloidosis. N Engl J Med 379(1):22–31CrossRefPubMed Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, Plante-Bordeneuve V, Barroso FA, Merlini G, Obici L, Scheinberg M, Brannagan TH 3rd, Litchy WJ, Whelan C, Drachman BM, Adams D, Heitner SB, Conceicao I, Schmidt HH, Vita G, Campistol JM, Gamez J, Gorevic PD, Gane E, Shah AM, Solomon SD, Monia BP, Hughes SG, Kwoh TJ, McEvoy BW, Jung SW, Baker BF, Ackermann EJ, Gertz MA, Coelho T (2018) Inotersen treatment for patients with hereditary transthyretin amyloidosis. N Engl J Med 379(1):22–31CrossRefPubMed
3.
go back to reference Aimo A, Buda G, Fontana M, Barison A, Vergaro G, Emdin M, Merlini G (2018) Therapies for cardiac light chain amyloidosis: an update. Int J Cardiol 271:152–160CrossRefPubMed Aimo A, Buda G, Fontana M, Barison A, Vergaro G, Emdin M, Merlini G (2018) Therapies for cardiac light chain amyloidosis: an update. Int J Cardiol 271:152–160CrossRefPubMed
4.
go back to reference Manwani R, Hegenbart U, Mahmood S, Sachchithanantham S, Kyriakou C, Yong K, Popat R, Rabin N, Whelan C, Dittrich T, Kimmich C, Hawkins P, Schonland S, Wechalekar A (2018) Deferred autologous stem cell transplantation in systemic AL amyloidosis. Blood Cancer J 8(11):101CrossRefPubMedPubMedCentral Manwani R, Hegenbart U, Mahmood S, Sachchithanantham S, Kyriakou C, Yong K, Popat R, Rabin N, Whelan C, Dittrich T, Kimmich C, Hawkins P, Schonland S, Wechalekar A (2018) Deferred autologous stem cell transplantation in systemic AL amyloidosis. Blood Cancer J 8(11):101CrossRefPubMedPubMedCentral
5.
go back to reference Gertz MA (2020) Immunoglobulin light chain amyloidosis: 2020 update on diagnosis, prognosis, and treatment. Am J Hematol 95(7):848–860CrossRefPubMed Gertz MA (2020) Immunoglobulin light chain amyloidosis: 2020 update on diagnosis, prognosis, and treatment. Am J Hematol 95(7):848–860CrossRefPubMed
6.
go back to reference Sperry BW, Reyes BA, Ikram A, Donnelly JP, Phelan D, Jaber WA, Shapiro D, Evans PJ, Maschke S, Kilpatrick SE, Tan CD, Rodriguez ER, Monteiro C, Tang WHW, Kelly JW, Seitz WH Jr, Hanna M (2018) Tenosynovial and cardiac amyloidosis in patients undergoing carpal tunnel release. J Am Coll Cardiol 72(17):2040–2050CrossRefPubMed Sperry BW, Reyes BA, Ikram A, Donnelly JP, Phelan D, Jaber WA, Shapiro D, Evans PJ, Maschke S, Kilpatrick SE, Tan CD, Rodriguez ER, Monteiro C, Tang WHW, Kelly JW, Seitz WH Jr, Hanna M (2018) Tenosynovial and cardiac amyloidosis in patients undergoing carpal tunnel release. J Am Coll Cardiol 72(17):2040–2050CrossRefPubMed
7.
go back to reference Ikram A, Donnelly JP, Sperry BW, Samaras C, Valent J, Hanna M (2018) Diflunisal tolerability in transthyretin cardiac amyloidosis: a single center’s experience. Amyloid 25(3):197–202CrossRefPubMed Ikram A, Donnelly JP, Sperry BW, Samaras C, Valent J, Hanna M (2018) Diflunisal tolerability in transthyretin cardiac amyloidosis: a single center’s experience. Amyloid 25(3):197–202CrossRefPubMed
8.
go back to reference Hu K, Liu D, Salinger T, Oder D, Knop S, Ertl G, Weidemann F, Frantz S, Stork S, Nordbeck P (2018) Value of cardiac biomarker measurement in the differential diagnosis of infiltrative cardiomyopathy patients with preserved left ventricular systolic function. J Thorac Dis 10(8):4966–4975CrossRefPubMedPubMedCentral Hu K, Liu D, Salinger T, Oder D, Knop S, Ertl G, Weidemann F, Frantz S, Stork S, Nordbeck P (2018) Value of cardiac biomarker measurement in the differential diagnosis of infiltrative cardiomyopathy patients with preserved left ventricular systolic function. J Thorac Dis 10(8):4966–4975CrossRefPubMedPubMedCentral
9.
go back to reference Lo Presti S, Mihos CG, Yucel E, Horvath SA, Santana O (2017) A focused review on the pathophysiology, diagnosis, and management of cardiac amyloidosis. Rev Cardiovasc Med 18(4):123–133CrossRefPubMed Lo Presti S, Mihos CG, Yucel E, Horvath SA, Santana O (2017) A focused review on the pathophysiology, diagnosis, and management of cardiac amyloidosis. Rev Cardiovasc Med 18(4):123–133CrossRefPubMed
10.
go back to reference Migrino RQ, Harmann L, Christenson R, Hari P (2014) Clinical and imaging predictors of 1-year and long-term mortality in light chain (AL) amyloidosis: a 5-year follow-up study. Heart Vessels 29(6):793–800CrossRefPubMed Migrino RQ, Harmann L, Christenson R, Hari P (2014) Clinical and imaging predictors of 1-year and long-term mortality in light chain (AL) amyloidosis: a 5-year follow-up study. Heart Vessels 29(6):793–800CrossRefPubMed
11.
go back to reference Swiger KJ, Friedman EA, Brittain EL, Tomasek KA, Huang S, Su YR, Sawyer DB, Lenihan DJ (2016) Plasma hepatocyte growth factor is a novel marker of AL cardiac amyloidosis. Amyloid 23(4):242–248CrossRefPubMed Swiger KJ, Friedman EA, Brittain EL, Tomasek KA, Huang S, Su YR, Sawyer DB, Lenihan DJ (2016) Plasma hepatocyte growth factor is a novel marker of AL cardiac amyloidosis. Amyloid 23(4):242–248CrossRefPubMed
12.
go back to reference Sattianayagam PT, Lane T, Fox Z, Petrie A, Gibbs SD, Pinney JH, Risom SS, Rowczenio DM, Wechalekar AD, Lachmann HJ, Gilbertson JA, Hawkins PN, Gillmore JD (2013) A prospective study of nutritional status in immunoglobulin light chain amyloidosis. Haematologica 98(1):136–140CrossRefPubMedPubMedCentral Sattianayagam PT, Lane T, Fox Z, Petrie A, Gibbs SD, Pinney JH, Risom SS, Rowczenio DM, Wechalekar AD, Lachmann HJ, Gilbertson JA, Hawkins PN, Gillmore JD (2013) A prospective study of nutritional status in immunoglobulin light chain amyloidosis. Haematologica 98(1):136–140CrossRefPubMedPubMedCentral
13.
go back to reference Ye L, Shi H, Wu HM, Wang FY (2016) Primarily isolated hepatic involvement of amyloidosis: a case report and overview. Medicine (Baltimore) 95(52):e5645CrossRefPubMed Ye L, Shi H, Wu HM, Wang FY (2016) Primarily isolated hepatic involvement of amyloidosis: a case report and overview. Medicine (Baltimore) 95(52):e5645CrossRefPubMed
14.
go back to reference Richter K, Amati AL, Padberg W, Grau V (2022) Negative regulation of ATP-induced inflammasome activation and cytokine secretion by acute phase proteins: a mini review. Front Pharmacol 13:981276CrossRefPubMedPubMedCentral Richter K, Amati AL, Padberg W, Grau V (2022) Negative regulation of ATP-induced inflammasome activation and cytokine secretion by acute phase proteins: a mini review. Front Pharmacol 13:981276CrossRefPubMedPubMedCentral
15.
go back to reference Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C, Laumann K, Zeldenrust SR, Leung N, Dingli D, Greipp PR, Lust JA, Russell SJ, Kyle RA, Rajkumar SV, Gertz MA (2012) Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol 30(9):989–995CrossRefPubMedPubMedCentral Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C, Laumann K, Zeldenrust SR, Leung N, Dingli D, Greipp PR, Lust JA, Russell SJ, Kyle RA, Rajkumar SV, Gertz MA (2012) Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol 30(9):989–995CrossRefPubMedPubMedCentral
16.
go back to reference Palladini G, Milani P, Merlini G (2020) Management of AL amyloidosis in 2020. Blood 136(23):2620–2627CrossRefPubMed Palladini G, Milani P, Merlini G (2020) Management of AL amyloidosis in 2020. Blood 136(23):2620–2627CrossRefPubMed
17.
go back to reference Mota A, Sahebghadam Lotfi A, Jamshidi AR, Najavand S (2014) Alpha 1-antitrypsin activity is markedly decreased in Wegener’s granulomatosis. Rheumatol Int 34(4):553–558CrossRefPubMed Mota A, Sahebghadam Lotfi A, Jamshidi AR, Najavand S (2014) Alpha 1-antitrypsin activity is markedly decreased in Wegener’s granulomatosis. Rheumatol Int 34(4):553–558CrossRefPubMed
18.
go back to reference Turhan Caglar FN, Ksanski V, Polat V, Ungan I, Kural A, Ciftci S, Demir B, Ugurlucan M, Akturk F, Karakaya O (2016) The association between alpha1-antitrypsin and coronary artery ectasia. Angiology 67(10):927–931CrossRefPubMed Turhan Caglar FN, Ksanski V, Polat V, Ungan I, Kural A, Ciftci S, Demir B, Ugurlucan M, Akturk F, Karakaya O (2016) The association between alpha1-antitrypsin and coronary artery ectasia. Angiology 67(10):927–931CrossRefPubMed
20.
go back to reference Edgar RG, Patel M, Bayliss S, Crossley D, Sapey E, Turner AM (2017) Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review. Int J Chron Obstruct Pulmon Dis 12:1295–1308CrossRefPubMedPubMedCentral Edgar RG, Patel M, Bayliss S, Crossley D, Sapey E, Turner AM (2017) Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review. Int J Chron Obstruct Pulmon Dis 12:1295–1308CrossRefPubMedPubMedCentral
21.
go back to reference Curjuric I, Imboden M, Bettschart R, Caviezel S, Dratva J, Pons M, Rothe T, Schmidt-Trucksass 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 270:166–172CrossRefPubMed Curjuric I, Imboden M, Bettschart R, Caviezel S, Dratva J, Pons M, Rothe T, Schmidt-Trucksass 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 270:166–172CrossRefPubMed
22.
go back to reference Lubrano V, Vergaro G, Maltinti M, Ghionzoli N, Emdin M, Papa A (2020) alpha-1 Antitrypsin as a potential biomarker in chronic heart failure. J Cardiovasc Med (Hagerstown) 21(3):209–215CrossRefPubMed Lubrano V, Vergaro G, Maltinti M, Ghionzoli N, Emdin M, Papa A (2020) alpha-1 Antitrypsin as a potential biomarker in chronic heart failure. J Cardiovasc Med (Hagerstown) 21(3):209–215CrossRefPubMed
23.
go back to reference Sharma S, Sarkar S, Choudhury C, Singh L, Singh H, Chakraborti A (2023) Alpha-1-antitrypsin in serum exosomes and pericardial fluid exosomes is associated with severity of rheumatic heart disease. Mol Cell Biochem 478(6):1383–1396CrossRefPubMed Sharma S, Sarkar S, Choudhury C, Singh L, Singh H, Chakraborti A (2023) Alpha-1-antitrypsin in serum exosomes and pericardial fluid exosomes is associated with severity of rheumatic heart disease. Mol Cell Biochem 478(6):1383–1396CrossRefPubMed
24.
go back to reference Jedicke N, Struever N, Aggrawal N, Welte T, Manns MP, Malek NP, Zender L, Janciauskiene S, Wuestefeld T (2014) alpha-1-antitrypsin inhibits acute liver failure in mice. Hepatology 59(6):2299–2308CrossRefPubMed Jedicke N, Struever N, Aggrawal N, Welte T, Manns MP, Malek NP, Zender L, Janciauskiene S, Wuestefeld T (2014) alpha-1-antitrypsin inhibits acute liver failure in mice. Hepatology 59(6):2299–2308CrossRefPubMed
26.
go back to reference Migrino RQ, Hari P, Gutterman DD, Bright M, Truran S, Schlundt B, Phillips SA (2010) Systemic and microvascular oxidative stress induced by light chain amyloidosis. Int J Cardiol 145(1):67–68CrossRefPubMed Migrino RQ, Hari P, Gutterman DD, Bright M, Truran S, Schlundt B, Phillips SA (2010) Systemic and microvascular oxidative stress induced by light chain amyloidosis. Int J Cardiol 145(1):67–68CrossRefPubMed
27.
go back to reference Ando Y, Suhr O, El-Salhy M (1998) Oxidative stress and amyloidosis. Histol Histopathol 13(3):845–850PubMed Ando Y, Suhr O, El-Salhy M (1998) Oxidative stress and amyloidosis. Histol Histopathol 13(3):845–850PubMed
Metadata
Title
Serum alpha 1 antitrypsin potent act as an early diagnostic biomarker for cardiac amyloidosis
Authors
Ye Zhu
Haitao Yuan
Huiting Qu
Publication date
05-04-2024
Publisher
Springer Japan
Published in
Heart and Vessels
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI
https://doi.org/10.1007/s00380-024-02396-4