Activin A in Carcinoid Heart Disease: A Possible Role in Diagnosis and Pathogenesis

被引:33
作者
Bergestuen, Deidi Strickland [1 ]
Edvardsen, Thor [2 ,5 ]
Aakhus, Svend [2 ]
Ueland, Thor [4 ]
Oie, Erik [2 ,4 ]
Vatn, Morten [1 ,5 ]
Aukrust, Pal [3 ,4 ,5 ]
Thiis-Evensen, Espen [1 ]
机构
[1] Natl Hosp Norway, Oslo Univ Hosp, Dept Med, Gastroenterol Sect, NO-0027 Oslo, Norway
[2] Natl Hosp Norway, Oslo Univ Hosp, Dept Cardiol, NO-0027 Oslo, Norway
[3] Natl Hosp Norway, Oslo Univ Hosp, Sect Immunol & Infect Dis, Dept Med, NO-0027 Oslo, Norway
[4] Natl Hosp Norway, Oslo Univ Hosp, Internal Med Res Inst, NO-0027 Oslo, Norway
[5] Univ Oslo, Fac Med, Oslo, Norway
关键词
Carcinoid heart disease; Fibrosis; Neuroendocrine tumors; Activin A; Growth factors/cytokines; ATRIAL-NATRIURETIC-PEPTIDE; NORMAL ENDOCRINE-CELLS; VALVE DISEASE; TGF-BETA; SERUM; TUMORS; OSTEOPROTEGERIN; LOCALIZATION; PROGRESSION; FOLLISTATIN;
D O I
10.1159/000318014
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background/Aims: Carcinoid heart disease (CHD), a complication of neuroendocrine tumors (NETs), is characterized by right heart fibrotic lesions. Though serotonin is likely involved, the pathogenesis of CHD remains unclear. Cytokines and growth factors with fibrogenic properties may play a role. We sought to examine the relationship between plasma levels of fibrogenic cytokines and growth factors and CHD, both to provide further insight into possible biomarkers of CHD as well as into the possible pathogenesis of CHD. Methods: Plasma samples obtained from 71 patients with NETs and 18 controls were analyzed using enzyme immunoassays. All patients underwent echocardiography. Results: 15 patients (21%) had CHD, all of whom had carcinoid syndrome compared to 82% of those without CHD. CHD patients were older (p = 0.01), had larger (p = 0.007) and more numerous liver metastases (p = 0.04), and had elevated 24-hour urinary 5-hydroxyindoleacetic acid (U-5HIAA) (p = 0.03) and serum chromogranin A levels (p = 0.02). CHD patients had higher plasma levels of C-reactive protein (p = 0.03), osteoprotegerin (p = 0.005), and activin A (p = 0.005) than patients without CHD. A significant direct correlation between activin A and U-5HIAA levels was observed in the total patient group (r = 0.30, p = 0.02). Activin A >= 0.34 ng/ml (odds ratio (OR) 5.35 [1.01; 28.17], p = 0.048) and age >= 69.5 (OR 6.10 [1.60; 23.24], p = 0.008) were independent predictors of CHD. Activin A levels were elevated to the same degree in both early and advanced CHD. Activin A >= 0.34 ng/ml had 87% sensitivity and 57% specificity for detecting CHD (p = 0.006). Conclusion: Elevated plasma activin A levels are associated with the presence of CHD. Copyright (C) 2010 S. Karger AG, Basel
引用
收藏
页码:168 / 177
页数:10
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