Activin A in carcinoid heart disease: a possible role in diagnosis and pathogenesis.
OBJECTIVE
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).


CONCLUSIONS
Elevated plasma activin A levels are associated with the presence of CHD.
Bergestuen
Deidi Strickland
DS
Section of Gastroenterology, Department of Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. deidi.bergestuen@rikshospitalet.no
Edvardsen
Thor
T
Aakhus
Svend
S
Ueland
Thor
T
Oie
Erik
E
Vatn
Morten
M
Aukrust
Pål
P
Thiis-Evensen
Espen
E
D028341:Activins / Q000097:blood*; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein; D002275:Carcinoid Heart Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000209:etiology; D016009:Chi-Square Distribution; D053379:Chromogranin A / Q000097:blood; D004452:Echocardiography; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D053244:Osteoprotegerin / Q000097:blood; D012372:ROC Curve
D015415:Biomarkers; D053379:Chromogranin A; D053244:Osteoprotegerin; C422405:activin A; D028341:Activins; D002097:C-Reactive Protein