Serum endothelin-1 and NT-proBNP, but not ADMA, endoglin and TIMP-1 levels, reflect impaired right ventricular function in patients with systemic sclerosis.
BACKGROUND
Heart and pulmonary involvement is a leading cause of systemic sclerosis (SSc)-related deaths.


OBJECTIVE
The aim of our study was to assess if biochemical markers of right ventricular (RV) overload, endothelial function and collagen metabolism can predict RV dysfunction assessed by Doppler echocardiography in SSc patients.


METHODS
We prospectively studied 111 consecutive patients (101 F, 10 M, age 54.2 ± 13.8 years) with diagnosed SSc (mean disease duration 9.4 ± 11.4 years) and a group of 21 age-matched subjects (18 F, 3 M, age 49.3 + 10.5 years). We performed transthoracic echocardiography (Phillips iE 33) and measured serum endothelin-1 (ET-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), asymmetric dimethylarginine (ADMA), endoglin and human tissue inhibitor of matrix metalloproteinase (TIMP-1) concentration.


RESULTS
Median serum NT-proBNP level in SSc patients was 133.5 (range 21.86-17,670 pg/ml) and was significantly higher than in controls (p = 0.0002). Moreover, the median serum ET-1 level of 1.49 (range 0.26-8.75 pg/ml) was higher in SSc patients (p = 0.002). However, no significant differences in ADMA, TIMP-1 and endoglin serum concentration between SSc patients and controls were observed. Serum NT-proBNP concentration correlated positively with echocardiographic signs of RV overload: tricuspid regurgitation pressure gradient (r = 0.38, p = 0.0004) and RV Tei index (r = 0.25, p = 0.01). ET-1 serum level correlated negatively with tricuspid annular plane systolic excursion (r = -0.4, p = 0.01) and positively with inferior vena cava diameter measured at expiration (r = 0.38, p = 0.0002). The echocardiographic signs of RV overload were significantly more pronounced in the highest NT-proBNP tertile (>195 pg/ml) group than in the lowest one (<88 pg/ml).


CONCLUSIONS
Serum ET-1 and NT-proBNP, but not endoglin, ADMA and TIMP-1 levels correlating with the echocardiographic parameters of RV overload, can be considered as noninvasive indicators of RV dysfunction in SSc patients.
Department of Internal Medicine and Cardiology, Medical University of Warsaw, Warsaw, Poland, michal.ciurzynski@wum.edu.pl.
Michał
M
Ciurzyński
Piotr
P
Bienias
Katarzyna
K
Irzyk
Maciej
M
Kostrubiec
Zbigniew
Z
Bartoszewicz
Maria
M
Siwicka
Anna
A
Stelmaszczyk-Emmel
Elżbieta
E
Górska
Urszula
U
Demkow
Piotr
P
Pruszczyk
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood*; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003094:Collagen / Q000737:chemistry; D004452:Echocardiography; D015150:Echocardiography, Doppler; D000071063:Endoglin; D019332:Endothelin-1 / Q000097:blood*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D008171:Lung Diseases / Q000150:complications / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000097:blood*; D012595:Scleroderma, Systemic / Q000097:blood* / Q000503:physiopathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D016278:Ventricular Function, Right
D015703:Antigens, CD; D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; D019332:Endothelin-1; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; C018524:N,N-dimethylarginine; D003094:Collagen; D001120:Arginine