Tumour necrosis factor {alpha} blockade reduces circulating N-terminal pro-brain natriuretic peptide levels in patients with active rheumatoid arthritis: results from a prospective cohort study.
BACKGROUND
Patients with rheumatoid arthritis (RA) are at increased risk of heart failure and vascular events. Small increases in circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with an increased risk of a cardiovascular event, and high levels signal left ventricular dysfunction. Data on the effects of tumour necrosis factor alpha(TNFalpha) blocking agents on circulating NT-proBNP levels in patients with active RA are lacking but may be informative.


METHODS
171 consecutive patients with RA (28-joint disease activity score >3.2) without congestive heart failure (NYHA class III or IV) were scheduled to receive adalimumab once every 2 weeks. Serum NT-proBNP concentrations were measured simultaneously on stored baseline and 16-week samples. Paired sample t tests were used to observe differences in biomarkers before and after adalimumab administration. Correlations between the biomarkers and changes in circulating log NT-proBNP levels were evaluated with the Pearson test and multivariable linear regression analyses of correlates were performed (forward selection procedure).


RESULTS
Circulating levels of NT-proBNP decreased significantly after 16 weeks of adalimumab administration (median NT-proBNP 83.0 pg/ml vs 69.5 pg/ml, p=0.004). Changes in NT-proBNP levels were associated with changes in pulse pressure (r=0.18, p=0.02), systolic blood pressure (r=0.16, p=0.04) and erythrocyte sedimentation rate (r=0.18, p=0.02). On multivariable analysis, changes in pulse pressure and erythrocyte sedimentation rate remained independently associated with changes in circulating NT-proBNP levels.


CONCLUSIONS
These observations show that blocking TNFalpha in patients with RA without evident heart failure decreases NT-proBNP levels by about 18%. This suggests no treatment-induced deterioration in cardiac function and a potential cardiovascular risk benefit.
Peters
Mike J L
MJ
Correspondence to Dr Mike Peters, VU University Medical Centre, P O Box 7057, 1007 MB Amsterdam, The Netherlands. mjl.peters@vumc.nl
Welsh
Paul
P
McInnes
Iain B
IB
Wolbink
Gertjan
G
Dijkmans
Ben A C
BA
Sattar
Naveed
N
Nurmohamed
Michael T
MT
D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001799:Blood Sedimentation; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000097:blood
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000068879:Adalimumab