Background/Purpose N-terminal pro-brain natriuretic peptide (NT-proBNP) is a strong marker of cardiovascular risk with recent evidence that short-term inflammation control reduces its levels in ankylosing spondylitis (AS) patients under TNF blockers. There are no data regarding long-term NT-proBNP assessment in AS patients using TNF blockers. Therefore, we evaluated longitudinally NT-proBNP in AS patients pre- and post-long-term TNF blockage therapy and its possible association with sustained disease activity.

Methods Forty-eight consecutive AS patients (NY criteria) without previous/current cardiovascular disease or systolic myocardial dysfunction in echocardiography, who were eligible to anti-TNF therapy, were prospectively enrolled. All patients received TNF blockers (infliximab, adalimumab or etanercept) and they were evaluated for circulating NT-proBNP levels, clinical and laboratory parameters of disease activity including BASDAI, ASDAS, ESR and CRP, traditional cardiovascular risk factors including blood pressure, body mass index, waist circumference and treatment data at baseline (BL), 12 (12M) and 24 months-after (24M). Statistical analysis included: ANOVA test or Friedman test to observe differences at BL, 12M and 24M evaluations; Mann-Whitney test or t-test to observe differences between patients with inactive/moderate active and high/very high disease activity at 24M; and multivariable linear regression analysis. All analyses used significance level of 0.05.

Results At BL, all patients had active AS. NT-proBNP levels had a median (IQR) of 23.5(8-53.7) pg/ml and 6.2% had high levels without any evidence of cardiac systolic dysfucntion. Multiple linear regression analysis revealed that this peptide, at BL, was independently correlated with ESR (p=0.003) and pulse pressure (p=0.025). Longitudinal evaluation after 12M and 24M showed that all disease parameters improved (p<0.05) and NT-proBNP levels significantly reduced [19(5-38) pg/mL and 14(5-35) pg/mL respectively, p=0.011]. Of note, NT-proBNP levels were higher in patients with persistent high/very high disease activity (ASDAS-CRP>2.1) at 24M (p<0.001) compared to inactive/ moderate active disease patients (ASDAS-CRP<2.1) at same time. Reinforcing this finding, this difference between these groups was present also at BL (p=0.024) and 12M (p=0.03).  Further comparison of BL parameters of patients that persists with ASDAS-CRP>2.1 at 24M identified that these patients are older (44.6±12.7 vs. 35±9.9 years-old, p=0.007), more often female (53.3% vs. 21.2%, p=0.043) and they have higher body mass index (29±5.0 vs. 25.7±4.7 kg/m2, p=0.028), BASDAI (6.6±2.4 vs.5.1±1.9, p=0.02) and ASDAS-ESR (3.9±1.0 vs.3.1±0.9, p=0.006) at BL.  Multivariate analysis did not show any independent factor related to higher ASDAS-CRP at 24M.

Conclusion The novel finding of sustained higher long-term NT-proBNP levels in AS patients with persistent high/very high disease activity during anti-TNF therapy and without systolic alteration suggest that this parameter may reflect longitudinal inflammatory status. (ClinicalTrials.govnumber:NCT01072058).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-evaluation-of-nt-probnp-levels-in-ankylosing-spondylitis-patients-under-tnf-blockers-a-marker-of-persistent-disease-activity/