• Maria Betânia Ferreira, Tomás Fonseca, Rita Costa, António Marinhoc, Henrique Cyrne Carvalho, José Carlos Oliveira, Faiez Zannad, Patrick Rossignol, Jacques-Eric Gottenberg, Francisca A Saraiva, Patrícia Rodrigues, António S Barros, and João Pedro Ferreira.
• Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal; Hospital da Luz Arrábida, Porto, Portugal.
• Eur. J. Intern. Med. 2021 Mar 1; 85: 41-49.

BackgroundRheumatoid arthritis (RA) patients have high risk of heart failure (HF).AimsIdentifying the risk factors and mechanistic pathways associated with HF in patients with RA.MethodsCohort study enrolling 355 RA patients. HF was defined according to the ESC criteria. 93 circulating protein-biomarkers (91CVDIIOlink®+troponin-T+c-reactive protein) were measured. Regression modeling (multivariate and multivariable) were built and network analyses were performed - based on the identified relevant protein biomarkers.Results115 (32.4%) patients fulfilled the ESC criteria for HF, but only 24 (6.8%) had a prior HF diagnosis. Patients with HF were older (67 vs. 55yr), had a longer RA duration (10 vs. 14yr), had more frequently diabetes, hypertension, obesity, dyslipidemia, atrial fibrillation, and ischemic arterial disease. Several protein-biomarkers remained independently associated with HF, the top (FDR1%) were adrenomedullin, placenta-growth-factor, TNF-receptor-11A, and angiotensin-converting-enzyme-2. The networks underlying the expression of these biomarkers pointed towards congestion, apoptosis, inflammation, immune system signaling and RAAS activation as central determinants of HF in RA. Similar HF-associated biomarker-pathways were externally found in patients without RA. Having RA plus HF increased the risk of cardiovascular events compared to RA patients without RF; adjusted-HR (95%CI)=2.37 (1.07-5.30), p=0.034 CONCLUSION: Age, cardiovascular risk factors, and RA duration increase the HF odds in patients with RA. Few RA patients had a correct prior HF diagnosis, but the presence of HF increased the patients` risk. RA patients with HF largely share the mechanistic pathways of HF patients without RA. Randomized HF trials should include patients with RA. CLINICALTRIALS.Gov IdNCT03960515.Copyright © 2020. Published by Elsevier B.V.

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