• Number of dead participants [ Time Frame: 11 to 32 months ]
  Death of any cause
• Number of Participants with New diagnosis of heart failure [ Time Frame: 11 to 32 months ]
  New onset of heart failure symptons with diuretic drugs starting

• Mortality events [ Time Frame: 11 to 32 months ]
  Death of any cause
• New diagnosis of heart failure [ Time Frame: 11 to 32 months ]
  New onset of heart failure symptons with diuretic drugs starting

• Number of Participants with worsening of previous heart failure [ Time Frame: 11 to 32 months ]
  Worsening of heart failure with increase of diuretic or diuretic IV
• Number of Participants with new onset atrial fibrillation [ Time Frame: 11 to 32 months ]
  New onset of Atrial Fibrillation
• Number of Participants with Hospitalization [ Time Frame: 11 to 32 months ]
  Any hospitalization for urgent or unplanned reasons
• Number of Participants with new onset of stroke or Transient ischemic attack [ Time Frame: 11 to 32 months ]
  New onset of stroke or transient ischemic attack
• Number of Participants with New onset of acute myocardial infarction [ Time Frame: 11-32 months ]
  New onset of acute myocardial infarction?

• Worsening of previous heart failure [ Time Frame: 11 to 32 months ]
  Worsening of heart failure with increase of diuretic or diuretic IV
• new onset atrial fibrillation [ Time Frame: 11 to 32 months ]
  New onset of Atrial Fibrillation
• Hospitalization [ Time Frame: 11 to 32 months ]
  Any hospitalization for urgent or unplanned reasons
• New onset of stroke or Transient ischemic attack [ Time Frame: 11 to 32 months ]
  New onset of stroke or transient ischemic attack
• New onset of acute myocardial infarction [ Time Frame: 11-32 months ]
  New onset of acute myocardial infarction?

Cardiovascular disease is the leading cause of death in RA patients. This increased risk may be apparent even before the clinical recognition of RA. The optimal approach for identification of patients with increased CV risk has yet to be fully established and a substantial proportion of RA patients at high risk remain unidentified.

Heart failure (HF) has been recently recognized as an important contributory factor to the excess CV mortality associated with RA (more than myocardial ischemia), and RA patients with concomitant HF have twice the risk of CV death compared with patients with RA alone. HF in RA typically presents with occult or atypical clinical symptomatology, tend to be managed less aggressively and have poorer outcomes.

For developing effective preventive strategies, the evaluation of patients in early asymptomatic stages is of great importance.

The investigators propose to perform an observational longitudinal study (with cases and controls) including RA patients (with and without HF) from a single centre to determine cardiovascular profiles that may be associated with higher risk for developing symptomatic HF and CV events. For this purpose the investigators will use clinical, echocardiographic, serum biomarker, and genetic data

Patient Selection:

Screen ~400 Rheumatoid Arthritis (RA) patients followed in Centro Hospitalar do Porto outpatient clinic. All RA patients with regular follow-up will be potentially included.

The investigators also aim to enrol age-matched controls for biomarker comparison.

Experimental Design:

Observacional study with matched control. No intervention will be performed. Outpatients fulfilling the inclusion criteria will be invited to participate in the study. All patients will have to sign written informed consent to participate in the study.

An external and independent data verification will be performed. The total trial enrolment period was 23 months. . Participants will continue to receive treatments as clinically indicated and according to the decision of their attending physicians.

A structured evaluation will be performed. Every 4 to 6 months the participants will be observed in the clinic for their physicians according clinic protocol. The participants will not require additional visits to the hospital other than the visits already prespecified by their attending physicians.

Clinical Evaluation:The clinical evaluation will be performed to all RA patients and for age-matched controls Each participant and group control will be evaluated for their cardiovascular symptoms, history and risk factors for cardiovascular disease, other comorbiditys as renal disease, dementia, liver or respiratory disease or anemia. The participants will be evaluated for their Rheumathoid Arthritis history (diagnosis date, rx erosion, other autoimune diseases or treatment). All will perform a 6-minute walk test (6MWT), point blood pressure, heart rate, chest exam, ankle-brachial index, measurement of abdominal circumference and visceral fat, disease activity score 28 (DAS-28), quality of life scores (QoL), Graffar scale (socio-economic), Mini-cog and Epworth scale.

Cardiac Function: Each participant will undergo a 12 lead ECG and a transthoracic echocardiography. M-mode, 2D and Doppler measurements will be acquired according to standard recommendations. LV mass and LV mass index, left atrial (LA) volume, LA volume index, isovolumetric relaxation time (IVRT), mitral inflow E to A ratio (mitral E/A), mitral deceleration time of early filling (mitral DT), PW Doppler early diastolic velocity of the septal (septal e') and lateral (lateral e') mitral annulus, mitral inflow E velocity to early diastolic tissue Doppler of both the septal (septal E/e') and lateral (lateral E/e') mitral annulus and the pulmonary artery systolic pressure (PASP) will be measured using standard techniques19. All measurements reflect an average of at least 4 consecutive cardiac cycles and will be performed by an experienced echocardiographer.

Regular Plasma and Urine Biomarkers:For all participants. Regular blood biomarkers: hemoglobin, hematocrit, RDW, Thrombocytes, Leucocytes, lymphocytes, neutrophils, NT-proBNP , Troponin I, C-reactive Protein, Alkaline phosphatase, Ƴ-GT, Sedimentation rate, Glucose, Total Cholesterol, Triglycerides, LDL-Cholesterol,HDL- Cholesterol, Transferrin saturation, Ferritin, HbA1c, Pre-albumin, C-Cistatin, homocystein, Sodium , Potassium, Chlorine, Calcium, Phosphorus, Magnesium, Creatinine, Urea, Folic Acid, Cianocobalamin, PTH, eGFR, D Vitamin, Uric Acid.

Urine biomarkers: Microalbumin, Creatinine, Potassium, Sodium.

Specific biomarkers: For all RA patients and control group. Include OLINK's panels for inflammation, fibrosis or matrix extracellular organization.

• Heart Failure
• Cardiovascular Risk Factor
• Rheumatoid Arthritis
• Myocardium; Injury
• Cardiovascular Diseases

• Gibofsky A. Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis. Am J Manag Care. 2012 Dec;18(13 Suppl):S295-302.
• Choy E, Ganeshalingam K, Semb AG, Szekanecz Z, Nurmohamed M. Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment. Rheumatology (Oxford). 2014 Dec;53(12):2143-54. doi: 10.1093/rheumatology/keu224. Epub 2014 Jun 6. Review.
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Inclusion Criteria:

• Diagnosis of Rheumatoid arthritis
• Regular follow up on Autoimmune diseases medical appointment
• Written informed consent to participate in this study prior to any study procedures

Exclusion Criteria:

• Presence of severe life-threatening disease before inclusion with an expected survival of less than 6 months after inclusion
• Mental or physical status not allowing written informed consent
• Active malignancy disease
• Patient unable to walk, in which SMWT is not possible to perform.

• Instituto de Ciências Biomédicas Abel Salazar
• Central Hospital, Nancy, France
• Unit Multidisciplinary Research in Biomedicine