Cardiovascular Profiles in Rheumatoid Arthritis (RA-HF)

May 22, 2019 updated by: Maria Betânia Almeida Dias Ferreira

Cardiovascular Risk, Myocardial Fibrosis and Heart Failure in Rheumatoid Arthritis: Screening and Prognosis

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

Study Overview

Status

Completed

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Actual)

400

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Adults patients with diagnosis of Rheumatoid Arthritis.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of dead participants Time Frame: 11 to 32 months	Death of any cause	11 to 32 months
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	11 to 32 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	11 to 32 months
Number of Participants with new onset atrial fibrillation Time Frame: 11 to 32 months	New onset of Atrial Fibrillation	11 to 32 months
Number of Participants with Hospitalization Time Frame: 11 to 32 months	Any hospitalization for urgent or unplanned reasons	11 to 32 months
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	11 to 32 months
Number of Participants with New onset of acute myocardial infarction Time Frame: 11-32 months	New onset of acute myocardial infarction?	11-32 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Maria Betânia Almeida Dias Ferreira

Collaborators

Central Hospital, Nancy, France

Instituto de Ciências Biomédicas Abel Salazar

Unit Multidisciplinary Research in Biomedicine

Investigators

Study Chair: António J. Marinho, MD, PhD, Centro Hospitalar do Porto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 22, 2016

Primary Completion (ACTUAL)

April 5, 2019

Study Completion (ACTUAL)

May 7, 2019

Study Registration Dates

First Submitted

May 21, 2019

First Submitted That Met QC Criteria

May 22, 2019

First Posted (ACTUAL)

May 23, 2019

Study Record Updates

Last Update Posted (ACTUAL)

May 24, 2019

Last Update Submitted That Met QC Criteria