Longitudinal study of subclinical cardiovascular abnormalities in a very early rheumatoid arthritis cohort: 11-year follow-up from the CADERA trial

Thursday, February 5, 2026

4:06 PM - 4:13 PM

Location: Galapagos / Aruba / Ilhabela (2nd Lower Level)

Presenting Author(s)

Nicholas Jex, PhD

Cardiologist
University of Leeds
Leeds, England, United Kingdom

Primary Author(s)

CY

Chin Yit Soo, MD

Clinical Research Fellow
University of Leeds
Leeds, England, United Kingdom

Co-Author(s)

Nicholas Jex, PhD

Cardiologist
University of Leeds
Leeds, England, United Kingdom
LB

Lesley-Anne Bissell, PhD

Consultant Rheumatologist
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds
Leeds, England, United Kingdom
BE

Bara Erhayiem, MD

Consultant Cardiologist
Nottingham University Hospitals NHS Trust, United Kingdom
GF

Graham Fent, MD

Consultant Cardiologist
Sheffield Teaching Hospitals NHS Foundation Trust, United Kingdom
JA

Jacqueline Andrews, MD

Executive Medical Director
Harrogate and District NHS Foundation Trust, United Kingdom
John Greenwood, MD, PhD, FSCMR

Director
Baker Heart and Diabetes Institute
Melbourne, Victoria, Australia
bD

bianca Dumitru, PhD

Consultant Rheumatologist
University Hospital Coventry & Warwickshire
Coventry, United Kingdom
Peter P. Swoboda, PhD

Consultant Cardiologist
Leeds Institute of Cardiovascular and Metabolic Medicine
Leeds, England, United Kingdom
TA

Thomas Anderton, MBChB

Clinical research fellow
University of Leeds, Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, LS2 9JT, United Kingdom
Leeds, England, United Kingdom
ML

May Lwin, MB

Clinical research fellow
University of Leeds, Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, LS2 9JT, United Kingdom
Leeds, England, United Kingdom
BC

Bradley Chambers, MBChB BSc MRCP

Cardiology Registrar
University of Leeds, England, United Kingdom
MA

Mehak Asad, MD, MPH

Clinical research fellow
University of Leeds, Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, LS2 9JT, United Kingdom
Leeds, England, United Kingdom
Maryum Farooq, MB

Research Fellow
Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds
Leeds, England, United Kingdom
CS

Ching-Hui Sia, MD

Dr
Leeds Institute of Cardiovascular and Metabolic Medicine, United Kingdom
MT

Masafumi Takafuji, MD, PhD

Assistant Professor
Mie University Hospital
Tsu, Mie, Japan
MA

Mohd Imree Azmi, MB

Consultant Radiologist
University of Leeds
Leeds, England, United Kingdom
RT

Raluca Tomoaia, MD, PhD

Clinical Research Fellow
University of Leeds
Leeds, England, United Kingdom
RJ

Rabeia Javid, BSc, MB

Cardiology Registrar
University of Leeds
Bradford, England, United Kingdom
JB

John D D. Biglands, PhD, MSc

Clinician scientist
Leeds Institute of Cardiovascular and Metabolic Medicine
Leeds, England, United Kingdom
MB

Maya Buch, PhD

Professor of Rheumatology
1. Centre for Musculoskeletal Research, University of Manchester 2. NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, United Kingdom
Sven Plein, MD, PhD

Professor of Cardiology
Leeds Institute of Cardiovascular and Metabolic Medicine
Leeds, England, United Kingdom

Background: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular (CV) disease. Guidelines recommend multiplying risk scores by 1.5 in RA. Whilst sub-clinical CV abnormalities by cardiovascular magnetic resonance (CMR) have been identified in cross sectional studies, the long-term cardiac impacts of these are unknown.

The Coronary Artery Disease Evaluation in Rheumatoid Arthritis (CADERA) study recruited 81 treatment-naïve patients with new diagnosis of RA (minimum Disease Activity Score-28 of 3.2) and without known CV disease (randomised to standard disease modifying anti-rheumatic drug (DMARD) therapy or early treatment with etanercept) and 30 age and sex-matched healthy volunteers (HV). CMR showed significant difference in aortic distensibility (AD) of descending thoracic aorta and extracellular volume (ECV) at baseline with interval improvement at years 1 and 2. Purpose of this study was to assess longer-term changes in CV structure and function.

Methods: Eleven years after the baseline CMR, all participants were invited to undergo a follow-up using the same protocol including volumetric analysis, aortic distensibility (AD) (primary endpoint of the original study), T1 mapping, and late gadolinium enhancement (LGE). Their original CMR studies were re-analysed for direct comparison with follow up CMR using cvi42 software 5.14.0 (Circle Cardiovascular Imaging, Canada).

Results: A total of 26 RA patients (of whom 81% and 42% were on ≥1, and ≥2 disease modifying anti-rheumatic drugs (DMARDs), respectively) had follow-up CMR 10.5±0.8 years from the year 1 CMR scan (Table-1). During follow-up, one patient experienced a major adverse cardiovascular event.

AD did not change significantly between 1-year and 11-year CMR in both RA (1-year: 3.3 [2.5, 4.64], 11-year: 3.24 [1.43, 5.58], p=0.5621) (Table-2) and 8 HVs who also had follow-up CMR.

Bi-ventricular systolic function and 3D strain were unchanged between baseline and 11-year follow-up. Indexed bi-ventricular end-diastolic volumes, LV maximal wall thickness, left atrial volume and ejection fraction, were statistically different between the 1-year and 11-year scan, but remained within local normal ranges.

Native T1 (1-year: 1176 [1147, 1229], 11-year: 1255 [1242, 1270], p=< 0.0001) increased significantly but remained within local normal range. Extracellular volume (ECV) was unchanged. There was a trend towards higher proportion of non-ischaemic LGE on interval scans (1-year: 8%, 11-year: 28%, p=0.0751). HVs showed a trend towards higher native T1 on interval CMR but within normal range (p=0.0568).

Conclusion: In a RA cohort treated as per standard of care following protocolised aggressive treatment from initial diagnosis, bi-ventricular size and function, aortic distensibility and ECV did not change, and there were minimal MACE events, suggesting overall good CV risk control.

Table 1: Clinical Characteristics and biochemistry

Variable	Interval CMR (n=26)
Age, y	62±12
Female, n (%)	16 (62)
BMI, kg/m²	26±4
Heart rate, bpm	71±12
Systolic BP, mmHg	118 [110, 135]
Diastolic BP, mmHg	75±8
Creatinine, umol/L	65±12
Haemoglobin, g/L	139±12
Haematocrit, L/L	0.43±0.03
Total cholesterol, mmol/L	5.2±1.1
HDL, mmol/L	1.7±0.4
LDL, mmol/L	2.8±1.1
TG, mmol/L	1.5±0.6
HbA1c, mmol/mol	37 [36, 38]
Non-fasting glucose, mmol/L	5.0±1.0
Triglyceride Glucose Index	3.4 [2.4, 4.8]
Troponin I, ng/mL	3 [3, 7]
NT- pro BNP, ng/L	101 [64, 227]
Medications
ACEi, n (%)	3 (12)
ARB, n (%)	2 (8)
Beta blocker, n (%)	5 (19)
CCB, n (%)	2 (8)
Loop diuretic, n (%)	0
Statin, n (%)	8 (31)
ASA, n (%)	1 (4)
DOAC, n (%)	2 (8)
Any DMARD, n (%)	21 (81)
On ≥ 2 DMARDs, n (%)	11 (42)
JAK inhibitor, n (%)	0
Corticosteroid, n (%)	0
Cardiovascular History and Risks
Stroke or TIA, n (%)	1 (4)
PAF, n (%)	2 (7)
Hypercholesterolaemia	16 (62)
Treated HTN, n (%)	3 (12)
Current smoker	4 (15)
Ex-smoker	8 (30)
Diabetes	1 (4)
Family history of CVD	1 (4)

Values are means ± standard deviations or percentages or median [interquartile range]. BMI, body mass index; bpm, beats per minute; BP, blood pressure; HDL, high density lipoprotein; LDL, low density lipoprotein; TG, triglycerides; HbA1c, glycated haemoglobin; NT-proBNP, N-terminal pro b-type natriuretic peptide; ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; ASA, aspirin; DOAC, direct oral anticoagulation; DMARD, disease modifying anti-rheumatic drug; JAK, Janus kinase; TIA, transient ischemic attack; PAF, paroxysmal atrial fibrillation; HTN, hypertension; CVD, cardiovascular diseaseTable 2: Cardiovascular magnetic resonance (CMR) data.

	1-year CMR (n=26)	11-year CMR (n=26)	Difference	P value
Interval from original CMR (years)	-	10.5±0.8	-	-
LV end-diastolic volume indexed to BSA, mL/m²	78 [69, 94]	74 [59, 81]	-3 [-14, 1]	0.0176
LV end-systolic volume indexed to BSA, ml/m²	37 [29, 51]	31 [25, 35]	0 [-6, 3]	0.6348
LV mass index, g/m²	47 [40, 55]	44 [40, 51]	0 [-6, 2]	0.6893
LV mass to LV end-diastolic volume, g/mL	0.60±0.09	0.63±0.10	0.03±0.08	0.0643
LV stroke volume, ml	85 [73, 91]	78 [62, 92]	-3 [-12, 4]	0.0941
LV ejection fraction, %	58±8	57±6	-1±8	0.6078
LV maximal wall thickness, mm	7 [6, 8]	8 [7, 9]	1 [0, 2]	0.0113
RV end-diastolic volume indexed to BSA, mL/m²	80 [67, 90]	71 [60, 80]	-8 [-16, 0]	0.0061
RV end-systolic volume indexed to BSA, ml/m²	34±10	31±12	-1±16	0.1828
RV ejection fraction, %	55 [51, 63]	56 [50, 62]	0 [-5, 4]	0.9578
LA biplane end-systolic volumes, mL	59 [47, 69]	66 [52, 73]	5 [-1, 11]	0.0172
Biplane LA ejection fraction, %	57 [49, 59]	55 [47, 56]	-3 [-10, 0]	0.0251
3D-Global LV radial strain, %	36 ± 10	34 ± 10	-3 ± 24	0.4484
3D-Global LV circumferential strain, negative (-), %	18 ± 3	17 ± 3	-1 ± 4	0.2204
3D-Global LV longitudinal strain, negative (-), %	14 [11, 16]	15 [13, 16]	0 [-2, 3]	0.4900
Mean native T1, (ms)	1176 [1147, 1229]	1255 [1242, 1270]	74 [42, 118]	< 0.0001
Extra cellular volume, (%)	27 [24, 28]	26 [24, 29]	0.2 [-2, 2]	0.7854
LGE, n (%)	2 (8)	7 (28)	5 (20)	0.0751
LGE with non-ischaemic pattern, n (%)	2 (100)	7 (100)	-	-
Aortic distensibility (1 / (10³ mmHg))	3.30 [2.50, 4.64]	3.24 [1.43, 5.58]	-0.28 [-1.74, 1.08]	0.5621

Values are means ± standard deviations or percentages or median [interquartile range]. CMR, cardiac magnetic resonance; LV, left ventricular; BSA, body surface area; RV, right ventricular; LA, left atrium; EF, ejection fraction; LGE, late gadolinium enhancement