UK CARDIOvascular Immune-Mediated Inflammatory Diseases (CARDIO-IMID) Registry Study

Not yet recruiting

Conditions: Immune-Mediated Inflammatory Diseases
Cardiovascular Diseases

Registration Number: NCT06478277

Lead Sponsor: University of Manchester

Brief Summary: The goal of this observational study is to develop a large, deeply characterised cohort that will be a platform for collaborative clinical and translational research into cardiovascular (CV) disease (CVD) and Immune-mediated-inflammatory-diseases (IMID). The main aim is to evaluate whether existing blood cardiac biomarkers predict adverse cardiovascular outcomes. The study will capture standard of care CV and associated health data (clinical, biochemistry/pathology and investigations) in patients across the IMIDs. Optional biological and/or imaging sub-studies will provide additional data and/or samples for associated analyses.

Detailed Description: Multimorbidity is a rapidly growing burden on our healthcare systems, especially with an ageing demographic. CVD is a major cause of morbidity and mortality. The co-association of IMIDs with CVD needs more sophisticated understanding of the underlying risk, earlier identification and tailored use of targeted therapeutics. Importantly, the investigation of CVD in IMID offers an effective human experimental model to improve not just the lives of people with IMIDs but also the general CVD population.

The UK CARDIOvascular Immune-Mediated Inflammatory Diseases (CARDIO-IMID) registry will be a key platform for United Kingdom (UK) multi-centre clinical and translational CARDIO-IMID research. The aim is that centres across the UK including all the devolved nations will collaborate and contribute patients such that the registry will provide deep phenotyping, linked to clinical outcomes, in, ultimately, many hundreds of patients. The planned study will establish a deeply phenotyped cohort and/or as part of the optional sub-study, an associated bioresource to support individual discrete studies and/or analyses that address the stated aims and objectives. All potential participants will be invited to participate in the longitudinal collection and evaluation of routine comprehensive clinical information, including pathology, imaging and other cardiovascular data. This programme will identify patients within defined IMID clinical cohorts at different stages of (rheumatology and cardiovascular) disease. These data will be invaluable in enabling a full characterisation of CVD in terms of the extent, presentation, risk factors, and pathophysiology. Patients are seen as per standard clinical practice determined by the index IMID and in this setting, also dependent on co-existing CV comorbidity, usually every 3-6 months at time of IMID/CVD diagnosis and then 6 to 12 monthly thereafter. Specific questionnaires and tests requested outside of standard of care (sub-studies) will depend on disease group and clinical context. Not all patients will be required to complete all the relevant questionnaires, instead, based on individual IMID and/or CVD profile.

In addition, there is the opportunity for subjects to include (i) longitudinal biological (blood) samples and (ii) extended cardiovascular magnetic resonance (CMR) imaging protocol for those receiving CMR as part of National Health Service (NHS) standard of care.

Collectively, the study and associated platform with appropriate biostatistical and machine learning approaches will inform on the pathophysiological sequence of events, identification of prognostic biomarkers and risk models; as well as enable evaluation of the influence of IMID-specific vascular +/- immunosuppressive therapies and traditional cardiac pharmacotherapy where indicated. It will also establish a platform for trials in IMIDs to capture CV outcomes. Moreover, it will provide cohorts of patients readily available for recruitment, with linkage in place for outcomes. It could be used to leverage commercial funding and participation, facilitated by simplified, single-point access for industry. It will enable scaled investigation aimed at understanding causes of CARDIO-IMID, improving risk stratification and providing better care.

Recruitment & Eligibility

Status: NOT_YET_RECRUITING

Sex: All

Target Recruitment: 600

Inclusion Criteria

Written informed consent
Diagnosis of an IMID by a rheumatologist with categorisation into one of the following:

i. IMID-'higher risk' CVD: individuals who have a risk of developing CVD (based on traditional risk factors and/or IMID-specific factors) but no history of CVD
1. Coronary artery disease (CAD): specifically, a high pre-test probability of CAD based on clinical risk factors (e.g. QRISK3 score ≥10%) and/or elevated biochemical markers (high-sensitivity C-reactive protein ≥2mg/L and/or Lipoprotein(a) ≥70mg/dL)
2. Myopericardial involvement: Specific IMID and/or cardiovascular indicators that place at increased risk e.g. autoantibody associations, presence of peripheral myositis or other major organ involvement; incidental raised serum cardiac biomarkers (troponin and/or NT-pro BNP), on routine testing
  
  ii. Incident (new) IMID-CVD: Patients with IMID that present with a new history of CVD

1. ASCVD i. Major adverse cardiovascular events (MACE):
  - Non-fatal myocardial infarction.
  - Non-fatal stroke of any classification, including reversible focal neurologic
  - Defects with imaging evidence of a new cerebral lesion consistent with ischemia or haemorrhage.
  ii. Other cardiovascular events not accounted for in the MACE-3 composite 2)a)i:
  - Hospitalization for unstable angina
  - Coronary revascularization
  - Hospitalization for heart failure
  - Transient Ischemic Attack (TIA)
  - Peripheral Vascular Disease (PVD)
  - Deep vein thrombosis (VTE) and/or pulmonary embolism [PE].
2. Myopericardial involvement: as diagnosed by a cardiology specialist with 'tier 2' cardiovascular imaging and/or other clinical and biochemical criteria in line with usual care
  
  iii. Established IMID-CVD
a) Patients with IMID and a history of past cardiovascular event as detailed in 2) a) above.

b) Patients with a known history of myopericardial involvement as defined above in 2) b)

Biological sub-study inclusion criteria

There are no additional inclusion criteria for this sub-study

Extended protocol standard CMR sub-study inclusion criteria.

Participants that receive a CMR scan as standard of care

Exclusion Criteria

Age less than 18 years
Unable to give informed consent

Biological sub-study exclusion criteria:

There are no additional exclusion criteria for this sub-study

CMR sub-study exclusion criteria:

Standard of care contraindications to:

CMR: metal implant eg metal fragments in the eye, pacemaker; claustrophobia; inability to lie flat
Magnetic Resonance Imaging (MRI) contrast: renal failure with estimated glomerular filtration rate (eGFR) <30,

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of participants with abnormal N-terminal pro B-type natriuretic peptide (NT-pro BNP) levels	5 years	The total number of participants with abnormal NT-pro BNP levels (assessed by blood draw) will be measured. Unit: number of participants
Number of participants with abnormal high-sensitivity cardiac troponin I/T levels	5 years	The total number of participants with abnormal high-sensitivity troponin I/T levels (assessed by blood draw) will be measured. Unit: number of participants

Secondary Outcome Measures

Name	Time	Method
Systolic and diastolic function	5 years	Systolic and diastolic function will be continuously measured. Mean values will be reported. Units: %
Global longitudinal strain	5 years	Global longitudinal strain will be continuously measured. Mean values will be reported. Units: %
Aortic distensibility	5 years	Aortic distensibility will be continuously measured in participants undergoing cardiac magnetic resonance imaging. Mean and median values will be reported. Unit: mm/Hg
Late gadolinium enhancement	5 years	Late gadolinium enhancement will be measured in participants undergoing cardiac magnetic resonance imaging as an indicator for the presence and extent of replacement fibrosis. Unit: no units (reported as either: presence or absence)
Atrial and ventricular volumetrics	5 years	Atrial and ventricular volumetrics will be continuously measured. Mean and median values will be reported. Units: mL/m2
Number of participants with atherosclerotic cardiovascular disease (ASCVD)	5 years	Total number of participants with ASCVD ASCVD: Death due to acute myocardial infarction (MI), Sudden cardiac death, Death due to heart failure, Death due to stroke, Death due to cardiovascular procedures, Death due to cardiovascular haemorrhage, Death due to other cardiovascular causes: peripheral artery disease, Non-fatal MI, Non-fatal stroke of any classification, including reversible focal neurologic, defects with imaging evidence of a new cerebral lesion consistent with ischemia or haemorrhage. Unit: number of participants
Number of participants with other cardiovascular events	5 years	The total number of participants with other cardiovascular events not already accounted for: Hospitalization for unstable angina; Coronary revascularization; Hospitalization for heart failure; Transient ischemic attack (TIA); Peripheral vascular disease (PVD); Venous thromboembolism (VTE) (deep vein thrombosis and/or pulmonary embolism \[PE\], all-cause mortality). Units: number of participants
Number of participants with myopericardial involvement	5 years	Total number of participants with primary myocardial events such as myocarditis, pericarditis. Units: number of participants
Abnormalities in regional wall motion	5 years	Abnormalities in regional wall motion will be reported as a descriptive measure. Unit: no units (descriptive measure of either: normal, hypokinetic (reduced endocardial excursion and wall thickening), akinetic (absent endocardial excursion and wall thickening) or diskinetic (systolic bulging with no thickening))
T1 relaxation time	5 years	T1 relaxation time will be continuously measured in participants undergoing cardiac magnetic resonance imaging as an indicator for the presence and extent of replacement fibrosis. Mean and median values will be reported. Unit: ms
T2 relaxation time	5 years	T2 relaxation time will be continuously measured in participants undergoing cardiac magnetic resonance imaging as an indicator of myocardial inflammation. Mean and median values will be reported. Unit: ms
Extracellular volume fraction	5 years	Extracellular volume fraction will be continuously measured in participants undergoing cardiac magnetic resonance imaging as an indicator for the presence and extent of replacement fibrosis. Mean values will be reported. Unit: %

UK CARDIOvascular Immune-Mediated Inflammatory Diseases (CARDIO-IMID) Registry Study

Recruitment & Eligibility

Study & Design

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