Cardiovascular abnormalities in immune-mediated inflammatory disease

Immune-mediated inflammatory disease (IMID) represents a group of diseases characterised by dysregulation of immune processes with a shared common inflammatory pathway, leading to end-organ damage, of which Rheumatoid Arthritis (RA) and Systemic Sclerosis (SSc) are two important examples. An accelerated risk of cardiovascular disease (CVD) with associated increased mortality is observed in those with IMID; the risk in RA being similar to those with diabetes mellitus. In addition, IMID can directly affect the myocardium independently of atherosclerosis, termed primary myocardial disease, causing further excess mortality; best described in SSc. Determining the disease phenotype most at risk of either macrovascular or primary myocardial disease and having a greater understanding of the underlying pathophysiology is vital to develop effective screening strategies to prevent and manage its complications. Surrogate markers of CVD, including soluble cardiovascular (CV) biomarkers and cardiovascular magnetic resonance (CMR) imaging, can inform of subclinical CVD or risk of progression to clinical CVD; with currently limited data in IMID. Using soluble CV biomarkers and CMR, this thesis demonstrates the presence of subclinical CVD in patients with RA and SSc free of clinical CVD. In RA, these abnormalities associate with traditional CV risk factors; emphasising the importance of their aggressive management. Using CMR, this thesis describes a reduction in left ventricular mass in RA; suggesting pathology other than atherosclerosis. This work investigates specific treatment strategies in the reduction of CV risk, reporting improvement in insulin resistance with TNF inhibition in a randomised controlled trial of early RA. In SSc, the utility of CMR in the assessment of primary myocardial disease is demonstrated, describing cardiac fibrosis in those free of known cardiac disease, associating with a poor prognostic phenotype. Finally, this thesis reports the novel use of an implantable loop recorder in SSc, detecting arrhythmias in patients free of known cardiac disease