Lipid and Metabolic Changes in Rheumatoid Arthritis

Abstract

While the most obvious manifestations of rheumatoid arthritis (RA) involve inflammation and damage in the synovial joints, the systemic effects of the condition are widespread and life-threatening. Of particular interest is the 'lipid paradox' of RA, where patients with a numerically equivocal starting lipid profile have a significantly raised risk of cardiovascular (CV) events and response to therapy results in a 'normalization' of lipid levels and reduction in events. Changes in lipids can be seen before overt disease manifestations which suggest that they are closely linked to the more widespread inflammation-driven metabolic changes associated with tumour necrosis factor (TNF). Cachexia involves a shift in body mass from muscle to fat, which may or may not directly increase the cardiovascular risk. However, since TNF inhibition is associated with reduction in cardiovascular events, it does suggest that these widespread metabolic changes involving lipids are of importance. Analysis of single lipids or metabolites have been used to identify some of the key changes, but more recently, metabolomic and lipidomic approaches have been applied to identify a broad spectrum of small molecule changes and identify potentially altered metabolic pathways. Further work is needed to understand fully the metabolic changes in lipid profiles and identify novel ways of targeting desired profile changes, but work so far does suggest that a better understanding may allow management of patients to downregulate the systemic effects of their disease that puts them at risk of cardiovascular complications.

Lipoprotein redox status evaluation as a marker of cardiovascular disease risk in patients with inflammatory disease

“…In addition, they strengthen the argument that reducing LDL serum levels does not necessary entail a positive change in patient lipid profiles or in their risk of developing CVD. In patients with RA in particular, the ‘lipid paradox’ describes the inverse correlation of CVD risk with serum LDL and TC levels (7,8). A notable decrease in the levels of TC and LDL, and in the TC/HDL ratio have been reported in the 5-year period before the clinical manifestations of RA appeared (6,13).…”

“…These pro-inflammatory molecules, apart from inducing endothelial and vessel abnormalities, have also been shown to induce changes in patient lipid profiles, alter insulin sensitivity and increase oxidative stress (5,8). The systemic inflammatory burden, found in patients with RA and DM, is further linked to an accelerated atherosclerotic process, with increased plaque instability and a high risk of life-threatening cardiovascular events (7,8). …”

Biological determinants of health: Genes, microbes, and metabolism exemplars of nursing science

“…Metabolomic approaches are increasingly used in the study of diabetes, dyslipidemia, cancer, chronic neurological disorders, pharmaceutics, and nutrition to name a few. Research into the metabotype of individuals during the disease processes has led to new biomarkers of disease status as well as new targets for interventions and the impact of nutritional interventions (Alvarez et al, 2017; McGrath & Young, 2015). Nutritional metabolomics is seeking to identify novel biomarkers of dietary intake to provide objective measures of dietary intake (Schmidt et al, 2015).…”

Improving cardiovascular health and metabolic comorbidities in patients with psoriatic arthritis

“…While patients with RA generally have altered lipid profiles (thought to be one of the reasons for increased adverse cardiovascular events), there may in fact be a paradoxical relationship between lipids and cardiovascular events in the setting of chronic inflammation, although this is debated [52]. This phenomenon is illustrated in RA patients where lipid levels rise as disease activity declines following initiation of treatment for RA [53]. Less is known about lipid levels and how they change with therapy in PsA [54].…”