Abstract
While the most common manifestations associated with rheumatoid arthritis (RA) are synovial damage and inflammation, the systemic effects of this autoimmune disorder are life-threatening, and are prevalent in 0.5–1% of the population, mainly associated with cardiovascular disorders (CVDs). Such effects have been instigated by an altered lipid profile in RA patients, which has been reported to correlate with CV risks. Altered lipid paradox is related to inflammatory burden in RA patients. The review highlights general lipid pathways (exogenous and endogenous), along with the changes in different forms of lipids and lipoproteins in RA conditions, which further contribute to elevated risks of CVDs like ischemic heart disease, atherosclerosis, myocardial infarction etc. The authors provide a deep insight on altered levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) in RA patients and their consequence on the cardiovascular health of the patient. This is followed by a detailed description of the impact of anti-rheumatoid therapy on the lipid profile in RA patients, comprising DMARDs, corticosteroids, anti-TNF agents, anti-IL-6 agents, JAK inhibitors and statins. Furthermore, this review elaborates on the prospects to be considered to optimize future investigation on management of RA and treatment therapies targeting altered lipid paradigms in patients.
Highlights
Rheumatoid arthritis (RA) is considered to be an autoimmune disorder which is prevalent in about 0.5–1% of the general population [1,2], with significant risks of comorbidities, disabilities and fatigue [3], along with cardiovascular disorders (CVDs), and long-term impact on socioeconomic and personal paradigms [4]
Based on the metabolic alterations observed in RA patients and the role of these changes in inducing CV, the aim of this review is to provide a detailed overview of the lipid paradox, along with its role in developing CV risks in such subjects; we focused on the impact of anti-rheumatoid therapies in the lipid scenario associated with RA
The lipids, primarily TGs and cholesterol, are water insoluble forms, which are transported by blood, and depending upon their association with proteins are known as lipoproteins, which are complex entities comprised of cholesterol ester and TGs containing a central core [113]
Summary
Rheumatoid arthritis (RA) is considered to be an autoimmune disorder which is prevalent in about 0.5–1% of the general population [1,2], with significant risks of comorbidities, disabilities and fatigue [3], along with cardiovascular disorders (CVDs), and long-term impact on socioeconomic and personal paradigms [4]. Based on the metabolic alterations observed in RA patients and the role of these changes in inducing CV, the aim of this review is to provide a detailed overview of the lipid paradox, along with its role in developing CV risks in such subjects; we focused on the impact of anti-rheumatoid therapies in the lipid scenario associated with RA. Lipid metabolism is found to play an important role in regulation of the functions of the immune cells, according to the recent studies [50], which has brought the lipid mediators into light, as significant therapeutic targets in various allergic and autoimmune disorders [51]. An indirect activator of AMPK, metformin (anti-diabetic drug), has been reported to curb the disease progression in mouse arthritic models [56] by inhibiting the mTOR pathway, elevating autophagic flux and suppressing nuclear factor-kappa B (NF-Kb)- induced production of inflammatory cytokines [53].
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