Lipid Profile In Rheumatoid Arthritis Patients Research Articles

Relationship between the complement system and serum lipid profile in patients with rheumatoid arthritis.

The complement system has been linked to the etiopathogenesis of rheumatoid arthritis (RA). Patients with RA exhibit a dysregulated profile of lipid molecules, which has been attributed to the inflammation present in the disease. In this study, we aimed to evaluate the association between a comprehensive assessment of the complement system and the lipid profile of patients with RA. 430 patients with RA were recruited. New-generation techniques were employed to conduct functional assays of the three pathways of the complement system. Serum levels of various complement components such as C1q, factor D, properdin, lectin, C1-inhibitor, C2, C4, C4b, C3, C3a, C5, C5a, and C9 were assessed. Furthermore, a complete pattern of lipid molecules was measured including high (HDL), low-density lipoproteins (LDL), and lipoprotein (a). Multivariable linear regression analysis was conducted to investigate the association between the complement system and lipid profile in RA patients. After multivariable analysis, several noteworthy associations emerged between the complement system and lipid molecules. Notably, complement components most strongly linked to the lipid profile were C1q and properdin, representing the upstream classical and alternative pathways, along with C3 from the common cascade. These associations demonstrated significance and positivity concerning total cholesterol, LDL, atherogenic index, apolipoprotein B, and lipoprotein(a), suggesting a connection with an unfavorable lipid profile. Interestingly, complement functional assays of the three pathways and activated products such as C3a and C5a showed no correlation with the lipid pattern. The correlation between the complement system and lipid molecule patterns is pronounced in patients with RA. This relationship is predominantly positive and primarily associated with upstream complement components rather than activated ones.

Lipid metabolism and rheumatoid arthritis.

As a chronic progressive autoimmune disease, rheumatoid arthritis (RA) is characterized by mainly damaging the synovium of peripheral joints and causing joint destruction and early disability. RA is also associated with a high incidence rate and mortality of cardiovascular disease. Recently, the relationship between lipid metabolism and RA has gradually attracted attention. Plasma lipid changes in RA patients are often detected in clinical tests, the systemic inflammatory status and drug treatment of RA patients can interact with the metabolic level of the body. With the development of lipid metabolomics, the changes of lipid small molecules and potential metabolic pathways have been gradually discovered, which makes the lipid metabolism of RA patients or the systemic changes of lipid metabolism after treatment more and more comprehensive. This article reviews the lipid level of RA patients, as well as the relationship between inflammation, joint destruction, cardiovascular disease, and lipid level. In addition, this review describes the effect of anti-rheumatic drugs or dietary intervention on the lipid profile of RA patients to better understand RA.

Effect of Biologics on Cardiovascular Inflammation: Mechanistic Insights and Risk Reduction.

It is increasingly recognized that atherosclerosis and consequently cardiovascular disease (CVD) are closely linked with inflammatory processes. The latter is in the center of the pathogenic mechanism underlying autoimmune rheumatic diseases (ARD). It follows then, that optimal control of inflammation in ARDs may lead to a decrease of the accompanied CVD risk. Major trials (eg, CANTOS, CIRT), aimed at examining the possible benefits of immunomodulatory treatments in CVD, demonstrated conflicting results. On the other hand, substantial evidence is accumulating about the possible beneficial effects of biologic disease modifying antirheumatic drugs (bDMARDs) in patients with ARDs, particularly those with rheumatoid arthritis (RA). It seems that bDMARDs (some more than others) alter the lipid profile in RA patients but do not adversely affect, in most cases, the TC/HDL ratio. Favorable effects are noted for arterial stiffness and endothelial function. This is reflected in the lower risk for CVD events, seen in observational studies of RA patients treated with bDMARDs. It should be stressed that more data exist for the TNF-inhibitors than for other bDMARDs, such as tocilizumab, abatacept and rituximab. As regards the spondyloarthropathies (SpA), data are less robust. For TNF-inhibitors, effects appear to be on par with those seen in RA but no conclusions can be drawn for newer biologic drugs used in SpA (eg, IL-17 blockers). Finally, there is accumulating evidence for a beneficial effect of immunosuppressive treatment in cardiac inflammation and function in several ARDs. Introduction of newer therapeutic options in clinical practice seem to have a positive impact on CVD in the setting of ARD. This is probably due to better control of inflammation, but direct improvement in vascular pathology is also a valid hypothesis. Most data are derived from observational studies and, therefore, randomized controlled trials are needed to assess the possible favorable effect of bDMARDs on CVD outcomes.

Features of dyslipidemia and its influence on endothelium functional state in patients with rheumatoid arthritis and arterial hypertension

Purpose of the study. Was to identify the features of blood lipid spectrum and endothelium functional state in patients with rheumatoid arthritis (RA) and arterial hypertension (AH).
 Materials and methods. 83 patients were examined (40 with RA combined with AH, 23 with RA and 20 with AH). The blood lipid spectrum and endothelial function were studied in all patients.
 Results. The analysis of blood serum lipid parameters demonstrated that in patients with RA, regardless of the presence of AH, there was a significant increase of proatherogenic lipid profile parameters in comparison with those in healthy subjects. It was shown, that lower concentrations of high-density lipoproteins and higher atherogenic coefficient indices was a characteristic feature of the lipid profile in RA patients both with and without AH – in contrast to the same parameters of the lipid spectrum in patients with AH without RA. In the groups of patients with RA a significant increase of the brachial artery diameter at rest and decreased indices of endothelium-dependent vasodilation and endothelium-independent vasodilation were revealed. Subjects with RA in combination with AH had significantly lower indices according to the tests with both reactive hyperemia and nitroglycerin, while in patients with RA without AH, only NG-test was significantly lower.
 Conclusion. Dyslipidemia of atherogenic type and endothelial dysfunction develops at the initial stages of rheumatoid process and depends on the activity of the inflammatory process, the presence of extra-articular manifestations and rheumatoid factor seropositivity.

The Lipid Paradox as a Metabolic Checkpoint and Its Therapeutic Significance in Ameliorating the Associated Cardiovascular Risks in Rheumatoid Arthritis Patients.

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.

The lipid paradox in rheumatoid arthritis: the dark horse of the augmented cardiovascular risk.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation that, if left untreated, can cause joint destruction and physical impairments. The inflammatory process is systematic, and it is associated with increased morbidity and mortality. Over the last years, mortality presents a decreasing trend; still, there is a high burden of cardiovascular disease (CVD) in RA that seems to be related to coronary atherosclerosis. Chronic inflammation, physical inactivity, and drugs used to treat RA are some of the reasons. Thus, the management of CVD risk is essential and involves the patient's stratification using distinct parameters that include assessment of the blood lipid profile. However, 'dyslipidemia' in RA patients follows a different pattern under the impact of inflammatory processes, while therapies that target the underlying disease change the levels of specific lipid components. In this review, we explore the relationship between blood lipids and inflammation in the so-called ΄lipid paradox΄ in RA, and we present the existing knowledge over the influence of antirheumatic drugs on the lipid profile of RA patients.

Tofacitinib restores the inhibition of reverse cholesterol transport induced by inflammation: understanding the lipid paradox associated with rheumatoid arthritis.

Patients with active rheumatoid arthritis (RA) have increased cardiovascular mortality, paradoxically associated with reduced circulating lipid levels. The JAK inhibitor tofacitinib ameliorates systemic and joint inflammation in RA with a concomitant increase in serum lipids. We analysed the effect of tofacitinib on the lipid profile of hyperlipidaemic rabbits with chronic arthritis (CA) and on the changes in reverse cholesterol transport (RCT) during chronic inflammation. CA was induced in previously immunized rabbits, fed a high-fat diet, by administering four intra-articular injections of ovalbumin. A group of rabbits received tofacitinib (10mg·kg-1 ·day-1 ) for 2weeks. Systemic and synovial inflammation and lipid content were evaluated. For in vitro studies, THP-1-derived macrophages were exposed to high lipid concentrations and then stimulated with IFNγ in the presence or absence of tofacitinib in order to study mediators of RCT. Tofacitinib decreased systemic and synovial inflammation and increased circulating lipid levels. Although it did not modify synovial macrophage density, it reduced the lipid content within synovial macrophages. In foam macrophages in culture, IFNγ further stimulated intracellular lipid accumulation, while the JAK/STAT inhibition provoked by tofacitinib induced lipid release by increasing the levels of cellular liver X receptor α and ATP-binding cassette transporter (ABCA1) synthesis. Active inflammation could be associated with lipid accumulation within macrophages of CA rabbits. JAK inhibition induced lipid release through RCT activation, providing a plausible explanation for the effect of tofacitinib on the lipid profile of RA patients.

Evaluation of Rosuvastatin Effect as Adjuvant Therapy to Methotrexate on Lipid Profile and the Possibility of its Cardioprotective Effect in Iraqi Patients with Active Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a common inflammatory disease that associated with increased morbidity and mortality due to accelerated atherosclerosis. Rosuvastatin is a unique hydroxy methyl glutaryl Co A (HMGCoA) reductase inhibitor that has anti inflammatory effects.
 The aim of this study was to evaluate the effect of rosuvastatin as adjuvant therapy to methotrexate (MTX) on lipid profile and its possible cardioprotective effect in RA patients. A double blinded placebo controlled clinical trial with 8 weeks follow up periods at which 40 patients with active RA using MTX were randomized into 2 groups to receive either rosuvastatin 10mg or placebo as adjuvant therapy to MTX. In addition to twenty healthy subjects as control group. Lipid profile and erythrocyte sedimentation rate (ESR) was assessed at the start and at the end of the study. At the start of the study total cholesterol (TC), low density lipoprotein cholesterol (LDLc) and high density lipoprotein cholesterol (HDLc) values were not significantly different between RA patients and control group. At the end of the study rosuvastatin significantly reduced ESR, TC and LDLc after 8 weeks of treatment.
 It can be concluded that MTX has the ability to normalize lipid profile in RA patients. Rosuvastatin effectively reduce ESR, TC and LDLc; Moreover, Rosuvastatin might have a possible cardioprotective effect in RA patients.
 Keywords: Active rheumatoid arthritis, Methotrexate, Rosuvastatin.

Changes in serum lipids in patients with rheumatoid arthritis treated with a combination of tocilizumab and methotrexate compared with methotrexate alone for 24 weeks of observation

Background. According to the some studies tocilizumab therapy (TCZ) in patients with rheumatoid arthritis (RA) is accompanied by deterioration of blood lipid profile. Aim. To study changes in serum lipid parameters in patients with RA treated with a combination of tocilizumab and methotrexate compared with methotrexate alone for 24 weeks of observation. Material and methods. Patients (n=72) with RA were included into the pilot non-randomized 24-week study and divided in two groups: 1) TCZ+MTX group (n=39; women 30; median age 51 [43-55] years; 6 i.v. infusions of TCZ 8 mg/kg + МТX 10-20 mg/week); 2) MTX group (n=33; women 23; mеdian age 56 [48-63] years; MTX 7.5-20 mg/week). Results. At the baseline, similar proatherogenic blood profile was observed in both groups. The patients of MTX group more frequently took statins (n=19; 57.6%) compared with the group TCZ+MTX (n=7; 18%), (p<0.05). The lipid levels correlated positively with traditional risk factors (p<0.05). RA activity and duration correlated negatively with high density lipoprotein cholesterol (HDL-C), (p<0.05). Good/satisfactory anti-inflammatory effect was achieved in both groups after 24 weeks of treatment. Patients of TCZ+MTX group showed an increase in total cholesterol and HDL-C levels by 11% and 110%, respectively and decrease in plasma atherogenic index (PAI) by 47%, (p<0.05). HDL-C level increased by 22% and PAI decreased by 16% in patients of MTX group (p<0.05). Among patients of MTX group without statin therapy HDL-C as well as non-HDL-C levels were increased by 24% and 27%, respectively (p<0.05); PAI did not change significantly in this subgroup. Among patients of MTX group treated with statins isolated increase in HDL-C level by 22% and decrease in PAI by 37.3% (p<0.05) were observed. A number of patients with achieved target levels of all studied lipid parameters did not change significantly in both groups. Conclusions. TCZ+MTX combined therapy as well as MTX monotherapy are associated with similar improvement in lipid parameters. Adjusted statin doses may be needed to achieve target serum lipid profile in RA patients.

TNF Antagonists, The Prevention of Myocardial Infarction in Rheumatoid Arthritis Patients?

Cardiovascular disease (CVD) has been acknowledged to be a major extra-articular comorbidity in patients with rheumatoid arthritis (RA), with myocardial infarction (MI) particularly being the most prominent. Contributory factors include the rise in traditional risk factors and proinflammatory changes seen in RA patients. Two drivers of proinflammatory changes are mainly emphasized in this review: insulin resistance and dyslipidaemia. Among the cytokines involved, tumour necrosis factor alpha (TNF-α) has been identified as one of the major molecules contributing to the proatherogenic state seen in these patients. As such, biological therapies such as anti-TNF drugs are hypothesized to have a secondary function in reducing CVD in these patients. Using TNF-α as an example, this review provides an overview of how chronic inflammation increases the risk of CVD, focusing mainly on the two drivers: insulin resistance (IR) state and dyslipidaemia. The review also investigates if anti-TNF drugs can reduce the effects of these two drivers and hence, determine if anti-TNF drugs can produce a clinical effect of reducing the risk of MI in RA patients. A literature search was conducted using Medline and Google Scholar (1990–January 2013). Studies were selected if they addressed the pathophysiology of TNF-α in CVD risk for RA patients or the effects of anti-TNF therapy on IR, dyslipidaemia or MI in RA patients. Although the studies were unable to establish if anti-TNF therapy can reduce CVD risk, responders to anti-TNF therapy appears to have a significant lower risk of MI. Despite its effects, additional studies should be conducted to determine its cost-benefit ratio. This is because of its high cost and its administration limitations. Future studies should also determine if the lipid profile in RA patients truly reflects their risk of CVD, as some studies have reflected an increased CVD risk as compared to the general population.

The effects of fenofibrate on inflammation and cardiovascular markers in patients with active rheumatoid arthritis: a pilot study

Peroxisome proliferator-activated receptors α (PPARα) agonists, or fibrates, are used in the treatment for dyslipidemia. Experimental data suggest that fibrates have anti-inflammatory properties, and PPARα is essential for the differentiation of endothelial progenitor cells (EPC) which diminished pool in rheumatoid arthritis (RA) contributes to accelerated atherosclerosis. The data on fibrates' effects in patients with RA are limited. The aim of this study was to investigate changes in disease activity, inflammatory markers, lipid profile, and circulating EPC in active RA patients treated with fenofibrate. Twenty-seven patients with active RA taking traditional disease-modifying antirheumatic drugs (DMARDs) were prescribed fenofibrate (145 mg/day) for 3 months. All patients received background traditional DMARDs in stable doses. The outcomes measured were clinical disease activity variables, circulating cytokines, adipokines, lipids, and EPC. Twenty-five patients completed the study. At the end of treatment, there was a significant reduction in DAS28, all individual DAS28 components except tender joint count, the duration of morning stiffness, and in the patient's assessment of disease activity. Fifteen (60 %) patients achieved good/moderate EULAR response, while 10 (40 %) patients satisfied ACR20 response criteria. Treatment with fenofibrate resulted in significant decrease in CRP and IL-6 concentrations and improvement in lipid profile. There was no change in the concentrations of circulating EPC. In conclusion, fenofibrate treatment is associated with reduced inflammation and improved lipid profile in RA patients. Large randomized controlled studies are needed to confirm these results and to define the role of fibrates in the treatment for RA.

The Safety and Efficacy of Etanercept on Cardiac Functions and Lipid Profile in Patients With Active Rheumatoid Arthritis

ObjectivesPatients with rheumatoid arthritis (RA) are known to be at increased cardiovascular risk. Etanercept is a tumor necrosis factor α (TNF-α) blocking agent that has been successfully used in the...

Effects of rituximab treatment on endothelial dysfunction, carotid atherosclerosis, and lipid profile in rheumatoid arthritis

Increased cardiovascular mortality has been associated with rheumatoid arthritis (RA). There have been reports indicating that tumor necrosis factor blockers may exert favorable but transient effects on lipid profile, flow-mediated vasodilation (FMD) of the brachial artery, and common carotid intima-media thickness (ccIMT) in RA. In this study, we assessed the effects of rituximab on FMD, ccIMT, and lipid profile. Five female RA patients received two infusions of 1000 mg rituximab i.v. High-resolution B-mode ultrasound was used to assess brachial FMD and ccIMT. We also determined plasma total cholesterol (TC), HDL-C, LDL-C, and triglyceride (Tg) levels. Assessments were performed at baseline, as well as at weeks 2, 6, and 16 after the first infusion. Rituximab (RTX) treatment resulted in a rapid and sustained improvement in FMD. The mean improvement was 30%, 22%, and 81% at weeks 2, 6, and 16, respectively. RTX had little effect on atherosclerosis within this short period of time; however, we observed 10%, 9%, and 2% decreases in ccIMT at weeks 2, 6, and 16, respectively. RTX therapy resulted in 3-11% decrease in TC, as well as 14-35% increase in HDL-C levels. Two infusions of RTX exerted early and sustained favorable effects on endothelial dysfunction, as well as plasma TC and HDL-C levels. RTX may also decrease ccIMT; however, longer follow-up is needed to assess the prolonged effects of RTX on vascular function and lipid profile in RA patients.

Effects of Anti‐TNF‐α Treatment on Lipid Profile in Patients with Active Rheumatoid Arthritis

Cardiovascular morbidity and mortality appear to be increased in rheumatoid arthritis (RA), which might be due to increased prevalence of risk factors for cardiovascular disease, such as an accelerated progression of atherosclerosis. Patients with active RA frequently show an atherogenic lipid profile, which has been linked with the inflammatory reaction. Tumor necrosis factor-alpha (TNF-alpha), a pivotal proinflammatory cytokine implicated in the pathogenesis of atherosclerosis in RA, may be involved in the development of the altered lipid profile observed in active RA. Our aim was to investigate the effects of anti-TNF-alpha treatment in combination with methotrexate (MTX) and corticosteroid therapy on lipid profile in patients with active RA. In this prospective study 34 consecutive RA patients were included (all women, mean age 51.6 +/- 7.9 years, range 46-72 years) with active (defined as Disease Activity Index 28 joint score [DAS-28], of at least 3.2) and refractory RA, in stable treatment with MTX (7.5-10 mg/week) and prednisone (7.5-10 mg/day) for 3 months. All patients received TNF-alpha blockers (n = 16, etanercept 25 mg twice weekly; n = 14, infliximab 3 mg/kg on 0, 2, 6, and every 8 weeks thereafter; and finally, n = 4, adalimumab 40 mg every other week). Total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), triglycerides (TG) and lipoprotein (a) [Lp(a)] levels and the atherogenic index (ratio cholesterol/HDL cholesterol) were measured at base line, and at 16 and 24 weeks. Results were as follows: The DAS-28 was 6.9 +/- 2.1 at base line and decreased to 4.6 +/- 1.8 after 16 weeks, and further to 4.1 +/- 1.3 after 24 weeks (both, P < 0.01). Following anti-TNF-alpha treatment, the mean levels of total cholesterol were 168 +/- 24 mg/dL at base line and increased to 188 +/- 28 mg/dL at 16 weeks (P < 0.01), and 197 +/- 26 mg/dL at 24 weeks (P < 0.001). However, also the mean levels of HDL cholesterol were significantly higher than basal values after 16 and 24 weeks of treatment (34 +/- 12 mg/dL versus 36 +/- 18 mg/dL [P < 0.05] and 38 +/- 14 mg/dL [P < 0.01], respectively). TG and Lp(a) levels, as well as the atherogenic index were not significantly changed. Interestingly, variations in disease activity were significantly and inversely correlated with HDL cholesterol levels. Short anti-TNF-alpha treatment was associated with a significant increase of both total cholesterol and HDL cholesterol levels, and correlated with decreased disease activity. The atherogenic index showed no changes during the study. Therefore, anti-TNF-alpha treatment might affect lipid profile in RA patients.