Risk Factor For Rheumatoid Arthritis Research Articles

A comparison of comorbidities and their risk factors prevalence across rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis with focus on cardiovascular diseases: data from a single center real-world cohort.

Management of comorbidities is essential to a patient-centered approach to the treatment of chronic inflammatory arthritis. The aim of this study was to compare the prevalence of comorbidities and their risk factors in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) in a single center outpatient cohort. This cross-sectional study included adult patients diagnosed with RA, PsA, and axSpA from a single rheumatology outpatient center. Comorbidities were documented by physicians, and patients were categorized into two age groups, younger (< 45years) and older (≥ 45years), with age- and gender-basedcomparisons. Disease activity, comorbidities, and cardiovascular(CV) risk factors were analyzed using chi-squared tests for categorical variables and independent samples t-tests for continuous variables, with p values < 0.05 considered statistically significant. Comorbidities were registered by physicians using GoTreatIt® Rheuma software. Among 508 RA, 267 PsA, and 285 axSpA patients, the four most common comorbidities were hypertension (36.4%, 25.1%, and19.7%, respectively), dyslipidemia (19.5%, 15.4%, 14.7% respectively), obesity (16.9%, 22.5%, 14% respectively) and thyroid disease (21.5%, 13.9%, 11.2% respectively). Other comorbidities differedamong thediseases and included osteoporosis, osteoarthritis, diabetes mellitus, arrhythmia, and asthma in RA, diabetes mellitus, depression and asthma in PsA, osteoporosis and serious infection in axSpA. RA patients, compared to axSpA had a higher prevalence of coronary artery disease (4.1% vs. 0.7%,p = 0.006), arrhythmia (6.9% vs. 2.5%,p = 0.008) and major adverse cardiac events (2.6% vs. 0.4%,p = 0.024) compared to axSpA. Osteoporosis was more frequent in RA (19.1%) and axSpA (8.4%) than in PsA (2.3%;p < 0.001) and was frequently diagnosed in patientsaged < 45. Depression prevalence was surprisingly low (1.6%,5.2%, and 1.8%, respectively). RA patients had the highest multimorbidity rate, with 26.6% reporting three or more comorbidities, compared to 16.8% in PsA and 10.6% in axSpA (p < 0.001). Health status was poorest in RA and worse in women compared to men for all diseases. RA, PsA, and axSpA share the same four most common comorbidities: hypertension, dyslipidemia, obesity, and thyroid disease but have different prevalence of other disorders and CV risk factors, indicating the need for an individual screening and prevention approach. The possible unrecognition of depression should be evaluated.

Association of PADI4 Gene Polymorphisms With Susceptibility to Rheumatoid Arthritis: Evidence From 24 Case-Control Studies.

This study aims to investigate the association of rs11203366, rs11203367, rs874881, rs2240340 and rs1748033 polymorphisms of protein-arginine deiminase type 4 (PADI4) gene with the risk of rheumatoid arthritis (RA) through a meta-analysis that was followed with a bioinformatics approach. The data were collected from reputable articles and underwent quantitative analysis, followed by in silico analysis using some bioinformatics tools. The results showed that rs874881 polymorphism in Latino (G vs. C: OR=1.35, 95% CI=1.11-1.65, p=0.003; GG+CG vs. CC: OR=2.02, 95% CI=1.41-2.89, p=0.0001; CG vs. CC+GG: OR=1.38, 95% CI=1.04-1.83, p=0.027; GG vs. CC: OR=2.09, 95% CI=1.35-3.23, p=0.001; CG vs. CC: OR=1.98, 95% CI=1.36-2.87, p=0.00033) and rs1748033 in Caucasian population (T vs. C: OR=1.25, 95% CI=1.07-1.45, p=0.005; TT vs. CT+CC: OR=1.34, 95% CI=1.09-1.64, p=0.005, TT+CT vs. CC: OR=1.26, 95% CI=1.09-1.44, p=0.001; TT vs. CC: OR=1.59, 95% CI=1.13-2.23, p=0.007; CT vs. CC: OR=1.20, 95% CI: 1.04-1.39, p=0.015) are associated with increased risk of RA. Moreover, rs11203366 (G vs. A: OR=1.46, 95% CI=1.19-1.78, p=0.0002, GG vs. AG+AA: OR=1.42, 95% CI=1.01-2.01, p=0.043; GG+AG vs. AA: OR=2.03, 95% CI=1.45-2.86, p=0.00004; GG vs. AA: OR=2.29, 95% CI=1.49-3.51, p=0.0002; AG vs. AA: OR=1.93, 95% CI=1.35-2.76, p=0.0003) and rs11203367 (T vs. C: OR=1.50, 95% CI=1.23-1.83, p=0.00007; TT vs. CT+CC: OR=1.56, 95% CI=1.12-2.18, p=0.009; TT+CT vs. CC: OR=2.02, 95% CI=1.43-2.84, p=0.00007, TT vs. CC: OR=2.43, 95% CI=1.59-3.71, p=0.0004; CT vs. CC: OR=1.86, 95% CI=1.30-2.68, p=0.0007) had an impact in the Latino population. Bioinformatics tools showed the effect of these polymorphisms on gene function. These findings suggest that rs11203366, rs11203367, rs874881 and rs1748033 polymorphisms may be genetic risk factors for RA. Moreover, differences between populations suggest that ethnicity may play an important role in the effect of these polymorphisms on RA risk.

The association between dietary inflammatory index with risk rheumatoid arthritis: A case-control study

Diet represents an important set of potential risk factors for rheumatoid arthritis (RA), a known inflammatory condition. This case-control study examined the association between the inflammatory potential of diet, as determined by the dietary inflammatory index (DII®), and RA risk in an Iranian population. The present Case–control study was conducted on 100 RA patients and 200 age- and sex-matched controls in Isfahan, Iran. The presence of RA was determined by expert Rheumatologist assessment based on the American College of Rheumatology definitions. A 168-item food frequency questionnaire was used to collect dietary intake from which DII scores were computed. Odds ratios (OR) and 95 % confidence intervals (CI) for the association between the DII, expressed in tertiles, and RA risk were estimated by two multivariable logistic regression models, one crude model and one in which we controlled for important potential confounders. In the crude model, individuals in the top DII tertile (most pro-inflammatory diet) had more than triple the risk of RA compared to those in the lowest tertile (ORtertile3vs1= 3.57; 95 % CI, 1.95–6.53; p< 0.001). The association was essentially unchanged after controlling for potential confounders (OR tertile3vs1 = 3.83; 95 % CI, 1.66–8.81; p<0.001). We found that a pro-inflammatory diet is associated with increased risk of RA. Higher volume studies are needed to confirm the results.

Dynamics of the gut microbiome in individuals at risk of rheumatoid arthritis: a cross-sectional and longitudinal observational study

ObjectivesThis work aimed to resolve the conflicting reports on Prevotellaceae abundance in the development of rheumatoid arthritis (RA) and to observe structural, functional and temporal changes in the gut microbiome...

Association between vitamin B6 levels and rheumatoid arthritis: a two-sample Mendelian randomization study.

Micronutrients play a crucial role in rheumatoid arthritis (RA). Changes in micronutrient levels in RA patients can lead to the worsening of their condition. Though significant correlations between RA and micronutrients have been found in earlier observational studies, their underlying causal relationship is still unknown. This study aimed to elucidate the causal genetic relationships between 15 micronutrients (copper, zinc, magnesium, vitamins A, C, E, D, B6, B12, folate, carotene, iron, selenium, calcium, potassium) and RA. The exposure factors and outcome data used in the two-sample Mendelian randomization (MR) were derived from publicly available summary statistics data of European populations. The GWAS data for exposure factors were obtained from the OpenGWAS database. For the outcome data of RA, we utilized data from the FinnGen database. We used the MR principle to remove confounding factors and conducted MR analyses using five methods: inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode, with IVW as the primary method. Then, we identified micronutrients related to RA and performed MR analyses on these elements, including heterogeneity analysis and pleiotropy analysis such as MR-Egger intercept, MR-PRESSO method, and "leave-one-out" analysis. Finally, we conducted multivariable MR analyses and performed sensitivity analyses again. The IVW analysis revealed a relationship between vitamin B6 and RA (p: 0.029, OR: 1.766, and 95% CI: 1.062-2.938). Sensitivity analysis confirmed the validity and reliability of this result. This study revealed a causal relationship between vitamin B6 and RA, with vitamin B6 being identified as a risk factor for RA. This finding could contribute to the diagnosis and supplementary treatment of RA patients, providing a reference for subsequent basic research and developing new drugs.

Relationship between albumin and rheumatoid arthritis: Evidence from NHANES and Mendelian randomization.

With the rising incidence of rheumatoid arthritis (RA) and the increasing percentage of serum RF negativity, more and more accurate methods are urgently needed for the early diagnosis and prevention of RA, among which serum albumin (ALB) is closely related to the development of RA, and it is expected to become a new auxiliary diagnostic means, but its relationship with RA is not clear, so the present study aimed to investigate the Causal relationship. In this study, we used a generalized linear model and smoothed curve fitting to comprehensively evaluate the relationship between ALB and RA through the data of ALB and RA in the NHANES database, in addition, we further used inverse variance weighted (IVW) in Mendelian randomization (MR) in conjunction with the other 4 methods to further validate and clarify the causal relationship. The results were also examined for heterogeneity and horizontal pleiotropy to assess whether the results were robust. Finally, we used Bayesian co-localization analysis to clarify that ALB and RA share common genetic loci. In the observational study, after correction for multiple confounders, ALB remained more significantly negatively associated with RA (OR = 0.66, [95% CI = 0.51-0.86], P = .003), and subgroup analyses showed significant negative associations in both men and women (men: OR = 0.67, [95% CI = 0.46-0.99], P = .046; females: OR = 0.66, [95% CI = 0.44-1.00], P = .049). In further MR analysis, IVW: ALB on RA, OR = 0.70 [95% 0.52-0.93], P = .013; RA on ALB, OR = 0.95 [95% CI = 0.93-0.98], P < .001. The results of the MR analyses were in agreement with those of NHANES, which did not share a common genetic locus in co-localization analysis. There is a significant relationship between ALB and RA, and the reduction of ALB may be one of the risk factors for RA, as well as one of the outcomes in the development of RA.

Association between IL-6, miRNA-146a, MALAT1 genetic polymorphisms and risk of rheumatoid arthritis.

Aim: This study aimed to investigate the associations between single nucleotide polymorphisms (SNPs) of IL-6 (-174G/C), microRNA146a (rs2910164C/G) and MALAT1 (rs619586A/G) and susceptibility to rheumatoid arthritis (RA) in Egyptians.Methods: SNPs were genotyped in 101 RA patients and 104 controls. Expression levels were evaluated either by Enzyme-linked immunosorbent assay (ELISA) for IL-6 or quantitative real-time PCR (qRT-PCR) for miR-146a and MALAT1.Results: IL-6-174 GC (OR=3.422) genotype, IL-6-174 C allele (OR=2.565), miR-146a (rs2910164) CG (OR=2.190) and MALAT1 (rs619586) AA (OR=4.125) genotypes and A allele (OR=6.122) could be considered as risk factors for RA. An increase in the expression of IL-6, miR-146a and MALAT1 was detected in RA patients, which was independent of any SNP.Conclusion: SNPs of IL-6, miR-146a and MALAT1were linked to RA predisposition in Egyptians.

Targeting Therapeutic Windows for Rheumatoid Arthritis Prevention.

Rheumatoid arthritis (RA) is a worldwide public health problem. Interventions to delay or prevent the onset of RA have attracted much attention in recent years, and researchers are now exploring various prevention strategies. At present, there is still no unified consensus for RA prevention, but targeting therapeutic windows and implementing interventions for at-risk individuals are extremely important. Due to the limited number of clinical trials on pharmacologic interventions, further studies are needed to explore and establish optimal intervention regimens and effective measures to prevent progression to RA. In this review, we introduce the RA disease process and risk factors, and present research on the use of both Western and Chinese medicine from clinical perspectives regarding RA prevention. Furthermore, we describe several complete and ongoing clinical studies on the use of Chinese herbal formulae for the prevention of RA.

Fcγ-receptor-IIIA bioactivity of circulating and synovial immune complexes in rheumatoid arthritis

ObjectivePrevious technical limitations prevented the proof of Fcγ-receptor (FcγR)-activation by soluble immune complexes (sICs) in patients. FcγRIIIa (CD16) is a risk factor in rheumatoid arthritis (RA). We aimed at determining...

Anti-CCP Antibodies in Unaffected First-Degree Relatives of Rheumatoid Arthritis Patient

Introduction: Rheumatoid arthritis (RA) is perhaps the most common inflammatory arthritis, affecting 0.5% to 1% of the general population worldwide. Environmental and genetic influences are important risk factors for pathogenesis of RA. First-degree relatives (FDRs) of RA patients sharing genetic and environmental risk factors for RA may represent as pre-RA state. Since anti-CCP antibody appears years before the onset of RA, it can be used to estimate risk-potential for future development of RA in unaffected FDRs of RA patient. Objective: To see the serum anti-CCP antibody in unaffected FDRs of RA patients. Materials and Methods: This cross-sectional study was conducted from July 2019 to June 2020 in Department of Biochemistry, Dhaka Medical College, Dhaka. A total number of 50 subjects were selected among which 25 were unaffected FDRs of RA patients and the other 25 were age &amp; gender matched healthy subjects. The related RA patients were selected from Rheumatology outdoor, Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka and the healthy subjects were taken from the attendants came to the same institute who did not have RA patient in their family. The key variables (age and gender) were recorded and outcome variable (anti-CCP antibody in study subjects) was estimated. Statistical analysis was done by SPSS 26.0 and the significance was defined as p &lt; 0.05. Results: Mean age of the FDRs of RA patient was 31.36 ± 10.51 years and that of healthy subjects was 31.56 ± 8.89 years. Most of the participants were in age group 20-29 years followed by 30-39 years. 4% of FDRs of RA patient were anti-CCP antibody positive and no positive case was recorded in healthy subjects. The median level of anti-CCP antibody in FDRs of RA patient was 0.50 U/mL and that in healthy subjects was 0.09 U/mL. The level of significance (p = 0.002) showed that serum anti-CCP antibody level was significantly higher (within normal range) in FDRs of RA patient than in healthy subjects, which was even more significant in FDRs of seropositive RA patients. Conclusion: This study revealed that serum anti-CCP antibody level was significantly higher (within normal range) in FDRs of RA patient than in healthy subjects and the proportion of positive anti-CCP antibody was more in FDRs of RA patient than in healthy subjects. Medicine Today 2024, Vol.36 (2): 76-81

Minor Genetic Overlap Among Rheumatoid Arthritis, Myocardial Infarction, and Myocardial Infarction Risk Determinants.

The aim of this study was to investigate whether a shared genetic susceptibility exists between individuals with rheumatoid arthritis (RA) and individuals with myocardial infarction (MI)-including major MI risk factors-and to quantify the degree of any such overlap. Genome-wide association study (GWAS) data for individuals with RA were constructed from a sample of 26,637 Swedish patients with RA and controls without RA. For patients with MI, GWAS data were obtained from a previously published meta-analysis. Genome-wide genetic correlation was estimated via linkage disequilibrium score regression. LAVA was employed to estimate local genetic correlations in ~2,500 nonoverlapping loci, including the major histocompatibility complex. The controls without RA were used for reference panel data. We also assessed stratified estimates of both genome-wide and local genetic correlation based on subsamples of individuals with seropositive RA and those with seronegative RA. Furthermore, genome-wide genetic correlation was estimated between RA and selected cardiovascular risk factors to elucidate pleiotropic relationships. Following quality control, our GWAS of patients with RA consisted of 25,826 individuas. Genome-wide genetic correlation between patients with RA and MI was estimated to 0.13 (95% confidence interval -0.03 to 0.29). Six regions exhibited significant local genetic correlation, though none harbored any known risk single-nucleotide polymorphisms for either of the two traits. Estimates were similar in both individuals with seropositive RA and those with seronegative RA. No statistically significant genetic correlations were observed between RA risk factors and any of the MI risk factors. Our findings indicate that genetic overlap between patients with RA and MI is minor. Furthermore, genetic overlap between RA and MI risk factors seem unlikely to provide a major contribution to the increased risk of MI observed in patients with RA.

Association between secondhand smoke exposure and rheumatoid arthritis in US never-smoking adults: a cross-sectional study from NHANES

While smoking is widely acknowledged as a risk factor for rheumatoid arthritis (RA), the connection between secondhand smoke (SHS) exposure and RA in never-smoking adults remains limited and inconsistent. This study aims to explore and quantify this association using serum cotinine levels. We conducted a cross-sectional study with 14,940 adults who self-report as never smokers, using National Health and Nutrition Examination Survey data from 1999 to 2018. Based on previous literature, SHS exposure was categorized into four groups according to serum cotinine levels. Compared to individuals in the unexposed group (serum cotinine < 0.05 ng/mL), the adjusted odds ratio (OR) for RA was 1.37 (95% CI 1.14–1.64, p = 0.001) in the low exposure group (serum cotinine at 0.05 to 0.99 ng/mL) after adjusting for covariates. However, no significant association was found in the moderate exposure group (serum cotinine at 1 to 10 ng/mL) or the heavy exposure group (serum cotinine ≥ 10 ng/mL). Furthermore, we detected a non-linear, positively saturated correlation between the cotinine levels after log2 transformation and RA, with a turning point at approximately − 2.756 ng/mL (OR = 1.163, 95% CI 1.073–1.261, p = 0.0002). The stability of the results was confirmed by subgroup analysis.

A review on cardiovascular risk in rheumatoid arthritis

A systemic inflammatory disease known as rheumatoid arthritis (RA) is distinguished by excessive cardiovascular disease (CVD) morbidity and death. Traditional CV risk factors may partially contribute to CV disease in RA. Shared inflammatory mediators, post-translational modifications of peptides/proteins and subsequent immune responses, changes in the composition and function of lipoproteins, increased oxidative stress, and endothelial dysfunction are some of the mechanisms that link RA and CVD. The detailed pathogenetic pathway by which this association between RA and CVD might be explained is still not entirely known. It is crucial for controlling cardiovascular risk in people with RA. Optimizing care of traditional risk factors in addition to those inherent to RA is necessary to lessen the burden caused by CVD. The potential effect of planned Cardiac risk management in these individuals is highlighted by findings for under diagnosis and inadequate treatment of conventional CVD risk factors in RA. Present cardiovascular standards suggest RA patients to be examined for and treated for CVD risk factors without appropriate treatment goals. Utilizing potent anti-rheumatic medications that can reduce disease activity and treating the conventional CV risk factors should both be part of the therapy of CV risk in RA. There is currently insufficient scientific data to develop therapy targets for RA-related CVD risk factors. Thus, more study is required on the traditional CVD risk factor screening and management in RA patients.

Cardiovascular Risk Management In Patients With Rheumatoid Arthritis: A Systematic Review.

Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory joint disease associated with pain, swelling, and morning stiffness. It not only affects the joints but also exhibits many extra-articular manifestations. It is recognized as an independent risk factor for cardiovascular (CV) abnormalities. The possibility of cardiovascular disease (CVD) risk in patients with RA is about twofold higher compared to non-RA individuals. Therefore, early risk assessment and management of risk factors are crucial to reduce the CV morbidity and mortality associated with RA. This systematic literature review summarizes the data available on the management of CVD risk factors in RA. A total of 61 articles from the most reputable journals published between 2013 and 2023 were reviewed, of which seven papers were selected for in-depth analysis. We tried to eliminate bias using various bias-eliminating tools. This analysis considers the proposed solution for CV risk prevention and management in RA patients. Optimal control of disease activity and persistent monitoring of other factors responsible for increased CV events in RA patients is the ultimate management of CV abnormalities. This study summarizes the recommendations for the management of CV risk factors in patients with RA.

Accelerated biological aging as a potential risk factor for rheumatoid arthritis.

Previous studies have suggested a potential correlation between rheumatoid arthritis (RA) and biological aging, but the intricate connections and mechanisms remain elusive. In our study, we focused on two specific measures of biological age (PhenoAge and BioAge), which are derived from clinical biomarkers. The residuals of these measures, when compared to chronological age, are defined as biological age accelerations (BAAs). Utilizing the extensive UK Biobank dataset along with various genetic datasets, we conducted a thorough assessment of the relationship between BAAs and RA at both the individual and aggregate levels. Our observational studies revealed positive correlations between the two BAAs and the risk of developing both RA and seropositive RA. Furthermore, the genetic risk score (GRS) for PhenoAgeAccel was associated with an increased risk of RA and seropositive RA. Linkage disequilibrium score regression (LDSC) analysis further supported these findings, revealing a positive genetic correlation between PhenoAgeAccel and RA. PLACO analysis identified 38 lead pleiotropic single nucleotide polymorphisms linked to 301 genes, providing valuable insights into the potential mechanisms connecting PhenoAgeAccel and RA. In summary, our study has successfully revealed a positive correlation between accelerated biological aging, as measured by BAAs, and the susceptibility to RA.

Association of HLA-DRB1 locus with treatment response to abatacept or TNF inhibitors in patients with seropositive rheumatoid arthritis

The strongest genetic risk factor for rheumatoid arthritis (RA) has been known as HLA-DRB1 based on amino acid positions 11, 71, and 74. This study analyzed the association between specific HLA-DRB1 locus and treatment response to abatacept or TNF inhibitors (TNFi) in patients with seropositive RA. A total of 374 Korean RA patients were treated with abatacept (n = 110) or TNFi (n = 264). Associations between HLA-DRB1 and treatment response after 6 months were analyzed using multivariable logistic regression. Seropositive RA patients with HLA-DRB1 shared epitope (SE) had a favorable response to abatacept (OR = 3.67, P = 0.067) and an inversely associated response to TNFi (OR 0.57, P = 0.058) based on EULAR response criteria, but the difference was not statistically significant in comparison to those without SE. In analyses using amino acid positions of HLA-DRB1, a significant association was found between valine at amino acid position 11 of SE and good response to abatacept (OR = 6.46, P = 5.4 × 10–3). The VRA haplotype also showed a good response to abatacept (OR = 4.56, P = 0.013), but not to TNFi. Our results suggest that treatment response to abatacept or TNFi may differ depending on HLA-DRB1 locus in seropositive RA, providing valuable insights for selecting optimal therapy.

Functional MICA Variants Are Differentially Associated with Immune-Mediated Inflammatory Diseases.

As the principal ligand for NKG2D, MICA elicits the recruitment of subsets of T cells and NK cells in innate immunity. MICA gene variants greatly impact the functionality and expression of MICA in humans. The current study evaluated whether MICA polymorphisms distinctively influence the pathogenesis of psoriasis (PSO), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) in Taiwanese subjects. The distributions of MICA alleles and levels of serum soluble NKG2D were compared between healthy controls and patients with PSO, RA, and SLE, respectively. The binding capacities and cell surface densities of MICA alleles were assessed by utilizing stable cell lines expressing four prominent Taiwanese MICA alleles. Our data revealed that MICA*010 was significantly associated with risks for PSO and RA (PFDR = 1.93 × 10-15 and 0.00112, respectively), while MICA*045 was significantly associated with predisposition to SLE (PFDR = 0.0002). On the other hand, MICA*002 was associated with protection against RA development (PFDR = 4.16 × 10-6), while MICA*009 was associated with a low risk for PSO (PFDR = 0.0058). MICA*002 exhibited the highest binding affinity for NKG2D compared to the other MICA alleles. Serum concentrations of soluble MICA were significantly elevated in SLE patients compared to healthy controls (p = 0.01). The lack of cell surface expression of the MICA*010 was caused by its entrapment in the endoplasmic reticulum. As a prevalent risk factor for PSO and RA, MICA*010 is deficient in cell surface expression and is unable to interact with NKG2D. Our study suggests that MICA alleles distinctively contribute to the pathogenesis of PSO, RA, and SLE in Taiwanese people.

Re-evaluating the mythical divide between traditional and novel cardiovascular risk factors in rheumatoid arthritis

Cardiovascular (CV) risk factors for rheumatoid arthritis (RA) are conventionally classified as ‘traditional‘ and ‘novel‘. We argue that this classification is obsolete and potentially counterproductive. Further, we discuss problems with...

Potential association of genetically predicted lipid and lipid-modifying drugs with rheumatoid arthritis: A Mendelian randomization study.

Past studies have demonstrated that patients diagnosed with rheumatoid arthritis (RA) often exhibit abnormal levels of lipids. Furthermore, certain lipid-modifying medications have shown effectiveness in alleviating clinical symptoms associated with RA. However, the current understanding of the causal relationship between lipids, lipid-modifying medications, and the risk of developing RA remains inconclusive. This study employed Mendelian randomization (MR) to investigate the causal connection between lipids, lipid-modifying drugs, and the occurrence of RA. We obtained genetic variation for lipid traits and drug targets related to lipid modification from three sources: the Global Lipids Genetics Consortium (GLGC), UK Biobank, and Nightingale Health 2020. The genetic data for RA were acquired from two comprehensive meta-analyses and the R8 of FINNGEN, respectively. These variants were employed in drug-target MR analyses to establish a causal relationship between genetically predicted lipid-modifying drug targets and the risk of RA. For suggestive lipid-modified drug targets, we conducted Summary-data-based Mendelian Randomization (SMR) analyses and using expression quantitative trait loci (eQTL) data in relevant tissues. In addition, we performed co-localization analyses to assess genetic confounders. Our analysis revealed no significant causal relationship between lipid and RA. We observed that the genetically predicted 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) -mediated low density lipoprotein cholesterol (LDL-C) (OR 0.704; 95% CI 0.56, 0.89; P = 3.43×10-3), Apolipoprotein C-III (APOC3) -mediated triglyceride (TG) (OR 0.844; 95% CI 0.77, 0.92; P = 1.50×10-4) and low density lipoprotein receptor (LDLR) -mediated LDL-C (OR 0.835; 95% CI 0.73, 0.95; P = 8.81×10-3) were significantly associated with a lowered risk of RA. while Apolipoprotein B-100 (APOB) -mediated LDL-C (OR 1.212; 95%CI 1.05,1.40; P = 9.66×10-3) was significantly associated with an increased risk of RA. Our study did not find any supporting evidence to suggest that lipids are a risk factor for RA. However, we observed significant associations between HMGCR, APOC3, LDLR, and APOB with the risk of RA.

Effect of dietary interventions on nutritional status in patients with rheumatoid arthritis and spondyloarthritis - A systematic review and meta-analysis

Background & AimPatients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) have an increased risk of developing altered body composition, such as low muscle mass, and an increased risk of developing cardiovascular diseases (CVD).Thus, investigating how to improve body composition and CVD risk factors is a relevant topic to improve management of RA and SpA. The aim of this study was to identify dietary interventions that can improve body composition, as well as reduce CVD risk factors in RA and SpA. MethodsWe searched the databases Medline, Embase and Cochrane. Duplicates were removed using Endnote and records were screened through Rayyan. The primary outcomes were muscle mass (kg) and fat mass (kg). Secondary outcomes were body weight (kg), body mass index (BMI: kg/m2), waist circumference (cm) and lipid profile (total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, mmol/L). ResultsA total of 4965 articles were identified, and 17 articles were included in this review, of which 15 were suitable for meta-analysis. We found a reduction in TC and LDL-C, (Mean difference, [95%CI]: -0.36, [-0.63, -0.10], I2 =43%, and -0.20, [-0.35, -0.05], I2=0% respectively). Otherwise, no other significant effect was seen in either primary or secondary outcomes. The evidence was graded as moderate for TC and low for LDL-C. ConclusionDietary interventions might reduce the levels of blood lipids, and consequently, the risk of cardiovascular diseases. However, body composition did not change significantly after a 2-4 month dietary intervention. Both short intervention period and lack of reliable methods to assess body composition are possible explanations for this finding. Further studies of longer duration are needed.