CVD in RA patients Personal non-commercial use only

ABSTRACT. Objective. To evaluate the incidence of cardiovascular disease (CVD) among Greek patients with rheumatoid arthritis (RA) under medical followup, and to assess the contribution of traditional CVD and RA-specific factors associated with CVD development. Methods. This is a historic cohort study; information was collected from medical records of patients who had > 2 years' followup. Sociodemographic, clinical, laboratory, and therapeutic variables were evaluated for association with development of CVD. Results. A total of 325 RA patients were studied: 250 women, mean age at RA onset 44 ± 15 years, and 75 men, mean age at RA onset 51 ± 15 years; median followup was 10 years. Fourteen women (5.6%) and 12 men (16%) developed CVD (p = 0.004). Multi-adjusted analysis revealed that hypertension (hazard ratio 3.76, 95% CI 0.99-15.06) was associated with incidence of CVD; late age at disease onset (HR 1.07, 95% CI 1.04-1.11), elevated C-reactive protein (CRP) level 1 year after start of followup (HR 1.03, 95% CI 1.00-1.05), and leflunomide treatment (HR per 1 year of treatment = 1.02, 95% CI 1.00-1.05) were also positively associated with CVD development. Conclusion. Hypertension was an important risk factor for CVD development in patients with RA

Replication of recently identified systemic lupus erythematosus genetic associations: a case–control study

Introduction We aimed to replicate association of newly identified systemic lupus erythematosus (SLE) loci. Methods We selected the most associated SNP in 10 SLE loci. These 10 SNPs were analysed in 1,579 patients with SLE and 1,726 controls of European origin by single-base extension. Comparison of allele frequencies between cases and controls was done with the Mantel–Haenszel approach to account for heterogeneity between sample collections. Results A previously controversial association with a SNP in the TYK2 gene was replicated (odds ratio (OR) = 0.79, P = 2.5 × 10-5), as well as association with the X chromosome MECP2 gene (OR = 1.26, P = 0.00085 in women), which had only been reported in a single study, and association with four other loci, 1q25.1 (OR = 0.81, P = 0.0001), PXK (OR = 1.19, P = 0.0038), BANK1 (OR = 0.83, P = 0.006) and KIAA1542 (OR = 0.84, P = 0.001), which have been identified in a genome-wide association study, but not found in any other study. All these replications showed the same disease-associated allele as originally reported. No association was found with the LY9 SNP, which had been reported in a single study. Conclusions Our results confirm nine SLE loci. For six of them, TYK2, MECP2, 1q25.1, PXK, BANK1 and KIAA1542, this replication is important. The other three loci, ITGAM, STAT4 and C8orf13-BLK, were already clearly confirmed. Our results also suggest that MECP2 association has no influence in the sex bias of SLE, contrary to what has been proposed. In addition, none of the other associations seems important in this respectThe present work was supported by Fondo de Investigacion Sanitaria of the Instituto de Salud Carlos III (Spain), grants 04/1651 and 06/0620 that are partially financed by the Fondo Europeo de Desarrollo Regional program of the European Union, by grants from the Xunta de Galicia, and by BMBF KN Rheuma grant C2.12 (to TW)S

Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA Study

Introduction Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA). Methods The cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents. Results Women had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P LT 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P LT 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but the statistical significance was marginal. Similar proportions of females and males were taking different therapies. Conclusions In this large multinational cohort, RA disease activity measures appear to be worse in women than in men. However, most of the gender differences in RA disease activity may originate from the measures of disease activity rather than from RA disease activity itself

Addressing the clinical unmet needs in primary Sjögren's Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts

For many decades, the clinical unmet needs of primary Sjögren's Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs. © 2022 The Author(s

:2; Personal non-commercial use only

ABSTRACT. Objective. To evaluate the incidence of cardiovascular disease (CVD) among Greek patients with rheumatoid arthritis (RA) under medical followup, and to assess the contribution of traditional CVD and RA-specific factors associated with CVD development. Methods. This is a historic cohort study; information was collected from medical records of patients who had > 2 years' followup. Sociodemographic, clinical, laboratory, and therapeutic variables were evaluated for association with development of CVD. Results. A total of 325 RA patients were studied: 250 women, mean age at RA onset 44 ± 15 years, and 75 men, mean age at RA onset 51 ± 15 years; median followup was 10 years. Fourteen women (5.6%) and 12 men (16%) developed CVD (p = 0.004). Multi-adjusted analysis revealed that hypertension (hazard ratio 3.76, 95% CI 0.99-15.06) was associated with incidence of CVD; late age at disease onset (HR 1.07, 95% CI 1.04-1.11), elevated C-reactive protein (CRP) level 1 year after start of followup (HR 1.03, 95% CI 1.00-1.05), and leflunomide treatment (HR per 1 year of treatment = 1.02, 95% CI 1.00-1.05) were also positively associated with CVD development. Conclusion. Hypertension was an important risk factor for CVD development in patients with RA

Analysis of SAA1 gene polymorphisms in the Greek population: rheumatoid arthritis and FMF patients relative to normal controls. Homogeneous distribution and low incidence of AA amyloidosis

Objective. To address whether or not the rarity of amyloidosis in Greek patients with rheumatoid arthritis (RA) is related to specific alleles of single nucleotide polymorphisms (SNPs) in the 5’-flanking region and the exon 3 of the SSA1 gene. Methods. The genotypes of the - 13T/C SNP in the 5’-flanking region of the SAA1 gene and the two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined in 88 Greek patients with RA, 14 patients with familial Mediterranean fever (IMF) and 110 healthy controls. Linkage disequilibrium and haplotype frequencies involving - 13T/C, 2995C/T and 3010C/T in these populations were tested and estimated, respectively. Results. The genotypic distribution and allelic frequencies were similar in all groups tested. SNPs 2995 and 3010 were in linkage disequilibrium for all study populations (p < 0.05), whereas SNP - 13 was not in linkage disequilibrium with either 2995 or 3010 (p >= 0.05). Two major haplotypes presented in all patients with RA and FMF and controls: - 13C; 2995T; 3010C (- 13C; alpha) and - 13C; 2995C; 3010T (- 13C; beta). The - 13T allele was linked with the 7 haplotype in Greek patients with RA and controls. The frequency of the - 13T allele was found to be very rare in all groups tested. Conclusions. In conclusion, the rarity of the putative amyloidogenic - 13T allele in Greek populations may be related to low prevalence of AA amyloidosis development in Greek RA patients