Ideal cardiovascular health in women with systemic lupus erythematosus: Association with arterial stiffness, inflammation, and fitness.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is closely related to cardiovascular morbidity and mortality. We aimed to examine the association of ideal cardiovascular health (ICH) with arterial stiffness, inflammation, and physical fitness in women with SLE. METHODS: This cross-sectional study included 76 women with SLE (age 43.4±13.8 years old). Ideal levels of 7 health metrics (smoking, body mass index, physical activity, healthy diet, blood pressure, cholesterol, and glucose) were used to define the ICH score (ranging from 0 to 7 ideal metrics) and the ICH status ( defined as presenting ≥4 ideal metrics). Arterial stiffness was measured through pulse wave velocity (PWV) and inflammation through serum high sensitivity C-reactive protein (hs-CRP). Cardiorespiratory fitness (CRF) was measured by 6-min walk test (6MWT), and Siconolfi step test and muscular strength by handgrip strength and 30-s chair stand, and range of motion (ROM) by the back-scratch test. RESULTS: Higher ICH score was associated with lower PWV (ß = -0.122, p = 0.002), lower hs-CRP (ß = -0.234, p = 0.056), higher CRF [6MWT (ß = 0.263, p = 0.041); Siconolfi step test (ß = 0.330, p < 0.001)], higher ROM (ß = 0.278, p = 0.013) and higher relative handgrip strength (ß = 0.248, p = 0.024). Women with ICH status presented lower PWV (mean difference 0.40 m/s, 95% CI 0.17 to 0.63, p = 0.001), and higher CRF [assessed by 6MWT (mean difference 43.9 m, 95% CI 5.0 to 82.7, p = 0.028)], than women with non-ICH status. Sensitivity analyses using ICH score ranging 0-14 and considering ICH status with ≥5 metrics revealed consistent results. CONCLUSION: ICH is associated with lower arterial stiffness, lower inflammation, and higher fitness in women with SLE. Although these results extend current knowledge about the potential role of ICH for primordial prevention of CVD in SLE, they are yet to be confirmed in future prospective research .

Association of physical fitness components and health-related quality of life in women with systemic lupus erythematosus with mild disease activity.

OBJECTIVES: To study the association of different components of physical fitness [flexibility, muscle strength and cardiorespiratory fitness (CRF)] and a clustered fitness score with health-related quality of life (HRQoL) in women with systemic lupus erythematosus (SLE) and to analyze whether participants with high fitness level have better HRQoL. METHODS: This cross-sectional study included 70 women with SLE (aged 42.5; SD 13.9 years). The back-scratch test assessed flexibility, the 30-sec chair stand and handgrip strength tests assessed muscle strength, and the 6-min walk test (n = 49) assessed CRF. HRQoL was assessed through the 36-item Short-Form Health Survey (SF-36). RESULTS: Flexibility was positively associated with the physical function dimension and the physical component summary (PCS) (rpartial between 0.26 and 0.31; p<0.05), and negatively related with social functioning dimension (rpartial = -0.26; p<0.05). Muscle strength was positively associated with the physical function, physical role, bodily pain dimensions and the PCS (rpartial between 0.27 and 0.49; all p<0.05). CRF was positively associated with the physical function and bodily pain dimensions, and PCS (rpartial between 0.39 and 0.65; all p<0.05). The clustered fitness score was associated with the physical function (B = 17.16) and bodily pain (B = 14.35) dimensions, and the PCS (B = 6.02), all p<0.005. Patients with high fitness level had greater scores in the physical function, physical role, and bodily pain dimensions and the PCS, all p≤0.05. CONCLUSIONS: Our study suggests that muscle strength and CRF are positively associated with HRQoL, while flexibility showed contradictory results. These findings highlight the importance of maintaining adequate fitness levels in women with SLE.

Association of objectively measured physical activity and sedentary time with arterial stiffness in women with systemic lupus erythematosus with mild disease activity.

OBJECTIVES: To examine the association of objectively measured physical activity (PA) intensity levels and sedentary time with arterial stiffness in women with systemic lupus erythematosus (SLE) with mild disease activity and to analyze whether participants meeting the international PA guidelines have lower arterial stiffness than those not meeting the PA guidelines. METHODS: The study comprised 47 women with SLE (average age 41.2 [standard deviation 13.9]) years, with clinical and treatment stability during the 6 months prior to the study. PA intensity levels and sedentary time were objectively measured with triaxial accelerometry. Arterial stiffness was assessed through pulse wave velocity, evaluated by Mobil-O-Graph® 24h pulse wave analysis monitor. RESULTS: The average time in moderate to vigorous PA in bouts of ≥10 consecutive minutes was 135.1±151.8 minutes per week. There was no association of PA intensity levels and sedentary time with arterial stiffness, either in crude analyses or after adjusting for potential confounders. Participants who met the international PA guidelines did not show lower pulse wave velocity than those not meeting them (b = -0.169; 95% CI: -0.480 to 0.143; P = 0.280). CONCLUSIONS: Our results suggest that PA intensity levels and sedentary time are not associated with arterial stiffness in patients with SLE. Further analyses revealed that patients with SLE meeting international PA guidelines did not present lower arterial stiffness than those not meeting the PA guidelines. Future prospective research is needed to better understand the association of PA and sedentary time with arterial stiffness in patients with SLE.

Effect of ethnicity on clinical presentation and risk of antiphospholipid syndrome in Roma and Caucasian patients with systemic lupus erythematosus: a multicenter cross-sectional study.

AIM: To determine if there are ethnic differences in the prevalence of antiphospholipid syndrome (APS), clinical presentation and autoantibody profile between Roma and Caucasian patients with systemic lupus erythematosus (SLE). METHOD: A cross-sectional study was conducted including data from Roma and Caucasian SLE patients consecutively attending six hospitals in Spain. Socio-demographic characteristics, prevalence of APS, clinical and analytical features of SLE and APS were compared between ethnic groups. RESULTS: Data from 52 Roma and 98 Caucasian SLE patients were included. Roma SLE patients had a higher risk (odds ratio 2.56, 95% CI 1.02-6.39) and prevalence of APS (28.8% vs. 13.3%, P = 0.027). Furthermore, Roma SLE patients had a statistically significant higher prevalence of abortions (23.5% vs. 10.2%, P = 0.049). In relation to other APS diagnostic criteria, Roma SLE patients had a non-statistically significant higher prevalence of fetal deaths (14.3% vs. 5.1%, P = 0.106) and thrombotic events (21.1% vs. 12.2%, P = 0.160). In relation to SLE clinical features, Roma patients had a significantly higher prevalence of arthritis (75% vs. 57.1%, P = 0.034) and non-significant higher prevalence of serositis (44.2% vs. 29.6%, P = 0.104), discoid lesions (11.5% vs. 5.1%, P = 0.191), oral ulcers (46.1% vs. 34.7%, P = 0.218) and livedo reticularis (21.1% vs. 15.3%, P = 0.374). No statistically significant differences were found in the Systemic Lupus International Collaborating Clinics Damage Index or the autoimmune serological profile. CONCLUSION: Prevalence and risk of APS were significantly higher in Roma SLE patients. Furthermore, Roma patients had a significantly higher prevalence of abortions and a non-significant higher prevalence of fetal deaths and thrombotic events.

Sleep quality, clinical and psychological manifestations in women with systemic lupus erythematosus.

AIM: Sleep problems are a common complaint in systemic lupus erythematosus (SLE) patients. We analyzed sleep quality with subjective and objective measures in a sample with SLE and its possible relationships with the main manifestations of the disease. METHODS: Twenty-one women with SLE and 20 healthy women participated in the study. All participants were evaluated with actigraphy for a week and they completed self-report instruments of sleep quality, quality of life, fatigue, anxiety, depression and perceived stress. Comparison analyses between the two groups were done using Chi-square and Student's t-tests. The association between sleep quality and the remaining variables was explored using Pearson correlation coefficients. RESULTS: SLE patients had higher fragmentation index in the actigraphic analysis and a perception of poorer sleep quality, more fatigue, anxiety and depression than the control group. Bivariate analyses showed that the perception of more sleep disturbance and daytime dysfunction was associated with a lower health-related quality of life, more fatigue, emotional discomfort and more perceived stress. Also, the fragmentation index in the actigraphy was significantly related to the perception of poorer quality of sleep. CONCLUSION: SLE women had a poorer sleep quality (objective and subjective). These alterations could play a modulatory role in clinical and psychological manifestations of the disease and affect the quality of life in this population. More research is needed to clarify these relations and to determine the potential benefits of interventions directed to improve sleep in the clinical managing of the patients with SLE.

A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.

Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21,109 (6835 cases and 14,274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10(-11), OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10(-11), OR = 1.20) and JAZF1 (P = 1.11 × 10(-8), OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.

A 3'-untranslated region variant is associated with impaired expression of CD226 in T and natural killer T cells and is associated with susceptibility to systemic lupus erythematosus.

OBJECTIVE: Costimulatory receptor CD226 plays an important role in T cell activation, differentiation, and cytotoxicity. This study was undertaken to investigate the genetic association of CD226 with susceptibility to systemic lupus erythematosus (SLE) and to assess the functional implications of this association. METHODS: Twelve tag single-nucleotide polymorphisms (SNPs) in CD226 were typed in 1,163 SLE patients and 1,482 healthy control subjects from Europe or of European ancestry. Analyses of association were performed by single-marker Cochran-Mantel-Haenszel meta-analysis, followed by haplotype analysis. Gene expression was analyzed by quantitative real-time polymerase chain reaction analyses of RNA from peripheral blood mononuclear cells, and by fluorescence-activated cell sorter analysis. To study the functional impact of the associated variants, luciferase reporter constructs containing different portions of the 3'-untranslated region (3'-UTR) of the gene were prepared and used in transfection experiments. RESULTS: A 3-variant haplotype, rs763361;rs34794968;rs727088 (ATC), in the last exon of CD226 was associated with SLE (P = 1.3 × 10(-4) , odds ratio 1.24, 95% confidence interval 1.11-1.38). This risk haplotype correlated with low CD226 transcript expression and low CD226 protein levels on the surface of CD4+ and CD8+ T cells and natural killer T (NKT) cells. NK cells expressed high levels of CD226, but this expression was independent of the haplotype. Reporter assays with deletion constructs indicated that only the presence of rs727088 could account for the differences in the levels of luciferase transcripts. CONCLUSION: This study identified an association of CD226 with SLE in individuals of European ancestry. These data support the importance of the 3'-UTR SNP rs727088 in the regulation of CD226 transcription both in T cells and in NKT cells.

Association of a CD24 gene polymorphism with susceptibility to systemic lupus erythematosus.

OBJECTIVE: To determine the potential role of the CD24 A57V gene polymorphism in systemic lupus erythematosus (SLE). METHODS: We studied 3 cohorts of Caucasian patients and controls. The Spanish cohort included 696 SLE patients and 539 controls, the German cohort included 257 SLE patients and 317 controls, and the Swedish cohort included 310 SLE patients and 247 controls. The CD24 A57V polymorphism was genotyped by polymerase chain reaction, using a predeveloped TaqMan allele discrimination assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: In the Spanish cohort there was a statistically significant difference in the distribution of the CD24 V allele between SLE patients and controls (OR 3.6 [95% CI 2.13-6.16], P < 0.0001). In addition, frequency of the CD24 V/V genotype was increased in SLE patients compared with controls (OR 3.7 [95% CI 2.16-6.34], P < 0.00001). We sought to replicate this association with SLE in a German population and a Swedish population. A similar trend was found in the German group. The CD24 V/V genotype and the CD24 V allele were more frequent in SLE patients than in controls, although this difference was not statistically significant. No differences were observed in the Swedish group. A meta-analysis of the Spanish and German cohorts demonstrated that the CD24 V allele has a risk effect in SLE patients (pooled OR 1.25 [95% CI 1.08-1.46], P = 0.003). In addition, homozygosity for the CD24 V risk allele significantly increased the effect (pooled OR 2.19 [95% CI 1.50-3.22], P = 0.00007). CONCLUSION: These findings suggest that the CD24 A57V polymorphism plays a role in susceptibility to SLE in a Spanish population.

Association study of genetic variants of pro-inflammatory chemokine and cytokine genes in systemic lupus erythematosus.

BACKGROUND: Several lines of evidence suggest that chemokines and cytokines play an important role in the inflammatory development and progression of systemic lupus erythematosus. The aim of this study was to evaluate the relevance of functional genetic variations of RANTES, IL-8, IL-1alpha, and MCP-1 for systemic lupus erythematosus. METHODS: The study was conducted on 500 SLE patients and 481 ethnically matched healthy controls. Genotyping of polymorphisms in the RANTES, IL-8, IL-1alpha, and MCP-1 genes were performed using a real-time polymerase chain reaction (PCR) system with pre-developed TaqMan allelic discrimination assay. RESULTS: No significant differences between SLE patients and healthy controls were observed when comparing genotype, allele or haplotype frequencies of the RANTES, IL-8, IL-1alpha, and MCP-1 polymorphisms. In addition, no evidence for association with clinical sub-features of SLE was found. CONCLUSION: These results suggest that the tested functional variation of RANTES, IL-8, IL-1alpha, and MCP-1 genes do not confer a relevant role in the susceptibility or severity of SLE in the Spanish population.

Analysis of a GT microsatellite in the promoter of the foxp3/scurfin gene in autoimmune diseases.

The aim of this study was to assess the possible association of the functional (GT)(n) microsatellite polymorphism in the FOXP3 gene with predisposition to several autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ulcerative colitis (UC), Crohn's disease, and celiac disease. We analyzed a case-control cohort composed of 231 SLE patients, 293 RA patients, 528 inflammatory bowel disease (354 Crohn's disease patients and 260 UC patients) patients, 103 celiac disease patients, and 274 healthy controls ethnically matched. Genotyping of (GT)(n) microsatellite was performed by polymerase chain reaction (PCR)-based method combined with fluorescent technology. We found no evidence for association of this polymorphism between controls and these autoimmune disease patients. Additionally, no differences in the genotype and allele distribution were found when patients were stratified according to clinical manifestation. The (GT)(n) microsatellite of the FOXP3 gene may not play a relevant role in the susceptibility to SLE, RA, inflammatory bowel disease, and celiac disease in our population.