Search

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.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.Higher ICH score was associated with lower PWV (β = -0.122, p = 0.002), lower hs-CRP (β = -0.234, p = 0.056), higher CRF [6MWT (β = 0.263, p = 0.041); Siconolfi step test (β = 0.330, p 0.001)], higher ROM (β = 0.278, p = 0.013) and higher relative handgrip strength (β = 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.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 .

BACKGROUND AND AIMS Cardiovascular disease (CVD) is one of the principal causes of death in antineutrophil cytoplasmic antibody-(ANCA)-associated vasculitis (AAV), partly due to the vascular inflammation itself, the associated organic damage and the treatment [1]. AAV has been associated with traditional risk factors, such as hypertension (HTN), diabetes mellitus (DM) or impared renal function [2], which also contribute to accelerated atherosclerosis. However, there are not specific recommendations about CVD treatment in AAV patients [3], and the vascular risk scores used for general population have not been extrapolated yet. Our objective is to assess the frequency of cardiovascular events (CVE) and mortality in AAV patients and to explore the possible vascular risk factors (VRF) and the therapeutic intervention on them. METHOD A descriptive and retrospective study of a multidisciplinary cohort of AAV patients followed prospectively was performed in 12 hospitals of the 8 provinces of Autonomous Community of Andalusia. Factors that presumably may influence in CVD and mortality were collected. Two CV risk scores were measured [4, 5]. The presence of a strategy carried out by clinicians on CV risk was analysed according guides ESC/ESH and KDIGO guides. Data was analysed using Chi-square, ANOVA and Cox proportional hazards regresion as uni and multivariate test with a 95% confidence interval. RESULTS A multicentre cohort of 220 AAV patients followed up from 1979 until June 2020 was studied, during a mean ± standard deviation follow-up of 96.79 ± 75.83 months. The mean age at diagnosis was 59.92 ± 16.25 years, 45% were female and all but one caucasians. Sociodemographic and clinical characteristics are shown in Table 1. After AAV diagnosis, 30/224 (13%) patients presented at least one CVE (Figure 1A and B), 37% IHD, 43% CVA and 50% PVD. Independent prognostic factors of CVE were age (HR 1.042, P = .005) and the presence of hypertension (HTN) 6 months after diagnosis (HR 4.641, P = .01). Regarding classic VRFs, 81% had HTN [33% already presented it before diagnosis and 48% after (35% in the first 6 months)]. Thirty-four patients presented DM at the end of following [12% already presented it before diagnosis and 22% presented it after (16% in the first 6 months)]. The independent predictor for HTN at 6 months was renal involvement at BVAS baseline, and DM in the first 6 months for HTN at the end of following. Attending to the ESC Vascular Risk scale, 8.4% presented low risk, 16.9% moderate, 29.8 high and 44.4% very high risk. According to the REGICOR scale, the mean value of suffering a CV event in the next 10 years was 4.6%±3.32%, with 59%, 34% and 7% of patients presenting low, moderate and high risk, respectively. Regarding VRF management strategies, just 14% of hypertensive patients, 16.2% of those that needed dyslipidemia treatment, and 8.6% of diabetic patients were not within the target guidelines recommendations. Fifty-one patients (23%) died (Figure 1C and D), 23.5% due to infectuous disease, 19.6% to cancer, 17.6% to CVD,13.7% to AAV relapse and 13 due to organic deficit, other or an unknown cause. In our final model of multivariate analysis, just age and renal function at baseline were independent predictors of mortality. Independent prognostic factors of mortality were age (HR 1.083, P = .00) and baseline creatinine (HR 4.41, P = .01). CONCLUSION Age and early HTN are risk factors for having a CVE, and age and renal function are predictors of mortality. HTN are more frecuent in AAV patients than in general population. CVD screening in AAV patients is demanded. The REGICOR and ESC scores could be extrapolated as a predictor of cardiovascular risk in AAV patients.

Objective The objective of this study was to determine the safety of tattoos in patients with systemic lupus erythematosus (SLE). Methods Patients ( N = 147; ≤55 years; 92% women) were asked if they had tattoos. The characteristics of the tattoos and the immediate complications were investigated and compared with those of a matched control group. We examined retrospectively after the tattoo was completed whether there had been flare-ups or increased organ damage (Systemic Lupus International Collaborating Clinics/American Collage of Rheumatology Damage Index (SDI)). Finally, we compared the SLE-related characteristics of patients with and without tattoos. Results Twenty-eight patients (19%, 26 women, median (interquartile range) age 33 (25–42) years, 65 tattoos in total) had ≥1 tattoo. At the time the tattoo was done the median (interquartile range) SLEDAI and SDI were 2 (0–2) and 0 (0–1), respectively. The characteristics of the tattoos were similar to those of controls. No patients experienced acute complications. After a median follow-up of 17 (12–20) months (3 (2–4) visits/year) four patients had five mild-to-moderate flare-ups. The median time between the tattoo and the flare-up was 9 (6–14) months. No increase in SDI was observed. The SLE-related characteristics of patients with and without tattoos were similar. Conclusion Tattoos seem to be safe in SLE patients with inactive or low active disease.

Abnormal heart rate variability (HRV) has been observed in patients with systemic lupus erythematosus (SLE). In a combined cross-sectional and interventional study approach, we investigated the association of HRV with inflammation and oxidative stress markers, patient-reported outcomes, and the effect of 12 weeks of aerobic exercise in HRV. Fifty-five women with SLE (mean age 43.5 ± 14.0 years) were assigned to either aerobic exercise (n = 26) or usual care (n = 29) in a non-randomized trial. HRV was assessed using a heart rate monitor during 10 min, inflammatory and oxidative stress markers were obtained, psychological stress (Perceived Stress Scale), sleep quality (Pittsburg Sleep Quality Index), fatigue (Multidimensional Fatigue Inventory), depressive symptoms (Beck Depression Inventory), and quality of life (36-item Short-Form Health Survey) were also assessed. Low frequency to high frequency power (LFHF) ratio was associated with physical fatigue (p = 0.019). Sample entropy was inversely associated with high-sensitivity C-reactive protein (p = 0.014) and myeloperoxidase (p = 0.007). There were no significant between-group differences in the changes in HRV derived parameters after the exercise intervention. High-sensitivity C-reactive protein and myeloperoxidase were negatively related to sample entropy and physical fatigue was positively related to LFHF ratio. However, an exercise intervention of 12 weeks of aerobic training did not produce any changes in HRV derived parameters in women with SLE in comparison to a control group., Fundacion para la Investigacion Biosanitaria de Andalucia Oriental PI-0525-2016 PIER-0223-2019, Spanish Ministry of Universities FPU18/01107

I read with great interest, the recently published article in your journal titled ‘Withdrawal of low-dose prednisone in systemic lupus erythematosus (SLE) patients with a clinically quiescent disease for more than 1 year: a randomised clinical trial’ by Mathian et al .1 In this article, the authors conclude that the maintenance of long-term 5 mg prednisone in SLE patients with inactive disease prevents relapses. In the recent update of European League Against Rheumatism (EULAR) recommendations for the management of SLE,2 the experts say that the …

To evaluate the effects of aerobic exercise on patient-reported outcomes (PROs) in women with systemic lupus erythematosus (SLE), and whether changes in cardiorespiratory fitness (CRF) mediate the changes in PROs. A total of 58 women with SLE were assigned to either an exercise group (EG; n = 26) or a control group (CG; n = 32) in this non-randomized clinical trial. The EG comprised 12 weeks of aerobic exercise (2 sessions/week) between 40%-75% of the individual’s heart rate reserve. At baseline, and at week 12, CRF (Bruce test) and PROs were assessed including psychological stress (Perceived Stress Scale), sleep quality (Pittsburg Sleep Quality Index), fatigue (Multidimensional Fatigue Inventory), depressive symptoms (Beck Depression Inventory), and quality of life (36-item Short-Form Health Survey). In comparison to the CG, the EG showed a significant reduction in general fatigue (mean difference (MD) −2.86 units; 95%CI −5.70 to −0.01; p = 0.049), physical fatigue (MD −4.33 units; 95%CI −7.02 to −1.65; p = 0.002) and a non-significant reduction of reduced motivation (MD − 1.29 units; 95%CI −2.60 to 0.03; p = 0.055). There were no significant between-group differences in the changes in psychological stress, sleep quality, depressive symptoms, quality of life, or other fatigue dimensions (all p > 0.05). Changes in CRF mediated the effects of the exercise intervention on general fatigue by 53.8%. The results suggest that 12 weeks of progressive aerobic exercise might improve relevant dimensions of fatigue in women with SLE, despite the absence of effects on other PROs. Improvements in CRF seem to mediate the effect of exercise on general fatigue.Implications for rehabilitationAerobic exercise could be safely introduced in rehabilitation programs for inactive patients with SLE with mild disease activity.Including physical activity recommendations as part of rehabilitation could improve relevant aspects of fatigue in women with SLE.When rehabilitation aims at reducing fatigue, cardiorespiratory fitness improvements derived from physical activity might enhance benefits. Aerobic exercise could be safely introduced in rehabilitation programs for inactive patients with SLE with mild disease activity. Including physical activity recommendations as part of rehabilitation could improve relevant aspects of fatigue in women with SLE. When rehabilitation aims at reducing fatigue, cardiorespiratory fitness improvements derived from physical activity might enhance benefits.

Background and objective Non-adherence to treatment is usually a clinical problem in patients with systemic lupus erythematosus (SLE). Increasing the knowledge of predictors of treatment adherence can be meaningful in the clinical setting. The main objective of the present study was to analyze the influence of sociodemographic, clinical and psychological variables on the degree of treatment adherence in a sample of Spanish women with SLE. Patients and method This is an observational–transversal study. All participants were evaluated for the degree of treatment adherence, their clinical status, psychopathological manifestations, the level of perceived stress and self-efficacy. The sample was divided into two groups (adherent vs non-adherent). The factors associated with a lack of adherence in this sample were analyzed by means of logistic regression. Results This study comprises 72 women with SLE (average age = 36.72 ± 12.2 years). Almost 64% of patients with SLE were non-adherent to treatment. The results showed that a low educational level, being unemployed, living with a partner and alcohol abuse were associated with low treatment adherence. There were significant mean differences between groups in psychopathological subscales of somatization, obsession–compulsion and general psychopathological indices. There were also mean differences between groups for the level of perceived stress. The use of non-steroidal anti-inflammatory drugs, suffering arthrosis and scoring higher in dimensions of psychopathology were significant predictors of treatment adherence, explaining between 35% and 47% of its variability. Conclusions Including the clinical and psychopathological manifestations as important aspects in the clinical reasoning of health professionals could improve the adherence to treatment of patients with SLE.

Resumen Antecedentes y objetivo El incumplimiento terapeutico constituye un importante problema asistencial en pacientes con lupus eritematoso sistemico (LES). Conocer los factores asociados de este puede ser de gran utilidad en el ambito clinico. El objetivo de esta investigacion fue analizar la influencia de las variables sociodemograficas, clinicas y psicologicas sobre la adherencia al tratamiento en una muestra espanola de mujeres con LES. Pacientes y metodo En este estudio transversal-observacional se evaluo el grado de adherencia al tratamiento, el estado clinico y psicopatologico, el estres psicologico y la autoeficacia en mujeres con LES. La muestra se dividio en 2 grupos: adherentes y no adherentes. Mediante un analisis de regresion logistica se identificaron los factores asociados a la falta de adherencia en esta poblacion. Resultados Se evaluaron 72 pacientes (edad media: 36,7 ± 12,2 anos). El 63,9% no tuvieron adherencia. Un bajo nivel educativo, estar desempleada, vivir en pareja y el consumo de alcohol se asociaron a una baja adhesion al tratamiento. Se encontraron diferencias entre el grupo adherente y el no adherente en las subescalas psicopatologicas de somatizacion, obsesion-compulsion e indices psicopatologicos generales, asi como en el estres percibido, obteniendo puntuaciones mas altas las pacientes adherentes. El uso de antiinflamatorios no esteroideos (AINE), tener artrosis y mayor alteracion psicopatologica fueron predictores significativos de la adherencia al tratamiento, explicando entre el 35 y el 47% de la variabilidad de esta. Conclusiones La falta de adherencia al tratamiento de las pacientes con LES fue alta y parece estar influida por factores clinicos y psicopatologicos.

Resting heart rate (RHR) is associated with arterial stiffness, inflammation, and cardiovascular (CV) and all-cause mortality in the general population and in patients at high CV risk. We assessed the association of RHR with arterial stiffness and low-grade inflammation (LGI) in a cross-sectional study that included 101 women with systemic lupus erythematosus (SLE) without a history of CV disease or arrhythmia or who were under treatment that may cause bradycardia. Pulse wave velocity (PWV; a measure of arterial stiffness), RHR, and markers of LGI (ie, C-reactive protein, fibrinogen, erythrocyte sedimentation rate, insulin, and homeostatic model assessment index) were measured. The patients with the highest RHR (quartile 4; mean RHR = 87.2 bpm) had a PWV 0.61 m/s (95% confidence interval [CI]: 0.08-1.14; P = .024) greater than patients with the lowest RHR (quartile 1; RHR = 63.0 bpm), independent of age, systolic blood pressure, disease activity, smoking, and being physically inactive. Similarly, patients with the highest RHR (quartile 4) showed a significantly less favorable clustered LGI index than patients in quartile 1 ( b = .58; 95% CI: 0.212-0.948; P = .002). Higher RHR is associated with greater arterial stiffness and LGI in women with SLE. Further research to determine the prognostic value of RHR in this population is warranted.

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.

Objectives: This study analyzed sleep quality in fibromyalgia (FM) and systemic lupus erythematosus (SLE) and explored its relationship with other clinical and psychological manifestations.Methods:...

Background: Despite the relevant advance in treatment options and survival rates in systemic lupus erythematosus (SLE), patient’s quality of life (QOL) and other patient-reported outcomes (PROs) do not seem to improve accordingly [1]. PROs provide valuable information about the patient’s perceptions across a variety of domains that should be considered in a successful management of this condition [2]. Exercise seems to be a safe way to improve cardiorespiratory fitness [3], and could have also a positive influence on PROs in SLE. Objectives: To evaluate the effects of 12-week aerobic exercise intervention on PROs (QOL, depression, stress, and fatigue) in women with SLE. Methods: These are secondary outcomes of a non-randomized clinical trial [NCT03107442]. A total of 58 participants with SLE were assigned to exercise group (n=26) or control group (n=32). The exercise intervention followed the American College of Sports Medicine guidelines, and consisted of 12-week progressive aerobic exercise on a treadmill (2 sessions/week) between 40%-75% of the individual’s heart rate reserve [3]. Attendance of ≥75% was set for inclusion in the analyses. The control group received verbal information about a healthy lifestyle. At baseline, and at week 12, PROs were assessed including the physical and mental summary scores of the 36-item Short-Form Health Survey (SF-36), depression (Beck Depression Inventory; BDI-II), perceived stress (visual analogue scale) and fatigue (Multidimensional Fatigue Inventory; MFI-20). A total of 49 women with SLE (age: 44.5±14.2 years) completed all the assessments (exercise=21; control=28) and were included in the per-protocol (primary) analyses. The exercise and control group were comparable in age, disease duration and SLE activity, sociodemographic characteristics, and BMI at baseline, although there were differences in BDI-II scores. Baseline values and BDI-II values were used as covariates in the analyses. Results: In comparison to the control group, the exercise group showed a significant reduction in general fatigue (mean difference -2.11 units; 95% CI -4.18 to -0.04; P=0.046) and physical fatigue (mean difference -3.90 units; 95% CI -6.3 to -1.5; P= 0.002) following the intervention. There were no between-group differences in the changes from baseline to week 12 either in physical (P=0.828) or mental (P=0.767) QOL, depression (P=0.498), perceived stress (P=0.247) or other fatigue dimensions (mental, reduced motivation, reduced activity, all P>0.05). Conclusion: The results of this study suggest that 12 weeks of progressive aerobic exercise might improve relevant dimensions of fatigue in women with SLE, despite absence of effects on QOL, depression or perceived stress. References: [1] Mcelhone K, Abbott J, Teh L-S. A review of health related quality of life in systemic lupus erythematosus. Lupus. 2006;15: 633–643. [2] Mahieu M, Yount S, Ramsey-Goldman R. Patient-reported outcomes in systemic lupus erythematosus. Rheum Dis Clin. Elsevier; 2016;42: 253–263. [3] Soriano-maldonado A, Morillas-de-laguno P, Sabio M. Effects of 12-week Aerobic Exercise on Arterial Stiffness, Inflammation, and Cardiorespiratory Fitness in Women with Systemic LUPUS Erythematosus: Non-Randomized Controlled Trial. J Clin Med. 2018; 1–17. Disclosure of Interests: None declared

Background and objectives: Higher physical fitness is associated with a more favorable weight and body composition in the general population, although this association has not been studied in patients with systemic lupus erythematosus (SLE). The aim of the present study was to examine the association of different components of physical fitness with body composition in women with SLE with mild disease activity. Materials and Methods: This cross-sectional study included 77 women with SLE (43.2 &plusmn, 13.8 years old) and clinical stability during the previous 6 months. Body composition (including body mass index (BMI), fat mass index (FMI), waist circumference, waist-to-height ratio and waist-to-hip ratio) was assessed using a stadiometer, an anthropometric tape, and a bioimpedance device. Physical fitness included cardiorespiratory fitness (Siconolfi step test and 6 min walk test), muscular strength (handgrip strength test as upper body measure and 30 s chair stand as lower body measure), and flexibility (back-scratch test). Participants with a fitness level equal or above the median of the study sample were categorized as &ldquo, fit&rdquo, and those below the median were categorized as &ldquo, unfit&rdquo, Linear regression assessed the association of physical fitness with body composition parameters. Results: Cardiorespiratory fitness and upper body muscular strength were negatively associated with BMI, FMI, waist circumference, and waist-to-height ratio (all, p &lt, 0.05). Lower body muscular strength and flexibility were negatively related to FMI, waist circumference, waist-to-height ratio, and waist-to-hip ratio (all, p &lt, 0.05). These relationships were still significant after controlling for age, disease duration, accrual damage, and SLE activity. Overall, fit patients presented significantly lower values in all body composition parameters compared to unfit patients (all, p &lt, 0.05). Conclusions: The main findings of the present study suggest that physical fitness is inversely associated with body composition in women with SLE. Given the cross-sectional nature of this study, future clinical trials should study the causal pathways underlying these relationships.

This study aimed to examine the association of relative handgrip strength (rHGS) with cardiometabolic disease risk factors in women with systemic lupus erythematosus (SLE). Methods: Seventy-seven women with SLE (mean age 43.2, SD 13.8) and clinical stability during the previous six months were included. Handgrip strength was assessed with a digital dynamometer and rHGS was defined as absolute handgrip strength (aHGS) divided by body mass index (BMI). We measured blood pressure, markers of lipid and glucose metabolism, inflammation (high sensitivity C-reactive protein [hs-CRP]), arterial stiffness (pulse wave velocity [PWV]), and renal function. A clustered cardiometabolic risk index (z-score) was computed. Results: Pearson0 s bivariate correlations revealed that higher rHGS was associated with lower systolic blood pressure (SBP), triglycerides, hs-CRP, PWV, and lower clustered cardiometabolic risk (rrange = from −0.43 to −0.23; all p < 0.05). Multivariable linear regression analyses adjusted for age, disease activity (SLEDAI), and accrual damage (SDI) confirmed these results (all p < 0.05) except for triglycerides. Conclusions: The findings suggest that higher rHGS is significantly associated with lower cardiometabolic risk in women with SLE., Consejería de Salud, Junta de Andalucía (grant numbers: PI-0525-2016 and PIER-0223-2019), Spanish Ministry of Education (FPU15/00002), Spanish Ministry of Science, Innovation and Universities (FPU18/01107), Gerty Cory pre-doctoral program for deficit areas at the University of Almería

To the Editor: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis affecting the small- and medium-sized arteries. It is characterized by bronchial asthma often accompanied by pulmonary infiltrates, chronic sinusitis, nasal polyps, and peripheral blood eosinophilia, and occasionally followed by a multisystem vasculitic phase involving several organs. Neurological involvement occurs in 51%–86%, usually affecting the peripheral nerves. Conversely, the central nervous system (CNS) is seldom affected (< 10%). In these cases, cerebral ischemic infarction (∼80%) and diffuse encephalopathy (∼10%) have been by far the findings most frequently reported. Published data on EGPA with CNS hemorrhage are limited to anecdotal case reports1–10,11–20,21,22,23,24,25,26. We described a case of EGPA presenting with intracerebral hemorrhage (ICH) and did a comprehensive review of the literature. Ethics board approval was not required in accordance with the policy of our hospital. A 48-year-old man was admitted because of malaise, intermittent low-grade fever, and mild weight loss in … Address correspondence to Dr. J.M. Sabio, Servicio de Medicina Interna, 9th planta Hospital Universitario Virgen de las Nieves, Avda. Fuerzas Armadas No. 2, 18012 Granada, Spain. E-mail: jomasabio{at}gmail.com

This study assessed the effect of 12-week aerobic exercise on arterial stiffness (primary outcome), inflammation, oxidative stress, and cardiorespiratory fitness (secondary outcomes) in women with systemic lupus erythematosus (SLE). In a non-randomized clinical trial, 58 women with SLE were assigned to either aerobic exercise (n = 26) or usual care (n = 32). The intervention comprised 12 weeks of aerobic exercise (2 sessions &times, 75 min/week) between 40&ndash, 75% of the individual&rsquo, s heart rate reserve. At baseline and at week 12, arterial stiffness was assessed through pulse wave velocity (PWV), inflammatory (i.e., high-sensitivity C-reactive protein [hsCRP], tumor necrosis factor alpha [TFN-&alpha, ], and inteleukin 6 [IL-6]) and oxidative stress (i.e., myeloperoxidase [MPO]) markers were obtained from blood samples, and cardiorespiratory fitness was assessed (Bruce test). There were no between-group differences in the changes in arterial stiffness (median PWV difference &minus, 0.034, 95% CI &minus, 0.42 to 0.36 m/s, p = 0.860) or hsCRP, TNF-&alpha, IL-6, and MPO (all p &gt, 0.05) at week 12. In comparison to the control group, the exercise group significantly increased cardiorespiratory fitness (median difference 2.26 minutes, 95% CI 0.98 to 3.55, p = 0.001). These results suggest that 12 weeks of progressive treadmill aerobic exercise increases cardiorespiratory fitness without exacerbating arterial stiffness, inflammation, or oxidative stress in women with SLE.

Background There is an increasing prevalence of insulin resistance and metabolic syndrome in Systemic Lupus Erythematosus (SLE). Follistatin-like 1 (FSTL-1) is a secreted glycoprotein recently identified as a proinflammatory cytokine and emerging as a potential mediator of inflammation. Its plasma levels are elevated in rheumatoid arthritis and correlate with disease activity. In fact, FSTL-1 has been proposed as a marker of autoimmune diseases. However, it is not clear whether this protein plays a role in SLE. We aimed to evaluate the plasma FSTL-1 value of patients with SLE and the interactions between their plasma concentration, metabolic syndrome variables, markers of activity and disease damage. Methods Plasma concentration of FSTL-1 of 40 female SLE patients and 20 healthy controls was measured by enzyme-linked immunosorbent assay (ELISA). Metabolic variables, activity and disease damage were measured and analyzed. The activity of SLE was determined by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K). Damage accumulated was calculated by the Index of Damage SLICC/ACR (SDI Damage index). A one-way ANOVA test was performed to assess the difference between the mean FSTL-1 values in different groups. Interactions between variables of the database and their effect on FSTL-1 was evaluated using a regression tree technique. Results Healthy controls and SLE females attended on an outpatient basis had a mean of 38±16 and 40±13 years old respectively. SLE patients had low levels of activity and damage measured both by the scores and by the individual parameters of inflammatory activity. The mean value of FSTL-1 was 12213±1424 pg/ml for healthy individuals. Of the SLE patients 57% had a mean value of 4855±662.8 pg/ml and 43% had a mean of 68000±4789 pg/ml. There was a significant difference between the subgroup of SLE with high value of FSTL-1 compared to the control (p-value Conclusions FSTL-1 is significantly elevated in patients with SLE compared to controls. Moreover, elevated levels were observed in SLE patients with elevated leptin, cholesterol or insulin. More studies are needed to determine if there is a pathogenic role, and if this population have a worse long-term cardiovascular prognosis.

The correct diagnosis, classification and therapeutic management of thrombotic microangiopathies (TMA) continue to be a challenge for the clinician. We report a rare case of eosinophilic granulomatosis with polyangiitis (EGPA) as a trigger for complement-mediated TMA in a 57-year-old man who was successfully treated with corticoids, cyclophosphamide and therapeutic plasma exchange. Additionally, we review few other cases reported in the literature and the pathophysiological pathway of association between TMA and EGPA. We found that the mutual relationships between the inflammation triggered by vasculitis, the exacerbated complement activation, together with hypereosinophilia and endothelial damage seem to be the key in explaining the connection between both entities. We suggest that an understanding of the multi-causal nature of TMAs is crucial for the correct diagnosis and treatment of these patients.

A rare variant (BAFF-var) of the tumor necrosis factor superfamily 13b (TNFSF13B) gene has been recently associated with multiple sclerosis (MS) and systemic lupus erythematosus (SLE). The aim of this study was to investigate the association between TNFSF13B BAFF-var and susceptibility to rheumatoid arthritis (RA) and replicate that association in SLE. 6,218 RA patients, 2,575 SLE patients and 4,403 healthy controls from three different countries were included in the study. TNFSF13B BAFF-var was genotyped using TaqMan allelic discrimination assay. PLINK software was used for statistical analyses. TNFSF13B BAFF-var was significantly associated with RA (p = 0.015, OR = 1.21, 95% CI = 1.03–1.41) in the Spanish cohort. A trend of association was observed in the Dutch (p = 0.115) and German (p = 0.228) RA cohorts. A meta-analysis of the three RA cohorts included in this study revealed a statistically significant association (p = 0.002, OR = 1.24, 95% CI = 1.10–1.38). In addition, TNFSF13B BAFF-var was significantly associated with SLE in the Spanish (p = 0.001, OR = 1.41, 95% CI = 1.14–1.74) and the German cohorts (p = 0.030, OR = 1.86, 95% CI = 1.05–3.28), with a statistically significant p-value obtained in the meta-analysis (p = 0.0002, OR = 1.46, 95% CI = 1.09–2.32). The results obtained confirm the known association of TNFSF13B BAFF-var with SLE and, for the first time, demonstrate that this variant contributes to susceptibility to RA., This work was supported by the following grants: P12-BIO-1395 from Consejería de Innovación, Ciencia y Tecnología, Junta de Andalucía (Spain), and the Cooperative Research Thematic Network (RETICS) program, RD16/0012/0004 (RIER), from Instituto de Salud Carlos III (ISCIII, Health Ministry, Madrid, Spain). DGS was supported by the Spanish Ministry of Economy and Competitiveness through the program FPI (SAF2015-66761-P).

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., This work was supported by Fundación para la Investigación Biosanitaria de Andalucia Oriental, Grant numbers: PI-0525-2016 (http:// www.fibao.es/; http://www.ibsgranada.es/) to JAVH. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Blood pressure (BP) physiologically declines more than 10% at night. Subjects who do not experience this drop are classified as non-dippers. They have a higher risk of cardiovascular diseases (CVD). Vitamin D deficiency and non-dipper pattern have been associated in the general population. Patients with systemic lupus erythematosus (SLE) are more likely to have vitamin D deficiency, a non-dipper pattern and CVD. We aimed to evaluate a possible relationship between vitamin D deficiency and non-dipper pattern in patients with SLE.Using 24-hour ambulatory BP monitoring, 77 women with SLE were divided into dippers and non-dippers. 25-hydroxyvitamin D (25(OH)D) levels were compared between both groups. A multivariate analysis was used to determine which variables were independently associated with non-dipper pattern.62% of patients were non-dippers. They had lower levels of 25(OH)D than dippers (19.4±8.9 vs. 25.9±10.1 ng/ml, p=0.005). Patients with lower 25(OH)D levels were more likely to be non-dippers (OR 3.7, 95%CI 1.2-11.4; p=0.025). The nocturnal decline of mean BP correlated with levels of 25(OH)D (r=0.227, p=0.047). Night-time systolic, diastolic and mean BP inversely correlated with the levels of 25(OH)D (r=-0.274, p=0.016; r=-0.238, p=0.037, and r=-0.260, p=0.022, respectively), but only night- time systolic BP remained significant after adjustment for age and body mass index (r=-0.228, p=0.049). 25(OH)D levels and the use of mycophenolate were found to be independently associated with non-dipper pattern in SLE patients.Vitamin D deficiency may contribute to the development of a non-dipper pattern in patients with SLE.

Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE. © 2015 Elsevier Inc.

Objective To compare the presence of subclinical atherosclerosis measured by means of pulse wave velocity (PWV) in women with primary Sjogren's syndrome (SS) versus a healthy age- and sex-matched control group, and to identify factors independently associated with PWV in primary SS. Methods Forty-four women with primary SS and 78 age-matched healthy women without overt cardiovascular (CV) diseases were assessed for traditional and nontraditional CV risk factors. PWV was also performed. A linear regression analysis was used to identify factors independently associated with PWV in primary SS. Results Women with primary SS had significantly higher PWV than controls (P = 0.030), and the frequency of increased PWV was significantly higher in this group (25% versus 8%; P = 0.013). The proportion of patients ages ≤50 years (ratio 4.6) with increased PWV was almost 2-fold higher than those ages >50 years (ratio 2.4) with respect to controls. Positivity for anti-SSB was more frequent in patients with normal PWV than in those with increased PWV (61% versus 18%; P = 0.034). Women with primary SS and increased PWV had lower levels of 25-hydroxyvitamin D (25[OH]D; P = 0.047) than primary SS patients with normal PWV. In addition, 25(OH)D levels tended to correlate inversely with PWV in women with primary SS (P = 0.067), but not in controls (P = 0.97). In multivariate analysis, the Framingham Risk Score (FRS) and Sjogren's Syndrome Damage Index emerged as factors independently correlated with PWV. Conclusion Women with primary SS had higher PWV than controls, but a similar FRS. The FRS and chronic damage were found to be independently associated with PWV.

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.

To evaluate psychopathological status and stress level from a sample with SLE; compare mental functioning and stress levels between women with SLE and healthy women; determine whether disease duration, disease activity, cumulative organ damage and stress have an influence on psychopathological symptoms in SLE patients; and evaluate whether perception of stress is related to SLE severity.We conducted a cross-sectional study of 425 participants; 202 women with SLE, with an average age (SD) of 36.61 (10.15), and 223 healthy women, with age-matched controls. The assessment included the clinical characteristics (disease duration, SLE activity, cumulative organ damage, pharmacotherapy), the Symptom Checklist-90-Revised (SCL-90-R) and the Perceived Stress Scale. Descriptive, comparative, univariate and multivariate analysis were performed.SLE patients showed psychopathological alterations in the somatisation, obsessive-compulsive and positive discomfort subscales of SCL-90-R. Women with SLE reported significantly higher scores on the psychopathological dimensions and perceived stress compared to healthy women, except for paranoid ideation. Disease duration, SLE activity, cumulative organ damage, and perceived stress were shown to be significant predictors of psychopathological manifestations, explaining a range, between 20 and 43%, of variance across SCL-90-R dimensions. Moreover, perceived stress was related to SLE activity, after controlling for psychopathological dimensions.The psychopathological manifestations in SLE appeared to be influenced by perceived stress, disease duration, disease activity and cumulative organ damage. In turn, perceived stress was associated with disease severity. This knowledge may contribute to a more comprehensive perspective of these manifestations in the SLE population in the clinical setting.

Background We tested whether GW0742, a peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) agonist, improves endothelial dysfunction induced by plasma from patients with systemic lupus erythematosus (SLE) involving the inhibition of endoplasmic reticulum (ER) stress. Methods A total of 12 non-pregnant women with lupus and 5 non-pregnant healthy women (controls) participated in the study. Cytokines and double-stranded DNA autoantibodies (anti-dsDNA) were tested in plasma samples. Endothelial cells, isolated from human umbilical cord veins (HUVECs), were used to measure nitric oxide (NO), intracellular reactive oxygen species (ROS) production, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and ER stress markers. Results Interferon-γ, interleukin-6, and interleukin-12 levels were significantly increased in plasma from patients with SLE with active nephritis (AN), as compared to both patients with SLE with inactive nephritis (IN) and the control group. The NO production stimulated by both the calcium ionophore A23187 and insulin was significantly reduced in HUVECs incubated with plasma from patients with AN-SLE as compared with the control group. Plasma from patients with IN-SLE did not modify A23187-stimulated NO production. Increased ROS production and NADPH oxidase activity were found in HUVECs incubated with plasma from patients with AN-SLE, which were suppressed by the ER stress inhibitor 4-PBA and the NADPH oxidase inhibitors, apocynin and VAS2870. GW0742 incubation restored the impaired NO production, the increased ROS levels, and the increased ER stress markers induced by plasma from patients with AN-SLE. These protective effects were abolished by the PPARβ/δ antagonist GSK0660 and by silencing PPARβ/δ. Conclusions PPARβ/δ activation may be an important target to control endothelial dysfunction in patients with SLE.

ObjectivesDuring the last years, genome-wide association studies (GWASs) have identified a number of common genetic risk factors for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, the genetic overlap between these two immune-mediated diseases has not been thoroughly examined so far. The aim of the present study was to identify additional risk loci shared between RA and SLE.MethodsWe performed a large-scale meta-analysis of GWAS data from RA (3911 cases and 4083 controls) and SLE (2237 cases and 6315 controls). The top-associated polymorphisms in the discovery phase were selected for replication in additional datasets comprising 13 641 RA cases and 31 921 controls and 1957 patients with SLE and 4588 controls.ResultsThe rs9603612 genetic variant, located nearby the COG6 gene, an established susceptibility locus for RA, reached genome-wide significance in the combined analysis including both discovery and replication sets (p value=2.95E−13). In silico expression quantitative trait locus analysis revealed that the associated polymorphism acts as a regulatory variant influencing COG6 expression. Moreover, protein–protein interaction and gene ontology enrichment analyses suggested the existence of overlap with specific biological processes, specially the type I interferon signalling pathway. Finally, genetic correlation and polygenic risk score analyses showed cross-phenotype associations between RA and SLE.ConclusionsIn conclusion, we have identified a new risk locus shared between RA and SLE through a meta-analysis including GWAS datasets of both diseases. This study represents the first comprehensive large-scale analysis on the genetic overlap between these two complex disorders.

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P, Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong ethnic and gender bias. In a transancestral genetic association study, Langefeld et al. identify 24 novel regions associated with risk to lupus and propose a cumulative hits hypothesis for loci conferring risk to SLE.

Objective Homocysteine has been linked to atherosclerosis and hypertension (HT) in the general population. However, there is limited evidence regarding the effect of homocysteine on blood pressure and arterial stiffness in systemic lupus erythematosus (SLE). We examined whether homocysteine is associated with HT and arterial stiffness in women with SLE. Methods In total, 99 women with SLE without a history of cardiovascular disease or diabetes mellitus and 101 matched controls were included in this cross-sectional study. Participants were analyzed for homocysteine levels, cardiovascular risk factors, and arterial stiffness assessed by means of carotid–femoral pulse wave velocity (PWV). Associations between homocysteine, systolic blood pressure (SBP), PWV, and HT were tested using univariate and multivariate analyses. Results Homocysteine levels (mean ± SD 12.3 ± 4.8 versus 9.3 ± 3.8 μmoles/liter), PWV (mean ± SD 7.54 ± 1.1 versus 7.10 ± 1.1 meters/second), SBP (mean ± SD 119 ± 13 versus 115 ± 12 mm Hg), and the prevalence of hyperhomocysteinemia (23% versus 7%) and HT (43% versus 12%) were significantly higher in women with SLE (P < 0.050 for all). In the univariate analysis, homocysteine correlated positively with SBP (P = 0.001) and PWV (P = 0.023) in women with SLE but not in controls. In the multiple linear regression analysis, SBP was independently associated with homocysteine and body mass index (BMI) in women with SLE. Similarly, in the multivariate logistic regression analysis, homocysteine levels (or hyperhomocysteinemia), BMI, and daily prednisone dose were independently associated with HT in women with SLE. Conclusion Homocysteine was independently associated with SBP and HT in women with SLE, but not in controls. Elevated homocysteine levels could increase the risk of HT in SLE.

Hydroxychloroquine has been shown to be efficacious in the treatment of autoimmune diseases, including systemic lupus erythematosus. Hydroxychloroquine-treated lupus patients showed a lower incidence of thromboembolic disease. Endothelial dysfunction, the earliest indicator of the development of cardiovascular disease, is present in lupus. Whether hydroxychloroquine improves endothelial function in lupus is not clear. The aim of this study was to analyze the effects of hydroxychloroquine on hypertension, endothelial dysfunction, and renal injury in a female mouse model of lupus. NZBWF1 (lupus) and NZW/LacJ (control) mice were treated with hydroxychloroquine 10 mg/kg per day by oral gavage, or with tempol and apocynin in the drinking water, for 5 weeks. Hydroxychloroquine treatment did not alter lupus disease activity (assessed by plasma double-stranded DNA autoantibodies) but prevented hypertension, cardiac and renal hypertrophy, proteinuria, and renal injury in lupus mice. Aortae from lupus mice showed reduced endothelium-dependent vasodilator responses to acetylcholine and enhanced contraction to phenylephrine, which were normalized by hydroxychloroquine or antioxidant treatments. No differences among all experimental groups were found in both the relaxant responses to acetylcholine and the contractile responses to phenylephrine in rings incubated with the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester. Vascular reactive oxygen species content and mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase subunits NOX-1 and p47phox were increased in lupus mice and reduced by hydroxychloroquine or antioxidants. Chronic hydroxychloroquine treatment reduced hypertension, endothelial dysfunction, and organ damage in severe lupus mice, despite the persistent elevation of anti–double-stranded DNA, suggesting the involvement of new additional mechanisms to improve cardiovascular complications. This work was supported by grants from Comisión Interministerial de Ciencia y Tecnología (SAF2010-22066-C02-01, SAF2011-28150), Junta de Andalucía (Proyecto de excelencia, P12-CTS-2722), Ministerio de Ciencia e Innovación Campus de Excelencia Internacional (Programa GREIB), and Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (Red HERACLES RD06/0009, RIC RD12/0042/0011 and RD12/0042/0040), Spain. M.J. Zarzuelo is a holder of studentship from Spanish Ministry of Science and Education.

Objective.To compare the prevalence and disability of headache in patients with systemic lupus erythematosus (SLE) with the general population and to assess the role of chronic psychological stress (CPS) in headache development.Methods.One hundred seventy patients with SLE and 102 control subjects matched for age, sex, and level of education were included in this multicenter, cross-sectional study. CPS, headache-related disability, and chronic analgesic intake (CAI) were evaluated in all participants.Results.No statistical differences in the prevalence of headache between both groups were observed but headache disability was significantly higher in patients with SLE. In addition, a higher average score in the Cohen Perceived Stress Scale (CPSS) and a higher prevalence of patients with CAI were observed in patients with SLE. In multivariate analysis, CPSS score was positively (OR 1.09; 95% CI: 1.03–1.14; p = 0.001) and CAI negatively (OR 0.43; 95% CI: 0.19–0.99; p = 0.049) associated with headache in patients with SLE.Conclusion.Despite the prevalence of headache in patients with SLE and the general population being similar, headache-related disability may be higher in patients with SLE. Moreover, CPS might play a role in the pathogenesis of SLE headache, whereas CAI might have a protective effect against it.

ObjectivesTo 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.MethodsThis 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).ResultsFlexibility was positively associated with the physical function dimension and the physical component summary (PCS) (rpartial between 0.26 and 0.31; pConclusionsOur 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.