Heart Rate Variability in Women with Systemic Lupus Erythematosus: Association with Health-Related Parameters and Effects of Aerobic Exercise

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-0223-2019Spanish Ministry of Universities FPU18/0110

Effects of 12-week Aerobic Exercise on Arterial Stiffness, Inflammation, and Cardiorespiratory Fitness in Women with Systemic LUPUS Erythematosus: Non-Randomized Controlled Trial

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 X 75 min/week) between 40–75% of the individual’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- α], 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 -0.034, 95% CI -0.42 to 0.36 m/s; p = 0.860) or hsCRP, TNF-α, IL-6, and MPO (all p > 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.This work was supported by Fundación para la Investigación Biosanitaria de Andalucía Oriental (grant number: PI-0525-2016) and the Ilustre Colegio Oficial de Médicos de Granada (Premios de Investigación 2017). BG-C was supported by the Spanish Ministry of Education (FPU15/00002)

Relative Handgrip Strength as Marker of Cardiometabolic Risk in Women with Systemic Lupus Erythematosus

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 Almerí

Does stress response axis activation differ between patients with autoimmune disease and healthy people?

Many studies have shown that patients with autoimmune disease present a hypoactive hypothalamic-pituitary-adrenal (HPA) axis, but the results are controversial. Our objective was to study differences in stress response axis activity between patients with autoimmune disease and healthy people. The study sample consisted of 97 women divided into four groups: 37 healthy women (HW), 21 with systemic lupus erythematosus (SLE), 21 with Sjögren's syndrome (SS), and 18 with systemic sclerosis (SSc). After being exposed to a stress task, participants' skin conductance and salivary cortisol levels were measured in order to assess their response to psychological stress. Diurnal cortisol concentrations were assessed by measuring salivary cortisol in samples collected five times over one day. In addition, self-administered questionnaires were used to assess psychological variables. A time × group interaction effect was found (p = 0.003) in salivary cortisol secretion in response to stressful challenge. The healthy group presented normal activation, the SS and SLE groups showed no activation, and the SSc group presented a similar activation pattern to the HW group, except at the time of recovery. Total cortisol production (AUCg) was higher in the SSc group than in the HW group (p = 0.001). Differences were also observed in the cortisol AUCg collected over one day between healthy women and patients with SLE (p = 0.004) as well as with SSc (p = 0.001): women with SLE and SSc presented higher total hormone production than healthy women. Patients with autoimmune disease present a different HPA axis response, which may contribute to the harmful effects of stress in these diseases.Spanish Ministry of Economy and Competitiveness, Grant/Award Number: PSI2010‐1578

A 62-year-old male with Raynaud’s phenomenon

Varón de 62 años que consulta por fenómeno de Raynaud en ambas manos de un mes de evolución acompañado de lesiones digitales necróticas e intenso dolor. La anamnesis y la exploración física no aportaron información adicional y la capilaroscopia solo evidenció pobreza vascular. Fueron normales o negativas tanto pruebas de laboratorio (hemograma, bioquímica, hormonas tiroideas, marcadores tumorales, serologías frente a hepatitis B y C, proteinograma, inmunoglobulinas, complemento, crioglobulinas y estudio de autoinmunidad), como de imagen (ecocardiografía, TAC toraco-abdominal y PET-TAC) e incluso una biopsia de las lesiones isquémicas. Sin embargo, el estudio de trombofilia mostró una mutación heterocigota para los genes de la metilen-tetrahidrofolato reductasa y del factor XII, así como positividad de los anticuerpos antifosfolipídicos (anti ß2-glicoproteína). Alcanzado el diagnóstico de síndrome antifosfolipídico y trombofilia genética, se inició tratamiento con vasodilatadores (prostaciclinas y bosentán) y anticoagulantes orales, los cuales permitieron una favorable evolución de las lesiones isquémicas.A 62-year-old male presented with a one month history of Raynaud’s phenomenon in both hands along with digital necrotic lesions and severe pain. The medical history and physical examination did not provide any additional information and nailfold capillaroscopy only showed escarce vasculature. Both laboratory (blood count, blood chemistry, thyroid hormones, tumor markers, serologies for hepatitis B and C, proteinogram, immunoglobulins, complement, cryoglobulins, autoimmunity tests) and imaging tests (echocardiography, thoracic and abdominal CT scan and a PET-CT) and even a biopsy of the ischemic lesions were normal or negative. However, the thrombophilia workup showed a heterozygous mutation in the genes of the methylenetetrahydrofolate reductase and the factor XII, and positivity for antiphospholipid antibodies (anti-beta2-glycoprotein). Once the diagnosis of antiphospholipid syndrome and genetic thrombophilia were made, treatment with oral vasodilators (prostacyclin and bosentan) and oral anticoagulants were started, which produced a satisfactory evolution of the ischemic lesions

Physical Fitness and Body Composition in Women with Systemic Lupus Erythematosus

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 ± 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 “fit” and those below the median were categorized as “unfit”. 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 waistto- height ratio (all, p < 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 < 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 < 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 work was supported by Consejería de Salud, Junta de Andalucía (grant number: PI-0525-2016) and by the Ilustre Colegio Oficial de Médicos de Granada (Premios de Investigación 2017). BGC was supported by the Spanish Ministry of Education (FPU15/00002)

Ambulatory follow-up of patients with lupus in a systemic autoimmune disease unit

Objetivos: Describir los síntomas referidos por los pacientes con lupus eritematoso sistémico (LES) durante su seguimiento ambulatorio en una Unidad de Enfermedades Autoinmunes Sistémicas (UEAS), la relación de éstos con el propio LES o con otras patologías y la necesidad de derivación a otros especialistas. Material y Métodos: Se realizó un análisis descriptivo prospectivo durante 5 meses que incluyó a 112 pacientes con LES en seguimiento ambulatorio por una UEAS. Se valoró la sintomatología padecida desde la última revisión, tuviera o no relación con el LES y la prevalencia de pacientes derivados a otros especialistas. Resultados: Ochenta (71.4%) pacientes presentaron sintomatología no explicable por el LES, destacando la artralgias por artrosis y el síndrome ansioso-depresivo. Presentaron síntomas asociados al LES 32 (23.5%) pacientes, siendo el brote articular en 10 (8.3%) pacientes, el brote renal en 8 (7.1%) y el brote cutáneo en 5 (4.4%) los más frecuentes. Por último, fueron derivados a otros especialistas 10 (8.3%) pacientes. Conclusiones: Durante el seguimiento ambulatorio en una UEAS de los pacientes con LES, la prevalencia de consultas por síntomas y enfermedades no relacionadas con el LES podría ser superior a aquellas atribuibles al propio LES, subrayando la necesidad de una visión global y multidisciplinar en el manejo de estos pacientes.Objectives: To describe the symptoms referred by the patients with systemic lupus erythematosus (SLE) during their ambulatory follow-up by an Autoinmune Disease Unit (ADU), the relationship between them and SLE itself or with other clinic entities and the need to refer lupus patients to other specialists. Methods: We performed a descriptive analysis during 5 months that included 112 patients with SLE with ambulatory follow-up by an ADU. We assessed the symptomatology suffered by the patients since the last visit, related or not to SLE, and the prevalence of patients referred to other specialists. Results: Eighty (71.4%) patients had symptoms no explainable by SLE, mainly due to arthralgias secondary to osteoarthrosis and anxiety-depressive syndrome. Thirty-two (23.5%) patients had symptoms related to SLE, the most frequent of which were articular flare in 10 (8.3%) patients, lupus nephritis in 8 (7.1%) and skin flare in 5 (4.4%). Finally, ten (8.3%) patients were referred to other specialists. Conclusions: During the ambulatory follow-up of patients with SLE in an ADU, the frequency of consultations for symptoms and illnesses no related to SLE may be higher than those secondary to SLE, highlighting the need of a global and multidisciplinary management of these patients

Differential diagnosis of systemic lupus erythematosus: Key aspects of day-to-day

Este artículo aborda el diagnóstico diferencial del Lupus eritematoso sistémic

Heart Rate Variability in Women with Systemic Lupus Erythematosus: Association with Health-Related Parameters and Effects of Aerobic Exercise

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

Association between perceived level of stress, clinical characteristics and psychopathological symptoms in women with systemic lupus erythematosus

Objective: 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. Methods: 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. Results: 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. Conclusion: 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.This research was developed in the framework of the I+D Project “SEJ2007-61857” and the I+D Project ‘‘PSI2010- 15780’’, funded by the Spanish Ministry of Education and Science. In addition, this study was supported by the Andalusian Health Service (grant no. PI-0059/2007)